Prevention

References



Baraff, L.J., Lee, T.J., Kader, S. and Della Penna, R. (1999), Effect of a practice

guideline on the process of emergency department care of falls in elder patients.

Academic Emergency Medicine, 6 (12), 1216-1223.



Abstract: Objective: To determine the effect of a practice guideline on the process of ED

care in a health maintenance organization. Methods: A pre- post-intervention

comparison with a one-year pre-intervention phase followed by a one-year

post-educational intervention phase was used to study the effect of the guideline

on ED care. Emergency physicians and nurses were provided the details of the

guideline during a two-week interval between the two periods. Results: During

the two years of the study, 1,140 preintervention and 759 post-intervention

patients met study eligibility criteria. More patients were diagnosed as having

had falls due to loss of consciousness, stroke, and seizures during the

post-intervention period (pre- intervention 3.8% vs post-intervention 8.4%, p 46%. Whole blood viscosity, at low and high

shear rates, plasma viscosity, and fibrinogen were measured on days 0 and 60. In

the ticlopidine group, we recorded a significant 13.14% reduction of the mean

fibrinogen level after treatment (390 +/- 63 vs. 449 +/- 97 mg/dl, p 25

% of all measurements were 140 - 179 mm Hg systolic or 90 - 109 mm Hg

diastolic; and as severe AH if > 25 % of all measurements were > 180 mm Hg

systolic or > 110 mm Hg diastolic. Bleeding complications were registered.

Results: Of the 235 patients (108 female, 67 +/- 12 years), 80 % suffered from

AH. Severe AH was present in 5 %. Only 56 % were aware of suffering from

AH. An improvement of antihypertensive therapy was needed in 64 %. Over 225

days, only one cerebral bleeding occurred. Blood pressure was normotensive in

30 % with known AH. Conclusions: Blood pressure control seems better in OAC

patients than in normals, if the patient is aware of AH. Patients with AH on OAC

are not aware of AH in > 50 %. Repeated blood pressure measurements in OAC

are recommended, even if patients are not aware of AH

Keywords: anticoagulation/antihypertensive therapy/ANTITHROMBOTIC

THERAPY/arterial/arterial hypertension/Austria/AWARENESS/bleeding/blood

pressure/blood pressure control/cerebral/cerebral bleeding/CHRONIC

ATRIAL-FIBRILLATION/COMPLICATIONS/control/HYPERTENSION/oral

anticoagulation/PREVALENCE/PREVENTION/risk/STROKE/therapy/UNIVE

RSITY HOSPITALS/WARFARIN USE



Schick, U., Zimmermann, M. and Stolke, D. (1996), Long-term evaluation of EG-IC

bypass patency. Acta Neurochirurgica, 138 (8), 938-942.



Abstract: The EC-IC Bypass Study Group could not detect any benefit from surgery

compared to medical management in the prevention of strokes in 1985 [15].

During the past years surgical revascularization was re-evaluated and considered

as an appropriate treatment for a small subgroup of patients with recurrent focal

cerebral ischaemia and impaired haemodynamics. This retrospective study

examines the long-term benefit and patency rats of bypass. We present a

follow-up of 5.6 years of 47 patients, all of whom underwent bypass surgery

after 1985. Forty patients suffered recurring transient ischaemic attacks due to

uni- or bilateral internal carotid artery occlusion. Examination included

neurologic status, TCD with CO2 or Diamox challenge, angiography, CT and

SPECT scans. Neurological improvement was seen in 23% of patients with

better results after early surgery, a worsening in 22% suffering further ischaemic

events on a postoperative average of 2.8 years. Patency rate for vein graft

material was 50%, for the STA-MCA procedure 91%. Occlusion of the vein graft

occurred on an average after 1.4 years, other anastomosis after 2.7 years. We

conclude that only few patients derived long-term benefit from EC-IC bypasses.

Functioning of the bypass worsens over time, suggesting a role for surgery

predominantly in the first year of ischaemic events due to insufficient collateral

supply. Actual indications for bypass surgery may be patients with failure of

maximal medical therapy and progressive ischaemia and haemodynamic

compromise



Keywords: ACETAZOLAMIDE/bypass function/bypass grafting/CEREBRAL

BLOOD-FLOW/cerebrovascular reserve capacity/CEREBROVASCULAR

RESERVE CAPACITY/CT/DISEASE/EC-IC bypass/focal/INTERNAL

CAROTID-ARTERY/ischaemia/ISCHEMIA/OCCLUSION/prevention/rats/RE

ACTIVITY/STROKE/SURGERY/treatment



Lowenthal, A. (1988), European Stroke Prevention Study. Acta Neurologica Belgica,

88 (1), 14-18



Lowenthal, A. and Buyse, M. (1994), Secondary Prevention of Stroke - Does

Dipyridamole Add to Aspirin. Acta Neurologica Belgica, 94 (1), 24-34.



Abstract: Background and Purpose : The purpose of this paper is to evaluate, in the light

of all available evidence, the place of aspirin alone and of aspirin combined with

dipyridamole in the secondary prevention of cerebrovascular accidents. Methods :

We performed a meta-analysis of all identified double blind, controlled, studies

in secondary prevention of cerebrovascular accidents for the following

categories : studies comparing aspirin with placebo ; studies comparing aspirin

plus dipyridamole with placebo ; studies comparing aspirin plus dipyridamole

with aspirin alone. An indirect comparison was carried out to compare the results

obtained with aspirin alone and those obtained with aspirin combined with

dipyridamole. Results : The meta-analysis of trials involving aspirin alone

against placebo showed a risk reduction on strokes (17% reduction, p = 0.02),

''important vascular events'', i.e. a combination of vascular deaths, non-fatal

strokes and non-fatal myocardial infarction (18% reduction, p = 0.003). Fatal

vascular events (vascular deaths and fatal strokes) did not seem to be reduced at

all. The overall mortality was reduced by 10%, but this reduction failed to reach

statistical significance (p = 0.23). The meta-analysis of trials involving aspirin

combined with dipyridamole showed more important risk reductions on every

outcome whether fatal or not. Strokes were reduced by 42% (p 65 years or patients with stroke. The overall risk reduction was best in

TIA patients > 65 years of age. The risk reduction with study medication was

40-50% in both sexes and in both age groups. Thus, age of the patient does not

influence the efficacy of antithrombotic therapy. However, since these results are

obtained from a secondary analysis of a subgroup of patients, the results may

need confirmation by further studies



Keywords: ASPIRIN/CEREBRAL-ISCHEMIA/CONTROLLED TRIAL/TRANSIENT

ISCHEMIC ATTACKS



Farina, E., Magni, E., Ambrosini, F., Manfredini, R., Binda, A., Sina, C. and Mariani, C.

(1997), Neuropsychological deficits in asymptomatic atrial fibrillation. Acta

Neurologica Scandinavica, 96 (5), 310-316.



Abstract: Objective - To assess the preclinical effects on cognitive functions of

nonrheumatic atrial fibrillation (NRAF) in patients with negative history for

cerebrovascular disease. Materials and methods - The study included 37

consecutive patients with chronic (n=16, mean age 65.3+/-6.6 years) or

paroxysmal (n=21, mean age 58.3+/-9.5 years) NRAF and an equal number of

control subjects in sinus rhythm, who were matched for age, education and

presence of hypertension, A comprehensive neuropsychological battery

including tests of attention, memory, language and visuospatial skills was

administered. Results - Patients with chronic NRAF showed significantly poorer

performances in tasks exploring attention and verbal memory functions, while

the paroxysmal group was significantly impaired in a long-term memory task,

The neuropsychological findings were confirmed excluding from both groups

patients viith CT evidence of cerebrovascular damage. A small subgroup of

patients was also submitted to cerebral MRI. Conclusion - Neurologically

asymptomatic NRAF is related to a subclinical but significant impairment in

attention and memory. These deficits could be produced by minor ischemic

lesions due to microembolization, or by diffuse hypoxic damage due to

hypoperfusion



Keywords: age/asymptomatic/atrial fibrillation/cerebral/CEREBRAL

BLOOD-FLOW/cerebrovascular/cerebrovascular disease/cognitive

impairment/COMPLICATIONS/control/COPENHAGEN/CT/DISEASE/educati

on/EPIDEMIOLOGIC

FEATURES/fibrillation/history/HYPERTENSION/INFARCTION/ischemic/MR

I/neuropsychological tests/PREVENTION/RISK/STROKE/VASCULAR

DEMENTIA



Sivenius, J., Cunha, L., Diener, H.C., Forbes, C., Laakso, M., Lowenthal, A., Smets, P.

and Riekkinen, P. (1999), Second European Stroke Prevention Study: antiplatelet

therapy is effective regardless of age. Acta Neurologica Scandinavica, 99 (1),

54-60.



Abstract: Background - The Second European Stroke Prevention Study (ESPS2) was a

randomized, placebo-controlled trial that investigated the efficacy of low-dose

acetylsalicylic acid (ASA) and modified-release dipyridamole (DP), alone or in

combination, in the secondary prevention of ischemic stroke. The trial

demonstrated that the combination was significantly more effective than either

agent used alone. The aim of the present study was to evaluate the influence of

age on the efficacy of ASA and DP, alone or in combination, in the secondary

prevention of stroke in the ESPS2 population. Methods and results - A total of

6602 patients were recruited to the ESPS2 and there were 4 treatment groups:

ASA (25 mg twice daily), DP (200 mg twice daily), ASA and DP in a combined

formulation, or placebo. Primary endpoints were stroke, death, and stroke or

death together. The endpoints evaluated in the present study were stroke, stroke

and/or death, and vascular events. Stroke was the qualifying event in 76% of the

patients, while 24% had a transient ischaemic attack. Patients were reviewed at

3-month intervals for 2 years. The study population consisted of 2565 (39%)

patients aged less than 65 years, 2240 (34%) patients aged between 65 and 74

years, and 1797 (27%) patients aged 75 years and over, Advancing age was

associated with an increased incidence of endpoints in all 4 treatment groups.

The combination of ASA and DP significantly reduced the incidence of all

endpoints, compared with placebo, in each age group. There was no influence of

age on the efficacy of antiplatelet therapy for any of the evaluated endpoints.

Relative risk reductions of treatment compared with placebo were 11.1-27.6% in

the ASA group, 8.0-18.7% in the DP group, and 20.3-45.2% in patients receiving

combination therapy. Conclusion - This study clearly demonstrates that

combination therapy with DP and ASA is superior to either agent used alone in

the secondary prevention of ischemic stroke, irrespective of the age of the patient



Keywords: acetylsalicylic acid/age/aged/antiplatelet/antiplatelet therapy/cerebrovascular

disease/COPENHAGEN/DENMARK/dipyridamole/Finland/incidence/ischemic/

ischemic stroke/population/prevention/randomized/risk/secondary

prevention/stroke/therapy/transient/treatment/vascular



Arboix, A., Morcillo, C., Garcia-Eroles, L., Oliveres, M., Massons, J. and Targa, C.

(2000), Different vascular risk factor profiles in ischemic stroke subtypes: a

study from the "Sagrat Cor Hospital of Barcelona Stroke Registry". Acta

Neurologica Scandinavica, 102 (4), 264-270.



Abstract: To characterize the vascular risk factor profiles in different subtypes of

ischemic stroke. Material and methods - The study population consisted of 1473

consecutive ischemic stroke patients collected in a prospective stroke registry.

The prevalence of vascular risk factors in each stroke subtype was analyzed

independently and in comparison with other subtypes of stroke pooled together

by means of univariate analysis and logistic regression models. Results

Hypertension was present in 52% of patients followed by atrial fibrillation in

27% and diabetes in 20"/o. The pattern of risk factors associated with

atherothrombotic stroke included chronic obstructive pulmonary disease (COPD)

(odds ratio [OR] = 2.63), hypertension (OR = 2.55), diabetes (OR = 2.26),

transient ischemic attack (OR = 1.61), and age (OR = 1.03). Previous cerebral

hemorrhage (OR =4.72), hypertension (OR =4.29), obesity (OR = 2.45), and

diabetes (OR = 1.73) were strong predictors of lacunar stroke. In the case of

cardioembolic stroke, atrial fibrillation (OR =22.24), valvular heart disease (OR

= 10.97), and female gender (OR = 1.66) occurred more frequently among

patients with this stroke subtype than among the other stroke subtypes combined.

Conclusion - Different potentially modifiable vascular risk factor profiles were

identified for each subtype of ischemic stroke, particularly COPD in the case of

atherothrombotic stroke and previous cerebral hemorrhage and hypertension in

the case of lacunar infarction



Keywords: age/ASSOCIATION/atrial fibrillation/BODY-FAT/cardioembolic

stroke/cerebral/cerebral hemorrhage/CEREBRAL INFARCTION/cerebral

infarction/CEREBROVASCULAR-DISEASE/cigarette

smoking/CIGARETTE-SMOKING/CONSECUTIVE

PATIENTS/COPENHAGEN/DENMARK/diabetes/diabetes

mellitus/fibrillation/heart/heart

disease/hemorrhage/hypertension/infarction/ischemic/ischemic stroke/lacunar

infarction/LACUNAR INFARCTS/lacunar

stroke/lifestyle/MORTALITY/obesity/POPULATION/predictors/prevalence/PR

EVENTION/risk/risk factor/risk factors/Spain/stroke/transient/transient ischemic

attack/vascular/vascular risk factors



Szolnoki, Z., Somogyvari, F., Kondacs, A., Szabo, M. and Fodor, L. (2001), Evaluation

of the roles of common genetic mutations in leukoaraiosis. Acta Neurologica

Scandinavica, 104 (5), 281-287.



Abstract: Objectives - Leukoaraiosis, a relatively frequent neuroimaging entity, is

presumed to be primarily a vascular problem. However, it can be explained only

in part by vascular risk factors. With the assumption of genetic susceptibility, the

roles of common genetic polymorphisms and mutations in leukoaraiosis were

examined in this study. Material and methods - A detailed clinical scrutiny of

843 Hungarian neurological patients with mild cognitive-like complaints

revealed 229 subjects with leukoaraiosis that was probably vascular in origin:

143 with leukoaraiosis alone (group 1), and 86 with leukoaraiosis plus cerebral

infarction (group 2). In all 229 patients, the methylenetetrahydrofolate reductase

C677T (MTHFR C677T) mutation and angiotensin-converting enzyme (ACE

I/D) polymorphism were examined by means of the PCR technique. The

prevalences of the different genotypes for the examined mutations in the 2

groups were analysed in comparison with the data on 362 neuroimaging

alteration-free subjects as controls. Results - The ACE D/D genotype (38.37%, P

70. The method of data collection in this

pretest proved to be apt for a multicenter study presently being conducted in 23

Neurology departments with an acute stroke unit



Keywords: acute/acute stroke/acute stroke

unit/COMMUNITY/complications/CONSECUTIVE

PATIENTS/COPENHAGEN- STROKE/data

collection/DATA-BANK/Germany/hemorrhage/hospital/hospitals/intracerebral/i

ntracerebral hemorrhage/ischemia/ischemic/ISCHEMIC STROKE/length of

stay/NEW-YORK/NORTH-CAROLINA/outcome/POPULATION/prevention/P

ROGRAMS/REGISTRY/risk/risk factors/secondary

prevention/severity/stroke/stroke treatment/stroke unit/stroke

units/therapy/transient/treatment/vascular



Diener, H.C. (2001), New publications on stroke. Aktuelle Neurologie, 28 (8), 353-358.



Abstract: This review summarizes the most important publications concerning stroke

from the second half of 1999 until the second half of 2000. The most important

studies were performed in the areas of primary prevention and acute therapy



Keywords: acute/ACUTE ISCHEMIC

STROKE/ALCOHOL-CONSUMPTION/ASPIRIN/CAROTID

ENDARTERECTOMY/CHOLESTEROL/CORONARY

HEART-DISEASE/DOUBLE-BLIND/Germany/PLASMINOGEN-ACTIVATO

R/PREVENTION/primary/primary prevention/RANDOMIZED CONTROLLED

TRIAL/review/stroke/therapy



Endres, M. and Masuhr, F. (2002), Is cholesterol a risk factor for stroke? Aktuelle

Neurologie, 29 (5), 247-253.



Abstract: Surprisingly, the question whether or not cholesterol is a stroke risk factor has

remained controversial and somewhat counterintuitive. In contrast to coronary

heart disease, large trials failed to demonstrate a correlation between elevated

serum cholesterol levels and stroke incidence. There is even evidence for an

inverse relation between cholesterol levels and risk of intracerebral hemorrhage.

Moreover, clinical trials in the pre-statin era failed to demonstrate an effect of

cholesterol-lowering on stroke incidence. On the other hand, in the 1990s large

randomized trials demonstrated unequivocally that HMG-CoA reductase

inhibitors (statins) lower stroke risk in patients with coronary heart disease

(CHD). Hence, lipid- lowering therapy with statins is established for stroke

prophylaxis in patients with CHD. The question, however, whether these

protective effects are cholesterol-dependent or rather mediated by cholesterol -

independent (,,pleiotropic") effects, and whether statins may be beneficial for

secondary prevention of stroke in patients without CHD, remains controversial



Keywords: CARDIOVASCULAR EVENTS/CAROTID

ARTERIES/CHD/cholesterol/cholesterol-lowering/clinical

trials/CONTROLLED TRIALS/coronary heart disease/CORONARY

HEART-DISEASE/DIETARY-FAT/disease/Germany/heart/heart

disease/hemorrhage/HMG-CoA reductase

inhibitors/incidence/intracerebral/intracerebral hemorrhage/JAPANESE

MEN/lipid

lowering/MYOCARDIAL-INFARCTION/prevention/prophylaxis/randomized/ra

ndomized trials/RECURRENT EVENTS CARE/REDUCTASE

INHIBITORS/risk/risk factor/secondary/secondary

prevention/serum/SERUM-CHOLESTEROL/statins/stroke/stroke

incidence/therapy/trials



Bosel, J. and Endres, M. (2002), The use of statins in clinical neurology. Aktuelle

Neurologie, 29 (5), 254-261.



Abstract: HMG-CoA reductase inhibitors (statins) are potent cholesterol- lowering drugs

and are established for the treatment of hypercholesterolemia. Furthermore, large

clinical trials (4S, CARE, LIPID) demonstrated that statins are indicated for

secondary prophylaxis of coronary heart disease (CHD) even in patients with

average cholesterol levels. Although hypercholesterolemia is not an established

risk factor for ischemic stroke, these studies demonstrated that statins also reduce

stroke incidence in patients with CHD. The question whether or not statins are

generally indicated for secondary prevention of stroke is subject of two ongoing

trials (i.e. PROSPER, SPARCL). Clinical as well as experimental evidence

supports the notion that statins exert cholesterol-independent

(so-called,pleiotropic") protective effects. These include anti-inflammatory and

anti-thrombotic effects, improvement of endothelial function and even direct

neuroprotective effects. Furthermore, experimental and preliminary clinical

studies suggest a potential role of statins for the treatment of dementia.

Regarding the use of statins in clinical neurology, current evidence only supports

the use for stroke prophylaxis in patients with a history of CHD



Keywords: 4S/ACUTE CORONARY

SYNDROMES/ALZHEIMERS-DISEASE/antithrombotic/C-REACTIVE

PROTEIN/CARE/CHD/cholesterol/CHOLESTEROL REDUCTION/clinical

studies/clinical trials/COA REDUCTASE INHIBITORS/coronary heart

disease/dementia/disease/drugs/endothelial

function/experimental/Germany/heart/heart disease/history/HMG-CoA reductase

inhibitors/HONOLULU-HEART- PROGRAM/HUMAN

GLIOMA-CELLS/hypercholesterolemia/incidence/INCREASES SERUM

CONCENTRATIONS/ischemic/ischemic

stroke/LIPID/neurology/NITRIC-OXIDE

SYNTHASE/prevention/prophylaxis/risk/risk factor/secondary/secondary

prevention/SMOOTH-MUSCLE/statins/stroke/stroke

incidence/treatment/trials/use



Klatsky, A.L. (1999), Moderate drinking and reduced risk of heart disease. Alcohol

Research & Health, 23 (1), 15-23.



Abstract: Although heavier drinkers are at increased risk for some heart diseases,

moderate drinkers are at lower risk for the most common form of heart disease,

coronary artery disease (CAD) than are either heavier drinkers or abstainers. This

association has been demonstrated in large-scale epidemiological studies from

many countries. Abstainers may share traits potentially related to CAD risk, such

as psychological characteristics, dietary habits, and physical exercise patterns.

However, evidence supports a direct protective effect of alcohol, even after data

have been adjusted for the presence of these factors. The alcohol-CAD

relationship is also independent of the hypothetically increased risk status among

abstainers who stopped drinking for medical reasons. All alcoholic beverages

prefect against CAD, although some additional protection may be attributable to

personal traits or drinking patterns among people who share some beverage

preferences or to nonalcohol ingredients in specific beverages. Alcohol's

protective effect may result from favorable alterations in blood chemistry and the

prevention of clot formation in arteries that deliver blood to the heart muscle.

Because CAD accounts for a large proportion of fetal mortality, the risk of death

from all causes is slightly lower among moderate drinkers than among abstainers,

but heavier drinkers are at considerably higher total mortality risk



Keywords: ALCOHOL/alcoholic beverage/ALCOHOLIC BEVERAGE USE/alcoholic

cardiomyopathy/AOD use frequency/AODR (alcohol and other drug related)

disorder/AODR mortality/BEER/BLOOD- PRESSURE/cardiac

arrhythmia/CARDIOVASCULAR MORTALITY/CONSUMPTION/coronary

artery disease/coronary artery

disorder/diseases/DRINKERS/exercise/formation/HEALTH/heart/heavy AOD

use/HIGH-DENSITY-LIPOPROTEIN/HOSPITALIZATION/hypertensive

disorder/literature review/moderate AOD

use/mortality/muscle/MYOCARDIAL-INFARCTION/prevention/protective

factors/public health/RED WINE/risk/risk factors/stroke



Hillbom, M. (1998), Alcohol consumption and stroke: Benefits and risks.

Alcoholism-Clinical and Experimental Research, 22 (7), 352S-358S.



Abstract: The complex relationship between alcohol consumption and stroke includes

both benefits and risks. Regular light-to-moderate consumption of alcohol seems

to decrease the risk for ischemic stroke by reducing atherothrombotic events, but

the underlying mechanism is still unclear. Recent and current (but not previous)

heavy drinking increases the risk for both hemorrhagic and ischemic strokes.

Young and middle-aged men are stricken more often than women or elderly

persons, probably because they are more often current heavy drinkers. Alcoholic

cardiomyopathy is a cause of cardioembolic brain infarction. Cardiac

arrhythmias caused by regular heavy drinking or binge drinking can precipitate

thrombus formation and propagate already existing thrombi from the heart. The

maintenance of high blood pressure by heavy drinking may promote cerebral

arterial degeneration, but the effect of drinking habits on aneurysm formation is

not known. Acute increases in systolic blood pressure and/or alterations in

cerebral arterial tone could serve as mechanisms triggering hemorrhagic strokes

during alcoholic intoxication. We lack studies to show that prevention of heavy

drinking can efficiently influence the occurrence of strokes



Keywords: ALCOHOL/alcohol drinking/blood pressure/cerebral

hemorrhage/CEREBRAL INFARCTION/cerebral

infarction/CEREBROVASCULAR-DISEASE/CIGARETTE-

SMOKING/CORONARY HEART-DISEASE/drug

abuse/elderly/Finland/formation/heart/high blood pressure/ISCHEMIC

STROKE/LOW-DENSITY-LIPOPROTEIN/NORTHERN MANHATTAN

STROKE/PLATELET-AGGREGATION/prevention/risk/SPONTANEOUS

INTRACEREBRAL HEMORRHAGE/stroke/SUBARACHNOID

HEMORRHAGE/subarachnoid hemorrhage/thrombus/women



Dammann, H.G., Burkhardt, F. and Wolf, N. (1999), Enteric coating of aspirin

significantly decreases gastroduodenal mucosal lesions. Alimentary

Pharmacology & Therapeutics, 13 (8), 1109-1114.



Abstract: Background: Low-dose aspirin (acetylsalicylic acid, ASA) increases the risk of

developing peptic ulceration. Aim: To investigate the gastroduodenal mucosal

tolerability of enteric- coated ASA (EC-ASA) 100 mg/day compared to either

placebo (study 1) or plain ASA 100 mg/day (study 2) in healthy volunteers,

Methods: Study 1: Tn this double-blind study 18 volunteers received randomized

dosing with either EC-ASA 100 mg or placebo for 15 days. Study 2: 41

volunteers underwent randomized 7-day dosing of either EC-ASA 100 mg or

plain ASA 100 mg in this double-blind, parallel-group, comparison study. In

both studies acute gastroduodenal mucosal lesions were assessed endoscopically

before treatment, on the morning of day 1 after the first dose (only in study 2),

and on the morning after the last dose of the test medication, Results: Study 1 did

not reveal any significant differences between the lesion scores of EC-ASA and

placebo, In contrast, in study 2 significantly higher total gastroduodenal mucosal

lesion scores were observed on day 1 after the first dose and after 7 days of

dosing with plain ASA (mean sum of the lesion scores in the gastric fundus,

body, antrum and in the duodenal bulb: day 1: plain ASA 3.95 +/- 3.38 vs.

EC-ASA 1.43 +/- 1.91, P = 0.03; day 7: plain ASA 6.35 +/- 4.10 vs, EC-ASA

2.00 +/- 2.02, P = 0.0004). Tolerance of the test drugs was good, and no other

adverse events were observed, Conclusions: Enteric-coated aspirin 100 mg/day

causes significantly less gastroduodenal damage over 7 days than the same dose

of plain aspirin, when given to healthy subjects, There was little gastric injury

and no significant differences between EC-ASA and placebo in this respect



Keywords: acetylsalicylic acid/acute/adverse events/ANTI-INFLAMMATORY

DRUGS/aspirin/BLEEDING PEPTIC-ULCER/BUFFERED

ASPIRIN/COATED

ASPIRIN/drugs/ENGLAND/GASTRIC-ULCER/INJURY/ISCHEMIC

STROKE/LOW-DOSE ASPIRIN/NONSTEROIDAL ANTIINFLAMMATORY

DRUGS/PREVENTION/randomized/risk/treatment



Okamoto, K., Tanaka, M. and Kondo, S. (2002), Treatment of vascular dementia.

Alzheimer'S Disease: Vascular Etiology and Pathology, 977 507-512.



Abstract: We report positron emission tomography (PET) findings of our patients with

vascular dementia, asymptomatic cerebral infarction, and chronic cerebral

circulatory insufficiency. According to the PET studies, it was suggested that

frontal lobe hypoperfusion and hypometabolism play important roles in dementia

caused by cerebral infarctions. It was also suggested that patients with subjective

complaints associated with asymptomatic strokes and patients with chronic

cerebral circulatory insufficiency already exhibited decreased cerebral circulation.

Since therapeutic approaches to vascular dementia after its development are

limited, active control of risk factors and prevention of recurrent stroke during

the developmental process of vascular dementia are important. We review recent

situations in prevention and treatment of vascular dementia



Keywords: asymptomatic/cerebral/cerebral circulation/cerebral

infarction/chronic/control/dementia/development/DOUBLE-BLIND/infarction/J

apan/MULTI-INFARCT DEMENTIA/MULTICENTER/MULTIINFARCT

DEMENTIA/NEW-YORK/NICERGOLINE/patient/patients/PET/positron

emission tomography/positron emission tomography

(PET)/PREVENTION/recurrent stroke/review/risk/risk

factors/STROKE/stroke/THERAPY/treatment/TRIAL/USA/vascular/vascular

dementia



Meyer, J.S., Chowdhury, M.H., Xu, G.L., Li, Y.S. and Quach, M. (2002), Donepezil

treatment of vascular dementia. Alzheimer'S Disease: Vascular Etiology and

Pathology, 977 482-486.



Abstract: Cholinergic deficits are clinicopathological hallmarks of Alzheimer's disease

(DAT) and during the past decade have been the sole target for clinically

effective treatments. By contrast, vascular dementia subtypes (VaD) are

heterogeneous clinical syndromes, and therapeutic approaches have been

directed toward control of vascular risk factors. Little attention has been paid to

cholinergic deficits as a mechanism contributing to cognitive impairments in

VaD as a potential target for treatment. The purpose of the study was to

determine whether there are therapeutic benefits from long-term treatment with

cholinesterase inhibitors among VaD patients. Ten VaD patients were diagnosed

according to DSM-III-R and NINDS-AIREN criteria and classified into subtypes

by neuroimaging. All were treated with titrated doses of donepezil for a mean

interval of 15 months. At baseline and follow-up clinic visits, patients underwent

medical and neurological examinations, as well as neuropsychological testing

including Mini-Mental Status Examinations (MMSE) and Cognitive Capacity

Screening Examinations (CCSE). Cognitive statuses of 10 treated patients were

then compared before and after treatment. Net changes were expressed as annual

MMSE score changes (DeltaMMSE/year) and annual CCSE score changes

(DeltaCCSE/year). Of the 10 treated VaD patients, cognitive improvements were

found when comparisons were made before and after treatment. Ten treated

patients also showed greater cognitive improvements, while untreated patients

showed continued cognitive decline. This study suggests that cholinergic deficits

in VaD are due to neuronal ischemic damage with loss of acetylcholine and that

treatment of VaD with cholinesterase inhibitors is a rational therapy



Keywords: Alzheimer's disease/ALZHEIMERS-DISEASE/benefits/changes/cholinergic

deficits/cholinesterase inhibitors/CLINICAL DETERMINANTS/cognitive

decline/control/dementia/disease/donepezil/ischemic/medical/MMSE/NEW-YO

RK/NINDS-AIREN/patients/PREVENTION/risk/risk

factors/STROKE/therapy/treatment/USA/vascular/vascular dementia/vascular

dementia (VaD)/vascular risk/vascular risk factors



Wade, J.P.H. (1991), Multiinfarct Dementia - Prevention and Treatment. Alzheimer

Disease & Associated Disorders, 5 (2), 144-148.



Abstract: Multi-infarct dementia (MID) characteristically presents with an acute event

followed by a stepwise and fluctuating downhill course. Progression is generally

considered the consequence of recurrent stroke (Hachinski, 1983): the mainstay

of treatment, therefore, is the prevention of further ischemic events



Keywords:

ALZHEIMERS-DISEASE/DOUBLE-BLIND/MULTICENTER/NALOXONE/P

REPARATION HYDERGINE/RISK-

FACTORS/THERAPY/TRIAL/VASODILATORS



Kuller, L.H. (1996), Potential prevention of Alzheimer disease and dementia. Alzheimer

Disease & Associated Disorders, 10 13-16.



Abstract: The prevention of dementia is of critical importance. The increasing

population of high-risk older individuals will result in an increasing prevalence

of dementia. Primary prevention of dementia and Alzheimer disease can take

either a public health or high-risk preventive medicine approach. At the present

time, there is little evidence to support a specific primary public health approach

such as a specific nutrient. The possible association of vascular disease with

dementia may offer the best preventive high-risk approach. The identification of

individuals with clinical and subclinical vascular disease is possible. There is a

very high prevalence of subclinical cerebral infarction in older individuals.

Specific treatments can prevent clinical disease such as stroke and coronary heart

disease. Whether therapies will prevent some dementia can be determined



Keywords: ALLELE/ASSOCIATION/clinical trials/COGNITIVE

FUNCTION/coronary heart disease/dementia/EDUCATION/ELDERLY

PEOPLE/health/heart/PHENOTYPE/POPULATION/prevention/preventive

medicine/RISK/STROKE/vascular disease/WOMEN



Gorelick, P.B., Erkinjuntti, T., Hofman, A., Rocca, W.A., Skoog, I. and Winblad, B.

(1999), Prevention of vascular dementia. Alzheimer Disease & Associated

Disorders, 13 S131-S139.



Abstract: Stroke is an important public health problem worldwide. Those at high risk of

stroke may be at high risk of cognitive impairment and dementia after stroke.

Modifiable cardiovascular risk factors in midlife including hypertension, alcohol

use, cigarette smoking, and certain dietary factors may be important targets for

prevention of vascular causes of cognitive impairment. These same types of

factors may also be associated with Alzheimer disease. Better control of

cardiovascular disease risk factors might lead to delay or prevention of vascular

dementia and Alzheimer disease



Keywords: alcohol/Alzheimer

disease/ALZHEIMERS-DISEASE/APOLIPOPROTEIN-E

EPSILON-4/BASE-LINE FREQUENCY/BRAIN

INFARCTION/cardiovascular/cardiovascular disease/cardiovascular disease risk

factors/CARDIOVASCULAR HEALTH/cardiovascular risk/cardiovascular risk

factors/cigarette smoking/COGNITIVE FUNCTION/cognitive

impairment/control/dementia/disease/disease risk/health/high

risk/hypertension/MIDLIFE BLOOD-PRESSURE/prevention/public

health/risk/risk factors/RISK- FACTORS/smoking/stroke/STROKE

PREVENTION/use/vascular/vascular dementia/WHITE- MATTER LESIONS



Crisby, M., Carlson, L.A. and Winblad, B. (2002), Statins in the prevention and

treatment of Alzheimer disease. Alzheimer Disease & Associated Disorders, 16

(3), 131-136.



Abstract: Vascular risk factors such as hypertension and hypercholesterolemia during

midlife increase the risk for Alzheimer's disease (AD). Treatment of

hypercholesterolemia and other vascular risk factors may have great implications

in the prevention of AD. Recent findings illustrate that the sterol metabolism in

the brain is an active process, well controlled and regulated by 24-hydroxylase,

an enzyme that is uniquely expressed in the brain. The use of statins in ischemic

heart disease (IHD) has proven to be a phenomenal advance in pharmacological

disease prevention and treatment. A growing body of evidence, suggest that

statins exhibit additional benefits that are independent of their

cholesterol-lowering actions. Statin treatment has also considerable effect in

prevention of ischemic stroke. In animal models of ischemic stroke, statins have

proven to reduce infarct size through up- regulation of endothelial nitric oxide

synthases. Data from recent observational studies have revealed a potential role

for statins in prevention of AD. The following review comments the processes

leading to dementia including the involvement of cholesterol regulation, cerebral

circulation and inflammation in development of dementia. The mechanisms by

which statins may be beneficial in controlling these processes is discussed



Keywords: AD/Alzheimer disease/Alzheimer's disease/AMYLOID PRECURSOR

PROTEIN/animal/APOLIPOPROTEIN-E/BETA-PEPTIDE/brain/cerebral/chole

sterol/CHOLESTEROL/cholesterol-lowering/dementia/development/disease/hea

rt/heart

disease/HEART-DISEASE/HIPPOCAMPAL-NEURONS/hypercholesterolemia/

hypertension/inflammation/ischemic/ischemic heart disease/ischemic

stroke/mechanisms/metabolism/MOUSE MODEL/nitric oxide/NITRIC-OXIDE

SYNTHASE/observational studies/prevention/REDUCTASE

INHIBITORS/review/risk/risk factors/SENILE

PLAQUES/statins/stroke/Sweden/treatment/use/vascular/vascular risk/vascular

risk factors

Sheng, F.C.L. and Busuttil, R.W. (1986), Carotid Surgery in Stroke Prevention.

American Family Physician, 33 (4), 109-124



Keywords: FAMILY/PHYSICIANS



Quest, D.O. (1987), Carotid Endarterectomy for Stroke Prevention. American Family

Physician, 35 (5), 185-191



Keywords: FAMILY/PHYSICIANS



Unwin, D.H. and Greenlee, R.G. (1993), Prophylactic Drug-Therapy in

Cerebrovascular-Disease. American Family Physician, 48 (1), 85-90.



Abstract: Aspirin in doses of 325 mg to 1,300 mg per day is the drug of choice for

prophylactic therapy in cerebrovascular disease. Ticlopidine, a platelet antagonist,

is available for use in patients who cannot tolerate aspirin or who have not had

success with aspirin therapy. Although ticlopidine is more effective than aspirin

in preventing stroke, its use may be somewhat limited due to cost and the

uncommon but serious side effect of neutropenia. Low-dose warfarin remains the

drug of choice for the prevention of cardioembolic stroke. The role of warfarin in

ischemic cerebrovascular disease is unknown



Kerle, K.K. and Nishimura, K.D. (1996), Exertional collapse and sudden death

associated with sickle cell trait. American Family Physician, 54 (1), 237-240.



Abstract: Although rare, exertional collapse and sudden death are the most serious

potential complications of sickle cell trait. Studies suggest that this condition

may occur in susceptible persons when poor physical conditioning, dehydration,

heat stress or hypoxic states precipitate sickling of the abnormal erythrocytes.

Sickling leads to endothelial damage, which can cause vasoconstriction,

disseminated intravascular coagulation and local tissue damage. Cardiac effects

include acute ischemia and arrhythmias. Muscle damage results in acute

compartment syndromes and release of myoglobin into the circulation. Acute

renal failure is possible. Diagnosis is based on a high index of suspicion, and

characteristic presentation and laboratory findings, including myoglobinuria,

hyperkalemia, hypocalcemia, hyperphosphatemia and elevated creatine kinase

levels. The differential diagnosis includes pulmonary embolism, acute cardiac

events, anaphylaxis and heat stroke. Management is based on stabilization,

rehydration, and the treatment and prevention of complications



Keywords:

ACUTE-RENAL-FAILURE/coagulation/COMMUNITY/EXERCISE/FAMILY/

PHYSICIANS/prevention/RHABDOMYOLYSIS/RISK

FACTOR/stroke/treatment



Santilli, J.D., Santilli, S.M. and Rodnick, J.E. (1996), Prevention of stroke caused by

carotid bifurcation stenosis. American Family Physician, 53 (2), 549-556.

Abstract: Prevention of stroke caused by carotid bifurcation stenosis can be achieved by

accurate identification and evaluation of patients at risk. A consensus report from

the National Institute of Neurologic Disorders and Stroke has standardized

diagnostic criteria and symptoms related to this disease. Recent prospective,

randomized trials have identified effective treatment for both asymptomatic and

symptomatic carotid stenosis. The risk factors for carotid stenosis are similar to

those for atherosclerosis-hypertension, diabetes, cigarette smoking and

hyperlipidemia. A carotid bruit is the most common clinical finding, although its

positive predictive value is only about 60 to 70 percent. Recent clinical trials

have identified patient groups that benefit from surgical and medical therapy,

depending on the degree of carotid stenosis and the presence or absence of

symptoms. Symptomatic patients with carotid stenosis greater than 70 percent

benefit from surgical therapy. Asymptomatic patients who have carotid stenosis

greater than 60 percent and are good surgical candidates should be referred for

surgical consultation



Keywords: carotid/carotid stenosis/clinical

trials/consensus/evaluation/FAMILY/FRAMINGHAM/PHYSICIANS/randomiz

ed trials/risk/risk factors/smoking/stroke/treatment/trials



Reddy, M.P. and Reddy, V. (1997), Stroke rehabilitation. American Family Physician,

55 (5), 1742-1748.



Abstract: Stroke is the leading cause of brain damage and resultant disability.

Rehabilitation measures help to restore lost abilities, improve quality of life and

decrease the long-term economic cost of stroke. Proper patient selection, realistic

goal setting, the active participation of both the patient and family, and the use of

an interdisciplinary team approach are important for the success of stroke

rehabilitation. Functional demand and intensive training are believed to trigger

central nervous system reorganization, which is responsible for late functional

recovery after stroke. The outcome following a stroke is most likely to be

positive when patients have bladder and bowel continence, are able to feed

themselves and have a healthy and caring spouse. Stroke rehabilitation must

include the prevention or early diagnosis of medical complications as well as

patient and family education concerning the prevention of recurrent stroke



Keywords:

brain/COMPLICATIONS/cost/diagnosis/education/FAMILY/FOLLOW-UP/LE

NGTH/MORTALITY/PHYSICIAN/PHYSICIANS/PREDICTION/PREVENTI

ON/quality of life/rehabilitation/STAY/stroke/UNIT



Wolf, P.A. and Singer, D.E. (1997), Preventing stroke in atrial fibrillation. American

Family Physician, 56 (9), 2242-2250.



Abstract: Atrial fibrillation, a common cardiac arrhythmia, is now recognized as a

powerful risk factor for stroke. Previously, atrial fibrillation was thought to

predispose persons to stroke only in the presence of rheumatic heart disease with

mitral stenosis. The significant impact of nonvalvular atrial fibrillation on stroke

incidence, recurrence and mortality was not fully appreciated. A series of clinical

trials have confirmed that a five-fold increase in stroke incidence occurs in

patients with atrial fibrillation, and that warfarin anticoagulation is efficacious in

stroke prevention. This anticoagulation benefit was achieved with an acceptably

low risk of serious hemorrhage



Keywords: ANTICOAGULATION/ASPIRIN/atrial fibrillation/clinical

trials/COMPLICATIONS/EMBOLISM/FAMILY/fibrillation/FRAMINGHAM/h

eart/hemorrhage/incidence/mortality/PHYSICIANS/prevention/recurrence/risk/R

ISK-FACTORS/stroke/stroke prevention/trials/WARFARIN



Akhtar, W., Reeves, W.C. and Movahed, A. (1998), Indications for anticoagulation in

atrial fibrillation. American Family Physician, 58 (1), 130-136.



Abstract: Factors associated with an increased risk of thromboembolic events in patients

with atrial fibrillation (AF) include increasing age, rheumatic heart disease poor

left ventricular function, previous myocardial infarction, hypertension and a past

history of a thromboembolic event. Patients with AF should be considered for

anticoagulation or antiplatelet therapy based on the patient's age, the presence of

other risk factors for stroke and the risk of complications from anticoagulation.

In general, Patients with risk factors for stroke should receive warfarin

anticoagulation, regardless of their age. In patients who are tinder age 65 and

have no other risk factors for stroke, either aspirin therapy or no therapy at all is

recommended Aspirin or warfarin is recommended for use in patients between

65 and 75 years of age with no other risk factors, and warfarin is recommended

for use in patients without risk factors who are older than 75 years of age



Keywords: AF/age/anticoagulation/antiplatelet therapy/aspirin/atrial

fibrillation/complications/FAMILY/fibrillation/FOLLOW-UP/FRAMINGHAM/

heart/history/hypertension/MANAGEMENT/myocardial

infarction/PHYSICIANS/PREVENTION/RISK/risk

factors/stroke/therapy/thromboembolic events/WARFARIN



Ryan, M., Combs, G. and Penix, L.P. (1999), Preventing stroke in patients with transient

ischemic attacks. American Family Physician, 60 (8), 2329-2336.



Abstract: Stroke is the third most common overall cause of death and the leading cause

of adult disability in the United States, New therapeutic interventions instituted

in the period immediately after a stroke have revolutionized the approach to

ischemic cerebrovascular disease. Recognition of a transient ischemic attack

provides an opportunity to prevent a subsequent stroke, Specific stroke

prevention treatment depends on the cause of the transient ischemic attack, its

cerebrovascular localization and the presence of associated coexisting medical

problems, Modification of stroke risk factors is the principal therapeutic

approach, Antiplatelet agents and anticoagulants have been shown to be effective

in reducing the occurrence of stroke in certain populations, Several

well-designed studies have recently demonstrated the effectiveness of carotid

endarterectomy in preventing strokes related to extracranial carotid artery disease



Keywords:

AMERICAN-HEART-ASSOCIATION/anticoagulants/ASPIRIN/carotid/carotid

artery/CAROTID ENDARTERECTOMY/cerebrovascular/cerebrovascular

disease/CHOLESTEROL/DISEASE/endarterectomy/FAMILY/ischemic/META

ANALYSIS/PHYSICIAN/PHYSICIANS/PRACTICE

GUIDELINES/prevention/REDUCTASE INHIBITORS/RISK/risk

factors/stroke/stroke prevention/transient/transient ischemic attack/transient

ischemic attacks/treatment/TRIALS/United States



Hart, R.G. and Benavente, O. (1999), Stroke: Part I. A clinical update on prevention.

American Family Physician, 59 (9), 2475-2482.



Abstract: Clinical trials conducted during the past five years have yielded important

results that have allowed us to refine our approach to stroke prevention.

Treatment of isolated systolic hypertension prevents stroke and is generally well

tolerated. New antiplatelet agents (clopidogrel and the combination of aspirin

plus high-dose dipyridamole) have been shown to be effective in reducing

vascular events in survivors of ischemic stroke, although aspirin remains the

mainstay of antiplatelet therapy for stroke prevention. Several clinical trials

support the benefit of lipid-lowering agents ("statins") in reducing stroke.

Warfarin reduces stroke for high-risk patients with atrial fibrillation. Carotid

endarterectomy is highly beneficial in reducing stroke for symptomatic patients

with severe carotid stenosis (greater than 70 percent), but the benefit is less for

symptomatic patients with a moderate degree of stenosis (50 to 69 percent) and

for patients with asymptomatic carotid disease of any severity



Keywords: antiplatelet/antiplatelet agents/antiplatelet

therapy/aspirin/asymptomatic/atrial fibrillation/carotid/CAROTID

ENDARTERECTOMY/carotid stenosis/clinical

trials/clopidogrel/dipyridamole/endarterectomy/FAMILY/fibrillation/hypertensio

n/ischemic/ischemic stroke/isolated systolic

hypertension/METAANALYSIS/PHYSICIAN/PHYSICIANS/prevention/RISK/

severity/STENOSIS/stroke/stroke prevention/therapy/trials/vascular/Warfarin



Pearce, K.A., Boosalis, M.G. and Yeager, B. (2000), Update on vitamin supplements for

the prevention of coronary disease and stroke. American Family Physician, 62

(6), 1359-1366.



Abstract: Dietary antioxidants and folic acid may play a role in the pathophysiology of

coronary disease and stroke. We review patient-oriented evidence on the

effectiveness of supplementation with antioxidants and/or folic acid in the

prevention of myocardial infarction and stroke. Observational data suggest

cardiovascular benefit of vitamin E supplementation, but results of controlled

clinical trials are inconsistent regarding the effect on nonfatal myocardial

infarction. Moreover, studies have not shown a protective effect of vitamin E

against fatal myocardial infarction and have not addressed stroke. For vitamin C

and folic acid supplementation, observational data are inconsistent and controlled

clinical trials are lacking. Thus, the available evidence is insufficient to

recommend the routine use of vitamin E, vitamin C or folate supplements for the

prevention of myocardial infarction or stroke. The evidence argues against the

use of beta carotene supplements for this purpose. The costs and risks associated

with these supplements are low, however, and physicians may choose to

recommend vitamin E. folate and/or vitamin C supplementation pending

conclusive evidence from clinical trials



Keywords: antioxidants/beta carotene/BETA-CAROTENE/C

INTAKE/cardiovascular/CARDIOVASCULAR- DISEASE/clinical

trials/coronary disease/costs/DIETARY ANTIOXIDANT VITAMINS/E

CONSUMPTION/FAMILY/HEART-DISEASE/infarction/myocardial/myocardi

al

infarction/MYOCARDIAL-INFARCTION/PHYSICIAN/PHYSICIANS/POST

MENOPAUSAL WOMEN/prevention/review/RISK FACTOR/stroke/TOTAL

HOMOCYSTEINE/trials/vitamin C/vitamin E



Biller, J. and Thies, W.H. (2000), When to operate in carotid artery disease. American

Family Physician, 61 (2), 400-406.



Abstract: Carotid endarterectomy has proved to be beneficial in the prevention of stroke

in selected patients. The procedure is indicated in symptomatic patients with

carotid-territory transient ischemic attacks or minor strokes who have carotid

artery stenosis of 70 to 99 percent. With a low surgical risk, carotid

endarterectomy provides modest benefit in symptomatic patients with carotid

artery stenosis of 50 to 69 percent. Platelet antiaggregants and risk factor

modification are recommended in symptomatic patients with less than 50 percent

stenosis. In the Asymptomatic Carotid Atherosclerosis Study, carotid

endarterectomy was beneficial in patients who had asymptomatic carotid artery

stenosis of 60 percent or greater and whose general health made them good

candidates for elective surgery, provided that the arteriographic and surgical

complication rates were low. However, in asymptomatic patients, surgery

reduced the absolute risk of stroke by only 1 percent per year



Keywords: absolute risk/asymptomatic/BRUITS/carotid/carotid artery/carotid artery

disease/carotid artery stenosis/carotid

endarterectomy/CLINICAL-SIGNIFICANCE/CONSENSUS/disease/ENDART

ERECTOMY/FAMILY/health/ischemic/MODERATE/PHYSICIAN/PHYSICIA

NS/PLAQUE/PREVENTION/RISK/risk

factor/STENOSIS/STROKE/surgery/transient/transient ischemic attacks



Chatfield, J. (2001), American Heart Association scientific statement on the primary

prevention of ischemic stroke. American Family Physician, 64 (3), 513-514

Keywords: FAMILY/ischemic/ischemic

stroke/PHYSICIAN/PHYSICIANS/prevention/primary/primary

prevention/stroke



Bicket, D.P. (2002), Using ACE inhibitors appropriately. American Family Physician,

66 (3), 461-468.



Abstract: When first introduced in 1981, angiotensin-converting enzyme (ACE)

inhibitors were indicated only for treatment of refractory hypertension. Since

then, they have been shown to reduce morbidity or mortality in congesive heart

failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and

atherosclerotic cardiovalcular disease. Pathologies underlying these conditions

are, in part attributable to the renin-angiotensin-aldosterone system.

Angiotension II contributes to endothelial dysfunction, altered renal

hemodynamics, and vascular and cardiac hypertrophy. ACE inhibitors attenuate

these effects. Clinical outcomes of AVE inhibiton include decreases in

myocardial infarction (fatal and nonfatal), reinfarction, angina, stroke, end-stage

renal disease, and morbidity and mortality associated with heart failure. ACE

inhibitors are generally well tolerated and few have few contraindications.

Copyright (C) 2002 American Academy of Family Physicians



Keywords: ACE inhibitors/ACUTE

MYOCARDIAL-INFARCTION/angina/ANTIHYPERTENSIVE

DRUGS/BENEFITS/CAPTOPRIL PREVENTION PROJECT/cardiac/cardiac

hypertrophy/chronic/CONVERTING ENZYME-INHIBITORS/diabetes/diabetes

mellitus/disease/end-stage renal disease/ENDOTHELIAL

DYSFUNCTION/FAMILY/heart/heart

failure/HEART-FAILURE/hemodynamics/hypertension/hypertrophy/infarction/

MORBIDITY/morbidity and mortality/MORTALITY/myocardial/myocardial

infarction/PHYSICIAN/PHYSICIANS/RANDOMIZED TRIAL/renal/renal

disease/stroke/treatment/vascular



King, D.E., Dickerson, L.M. and Sack, J.L. (2002), Acute management of atrial

fibrillation: Part II. Prevention of thromboembolic complications. American

Family Physician, 66 (2), 261-264.



Abstract: Family physicians should be familiar with the acute management of atrial

fibrillation and the initiation of chronic therapy for this common arrhythmia.

Initial management should include hemodynamic stabilization, rate control,

restoration of sinus rhythm, and initiation of antithrombotic therapy. Part 11 of

this two-part article focuses on the prevention of thromboembolic complications

using anticoagulation. Heparin is routinely administered before medical or

electrical cardioversion. Warfarin is used in patients with persistent atrial

fibrillation who are at higher risk for thromboembolic complications because of

advanced age, history of coronary artery disease or stroke, or presence of

left-sided heart failure. Aspirin is preferred in patients at low risk for

thromboembolic complications and patients with a high risk for falls, a history of

noncompliance, active bleeding, or poorly controlled hypertension. The

recommendations provided in this article are consistent with guidelines published

by the American Heart Association and the Agency for Healthcare Research and

Quality



Keywords: acute/age/anticoagulation/antithrombotic/ANTITHROMBOTIC

THERAPY/arrhythmia/atrial/atrial

fibrillation/bleeding/CARDIOVERSION/chronic/complications/control/coronary

artery disease/disease/DRUGS/falls/FAMILY/fibrillation/guidelines/heart/heart

failure/high

risk/history/hypertension/management/medical/METAANALYSIS/PHYSICIAN

/PHYSICIANS/prevention/risk/sinus rhythm/stroke/therapy/thromboembolic

complications/TRANSESOPHAGEAL ECHOCARDIOGRAPHY/Warfarin



Kannel, W.B., Wilson, P.W.F. and Zhang, T.J. (1991), The Epidemiology of Impaired

Glucose-Tolerance and Hypertension. American Heart Journal, 121 (4),

1268-1273.



Abstract: Epidemiologic research indicates that glucose intolerance and hypertension are

interrelated phenomena, each powerfully predisposing to atherosclerotic

cardiovascular disease. Both diabetic and hypertensive patients have greater

amounts of atherogenic risk factors, including dyslipidemia, hyperuricemia,

elevated fibrinogen, and left ventricular hypertrophy. Diabetic persons have an

increased prevalence of hypertension (50%), and glucose intolerance is more

common in hypertension (15% to 18%). Both share a strong relationship to

excess weight, but the excess of hypertension in diabetic persons occurs in both

lean and obese subjects. Diabetes doubles the risk of hypertension associated

with overweight. The risk of coronary disease, stroke, and peripheral arterial

disease increases with increasing blood pressure to the same degree in diabetic

persons as in nondiabetic persons, but at any level of blood pressure, diabetic

persons have a doubled risk of these outcomes. Both diabetic and hypertensive

patients are particularly prone to silent or unrecognized myocardial infarctions.

Greater efforts at primary prevention of both hypertension and diabetes are

clearly needed, including efforts at weight control, exercise, limitation of salt

intake, and control of blood lipid levels. In either diabetic or hypertensive

candidates for cardiovascular disease, optimization of the chances of avoiding

sequelae requires a comprehensive multifactorial approach. Prevention requires

more than normalization of either the blood sugar or blood pressure. Rational

preventive measures must also include weight reduction, a fat-modified diet,

cessation of smoking cigarettes, raising high-density lipoprotein, lowering low-

density lipoprotein, and reduction of fibrinogen. Hypertension, obesity, insulin

resistance, hyperinsulinemia, hypertriglyceridemia, and low high-density

lipoprotein cholesterol tend to coexist. All these factors accelerate atherogenesis

and may be responsible for the increased propensity of either diabetic or

hypertensive patients to develop coronary heart disease. Treatments that worsen

these features in hypertensive or diabetic patients are best avoided

Keywords:

DISEASE/FRAMINGHAM/HEART/MYOCARDIAL-INFARCTION/RISK-FA

CTORS



Singer, D.E., Hughes, R.A., Gress, D.R., Sheehan, M.A., Oertel, L.B., Maraventano,

S.W., Blewett, D.R., Rosner, B. and Kistler, J.P. (1992), The Effect of Aspirin on

the Risk of Stroke in Patients with Nonrheumatic Atrial-Fibrillation - the Baataf

Study. American Heart Journal, 124 (6), 1567-1573.



Abstract: Recent randomized trials have consistently demonstrated the marked efficacy

of warfarin in reducing the risk of stroke caused by nonrheumatic atrial

fibrillation. These trials have provided conflicting evidence on the effect of

aspirin. We report the aspirin analysis from the BAATAF study, a trial in which

control patients could choose to take aspirin. There were two strokes in 446

person-years with warfarin (annual rate of 0.45%); eight strokes in 206

person-years with aspirin, most at 325 mg per day (annual rate of 3.9%); and five

strokes in 271 person-years among patients taking neither aspirin nor warfarin

(annual rate of 1.8%). Simultaneously controlling for the other significant

determinants of stroke in the BAATAF study (age, mitral annular calcification,

and clinical heart disease), the relative rates (95% confidence interval) of stroke

were: (1) warfarin/aspirin = 0.135 (0.029 to 0.64); (2) aspirin/(no aspirin and no

warfarin) = 1.95 (0.64 to 5.97); and (3) warfarin/(no aspirin and no warfarin)

0.263 (0.051 to 1.36). Our "treatment received" analysis argues that warfarin is

strikingly more effective than aspirin in preventing stroke in nonrheumatic atrial

fibrillation



Keywords: FRAMINGHAM/HEART/INTERNAL/PREVENTION/RANDOMIZED

TRIAL/THERAPY/THROMBOEMBOLIC COMPLICATIONS/WARFARIN



Black, I.W., Hopkins, A.P., Lee, L.C.L. and Walsh, W.F. (1993), Evaluation of

Transesophageal Echocardiography Before Cardioversion of Atrial-Fibrillation

and Flutter in Nonanticoagulated Patients. American Heart Journal, 126 (2),

375-381.



Abstract: This study prospectively evaluated the role of transesophageal

echocardiography (TEE) in screening for atrial thrombi before electrical

cardioversion in 40 nonanticoagulated patients with nonvalvular atrial fibrillation

(n = 33) or atrial flutter (n = 7). Transthoracic echocardiography did not detect

atrial thrombus in any patient. TEE detected left atrial appendage thrombi in five

patients (12%, p = 0.03), significantly associated with left ventricular systolic

dysfunction (p = 0.02) and left atrial spontaneous echo contrast (p = 0.04).

Cardioversion was cancelled in the five patients with thrombi and in two patients

with spontaneous reversion before planned cardioversion. Cardioversion was

successful in 25 (76%) of the 33 remaining patients. Cerebral embolism occurred

24 hours after successful cardioversion in one patient with atrial fibrillation and

left ventricular dysfunction, who had left atrial spontaneous echo contrast, but no

thrombus was detected by TEE before cardioversion. Repeat TEE after embolism

showed a fresh left atrial appendage thrombus and increased left atrial

spontaneous echo contrast. These results indicate that TEE improves the

detection of left atrial appendage thrombi in candidates for cardioversion, in

whom the procedure may be deferred. However, the exclusion by TEE of

preexisting atrial thrombi before cardioversion does not eliminate the risk of

embolism after cardioversion because of persistent atrial stasis and de novo

thrombosis



Keywords:

ANTICOAGULATION/HEART/MITRAL-STENOSIS/PREVENTION/RISK/S

TROKE/THERAPY/THROMBUS



Hennekens, C.H. (1994), Platelet Inhibitors and Antioxidant Vitamins in

Cardiovascular- Disease. American Heart Journal, 128 (6), 1333-1336.



Abstract: Considerable research attention has focused on the possible roles of platelet

inhibition, principally using aspirin, and antioxidant vitamins in reducing the

risks of cardiovascular disease. Data from large-scale randomized trials indicate

that aspirin reduces subsequent vascular events among patients with prior

myocardial infarction, stroke, transient ischemic attacks, or unstable angina, as

well as among patients with acute evolving myocardial infarction. In primary

prevention trials, the Physicians' Health Study showed a clear benefit in

decreasing risk of a first myocardial infarction in men; the data on stroke and

total number of deaths from vascular causes are inadequate. The Women's Health

Study, a trial now under way among apparently healthy women, will provide

direct evidence on the balance of risks and benefits of aspirin in primary

prevention. Antioxidant vitamins are hypothesized to decrease cardiovascular

disease risk by several mechanisms, including inhibition of oxidation of

low-density lipoprotein cholesterol and decreasing uptake into the coronary

endothelium. Promising results have emerged from observational studies, which

show that people with high intakes of antioxidant vitamins through diet or

supplements have lowered risks of cardiovascular disease; however, unknown or

unmeasured factors associated with high antioxidant vitamin intake may explain

all or part of the observed associations. Randomized trials to provide reliable

data are now ongoing among apparently healthy men and women, as well as

among survivors of prior cardiovascular disease events



Keywords: angina/ASPIRIN/cardiovascular disease/CHOLESTEROL/diet/disease

risk/E CONSUMPTION/endothelium/HEART/LOW-DENSITY

LIPOPROTEIN/myocardial infarction/observational

studies/prevention/PRIMARY PREVENTION/randomized

trials/RISK/stroke/transient/trials/vascular/WOMEN



Cheng, T.O. (1994), Atrial-Fibrillation, Stroke, and Antithrombotic Treatment.

American Heart Journal, 127 (4), 961-968

Keywords: COMPLICATIONS/FRAMINGHAM/HEART/INTENSITIES/ORAL

ANTICOAGULANT-THERAPY/PREVENTION/RISK/VALVULAR

HEART-DISEASE/WARFARIN



Archer, S.L., James, K.E., Kvernen, L.R., Cohen, I.S., Ezekowitz, M.D. and Gornick,

C.C. (1995), Role of Transesophageal Echocardiography in the Detection of Left

Atrial Thrombus in Patients with Chronic Nonrheumatic Atrial-Fibrillation.

American Heart Journal, 130 (2), 287-295.



Abstract: Transesophageal echocardiography was used to assess cardiac abnormalities

associated with embolization in patients who had completed the Department of

Veterans Affairs Cooperative Study of Stroke Prevention in Nonrheumatic Atrial

Fibrillation at the Minneapolis and West Haven Department of Veterans Affairs

Medical Centers without an embolic event. Patients were men, 71 +/- 7 years old,

with atrial fibrillation of 6.2 +/- 4.3 years' duration who had received warfarin (n

= 32) or placebo (n = 23) for 2 years. Thrombi were found in 5 of 55 patients

(warfarin 4 and placebo 1; p = 0.39); spontaneous echo contrast was seen in 4 of

5 patients. Other abnormalities identified included spontaneous echo contrast

(47%), patent foramen ovale (54%), atrial septal aneurysm (7.3%), and left

ventricular thrombus (3.6%). During 34 months of posttreatment follow-up, 5

patients had a stroke (1 fatal), and 10 died. Potential sources of emboli did not

predict subsequent outcome. Thus warfarin therapy did not preclude the presence

of thrombi. Stroke reduction likely involves the prevention of emboli from

sources in addition to the atrial appendage



Keywords: APPENDAGE THROMBI/atrial fibrillation/atrial septal

aneurysm/DIAGNOSIS/echocardiography/emboli/fibrillation/HEART/LEFT-VE

NTRICULAR THROMBI/patent foramen ovale/PLATELET

SCINTIGRAPHY/PREVALENCE/PREVENTION/SPONTANEOUS ECHO

CONTRAST/STROKE/thrombus/TWO-DIMENSIONAL

ECHOCARDIOGRAPHY/WARFARIN



Nendaz, M.R., Sarasin, F.P., Junod, A.F. and Bogousslavsky, J. (1998), Preventing

stroke recurrence in patients with patent foramen ovale: Antithrombotic therapy,

foramen closure, or therapeutic abstention? A decision analytic perspective.

American Heart Journal, 135 (3), 532-541.



Abstract: Emphasis on the role of patent foramen ovale as a potential risk factor for

ischemic paradoxical stroke has recently increased. Current therapeutic options

for secondary stroke prevention include long-term antithrombotic therapies and

invasive closure of the defect, but selective indications have not been evaluated.

Therefore we developed a Markov-based decision analysis model for a

hypothetical cohort of patients 55 years of age with presumed paradoxical

embolism, measuring for each therapy the risks of stroke recurrence, treatment-

related complications, and death after 5 years and the quality- adjusted life-years.

Over a wide range of stroke risk recurrence (0.8% per year to 7% per year), the

gain provided by closure of the defect exceeded the one obtained by other

therapeutic options. When the risk exceeded 0.8% per year and 1.4% per year,

respectively, this was also verified for anticoagulation and antiplatelet therapies

compared with therapeutic abstention. Therapeutic abstention was the preferred

strategy under 0.8% per year. Sensitivity analyses identified key parameters

influencing the choice of therapy. These included estimates of stroke recurrence,

bleeding rates, surgery-related case fatality rates, and age. Considering the risks

of treatment and the devastating consequences of a recurrent stroke, our model

suggests that if the estimated risk of paradoxical stroke recurrence is >0.8% per

year, therapeutic abstention becomes the worst option. Above this threshold

secondary stroke prevention with anticoagulation therapy or surgical closure of

the defect is the preferred strategy, and assessment of both the risk of stroke

recurrence and the risk related to therapeutic options should guide individual

therapeutic decision making



Keywords: age/anticoagulation/ATRIAL SEPTAL-DEFECT/case

fatality/complications/CRYPTOGENIC STROKE/decision

analysis/decision-making/embolism/FOLLOW-UP/foramen

ovale/HEART/LIFE/NATURAL-HISTORY/PARADOXICAL

EMBOLISM/patent/patent foramen

ovale/prevention/recurrence/RISK/stroke/stroke prevention/SURGICAL

CLOSURE/therapy/TRANSCATHETER CLOSURE/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/treatment



Sherman, S.E., D'Agostino, R.B., Silbershatz, H. and Kannel, W.B. (1999), Comparison

of past versus recent physical activity in the prevention of premature death and

coronary artery disease. American Heart Journal, 138 (5), 900-907.



Abstract: Background People who are physically active live longer, but it is unclear

whether this is because of physical activity in the distant or more recent post.

Methods We assessed activity levels in 5209 men and women in the Framingham

Heart Study from 1956 to 1958 and again from 1969 to 1973. We included

individuals who were alive and without cardiovascular disease in the period 1969

to 1973. The primary outcome was death from all causes during the 16 years

after the 1969 to 1973 assessment. Secondary outcomes were incidence and

mortality rate of: cardiovascular disease. We used Cox proportional hazards

regression to calculate the relative risk of being sedentary, both unadjusted and

controlling for smoking, weight, systolic blood pressure, cholesterol, glucose

intolerance, left ventricular hypertrophy, chronic obstructive pulmonary disease,

and cancer. Results The overall 16-year mortality rate was 37% for men and 27%

For women. When both distant and recent activity levels were included along

with major cardiovascular disease risk Factors, for recent activity the most active

tertile had lower overall mortality rate than the least active tertile for men (risk

ratio 0.58, 95% confidence interval, 0.43-0.79) and women (risk ratio 0.61, 95%

confidence interval, 0.45-0.82). For distant activity there was no difference in

overall mortality rate between the most and least active tertiles either for men or

for women. Adjusting for major cardiovascular disease risk factors had little

effect on the results. Conclusions The reduction in overall mortality rates is more

associated with recent activity than distant activity. These results suggest that for

sedentary patients, it may never be tao late to begin exercising



Keywords: blood pressure/cardiovascular/cardiovascular disease/cholesterol/coronary

artery disease/DEPRESSION/disease

risk/EXERCISE/glucose/HEALTH/HEART/hypertrophy/incidence/left

ventricular hypertrophy/MEN/MORTALITY/physical

activity/prevention/relative risk/risk/risk factors/smoking/STROKE/systolic

blood pressure/WOMEN



Flaker, G.C., McGowan, D.J., Boechler, M., Fortune, G. and Gage, B. (1999),

Underutilization of antithrombotic therapy in elderly rural patients with atrial

fibrillation. American Heart Journal, 137 (2), 307-312.



Abstract: Background Antithrombotic agents are underutilized in elderly patients with

atrial fibrillation. In a peer-review audit of antithrombotic use in Missouri, rural

patients were given antithrombotic therapy less often than rural patients for

unclear reasons. Methods and Results The charts of 597 hospitalized Medicare

patients discharged between October 1, 1993, and December 31, 1994, from

urban and rural hospitals in Missouri were reviewed. In addition to

antithrombotic therapy prescribed at the time of discharge, patient and physician

information, relative contraindications to antithrombotic therapy, and risk factors

for stroke were identified. Rural and urban patients were similar in terms of age,

sex, and risk factors for stroke. At least one stroke risk factor was noted in 87%

of rural patients and in 84% of urban patients. Urban patients were more likely to

have a relative contraindication to antithrombotic therapy compared with rural

patients (66% vs 54%, P = .04) but received antithrombotic therapy more often

(58% vs 47%, P = .02). Cardiologists prescribed antithrombotic therapy

significantly more often than noncardiologists (69% vs 52%, P = .003).

Conclusions Elderly rural patients with atrial fibrillation receive antithrombotic

therapy less frequently than urban patients despite having a similar high-risk

profile and fewer relative contraindications. Primary care physicians prescribe

antithrombotic therapy less often than cardiologists, which is one of the reasons

for this underutilization



Keywords: ACUTE

MYOCARDIAL-INFARCTION/age/ANTICOAGULATION/antithrombotic/ant

ithrombotic therapy/atrial fibrillation/audit/DRUG-

THERAPY/elderly/EXPERIENCE/fibrillation/HEART/high risk/HOSPITAL

CARDIAC-ARREST/hospitals/PHYSICIANS/PREVENTION/risk/risk

factor/risk factors/risk factors for

stroke/sex/STROKE/therapy/URBAN/WARFARIN



Labovitz, A.J. (1999), Transesophageal echocardiography and unexplained cerebral

ischemia: A multicenter follow-up study. American Heart Journal, 137 (6),

1082-1087.

Abstract: Background Transesophageal echocardiography (TEE) continues to play a

prominent role in the evaluation of patients with unexplained cerebral ischemia.

The STEPS Study Group (Significance of Transesophageal Echocardiography in

the Prevention of Recurrent Stroke) was established to further examine the

clinical significance of TEE findings in patients with suspected cardiac source of

embolus and to assess the impact of these findings with respect to specific

therapy and the prevention of recurrent events. Methods A total of 242 patients

from 15 institutions within the United States underwent TEE study for evaluation

of unexplained cerebral ischemia. Over a 1-year period, detailed follow-vp was

obtained with respect to recurrent stroke, transient ischemia attacks, or

documented embolic events as well as detailed information concerning

nonrandomized antithrombotic therapy. Results Recurrent stroke occurred in 17

of 132 (13%) of the patients in the aspirin group versus 5 of 110 (5%) of the

patients receiving warfarin therapy (P .05) for any

events except hospitalization for unstable angina. There were too few events to

demonstrate separately significant effects in women; the estimated relative risk

reduction with pravastatin was 11% (95% Cl -18%-33%) for coronary heart

disease death or nonfatal myocardial infarction, 18% (95% Cl -25%-46%) for

coronary heart disease death, 16% (95% Cl -19%-41%) for myocardial infarction,

and 17% (95% Cl -2%-33%) for coronary heart disease death, myocardial

infarction, or coronary revascularization. Conclusions The study had the largest

secondary-prevention female cohort studied thus far, but was not adequately

powered to show separate effects in women. Nevertheless, the results were

consistent with the main results of this and other trials in showing reduced risks

with cholesterol-lowering treatment



Keywords: angina/Australia/cardiovascular/cardiovascular disease/cardiovascular

events/CHOLESTEROL/cholesterol-lowering/coronary heart disease/coronary

revascularization/death/DESIGN/disease/heart/heart

disease/hospitalization/infarction/LIPID/men/mortality/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/pravastatin/rehabilitation/relative

risk/results/revascularization/risk/risks/secondary

prevention/stroke/therapy/treatment/TRIAL/trials/unstable angina/USA/women



Connolly, S.J. (2003), Preventing stroke in patients with atrial fibrillation: Current

treatments and new concepts. American Heart Journal, 145 (3), 418-423.



Abstract: Atrial fibrillation (AF), is common, and it increases the risk of stroke.

Placebo-controlled trials consistently showed that warfarin reduces the risk of

stroke by two thirds, and a meta- analysis of trials of aspirin show a one-fifth

reduction. Meta- analysis of trials directly comparing warfarin and aspirin shows

that warfarin reduces the risk of stroke compared with aspirin by about one third.

Major advisory bodies recommend risk stratification of patients with AF and

prophylactic therapy with warfarin for patients at higher risk. There are several

problems with warfarin therapy, which have resulted in a widely documented

underuse. These problems include a narrow therapeutic window, marked

variability in pharmacokinetics, and contraindications. There are new promising

approaches to stroke prevention in AF. One of these is combination antiplatelet

therapy. In a large randomized trial, the combination of dipyridamole and aspirin

has been shown to have additive benefits against stroke. The combination of

clopidogrel and aspirin results in additive benefits against vascular events, with

only a modest increase in bleeding. A trial of combined antiplatelet therapy in

AF is warranted. Occlusion of the left atrial appendage, either with a transvenous

device or with surgery, is another strategy that is being explored. A direct

thrombin inhibitor, ximelagatran, has been shown to have an excellent

pharmacokinetic profile and is being developed as an oral agent for stroke

prevention in AF, and it will not need regular monitoring



Keywords: AF/antiplatelet/ANTIPLATELET THERAPY/ANTITHROMBOTIC

THERAPY/ASPIRIN/atrial/atrial appendage/atrial

fibrillation/benefits/bleeding/CARDIOVERSION/clopidogrel/combination/dipyr

idamole/fibrillation/HEART/HIGH-RISK PATIENTS/left atrial

appendage/monitoring/new

concepts/pharmacokinetics/prevention/randomized/randomized

trial/results/risk/risk stratification/SECONDARY PREVENTION/stroke/stroke

prevention/surgery/TERM ANTICOAGULATION/therapy/thrombin/thrombin

inhibitor/THROMBOEMBOLISM/TRIAL/trials/USA/vascular/vascular

events/warfarin/WARFARIN USE/ximelagatran



Malinin, A.I., O'Connor, C.M., Dzhanashvili, A.I., Sane, D.C. and Serebruany, V.L.

(2003), Platelet activation in patients with congestive heart failure: Do we have

enough evidence to consider clopidogrel? American Heart Journal, 145 (3),

397-403.



Abstract: Our understanding of the pathogenesis of congestive heart failure (CHF) has

improved remarkably in recent years. However, despite better knowledge and

novel pharmaceutical strategies, this disease is still one of the most brutal killers

in the Western world. The pathophysiology of CHF is complex, and much of our

comprehension revolves strictly around the neurohormonal and mechanical.

mechanisms involved. It has been suggested that CHF is associated with altered

hemostasis, but whether a prothrombotic state contributes to the pathogenesis

and progression of the disease is still not well known. The purpose of this review

article is to discuss our current knowledge of platelet activation in patients with

CHF and the potential role of antiplatelet agents in preventing these hemostatic

abnormalities. Clopidogrel is an established medication that reduces the

incidence of,stroke, myocardial ischemia, or vascular death. It is currently the

drug of choice in the prophylaxis of subacute stent thrombosis and postischemic

stroke treatment. Promising results of the most resent trials (Clopidogrel versus

Aspirin in Patients at Risk of Ischemic Events [CAPRIE] and Clopidogrel in

Unstable angina to prevent Recurrent Events [CURE]) may expand future

indications of this ADP receptor antagonist for prevention of thrombotic

complications in the CHF population. Currently conducted clinical trials

(Warfarin and Antiplatelet Therapy in Chronic Heart Failure [WATCH] and

Plavix Use for Treatment of Congestive Heart Failure [PLUTO-CHF] should

clarify the, role of clopidogrel in these patients



Keywords: abnormalities/activation/ACUTE

MYOCARDIAL-INFARCTION/ADHESION MOLECULES/ADP/ADP

receptor/ADP receptor antagonist/ADP

RECEPTORS/angina/antiplatelet/antiplatelet agents/clinical

trials/clopidogrel/complications/congestive heart failure/CONVERTING

ENZYME-INHIBITORS/CORONARY-ARTERY DISEASE/death/DILATED

CARDIOMYOPATHY/disease/drug/ESSENTIAL-HYPERTENSION/FLOW

CONDITIONS/heart/heart

failure/hemostasis/incidence/ischemia/knowledge/mechanisms/myocardial/patho

genesis/pathophysiology/platelet/platelet

activation/population/prevention/progression/prophylaxis/results/review/review

article/stent/stroke/stroke

treatment/thrombosis/treatment/trials/UNITED-STATES/USA/vascular/VON-W

ILLEBRAND-FACTOR/Warfarin



Fields, W.S. (1983), Aspirin for Prevention of Stroke - A Review. American Journal of

Medicine, 74 (6A), 61-65



Mcginnis, J.M. (1990), Prevention in 1989 - the State of the Nation. American Journal

of Preventive Medicine, 6 (1), 1-5.



Abstract: Substantial gains have been made in the health of Americans since 1970,

notably the 50% decline in infant mortality; the increase of nearly 4 years in life

expectancy for both men and women; the declines in stroke and coronary heart

disease mortality of 54% and 43%, respectively; the decline of injury deaths by

about 30%; and the decline in deaths from nontobacco related cancers by about

10%. These improvements in the overall national health profile have been

accompanied by enhanced public awareness of the relationship between behavior

and health outcomes as well as sustained behavior change among certain groups.

On the other hand, the research advances of the last two decades have given the

nation an even keener understanding of how short of our full potential we are

falling. International comparisons as well as data on the status of minority and

disadvantaged groups in the United States confirm some of these shortfalls-in

particular with respect ot infant mortality, diabetes, motor vehicle deaths, suicide,

and homicide. The complex etiologies of these problems require the forging of

strong alliances with sectors outside the health arena, such as business and

education, to seek solutions. [Am J Prev Med 1990;6:1-5]



Avis, N.E., Mckinlay, J.B. and Smith, K.W. (1990), Is Cardiovascular Risk Factor

Knowledge Sufficient to Influence Behavior. American Journal of Preventive

Medicine, 6 (3), 137-144.



Abstract: This paper examines the level of cardiovascular risk knowledge in the general

population and the relationship between such knowledge and behavior. The

following questions are addressed: (1) How informed is the general population

about what persons can do to reduce their risk of cardiovascular disease? (2)

How do sociodemographic factors, self-perceptions of health, and cardiovascular

risk factors relate to knowledge? (3) Is there a relationship between knowledge

and behavior? (4) What might explain apparent inconsistencies between

knowledge and behavior? The data used in this paper derive from a random

sample of 732 men and women form the greater Boston area. We assessed

cardiovascular risk factor knowledge by asking respondents what specific steps a

person could take to make a heart attack or stroke less likely. Risk factors

(including physiological measures), sociodemographic factors, and self-

perceptions of health also were measured. Results showed that respondents were

most knowledgeable about the relationships of exercise and cholesterol to heart

disease. Knowledge was related positively to education, being female, and

exercising. When we compared knowledge with behavior, results showed that for

smokers and those who were overweight, risk was related to awareness, thus

suggesting that knowledge does not lead necessarily to risk-reducing behavior.

Implications of these results in terms of education and prevention are discussed



Schoenberger, J.A. (1991), Epidemiology and Evaluation - Steps Toward Hypertension

Treatment in the 1990S. American Journal of Medicine, 90 S3-S7.



Abstract: The percentage of persons in the United States over age 65- especially over

85-is increasing more rapidly than other age groups. Two thirds of people over

age 65 have blood pressure higher than 140 mm Hg systolic or 90 mm Hg

diastolic. Isolated systolic hypertension (systolic blood pressure > 160 mm Hg

with diastolic blood pressure 5 cm) left

atrium, better left ventricular performance by echo, and less mitral regurgitation.

After a mean follow-up of 26 months, 51% of patients remained in sinus rhythm

and 49% of patients developed recurrent AF, including 12% who had AF, as seen

on all follow- up electrocardiograms. Clinical factors predicting recurrent AF

were age, heart failure, and myocardial infarction. An enlarged left atrium was

associated with recurrent intermittent AF; an enlarged left ventricle predicted

conversion to constant AF. Thus, clinical and echocardiographic parameters

predict recurrent AF in patients with intermittent nonvalvular AF



Keywords: atrial

fibrillation/CARDIOVERSION/DISEASE/fibrillation/heart/hypertension/MAIN

TENANCE/MORTALITY/myocardial infarction/SINUS

RHYTHM/THERAPY/treatment



Jacobowitz, G.R., Adelman, M.A., Riles, T.S., Lamparello, P.J. and Imparato, A.M.

(1995), Long-Term Follow-Up of Patients Undergoing Carotid Endarterectomy

in the Presence of A Contralateral Occlusion. American Journal of Surgery, 170

(2), 165-167.



Abstract: BACKGROUND: Patients with stenos4is of one carotid artery and occlusion

of the contralateral carotid artery (stenosis- occlusion) who are treated medically

am at high risk for stroke. We have recently reported that carotid endarterectomy

on the stenotic artery has a low perioperative risk in these patients, We now

present follow-up data to define the long-term effectiveness of this operation.

PATIENTs AND METHODS: From 1985 to 1991, 135 patients with

stenosis-occlusion underwent endarterectomy of the stenotic carotid artery:

Selective intra- arterial shunting was performed based on mental status changes

under regional anesthesia, preoperative neurologic deficit, or evidence of

preoperative cerebral infarction on computed tomography scan. Shunting was

used in 70 patients (52%), Saphenous vein was used for parch closure in 132

patients (98%), and polytetrafluroethylene in 3 (2%). RESULTS: By life- table

analysis, 92% of patients have remained stroke-free at 5 years. Fourteen deaths,

none related to cerebrovascular disease, have occurred during follow-up. The

life-table cumulative Stroke-free survival rate at 5 years is 74%, and the overall

survival rate is 82%. CONCLUSION: Carotid endarterectomy in the presence of

a contralateral occlusion provides long-term benefit to the patient with respect to

prevention of stroke. With lower perioperative stroke rates and proven long-term

benefit, carotid endarterectomy of the stenotic artery should be the treatment of

choice in the patient with stenosis-occlusion



Keywords: ARTERY OCCLUSION/carotid/carotid endarterectomy/cerebrovascular

disease/computed

tomography/endarterectomy/NATURAL-HISTORY/prevention/RISK/STENOSI

S/stroke/treatment



Giles, W.H., Croft, J.B., Keenan, N.L., Lane, M.J. and Wheeler, F.C. (1995), The

Validity of Self-Reported Hypertension and Correlates of Hypertension

Awareness Among Blacks and Whites Within the Stroke Belt. American Journal

of Preventive Medicine, 11 (3), 163-169.



Abstract: Hypertension surveillance activities increasingly are relying on information

obtained by self-report. However, limited information is available concerning the

validity of such data, especially among populations residing within the stroke

belt. We used interview information and blood pressure measurements from the

South Carolina Cardiovascular Disease Prevention Project to determine the

validity of self-reported hypertension and the correlates of hypertension

awareness among 2,210 whites and 704 blacks who participated in the program

in 1987. The sensitivity, specificity, positive predictive value, and negative

predictive value of self-reported hypertension were 79%, 91%, 76%, and 93%

among white women; 82%, 88%, 79%, and 89% among black women; 62%,

91%, 75%, and 85% among white men; and 72%, 89%, 78%, and 85% among

black men, respectively. Groups with highest sensitivity included women,

persons older than age 39 years, and those who had seen a physician for

preventive care within the last year. Correlates of hypertension awareness

included an older age, visit to a physician for preventive care, and a family

history of high blood pressure. Among hypertensive blacks, overweight persons

were substantially more likely than nonoverweight persons to be aware of their

hypertension (odds ratio [OR] = 4.6, 95% confidence intervals [CI] = 1.9, 10.7 in

black women and OR = 4.4, 95% CI = 1.0, 17.9 in black men). The validity of

self- reported hypertension was relatively high in all race-sex groups. There is a

need to increase hypertension awareness among hypertensive blacks who are not

overweight



Keywords: blood pressure/high blood pressure/history/hypertension/stroke/women



Mansour, M.A., Mattos, M.A., Hood, D.B., Hodgson, K.J., Barkmeier, L.D., Ramsey,

D.E. and Sumner, D.S. (1995), Detection of Total Occlusion, String Sign, and

Preocclusive Stenosis of the Internal Carotid-Artery by Color-Flow Duplex

Scanning. American Journal of Surgery, 170 (2), 154-158.



Abstract: BACKGROUND: Stroke prevention depends on the accurate differentiation of

surgically treatable preocclusive lesions from total occlusions of the internal

carotid artery. This prospective study was undertaken to review the accuracy of

color-flow duplex scanning for identifying carotid string signs, focal

preocclusive lesions (95% to 99% stenoses), and total occlusion of the internal

carotid artery. MATERIALS AND METHODS: Over an 18-month period, 4,362

patients underwent color-flow duplex scanning of the carotid arteries.

Angiograms of 596 internal carotid arteries were available for comparison with

the duplex scan findings, Total occlusion was diagnosed by the absence of flow

in internal carotid arteries visualized on B-mode scanning. Preocclusive lesions

were identified by a trickle of flow in the vessel lumen. RESULTS: Of 65

color-flow duplex scans that predicted total occlusion, 64 (98%) were confirmed

by angiography. The negative predictive value for total occlusion was 99%,

Twenty-six (87%) of 30 string signs and focal 95% to 99% stenoses were

correctly identified. Color- flow scanning prediction of preocclusive lesions was

accurate in 84% of 31 cases, Low velocities in the internal carotid artery were

usually associated with a string sign, and high velocities with a focal

preocclusive lesion. CONCLUSIONS: Color-flow duplex scanning accurately

differentiates between stenotic and totally occluded internal carotid arteries.

Identification of preocclusive lesions is not as accurate but the results are

promising, Arteriographic confirmation of duplex scan findings is necessary only

when scans are equivocal



Keywords: ARTERIOGRAPHY/carotid/carotid arteries/DISEASE/DOPPLER

ULTRASOUND/duplex

scanning/ENDARTERECTOMY/focal/prevention/prospective study



Ende, D.J., Chopra, P.S. and Rao, P.S. (1996), Transcatheter closure of atrial septal

defect or patent foramen ovale with the buttoned device for prevention of

recurrence of paradoxic embolism. American Journal of Cardiology, 78 (2),

233-236



Keywords: patent foramen ovale/prevention/STROKE



Graafmans, W.C., Ooms, M.E., Hofstee, H.M.W., Bezemer, P.D., Bouter, L.M. and Lips,

P. (1996), Falls in the elderly: A prospective study of risk factors and risk

profiles. American Journal of Epidemiology , 143 (11), 1129-1136.



Abstract: xIn this prospective study, the authors determined intrinsic risk factors for falls

and recurrent falls and constructed a risk profile that indicated the relative

contribution of each risk factor and also estimated the probabilities of falls and

recurrent falls, In 1992, over a 28-week period, falls were recorded among 354

elderly subjects aged 70 years or over who were living in homes or apartments

for the elderly in Amsterdam and the vicinity, During the study period, 251 falls

were reported by 126 subjects (36%), and recurrent falls (greater than or equal to

2 falls) were reported by 57 subjects (16%). Associations of falls and recurrent

falls with potential risk factors were identified in logistic regression models.

Mobility impairment regarding one or more of the tested items (i.e., impairment

of balance, leg-extension strength, and gait) was associated with falls (adjusted

odds ratio (OR) = 2.6) and was strongly associated with recurrent falls (OR =

5.0). Dizziness upon standing was associated with falls (OR = 2.1) and recurrent

falls (OR = 2.1). However, several risk factors were associated with recurrent

falls only: history of stroke (OR = 3.4), poor mental state (OR = 2.4), and

postural hypotension (OR = 2.0). The authors constructed a risk profile for

recurrent falls that included the five risk factors mentioned above. Inclusion of

all risk factors in the profile implied an 84% probability of recurrent falls over a

period of 28 weeks, compared with 3% when no risk factor was present. The

probability of recurrent falls ranged only from 11% to 29% when predicted by

number of falls occurring in the previous year. Physical activity, use of high-risk

medication, and the use of vitamin D-3, which was randomly allocated to the

participants, were not strongly related to either falls or recurrent falls. In

conclusion, a large range of probabilities of falls, especially of recurrent falls,

was estimated by the risk profiles, in which mobility impairment was the major

risk factor. Recurrent fallers may therefore be especially amenable to prevention

based on mobility improvement



Keywords: accidental

falls/aged/COMMUNITY/elderly/EPIDEMIOLOGY/history/INJURIOUS

FALLS/MUSCLE STRENGTH/prevention/risk factors/stroke/WOMEN



Morley, J., Marinchak, R., Rials, S.J. and Kowey, P. (1996), Atrial fibrillation,

anticoagulation, and stroke. American Journal of Cardiology, 77 (3), A38-A44.



Abstract: There is a demonstrated statistical association between atrial fibrillation,

rheumatic valvular disease, and embolic stroke. This article assesses the results

of 6 major clinical trials (AFASAK, BAATAF, SPINAF, SPAF [parts I and II],

CAFA and EAFTA- see text for trial names). Multivariate analysis revealed 4

independent clinical features that identified patients with atrial fibrillation at an

increased risk for stroke: hypertension, increasing age, previous transient

ischemic attack, and diabetes mellitus. Without anticoagulation therapy, patients

with any of these risk factors had a 4% annual risk of stroke. Patients with

cardiac disorders such as congestive heart failure and coronary artery disease

have a stroke rate 3 times higher than patients without any risk factors; patients

with atrial fibrillation but no concomitant risk factors or structural heart disease

seemed to have little concomitant risk for stroke. Meta-analysis revealed a 64%

reduction of risk for stroke in patients treated with warfarin, as compared with

placebo. The value of warfarin therapy in patients >75 years old is less clear

because of a high risk of hemorrhagic complications



Keywords: anticoagulation/atrial fibrillation/clinical trials/COMPLICATIONS/diabetes

mellitus/fibrillation/heart/hypertension/MANAGEMENT/PREVENTION/risk/ris

k factors/stroke/THERAPY/transient/transient ischemic

attack/trials/WARFARIN



Lonn, E.M., Yusuf, S., Doris, C.I., Sabine, M.J., Dzavik, V., Hutchison, K., Riley, W.A.,

Tucker, J., Pogue, J. and Taylor, W. (1996), Study design and baseline

characteristics of the study to evaluate carotid ultrasound changes in patients

treated with Ramipril and vitamin E: SECURE. American Journal of Cardiology,

78 (8), 914-919.



Abstract: Atherosclerotic cardiovascular disease remains a major cause of mortality and

morbidity in most developed countries. Experimental and clinical evidence

suggests that angiotensin- converting enzyme inhibitors and vitamin E therapy

may retard the atherosclerotic process; however, definitive proof in humans is

lacking. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated

with Ramipril and Vitamin E (SECURE) is designed to assess the effects of

ramipril-an angiotensin-converting enzyme inhibitor, at 2 doses: 2.5 mg daily

(which has little effect on lowering blood pressure) and 10 mg daily-and the

antioxidant vitamin E, 400 IU daily, on atherosclerosis progression in 732

patients using ct factorial 3 x 2 study design. High-risk patients with a

documented history of significant cardiovascular disease or with diabetes and

additional risk factors were enrolled and will be followed for 4 years. The extent

and progression of atherosclerosis are assessed noninvasively by B-mode carotid

ultrasonography. The SECURE trial is a substudy of the larger Heart Outcomes

Prevention Evaluation (HOPE) study of 9,541 high-risk patients evaluating the

effects of ramipril and vitamin E on major cardiovascular events (cardiovascular

death, myocardial infarction, and stroke), The 2 studies are complementary.

Whereas HOPE is expected to provide information on major clinical outcomes,

SECURE will shed light on the mechanisms by which these effects may be

mediated



Keywords: angiotensin converting enzyme

inhibitors/ATHEROSCLEROSIS/cardiovascular

events/CLINICAL-TRIAL/CORONARY-DISEASE/E

CONSUMPTION/EVENTS/HEART-

DISEASE/LIPIDS/morbidity/mortality/MYOCARDIAL-INFARCTION/PRAV

ASTATIN/PROGRESSION/risk factors/stroke



Gold, M.R., Ogara, P.T., Buckley, M.J. and DeSanctis, R.W. (1996), Efficacy and safely

of Procainamide in preventing arrhythmias after coronary artery bypass surgery.

American Journal of Cardiology, 78 (9), 975-979.



Abstract: Arrhythmias are common after cardiac surgery and are associated with

hemodynamic compromise, stroke, and prolonged hospitalization. Beta blockers

prevent atrial fibrillation postoperatively, but there are few data regarding the

prophylactic use of type I antiarrhythmic agents or the prevention of ventricular

arrhythmias, Accordingly, we performed a randomized, double-blind,

placebo-controlled study of the effects of oral procainamide on 100 patients

undergoing elective coronary artery bypass surgery, Procainamide was received

for 4 days; the dosage was adjusted for body weight Patients receiving

procainamide had a significant reduction in atrial fibrillation (16 vs 29

patient-days, p 65 years or initial stenosis greater

than or equal to 50% progressed to critical disease in 27% and 39%, respectively

(P less than or equal to 0.05). The cost per stroke prevented ranged from

$143,500 to $418,200 when stratified by initial stenosis. CONCLUSION:

Patients who have undergone a carotid endarterectomy demonstrate a propensity

for progression of carotid stenosis in the unoperated (contralateral) artery, The

cost/benefit ratio may be improved by varying the intensity of duplex

surveillance of the contralateral carotid based on the patient's age and initial

degree of stenosis



Keywords: COST-EFFECTIVENESS/ENDARTERECTOMY/STENOSIS/stroke/stroke

prevention



Johnstone, M.T., Mittleman, M., Tofler, G. and Muller, J.E. (1996), The

pathophysiology of the onset of morning cardiovascular events. American

Journal of Hypertension, 9 (4), S22-S28.



Abstract: Evidence obtained over the past decade indicates that myocardial infarction

(MI) and sudden death are not random events but rather, in many cases, may be

triggered by the daily activities of the subject, The importance of physical or

mental stresses as triggers is suggested by the parallel morning increased onsets

of MI, sudden cardiac death, and stroke. Unstable angina and MI are usually

precipitated by thrombus formation over a disrupted plaque that causes partial or

complete obstruction of coronary artery blood now. This process may be caused

by physiologic factors that lead to rupture of a vulnerable plaque and subsequent

thrombosis. beta-Blockers and aspirin, which can diminish these physiologic

processes, have been shown to blunt or abolish the morning peak of onset of

acute MI. It is hypothesized that occlusive coronary thrombosis occurs when an

atherosclerotic plaque becomes vulnerable to rupture, and mental or physical

stress causes the plaque to rupture. Increases in coagulability or vasoconstriction

triggered by daily activities may also contribute to complete occlusion of the

coronary artery lumen. Recognition of the circadian variation of the onset of

acute cardiovascular disease suggests the need for pharmacologic protection of

patients during the vulnerable periods and provides clues to the mechanism of

disease onset, the investigation of which may lead to improved methods of

prevention



Keywords: acute cardiovascular disease/acute myocardial infarction/ACUTE

MYOCARDIAL-INFARCTION/angina/arterial

thrombosis/aspirin/cardiovascular disease/cardiovascular

events/CASE-CROSSOVER/circadian rhythm/CIRCADIAN

VARIATION/CORONARY-ARTERY

DISEASE/HEART-DISEASE/myocardial infarction/plaque rupture/PLATELET

AGGREGABILITY/POSSIBLE

TRIGGERS/prevention/RESPIRATORY-DISEASE/stroke/SUDDEN

CARDIAC DEATH/thrombosis/thrombus/triggers/UNSTABLE

ANGINA-PECTORIS/vulnerable plaque



Alderman, M.H. (1996), Absolute cardiovascular risk: The basis for deciding to treat.

American Journal of Nephrology, 16 (3), 182-189.



Abstract: It has been convincingly demonstrated that raised blood pressure is a risk

factor for cardiovascular disease and that its reduction saves lives. It seems

logical to suggest that the whole population's blood pressure distribution should

be displaced downwards, since the reduction of blood pressure by only a few

millimeters of mercury, if easily and safely achieved, would produce more

disease prevention than could be attained by any other conceivable clinical

strategy. Physicians already have powerful tools to lower blood pressure in

individual patients, but must make challenging decisions as to when and how to

use them. Blood pressure level is a reflection of relative risk and one of many

risk factors that determine absolute risk. Reduction of blood pressure therefore

does not cure cardiovascular disease, but reduces the risk of developing disease.

The need for hypotensive therapy should be determined by absolute risk and the

opportunity for successful prevention, rather than by a threshold level of blood

pressure. The task of the physician is to assist the patient in assessing the balance

between the potential for benefit and the burden of intervention, and to provide

the best possible care to implement the therapeutic choice that is made



Keywords: absolute risk/blood pressure/BLOOD-PRESSURE

REDUCTION/cardiovascular disease/CORONARY

HEART-DISEASE/EPIDEMIOLOGY/FRAMINGHAM/HYPERTENSION/hyp

otensive therapy/MANAGEMENT/MORTALITY/MYOCARDIAL-

INFARCTION/prevention/PROFILE/relative risk/risk factors/STROKE



Antman, E.M. (1996), Maintaining sinus rhythm with antifibrillatory drugs in atrial

fibrillation. American Journal of Cardiology, 78 67-72.

Abstract: Management of atrial fibrillation is a common and complex clinical problem,

Two major treatment strategies have emerged: suppression of recurrences versus

control of ventricular rate and anticoagulation to reduce the risk of stroke.

Maintaining sinus rhythm offers the hemodynamic benefits of improving

ventricular performance and exercise capacity but may expose the patient to the

risk of proarrhythmia/sudden death and drug- related morbidity, Controlling

ventricular rate helps decrease symptomatic palpitations and improve exercise

capacity but necessitates long-term anticoagulation (which may also be needed

despite the use of antiarrhythmics to suppress recurrences of atrial fibrillation)

with some risk of bleeding, Randomized trials are now needed to define the

relative benefits of these 2 treatment strategies, Such trials should be designed to

provide information on the impact of the 2 approaches on symptoms, exercise

capacity, quality of life, and mortality rate in patients with atrial fibrillation



Keywords: AMIODARONE/anticoagulation/atrial

fibrillation/CARDIOVERSION/control/CONVERSION/drugs/exercise/fibrillati

on/MAINTENANCE/morbidity/mortality/NEW-YORK/PREVENTION/quality

of life/QUINIDINE

THERAPY/risk/SOTALOL/stroke/treatment/trials/WARFARIN/WOMEN



Flam, E., Berry, S., Coyle, A., Dardik, H. and Raab, L. (1996), Blood flow augmentation

of intermittent pneumatic compression systems used for the prevention of deep

vein thrombosis prior to surgery. American Journal of Surgery, 171 (3), 312-315.



Abstract: PURPOSE: TO compare, using Duplex ultrasonography, different intermittent

pneumatic compression (IPC) systems to augment venous blood flow for deep

venous thrombosis (DVT) prevention during and after surgery and during

periods of immobility. METHODS: This cross-over study randomly assigned 26

young, healthy, adult subjects, without history of DVT, hypertension, diabetes,

stroke, vascular or cardiac pathologies, to an order of knee-high, foam,

single-pulse IPC device and thigh-high, vinyl, sequential-pulse pneumatic

compression systems. Prior to making the flow measurement, the girth of the calf

and thigh and length of the leg of each subject were determined. The right leg

was used in this evaluation. RESULTS: The average flow augmentation, which

is a direct measure of the amount of femoral vein blood flow velocity increase

over the base, was 107% +/- 49% with the knee-high system, and 77% +/- 35%

with the thigh-high IPC system (P 0.8) at each speed were then examined for

differences associated with speed. The tangential, radial, and medial-lateral

forces were found to comprise approximately 55, 35, and 10% of the resultant

force, respectively. in addition to duration of stroke and propulsion, the

following variables were found to be stable and to differ with speed (1.3 m/s +/-

SD; 2.2 m/s +/- SD): peak force tangential to the pushrim (45.9 +/- 17.9 N; 62.1

+/- 30 N), peak moment radial to the hub (9.8 +/- 4.5 N.m 13.3 +/- 6 N.m),

maximum rate of rise of the tangential force (911.7 +/- 631.7 N/sec; 1262.3 +/-

570.7 N/sec), and maximum rate of rise of the moment about the hub (161.9 +/-

78.3 N.m/s; 255.2 +/- 115.4 N.m/s). This study found stable parameters that

characterize pushrim forces during wheelchair propulsion and varied with speed,

Almost 50% of the forces exerted at the pushrim are not directed toward forward

motion and, therefore, either apply friction to the pushrim or are wasted.

Ultimately this type of investigation may provide insight into the cause and

prevention of upper limb injuries in manual wheelchair users



Keywords: BIOMECHANICS/biomechanics/CARPAL-TUNNEL

SYNDROME/ERGOMETER/kinetics/MODEL/motion/pain/PARAPLEGIA/PO

WER OUTPUT/prevention/RELIABILITY/spinal cord injury/stroke/UPPER

EXTREMITY/wheelchair/wheelchair propulsion



Arnsten, J.H., Gelfand, J.M. and Singer, D.E. (1997), Determinants of compliance with

anticoagulation: A case-control study. American Journal of Medicine, 103 (1),

11-17.



Abstract: BACKGROUND: The number of patients for whom long-term anticoagulation

is indicated has increased dramatically over the past decade. Good patient

compliance is necessary to safely realize the benefits of anticoagulation, yet

barriers to compliance with anticoagulation therapy have not been studied.

METHODS: We conducted a case-control study in the Anticoagulation Therapy

Unit (ATU) at Massachusetts General Hospital. Forty-three patients who had

been discharged from the ATU for noncompliance (cases) and 89 randomly

selected compliant ATU controls were interviewed. Noncompliant cases had

self-discontinued warfarin or were taking warfarin with inadequate monitoring of

international normalized ratio (INR) levels. Telephone interviews assessed

sociodemographic features, indication for anticoagulation, patient satisfaction,

and health beliefs. RESULTS: Noncompliant cases were more likely to be

younger (mean 53.7 years versus 68.7 years, P 1.2 L, or > 8 cups/d) had an RR of 2.4 (95% CI: 1.5, 3.9)

of dying in the follow-up period compared with men consuming 75 years) who had associated risk factors, warfarin therapy at the

target international normalized ratio (INR) of 2-3, is the best treatment; however,

a combination of low intensity fixed-dose warfarin and aspirin is ineffective.

Thus, the guidelines recommended by the American College of Chest Physicians

should be followed in treating patients with AF. (C)1998 by Excerpta Medica,

Inc



Keywords: AF/ANTICOAGULATION/aspirin/atrial fibrillation/CAFA/clinical

trials/complications/emboli/fibrillation/NEW-YORK/PREVENTION/risk/risk

factors/STROKE/treatment/trials/WARFARIN



Pengo, V., Zasso, A., Barbero, F., Banzato, A., Nante, G., Parissenti, L., John, N.,

Noventa, F. and Dalla Volta, S. (1998), Effectiveness of fixed minidose warfarin

in the prevention of thromboembolism and vascular death in nonrheumatic atrial

fibrillation. American Journal of Cardiology, 82 (4), 433-437.



Abstract: Adjusted-dose warfarin is effective for stroke prevention in patients with

nonrheumatic atrial fibrillation (AF), but the risk of bleeding is high, especially

among the elderly. Fixed minidose warfarin is effective in preventing venous

thromboembolism with low risk of bleeding and no need for frequent clinical

monitoring. Patients > 60 years with nonrheumatic AF were randomized in an

open-labeled trial to receive fixed minidose warfarin (1.25 mg/day) or standard

adjusted-dose warfarin (International Normalized Patio [INR] between 2.0 and

3.0). Primary outcome events were ischemic stroke, peripheral or visceral

embolism, cerebral or fatal bleeding, and vascular death. Secondary end points

were major bleeding, myocardial infarction, and death. This study was

discontinued before completion in light of publication of the Stroke Prevention in

Atrial Fibrillation III trial, which indicated that low-intensity fixed-dose warfarin

treatment (i.e., INP 3.0. No significant difference in primary outcome events was

observed in the abbreviated study. However, the significantly increased

occurrence of ischemic stroke in the fixed minidose warfarin group suggests that

this regimen does not protect patients with nonrheumatic AF. (C)1998 by

Excerpta Medica, Inc

Keywords: AF/atrial

fibrillation/COMPLICATIONS/elderly/embolism/fibrillation/INTENSITY/ische

mic stroke/LOW-DOSE WARFARIN/myocardial

infarction/NEW-YORK/ORAL ANTICOAGULANT

TREATMENT/prevention/PROPHYLAXIS/RABBITS/RANDOMIZED

TRIAL/risk/stroke/stroke

prevention/THERAPY/thromboembolism/THROMBOPLASTIN/THROMBOSI

S/treatment/vascular/warfarin



Keane, D., Zou, L. and Ruskin, J. (1998), Nonpharmacologic therapies for atrial

fibrillation. American Journal of Cardiology , 81 (5A), 41C-45C.



Abstract: The limited efficacy and proarrhythmic risks of antiarrhythmic drug therapies

for atrial fibrillation have led to the exploration of a wide spectrum of alternative

therapeutic approaches. The diversity of the approaches is warranted by the

current absence of a single procedure that can safety and effectively cure atrial

fibrillation. The interventional therapies that are currently under most active

development include implantable atrial defibrillator therapy, prophylactic atrial

pacing in combination with drug therapy, multisite regional pace-entrainment of

atrial fibrillation by rapid pacing, atrial surgery, and catheter ablation for atrial

fibrillation. The current limitations of these procedures include: (1) for the

implantable atrial defibrillator-patient tolerance of low energy shocks and early

recurrence of atrial fibrillation; (2) for prophylactic pacing-limited efficacy in a

small proportion of the total atrial fibrillation population; (3) for multisite

regional pace-entrainment-lack of proved efficacy and difficulty in the expansion

and merging of the entrained regions; (4) for atrial surgery-highly invasive as a

stand-alone procedure; and (5) for catheter ablation-lack of proved long-term

efficacy, shortcomings of currently available technology, and risk of

thromboembolic stroke. It is evident that more basic and clinical research as well

as technologic innovation are needed. However, it is likely that some of these

new therapies, possibly in combination with antiarrhythmic drug therapy, will

offer considerable clinical benefit to selected patients with symptomatic atrial

fibrillation. (C) 1998 by Excerpta Medica, Inc



Keywords: ARRHYTHMIAS/atrial fibrillation/DEFIBRILLATION/development/drug

therapy/fibrillation/HUMANS/implantable atrial defibrillator/INTERNAL

CARDIOVERSION/NEW-YORK/P-WAVE/PREVENTION/recurrence/risk/saf

ety/SHEEP/SINUS RHYTHM/stroke/surgery/therapy/VENTRICULAR CYCLE

LENGTH/WAVE-FORMS



[Anon]. (1998), Secondary prevention. American Journal of Managed Care, 4 (4),

S201-S208.



Abstract: Landmark trials in secondary prevention-the Scandinavian Simvastatin

Survival Study (4S), the Cholesterol and Recurrent Events (CARE) study, and

the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID)

Study-have consistently demonstrated that lowering low-density lipoprotein

cholesterol (LDL-C) reduces the number of coronary events among patients with

coronary heart disease (CHD). The Pravastatin Atherosclerosis and Myocardial

Infarction (MI) Reduction Analysis, which pooled data from four atherosclerosis

regression trials, revealed that the rate of MI decreased 62% after 3 years and

that all-cause mortality decreased by 46%. The CARE study, the first trial with a

North American population, demonstrated significant reduction in risk for fatal

(CHD) or nonfatal MI (24%), total MI (25%), revascularization procedures

(27%), and stroke (31%). The LIPID, the largest statin trial to date, demonstrated

significant reductions in total mortality (23%), and stroke (20%). The results of

these trials are explored in detail, and a comparison of the populations in the 4S

and CARE trials is provided. The issue of what level of LDL-C reduction

provides maximum benefit is addressed. Although clinical trials have

demonstrated that statins are efficacious, safe, and well tolerated, there is

potential for drug-drug interactions. Pravastatin is metabolized in a different

manner than the other statins and therefore has fewer drug-drug interactions and

serious adverse effects. Pravastatin, with more than 50,000 patient-years of

experience in confirmed clinical trials, is shown to be an optimal therapeutic

choice in secondary prevention for managed care organizations. It reduces the

costs of managing CHD-related events and is cost effective in the treatment of

most CHD patients and compared with other cardiovascular interventions.

Improving physician involvement in secondary prevention is a challenge that

must be met



Keywords: atherosclerosis/CARE/cholesterol/clinical trials/coronary heart

disease/costs/EVENTS/heart/low density

lipoprotein/mortality/PRAVASTATIN/prevention/risk/secondary

prevention/statins/stroke/treatment/trials



Harbison, J.W. (1998), Clinical considerations in selecting antiplatelet therapy in

cerebrovascular disease. American Journal of Health-System Pharmacy, 55

S17-S20.



Abstract: Effective antiplatelet drugs-aspirin, ticlopidine, dipyridamole, and

clopidogrel-are reviewed. Aspirin has remained the pharmacologic foundation of

stroke prevention, primarily because of its low cost. It has been shown to provide

a 22% relative risk reduction of stroke in high-risk patients. Its principal adverse

effect is gastrotoxicity. Ticlopidine has been widely used in patients with a high

risk of stroke who are sensitive to aspirin or in whom aspirin has failed. It has

been associated with a median reduction in adenosine diphosphate- induced

platelet aggregation of 70% in about 8-11 days. Ticlopidine has been shown to

be superior to aspirin at three years in preventing stroke. The principal adverse

effects are diarrhea and rash; there has been a 2.4% occurrence of neutropenia. In

a trial comparing aspirin, dipyridamole, and a combination of the two, the risk of

stroke was 18% lower with aspirin, 16% lower with dipyridamole, and 37%

lower with combination therapy compared with placebo. The adverse-effect

profile of dipyridamole has proven to be less problematic than that of aspirin or

ticlopidine. In a trial comparing clopidogrel with aspirin, patients receiving

clopidogrel had an annual 5.32% risk of ischemic stroke, myocardial infarction,

or vascular death compared with 5.83% for patients receiving aspirin.

Clopidogrel has been associated with a small occurrence of rash and diarrhea,

and gastrointestinal intolerance and hemorrhage were less frequent with

clopidogrel than with aspirin. Both aspirin and clopidogrel are associated with a

low occurrence of neutropenia. Aspirin, ticlopidine,dipyridamole, and

clopidogrel have earned a role in stroke prevention; the different adverse-effect

profiles of the drugs will influence the choice of agent



Keywords: aggregation/antiplatelet therapy/aspirin/ASPIRIN/cerebral

ischemia/cerebrovascular disease/cerebrovascular

disorders/clopidogrel/dipyridamole/DIPYRIDAMOLE/drugs/hemorrhage/ische

mic stroke/mechanism of action/myocardial infarction/platelet

aggregation/platelet aggregation inhibitors/prevention/RANDOMIZED

TRIAL/relative risk/risk/SECONDARY PREVENTION/STROKE/stroke

prevention/TICLOPIDINE/ticlopidine/toxicity/vascular



Hornberger, J. (1998), A cost-benefit analysis of a cardiovascular disease prevention

trial, using folate supplementation as an example. American Journal of Public

Health, 88 (1), 61-67.



Abstract: Objectives. This study illustrates a cost-benefit analysis of clinical trial design,

using as an example a trial of folate supplementation to prevent cardiovascular

disease. Methods. Bayesian statistical and decision-analytic techniques were

used to estimate the cost-benefit and sample size of a placebo- controled trial of

folate targeted to US citizens, aged 35 to 84 years, with elevated serum

homocysteine levels. The main end point is event-free survival (i.e., survival

without new ischemic heart disease or stroke) at 5 years. Results. Because the

screening cost and annual cost and inconvenience of taking folate is small

compared with the consequences of stroke, ischemic heart disease, or death, the

increase in 5-year event- free survival with folate that should compel the use of

folate is just 1.1%. The sample size per group needed to establish this level of

folate's medical effectiveness is estimated to be 17 310. Such a trial would

provide an expected societal cost- benefit savings exceeding $11 billion within

15 years. Conclusions. This study illustrates how Bayesian methods may help in

assessing the societal cost-benefit consequences of proposed disease prevention

trials, deciding which trials are worth sponsoring, and designing cost-effective

trials



Keywords: aged/ATHEROSCLEROSIS/cardiovascular

disease/CLINICAL-TRIALS/cost/cost-benefit

analysis/HEALTH/heart/HOMOCYSTEINE/HYPERHOMOCYSTEINEMIA/is

chemic heart disease/NEURAL-TUBE DEFECTS/prevention/RISK

FACTOR/serum/stroke/trials/VASCULAR-DISEASE

[Anon]. (1998), ASHP therapeutic position statement on antithrombotic therapy in

chronic atrial fibrillation. American Journal of Health-System Pharmacy, 55 (4),

376-381



Keywords: American Society of Health-System

Pharmacists/anticoagulants/ANTICOAGULATION/antithrombotic

therapy/ASPIRIN/aspirin/atrial fibrillation/BLEEDING

COMPLICATIONS/cerebrovascular

disorders/COST-EFFECTIVENESS/fibrillation/organizations/patient

education/pharmacists/platelet aggregation

inhibitors/PREVALENCE/PREVENTION/PROPHYLAXIS/protocols/RISK/ST

ROKE/therapy/warfarin/WARFARIN



Sheps, S.G. (1999), Overview of JNC VI: New directions in the management of

hypertension and cardiovascular risk. American Journal of Hypertension, 12 (8),

65S-72S.



Abstract: Treatment recommendations for hypertension as outlined in the Sixth Report

of the Joint National Committee on Prevention, Detection, Evaluation, and

Treatment of High Blood Pressure (JNC VI) are constantly evolving and being

refined as new information on the disease becomes evident. Uncontrolled

hypertension is a major antecedent of stroke, heart failure, coronary heart disease,

and end-stage renal disease. The increasing incidences of both cardiovascular

and renal diseases fuel the need for improved control of hypertension. In fact,

according to the National Health and Nutrition Examination Survey (NHANES),

about 69% of Americans whose blood pressure is greater than 140/90 mm Hg are

aware of it, about half are getting treatment for it, and only about one-quarter are

adequately controlled. These observations fuel the need for improved patient

management guidelines. JNC VI makes several changes from the previous JNC

V to assist physicians in the diagnosis, treatment, and improved management of

patients with hypertension. These changes include reporting adult blood pressure

in two new ways, via staging and risk factor classification. A high-normal

classification (systolic: 130 to 139 mm Hg, or diastolic: 85 to 89 mm Hg) is

included in JNC VI because of the clinical importance of such blood pressure

contributing to cardiovascular disease. Additionally, clinicians are advised to

assign a patient to one of three risk categories that, in addition to hypertension

stage, influence the decision to select antihypertensive drug therapy. Lifestyle

modification is an important component at each stage. These and other changes

and highlights of recent studies supporting the need for more intensive blood

pressure control are discussed in this paper. Am J Hypertens 1999; 12:65S-72S

(C) 1999 American Journal of Hypertension, Ltd



Keywords: antihypertensive therapy/AWARENESS/blood pressure/blood pressure

control/cardiovascular/cardiovascular disease/cardiovascular risk/cardiovascular

risk factors/control/control of hypertension/coronary heart

disease/diagnosis/diseases/drug therapy/end-stage renal

disease/guidelines/HEALTH/heart/heart failure/hypertension/incidences/JNC

V/lifestyle

modification/MINNESOTA/NEW-YORK/POPULATION/PREVALENCE/renal

/renal disease/risk/risk factor/STROKE/therapy/treatment/TRENDS



White, R.H., McBurnie, M.A., Manolio, T., Furberg, C.D., Gardin, J.M., Kittner, S.J.,

Bovill, E. and Knepper, L. (1999), Oral anticoagulation in patients with atrial

fibrillation: Adherence with guidelines in an elderly cohort. American Journal of

Medicine, 106 (2), 165-171.



Abstract: PURPOSE: To determine adherence with practice guidelines in a

population-based cohort of elderly persons aged 70 years or older with atrial

fibrillation. SUBJECTS AND METHODS: This was a cross-sectional analysis of

a subgroup of participants in the Cardiovascular Health Study, a prospective

observational study involving four communities in the United States. Subjects

were participants with atrial fibrillation on electrocardiogram at one or more

yearly examinations from 1993 to 1995. The outcome measure was self-reported

use of warfarin in 1995. RESULTS: In 1995, 172 (4.1%) participants had atrial

fibrillation together with information regarding warfarin use and no preexisting

indication for its use, Warfarin was used by 63 (37%) of these participants. Of

the 109 participants not reporting warfarin use, 92 (84%) had at least one of the

clinical risk factors (aside from age) associated with stroke in patients with atrial

fibrillation. Among participants not taking warfarin, 47% were taking aspirin.

Several characteristics were independently associated with warfarin use,

including age [odds ratio (OR) = 0.6 per 5-year increment, 95% CI 0.5-0.9], a

modified mini- mental examination score 70%) and mild neurologic deficits

(NIH stroke scale 50% of regional adults, broadly distributed

by site, gender, and age, Interventions: From 1974 to 1994, a community

program, integrated with primary medic;ll care and staffed by professional nurses,

provided education, screening, counseling, referral, tracking, and followup for

cardiovascular risk factors. Main Outcome Measures: Age-adjusted mortality

rates (total, heart, coronary, cerebrovascular, cancer) for three counties and

Maine, plus annual program encounters. Results: Relative to Maine, the Franklin

heart disease death rate was 0.97 at baseline (1960-1969; 95% confidence

interval, 0.91 to 1.03), 0.91 during the program (0.85 to 0.97), 0.83 during the 11

years of program growth (0.78 to 0.88), but 1.0 during the 10 years of decreasing

encounters. Franklin's total death rate was 1.01 at baseline, 0.95 during the

program (0.92 to 0.98), and 0.90 during program growth (0.86 to 0.94). Results

were similar for coronary disease, stroke, and cancer. Relative death rates did not

fall in either comparison county. Nurse- client encounters totaled 120,280 over

21 years. Relative to Maine, heart disease death rates correlated inversely with

program encounters (r = -0.53) but not with unemployment or physician supply.

Conclusions: Integrated with primary medical care, a comprehensive,

nurse-mediated community cardiovascular health program in rural Maine has

been associated with significant time-dependent and dose-dependent reductions

in cardiovascular and total mortality. (C) 2000 American Journal of Preventive

Medicine



Keywords: ACUTE

MYOCARDIAL-INFARCTION/adults/age/cancer/cardiovascular/cardiovascular

disease/cardiovascular diseases/cardiovascular risk/cardiovascular risk

factors/cerebrovascular/community/coronary disease/CORONARY

HEART-DISEASE/COST-EFFECTIVENESS/DEATH/disease/education/EDU

CATION-PROGRAM/evaluation/gender/health/heart/heart

disease/mortality/NEW-YORK/NORTH-KARELIA/nursing/PREVENTION/pri

mary/primary prevention/PROJECT/public health/residence

characteristics/risk/risk factors/RISK- FACTORS/screening/stroke/TRENDS



Li-Saw-Hee, F.L., Blann, A.D. and Lip, G.Y.H. (2000), Effect of degree of blood

pressure on the hypercoagulable slate in chronic atrial fibrillation. American

Journal of Cardiology, 86 (7), 795-+.



Abstract: Both chronic nonvalvular atrial fibrillation (AF) and hypertension are common

cardiovascular conditions that are independently associated with an increased

risk of stroke.(1,2) However, AF and hypertension often coexist, and such

patients have an additive risk of stroke and thromboembolism, thus representing

a "high-risk" population, In the multivariate analysis of pooled data from the 5

initial randomized controlled anticoagulation trials of nonvalvular AF, a history

of hypertension conferred a 1.6-fold increase in risk of stroke over those without

risk factors.(3) The contribution of hypertension was further confirmed by the

Stroke Prevention in Atrial Fibrillation Investigators(4) who found that patients

with AF with a history of hypertension (defined as a systolic blood pressure [BP]

> 160 mm Hg) had a higher rate of primary events (ischemic stroke and systemic

embolism; 3.6%/year) than those with no history of hypertension (1.1%/year; p 0.05). Furthermore, detailed analysis of 24-hour

ambulatory blood pressure data (available in 253 subjects) showed no association

between various blood pressure parameters (systolic and diastolic blood pressure,

out-of-bed and in-bed measurements) and LAA flow velocities (all p > 0.05). In

summary, the present study establishes the reference values for LAA flow

velocities in a large sample of the general population. LAA flow velocities

progressively decline with age in subjects with preserved left ventricular systolic

function. (C) 2000 by Excerpta Medica, Inc



Keywords: age/aged/ALTERED LOADING CONDITIONS/ANATOMY/blood

pressure/BLOOD-PRESSURE/diastolic blood

pressure/DISEASE/DOPPLER-ECHOCARDIOGRAPHY/echocardiography/hea

rt/history/hypertension/IMPACT/IN-VIVO/left atrial

appendage/men/NEW-YORK/population/population-based/RISK/sex/sinus

rhythm/STROKE/TRANSESOPHAGEAL ECHOCARDIOGRAPHY/women



Pearce, L.A., Hart, R.G. and Halperin, J.L. (2000), Assessment of three schemes for

stratifying stroke risk in patients with nonvalvular atrial fibrillation. American

Journal of Medicine, 109 (1), 45-51.

Abstract: PURPOSE: The risk of ischemic stroke varies widely among patients with

nonvalvular atrial fibrillation, influencing the choice of prophylactic

antithrombotic therapy. We assessed three schemes for stroke risk stratification

in these patients who were treated with aspirin and who did not have prior

cerebral ischemia. SUBJECTS AND METHODS: Criteria from three schemes of

risk stratification were applied to a longitudinally observed cohort of patients

with atrial fibrillation who did not have prior cerebral ischemia and who were

treated with aspirin alone or aspirin combined with low, ineffective doses of

warfarin in a multicenter clinical trial. The ability of the schemes to identify

patients at high (greater than or equal to 6%), low (less than or equal to 2%), and

intermediate annual risks of ischemic stroke was assessed. RESULTS: During a

mean follow-up of 1.8 years. 48 ischemic strokes occurred among 1,073 patients

with atrial fibrillation who were taking aspirin (rate = 2.5 per 100 person-years).

Each of the three schemes predicted stroke and disabling stroke, and successfully

identified patients at low risk (observed stroke rates of 0.3 to 1.1 per 100

person-years), although the fractions of the cohort that were categorized as low

risk varied from 14% to 45%. The observed rates of ischemic stroke among

patients categorized as high risk ranged from 3.5 to 7.2 per 100 person- years

among the stratification schemes. Two schemes considered all patients >75 years

old as high risk (observed stroke rate 4.2 per 100 person-years), while the

remaining scheme classified one third of patients in this age group as low risk

(observed stroke rate 0.6 per 100 person-years). CONCLUSIONS: When tested

in a large cohort of patients with atrial fibrillation who were treated with aspirin,

available risk- stratification schemes successfully identified patients with low

rates of ischemic stroke, but less consistently identified high-risk patients. Am J

Med. 2000;109:45-51. (C) 2000 by Excerpta Medica, Inc



Keywords: age/antithrombotic/ANTITHROMBOTIC THERAPY/ASPIRIN/atrial

fibrillation/cerebral/cerebral

ischemia/COMMUNITY/fibrillation/GENERAL-PRACTICE/high

risk/ischemia/ischemic/ischemic stroke/NEW-YORK/nonvalvular atrial

fibrillation/POPULATION/PREVALENCE/PREVENTION/PRIMARY-CARE/r

isk/risk stratification/stroke/therapy/THROMBOEMBOLISM/warfarin



De, B.K., Sen, S., Biswas, P.K., Sengupta, D., Biswas, J., Santra, A., Hazra, B. and

Maity, A.K. (2000), Propranolol in primary and secondary prophylaxis of

variceal bleeding among cirrhotics in India: A hemodynamic evaluation.

American Journal of Gastroenterology, 95 (8), 2023-2028.



Abstract: OBJECTIVE: In the present study, we attempted to complete the

hemodynamic assessment of propranolol response in cirrhotics with esophageal

varices at high risk of bleeding, in one sitting, so as to identify nonresponders at

the earliest. Some noninvasive indicators of this response were also evaluated.

METHODS: Hepatic venous pressure gradient (HVPG) was measured in 33 such

cases (18 nonbleeders, 15 bleeders) before and 90 min after an oral dose of 80

mg propranolol, and reduction by greater than or equal to 20% taken as

responder. RESULTS: Twenty-two patients (66.67%) responded (HVPG

reduction greater than or equal to 26%), whereas 11 (33.33%) did not (HVPG

reduction less than or equal to 6%). Postdrug HVPG between responders and

nonresponders showed a significant difference (p 0.1), baseline CI (p = 0.665), nor baseline stroke volume index (p >

0.1) could predict responder status. Difference of HVPG reduction (percent)

between bleeders (21.49 +/- 35.53) and nonbleeders (40.58 +/- 23.95)

approached, but did not reach, statistical significance (p = 0.076). However,

logistic regression showed this difference to be significant (p = 0.026). Age of

responders was found to be significantly lower than that of nonresponders (p

approximate to 0.05). During a follow-up of 9- 38 months, only one of 22

responders (on propranolol) had an episode of variceal bleed. None in whom

HVPG fell to less than or equal to 12 mm Hg bled. CONCLUSION: The study

suggests that single-sitting hemodynamic assessment of acute response to

high-dose oral propranolol clearly differentiates between responders and

nonresponders. Moreover, it appears that prior history of variceal bleeding and

old age negatively influences the effect of propranolol. (C) 2000 by Am. Cell. of

Gastroenterology



Keywords: acute/age/bleeding/CIRRHOSIS/evaluation/HEMORRHAGE/high

risk/history/NEW-YORK/PORTAL-

HYPERTENSION/PREVENTION/primary/prophylaxis/PROSPECTIVE

RANDOMIZED

TRIAL/risk/SCLEROTHERAPY/status/stroke/VENOUS-PRESSURE



Prystowsky, E.N. (2000), Management of atrial fibrillation: Therapeutic options and

clinical decisions. American Journal of Cardiology, 85 (10A), 3D-11D.



Abstract: Atrial fibrillation (AF) is the most common, sustained tachyarrhythmia seen in

clinical practice. Although it is not immediately life threatening, AF can cause

troublesome symptoms and poses a risk of stroke. The patient's clinical status is

often complicated by the presence of other cardiovascular or concomitant

diseases. As a result, management of the patient with AF involves many

questions and choices, all of which must be individualized. There ore 3 general

strategies for the management of patients with AF, including (1) restoration and

maintenance of sinus rhythm, (2) control of ventricular rate, and (3) prevention

of stroke. More than 1 strategy may be appropriate in some patients, Furthermore,

either pharmacologic or nonpharmacologic options can be chosen in certain

situations. Although some data from randomized clinical trials are available to

aid in clinical decision-making, only the benefits of anticoagulation are

supported by substantial evidence. This article explores practical approaches to

several management issues and scenarios for which there ore limited relevant

clinical date. These include: (1) patient selection for ventricular rate control and

assessment of treatment, (2) choice of antiarrhythmic drug for maintenance of

sinus rhythm, (3) inpatient versus outpatient initiation of therapy, (4) definition

of antiarrhythmic drug success, (5) methods of transthoracic direct cardioversion,

and (6) prediction and prevention of AF after cardiac surgery. (C) 2000 by

Excerpta Medica, Inc

Keywords: AF/AMIODARONE/anticoagulation/atrial fibrillation/cardiac/cardiac

surgery/CARDIAC-SURGERY/cardiovascular/CARDIOVERSION/clinical

practice/clinical trials/CONGESTIVE-HEART-FAILURE/control/decision

making/decision-making/diseases/EFFICACY/fibrillation/HUMANS/IBUTILID

E/LEFT-VENTRICULAR

DYSFUNCTION/NEW-YORK/prevention/RADIOFREQUENCY

ABLATION/randomized/risk/sinus

rhythm/status/stroke/surgery/therapy/treatment/TRIAL/trials



Fraisse, F., Holzapfel, L., Coulaud, J.M., Simmoneau, G., Bedock, B., Feissel, M.,

Herbecq, P., Pordes, R., Poussel, J.F. and Roux, L. (2000), Nadroparin in the

prevention of deep vein thrombosis in acute decompensated COPD. American

Journal of Respiratory and Critical Care Medicine, 161 (4), 1109-1114.



Abstract: Low molecular weight heparins are as effective as unfractionated heparin in

deep-vein thrombosis (DVT) prophylaxis for major surgery. However, there is

no evidence nor consensus for prophylaxis in medical patients. We compared the

efficacy and safety of nadroparin calcium (nadroparin) with placebo in medical

patients at high risk of DVT. A total of 223 patients mechanically ventilated for

acute, decompensated chronic obstructive pulmonary disease, were randomized

to treatment with subcutaneous nadroparin adjusted for body weight (0.4 ml, i.e.,

3,800 AXa IU, or 0.6 ml, i.e., 5,700 AXa IU) or placebo. The average duration of

treatment was 11 d. The incidence of DVT in patients receiving nadroparin was

significantly lower than that in patients receiving placebo (15.5 versus 28.2%; p

= 0.045). Although the incidence of adverse events was high in both groups,

there were no significant differences between nadroparin and placebo for total

adverse events (46.3 versus 39.8%; p = 0.33), serious adverse events (25.0 versus

19.5%; p = 0.32), or those resulting in early permanent discontinuation of

treatment (12.0 versus 8.8%; p = 0.44). The most common adverse event was

hemorrhage. There was the same number of deaths in both treatment groups.

Subcutaneous nadroparin resulted in 45% decrease in incidence of DVT

compared with placebo



Keywords: acute/ACUTE ISCHEMIC STROKE/adverse

events/calcium/CARE/consensus/deep vein thrombosis/deep-vein

thrombosis/disease/DOUBLE-BLIND/DVT/ENOXAPARIN/hemorrhage/hepari

n/heparins/high risk/HIP-

REPLACEMENT/incidence/INPATIENTS/LUNG/medical

patients/MOLECULAR-WEIGHT

HEPARIN/NEW-YORK/prevention/prophylaxis/randomized/RISK/safety/surger

y/thrombosis/treatment/TRIAL/UNFRACTIONATED HEPARIN/VENOUS

THROMBOEMBOLISM



Johnson, L.N., Stetson, S.W., Krohel, G.B., Cipollo, C.L. and Madsen, R.W. (2000),

Aspirin use and the prevention of acute ischemic cranial nerve palsy. American

Journal of Ophthalmology, 129 (3), 367-371.

Abstract: PURPOSE: To assess the relationship of aspirin use and ischemic cranial

nerve palsies among patients with diabetes mellitus and hypertension,

METHODS: This retrospective case-control study involved 100 patients with

ischemic cranial nerve palsies in association with diabetes, hypertension, or both

(palsy cases) and 163 age-matched and sex-matched patients with diabetes,

hypertension, or both but without ischemic cranial nerve palsies (nonpalsy

control subjects). Comparisons were made with respect to duration of diabetes,

dose and duration of aspirin use, dose and duration of tobacco use, and presence

of cardiac or cerebrovascular disease. RESULTS: There were 20 oculomotor, 33

trochlear, 37 abducens, and 10 facial nerve palsy cases. The median duration of

diabetes was 6 years for cases and 7 years for control subjects. There were 34

cases (34%) who had used aspirin for a mean duration of 5.5 years before the

onset of the cranial nerve palsy and 49 control subjects (30.1%) who had used

aspirin for a mean duration of 4.3 years. There were no significant differences

between cases and control subjects for duration of diabetes (P = .94); aspirin use

(P = .51), duration (P = .50), and dosage (P = .89); tobacco use (P = .73) and

consumption (P = .45); and proportion of cardiac disease (P = .17).

Cerebrovascular disease was significantly less common among palsy cases than

nonpalsy control subjects (P 40.6 degrees C) in the presence of altered mental status and anhidrosis) and

tried to explore the possible cause of this unusual phenomenon. Through a

emergency department (ED) chart review, case retraction from International

Classification of Diseases (ICD) code, and ED conferences, six patients were

found for the period from June to August (the hottest months in Taiwan) 1998.

We found that the most common comorbid conditions were hypertension (4/6)

and preexisting mental problems (3/6). All patients lived in the inner part of an

urban area, were middle class, and were not socially isolated. Most of our

patients felt unhealthy being exposed to the cold and avoided staying in

air-conditioned rooms. Laboratory abnormalities and clinical presentations,

except for a high fever and conscious change, seemed to be nonspecific. All

cases occurred during two periods of sustained hotter-than average weather and,

to our surprise, we found that three episodes occurred around the day of the

highest weather temperature (38.1 degrees C). However, the higher temperatures

(around 30 degrees to 31 degrees C and 32 degrees to 33 degrees C) did not

reach the criteria of a heat wave. Compared with the other study, our patients

seemed to have initial worse outcomes. Because of special environment and

social factors, classic heat stroke may occur occasion ally in subtropic regions,

without previous history of heat waves and where heat stroke rarely occurs,

during periods of the persistently high temperatures. Prevention of heat stroke in

an area with a low incidence includes early health organizations' issue of

advisories or warnings through the media and reminding at teaching emergency

physicians about heat stroke during sustained hot weather, especially when

record temperatures are set



Keywords: CHICAGO/classic heat stroke/disease/health/heat/heat stroke/heat

wave/HEATSTROKE/history/hypertension/hyperthermia/incidence/organization

s/review/status/stroke/subtropics/urban/WAVE



Rimmer, J.H., Braunschweig, C., Silverman, K., Riley, B., Creviston, T. and Nicola, T.

(2000), Effects of a short-term health promotion intervention for a predominantly

African-American group of stroke survivors. American Journal of Preventive

Medicine, 18 (4), 332-338.



Abstract: The study examined the effects of a 12-week health promotion intervention for

a predominantly urban African-American population of stroke survivors. Design:

A pre-test/post-test lag control group design was employed. Participants/Setting:

Participants were 35 stroke survivors (9 male, 26 female) recruited fi om local

area hospitals and clinics. Main Outcome Measures: Biomedical, fitness,

nutritional, and psychosocial measures were employed to assess program

outcomes. Results: Treatment group made significant gains over lag controls in

the following areas: (1) reduced total cholesterol, (2) reduced weight, (3)

increased cardiovascular fitness, (4) increased strength, (5) increased flexibility,

(6) increased life satisfaction and ability to manege self-care needs, and (7)

decreased social isolation. Conclusions: A short-term health pr-emotion

intervention for predominantly African-American stroke survivors was effective

in improving several physiological and psychological health outcomes



Keywords: cardiovascular/CARE/cerebrovascular

accident/cholesterol/control/design/disabled

persons/exercise/EXERCISE/health/health behavior/health

promotion/hospitals/minorities/NEW-YORK/nutrition/PEOPLE/physical

fitness/PHYSICAL-DISABILITIES/population/PREVENTION/RISK/SERVICE

/stroke/urban/WOMEN



Mcgill, H.C., McMahan, C.A., Herderick, E.E., Malcom, G.T., Tracy, R.E. and Strong,

J.P. (2000), Origin of atherosclerosis in childhood and adolescence. American

Journal of Clinical Nutrition, 72 (5), 1307S-1315S.



Abstract: Atherosclerosis begins in childhood as deposits of cholesterol and its esters,

referred to as fatty streaks, in the intima of large muscular arteries. In some

persons and at certain arterial sites, more lipid accumulates and is covered by a

fibromuscular cap to form a fibrous plaque. Further changes in fibrous plaques

render them vulnerable to rupture, an event that precipitates occlusive thrombosis

and clinically manifest disease (sudden cardiac death, myocardial infarction,

stroke, or peripheral arterial disease). In adults, elevated non-HDL- cholesterol

concentrations, low HDL-cholesterol concentrations, hypertension, smoking,

diabetes, and obesity are associated with advanced atherosclerotic lesions and

increased risk of clinically manifest atherosclerotic disease. Control of these risk

factors is the major strategy for preventing atherosclerotic disease. To determine

whether these risk factors also are associated with early atherosclerosis in young

persons, we examined arteries and tissue from approximate to 3000 autopsied

persons aged 15-34 y who died of accidental injury, homicide, or suicide. The

extent of both fatty streaks and raised lesions (fibrous plaques and other

advanced lesions) in the right coronary artery and in the abdominal aorta was

associated positively with non-HDL-cholesterol concentration, hypertension,

impaired glucose tolerance, and obesity and associated negatively with

HDL-cholesterol concentration. Atherosclerosis of the abdominal aorta also was

associated positively with smoking. These observations indicate that long- range

prevention of atherosclerosis and its sequelae by control of the risk factors for

adult coronary artery disease should begin in adolescence and young adulthood



Keywords:

adolescents/adults/aged/aorta/arteries/atherosclerosis/cholesterol/COMMUNITY

- PATHOLOGY/control/coronary arteries/coronary artery disease/CORONARY

HEART-DISEASE/diabetes/fatty streaks/FATTY STREAKS/glucose/HDL

cholesterol/hypertension/infarction/LOW-DENSITY-LIPOPROTEIN/MACROP

HAGE FOAM CELLS/myocardial/myocardial

infarction/NUTRITION/obesity/peripheral arterial

disease/plaque/POSTMORTEM RENAL INDEX/prevention/risk/risk

factors/RISK-FACTORS/smoking/STATISTICAL-ANALYSIS/stroke/thrombos

is/WHITE MALES/young adults/YOUNG BLACK



Boden, W.E. (2000), High-density lipoprotein cholesterol as an independent risk factor

in cardiovascular disease: Assessing the data from Framingham to the Veterans

Affairs high-density lipoprotein intervention trial. American Journal of

Cardiology, 86 (12A), 19L-22L.



Abstract: The Framingham Heart Study found that high-density lipoprotein cholesterol

(HDL-C) was the most potent lipid predictor of coronary artery disease risk in

men and women >49 years of age. The Air Force/Texas Coronary

Atherosclerosis Prevention Study (AFCAPS/Tex-CAPS), in which subjects were

randomized to treatment with lovastatin or placebo, also reported a striking

benefit of treatment, particularly in patients with HDL-C less than or equal to 35

mg/dL at baseline. Treatment with lovastatin was associated with a remarkable

45% reduction in events for this group. The Veterans Affairs HDL Intervention

Trial (VA-HIT) randomized subjects to gemfibrozil or placebo. A high

proportion of enrolled subjects with low HDL-C also had characteristics of the

dysmetabolic syndrome. HDL-C likewise increased by 6% on treatment, total

cholesterol was reduced by 4% and triglycerides by 31%. There was no change

in low-density lipoprotein cholesterol (LDL-C) levels. These changes in lipid

were associated with a cumulative 22% reduction in the trial primary endpoint of

all-cause mortality and nonfatal myocardial infarction (MI). Additionally,

significant reductions in secondary endpoints including death from coronary

artery disease, nonfatal MI, stroke, transient ischemic attack, and carotid

endarterectomy were associated with the increase in HDL-C. In VA-HIT, for

every 1% increase in HDL-C, there was a 3% reduction in death or MI, a

therapeutic benefit that eclipses the benefit associated with LDL-C reduction. (C)

2000 by Excerpta Medica, Inc



Keywords: age/all-cause mortality/ARTERY DISEASE/cardiovascular/cardiovascular

disease/carotid/carotid endarterectomy/cholesterol/coronary artery

disease/CORONARY HEART-DISEASE/CT/death/disease/disease

risk/endarterectomy/gemfibrozil/HDL/high density lipoprotein/high-density

lipoprotein cholesterol/infarction/ischemic/low density lipoprotein/low-density

lipoprotein cholesterol/MEN/mortality/myocardial/myocardial

infarction/NEW-YORK/PREVENTION/primary/randomized/risk/risk

factor/secondary/stroke/transient/transient ischemic

attack/treatment/trial/triglycerides/women

Waters, D.D. (2001), What do the statin trials tell us? American Journal of Managed

Care, 7 (5), S138-S143.



Abstract: The results of 5 major placebo-controlled trials evaluating the effects of statins

in approximately 31,000 individuals with and without known coronary

disease,have demonstrated the following: statins reduce the incidence of

coronary events, the reduction in relative risk for coronary events increases with

the duration of therapy, the reduction in coronary events is proportional to the

reduction in low-density lipoprotein cholesterol (LDL-C) levels, and lower

LDL-C levels are associated with lower event rates. The studies have also shown

that statins are safe and effective in reducing the incidence of coronary events in

women, individuals with diabetes, and patients older than 65 years of age and in

reducing the risk of stroke and transient ischemic attacks in patients with

coronary disease. Finally studies indicate that statins ameliorate a variety of

pathophysiologic processes that are associated with increased risk for

atherosclerosis



Keywords: 4S/age/atherosclerosis/CARE/cholesterol/coronary disease/CORONARY

HEART-DISEASE/diabetes/disease/EVENTS/HYPERCHOLESTEROLEMIA/i

ncidence/ischemic/low density lipoprotein/low-density lipoprotein

cholesterol/MEN/PREVENTION/relative risk/RISK/SCANDINAVIAN

SIMVASTATIN SURVIVAL/statin/statins/stroke/therapy/transient/transient

ischemic attacks/trials/WOMEN



Tanne, D., Benderly, M., Goldbourt, U., Boyko, V., Brunner, D., Graff, E.,

Reicher-Reiss, H., Shotan, A., Mandelzweig, L. and Behar, S. (2001), A

prospective study of plasma fibrinogen levels and the risk of stroke among

participants in the Bezafibrate Infarction Prevention Study. American Journal of

Medicine, 111 (6), 457-463.



Abstract: PURPOSE: Plasma fibrinogen has emerged as an important predictor of

cardiovascular disease, but few data are available on its association with stroke.

We sought to determine if plasma fibrinogen is a marker of increased risk or a

direct causative risk factor for stroke. SUBJECTS AND METHODS: Patients

from the Bezafibrate Infarction Prevention Study, a placebo-controlled,

randomized clinical trial of secondary prevention of coronary heart disease by

lipid modification with bezafibrate retard (400 mg daily), were studied. Plasma

fibrinogen levels were measured at baseline and yearly thereafter. Stroke, a

prospectively monitored endpoint, was systematically assessed regarding stroke

type, subtype, and functional outcome. RESULTS: Mean baseline fibrinogen

levels were significantly higher in patients subsequently having a

cerebrovascular event (140 strokes, 36 transient ischemic attacks; mean

follow-up, 6.2 years) than in patients who did not (375 vs. 349 mg/dL, P

373 mg/dL, P 65 years (5.90, p = 0.0001),

moderate to severe hypertension (6.8, p = 0.0017), weight gain of >2 kg between

dialyses as a marker of poor patient compliance (6.47, p = 0.0433), and

antithrombotic therapy with salicylates or warfarin (8.33, p = 0.0002), as

compared with corresponding groups without these risk factors. Our data suggest

that in contrast to other risk factors nonrheumatic atrial fibrillation in itself is not

associated with an increased risk of stroke in patients on maintenance

hemodialysis treatment. Copyright (C) 2001 S. Karger AG, Basel



Keywords: age/anticoagulation/ANTICOAGULATION/antithrombotic/antithrombotic

therapy/arrhythmia/atrial fibrillation/Austria/chronic atrial

fibrillation/EVENTS/fibrillation/GENERATION/hemodialysis/HEMOSTASIS/h

igh risk/hypertension/incidence/nonrheumatic/patient

compliance/PLATELET-AGGREGATION/PREVALENCE/PREVENTION/RE

NAL-DISEASE/risk/risk factors/risk factors of stroke/stroke/stroke

incidence/therapy/treatment/uremia/WARFARIN/weight

Ikai, T., Uematsu, M., Eun, S.S., Kimura, C., Hasegawa, C. and Miyano, S. (2001),

Prevention of secondary osteoporosis postmenopause in hemiplegia. American

Journal of Physical Medicine & Rehabilitation, 80 (3), 169-174.



Abstract: Objectives: To study secondary osteoporosis postmenopause in women with

hemiplegia and to show the therapeutic effects of etidronate and how

osteoporotic conditions relate to the activities of daily living (ADL). Design:

Eighty-one postmenopausal women with hemiplegia were admitted within 6 mo

of their first cerebrovascular accident. The bone mineral density (BMD) and

biochemical markers of bone turnover were measured at the time of admission.

Forty women (treatment group) received a 2-wk administration of etidronate.

Forty-one women (control group) were not administered etidronate. Results:

After completing a 3-mo rehabilitation program, BMD levels were remeasured.

ADL was evaluated by FIM(TM). The low ADL group had a larger decrease in

BMD than the high ADL group. For the control group, the BMD rate of change

on the paretic side of the femoral neck was -9.6%/3 mo for the low ADL group.

BMD loss was reduced significantly by the administration of etidronate for the

low ADL group. Conclusions: Results indicate that ADL corresponds to the

progression of osteoporosis in postmenopausal women with hemiplegia and that

increasing the level of ADL will reduce the progression of osteoporosis. Use of

etidronate has also been proven to have a suppressive effect on the BMD

decrease in women



Keywords: activities of daily

living/ADL/administration/BISPHOSPHONATES/BONE-MINERAL

DENSITY/cerebrovascular/cerebrovascular

accident/COLLAGEN/control/etidronate/hemiplegia/hemiplegic

women/IMMOBILIZATION/Japan/markers/MASS/osteoporosis/postmenopausa

l women/RADIOIMMUNOASSAY/rehabilitation/secondary/secondary

osteoporosis/STROKE/treatment/women



Aikimbaev, K., Guvenc, B., Canataroglu, A., Canataroglu, H., Baslamisli, F. and Oguz,

M. (2001), Value of duplex and color Doppler ultrasonography in the evaluation

of orbital vascular flow and resistance in sickle cell disease. American Journal of

Hematology, 67 (3), 163-167.



Abstract: The aim of the present study was to assess and to compare the orbital and

retinal vascular flow dynamics and resistance in patients with homozygous sickle

cell disease with controls by means of duplex and color Doppler ultrasonography.

Forty-six patients with homozygous sickle cell disease (SCD) and 20 healthy

subjects were included in the study. None of the patients had objective signs of

ocular involvement. Duplex and color Doppler ultrasonography of the

ophthalmic, short posterior ciliary, and central retinal arterial flows of the both

eyes were performed to assess peak systolic flow velocity (PSFV), end-diastolic

flow velocity (EDFV), and mean flow velocity (MFV) through entire cardiac

cycle with further calculation of resistive indices (RI) and pulsatility indices (PI).

Ophthalmic arterial flow velocities were significantly increased in patients with

SCD than in controls (P 0.03) in patients with SCD

compared to controls. Reduction of retinal vascular flow velocities and increase

of retinal vascular resistance were significantly related to the mean hemoglobin

and hematocrit levels, red blood cell count, and mean corpuscular hemoglobin

volume (P 4-mm thick, ulcerated plaques, or mobile

debris), adjusting for age and gender (p 0.2). Thus, coronary artery disease is strongly associated

with aortic atherosclerosis and complex atherosclerosis in the general population.

Cerebrovascular disease is weakly associated with aortic atherosclerosis, thereby

questioning the overall importance of aortic atherosclerosis in the pathogenesis

of cerebrovascular events in the general population. (C) 2002 by Excerpta

Medica, Inc



Keywords: age/aged/angina/angina

pectoris/aorta/ARCH/ATHEROMAS/atherosclerosis/ATRIAL-FIBRILLATION

/bypass/bypass surgery/cerebrovascular/cerebrovascular disease/coronary artery

bypass/coronary artery disease/disease/echocardiography/gender/HIGH

BLOOD-PRESSURE/hypertension/hypertension

treatment/infarction/ischemic/ISCHEMIC STROKE/myocardial/myocardial

infarction/NEW-YORK/pathogenesis/PLAQUE/population/PREVALENCE/puls

e pressure/RISK-

FACTORS/severity/smoking/stroke/surgery/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/transient/transient ischemic

attack/treatment/VASCULAR EVENTS



Kong, D.F., Hasselblad, V., Kandzari, D.E., Newby, L.K. and Califf, R.M. (2002),

Seeking the optimal aspirin dose in acute coronary syndromes. American Journal

of Cardiology, 90 (6), 622-+.



Abstract: We reexamined the Antiplatelet Trialists' Collaboration data (11 studies) to

evaluate optimal dosing of aspirin for secondary prevention after acute coronary

syndromes, while adjusting for patient population and temporal trends. Although

aspirin reduced the risks of mortality (odds ratio, 0.82; 95% confidence interval,

0.71 to 0.96), death or myocardial infarction, and death, infarction, or stroke,

unadjusted analysis suggested greater benefit in unstable angina versus

myocardial infarction and with higher versus lower aspirin doses, highlighting

the need for larger, randomized comparisons of aspirin dosing in these patients



Keywords: acute/acute coronary

syndromes/ANGINA/aspirin/death/infarction/mortality/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/NEW-YORK/population/prevention/

randomized/secondary/secondary prevention/stroke/trends/TRIAL/unstable

angina



Disler, P., Hansford, A., Skelton, J., Wright, P., Kerr, J., O'Reilly, J., Hepworth, J.,

Middleton, S. and Sullivan, C. (2002), Diagnosis and treatment of obstructive

sleep apnea in a stroke rehabilitation unit - A feasibility study. American Journal

of Physical Medicine & Rehabilitation, 81 (8), 622-625.



Abstract: Obstructive sleep apnea can be diagnosed in approximately 60% of stroke

survivors in the postacute period and has been found to be associated with

increased mortality and a worse functional outcome at 3 and 12 mo after

discharge. In this study, 38 patients undergoing rehabilitation after stroke

underwent sleep studies by using the AutoSet Portable II Plus device; obstructive

sleep apnea was found in 18 of the patients, and five consecutively diagnosed

patients were treated on the ward with nasal continuous positive airway pressure.

The research has shown that it is feasible to routinely implement a diagnostic and

therapeutic approach to sleep apnea on the rehabilitation ward, which is hoped to

have a positive influence on mortality, functional outcome, and secondary

prevention



Keywords: Australia/AUTOSET/BRAIN INFARCTION/continuous positive airway

pressure/diagnostic/DISEASE/hemiplegia/mortality/outcome/POLYSOMNOGR

APHY/prevention/rehabilitation/research/RISK FACTOR/secondary/secondary

prevention/sleep/sleep apnea/stroke/treatment



Stewart, S., Hart, C.L., Hole, D.J. and McMurray, J.J.V. (2002), A population-based

study of the long-term risks associated with atrial fibrillation: 20-year follow-up

of the Renfrew/Paisley study. American Journal of Medicine, 113 (5), 359-364.



Abstract: PURPOSE: To describe the effect of atrial fibrillation on long- term morbidity

and mortality. SUBJECTS AND METHODS: The Renfrew/Paisley Study

surveyed 7052 men and 8354 women aged 45- 64 years between 1972 and 1976.

All hospitalizations and deaths occurring during the subsequent 20 years were

analyzed by the presence or absence of atrial fibrillation at baseline. Lone atrial

fibrillation was defined in the absence of other cardiovascular signs or symptoms.

Cox proportional hazards models were used to adjust for age and cardiovascular

conditions. RESULTS: After 20 years, 42 (89%) of the 47 women with atrial

fibrillation had a cardiovascular event (death or hospitalization), compared with

2276 (27%) of the 8307 women without this arrhythmia. Among men, 35 (66%)

of 53 with atrial fibrillation had an event, compared with 3151 (45%) of 6999

without atrial fibrillation. In women, atrial fibrillation was an independent

predictor of cardiovascular events (rate ratio [RR] = 3.0; 95% confidence interval

[CI]: 2.1-4.2), fatal or nonfatal strokes (RR = 3.2; 95% CI: 1.0-5.0), and heart

failure (RR = 3.4; 95% CI: 1.9-6.2). The rate ratios among men were 1.8 (95%

CI: 1.3-2.5) for cardiovascular events, 2.5 (95% CI: 1.3- 4.8) for strokes, and 3.4

(95% CI: 1.7-6.8) for heart failure. Atrial fibrillation was an independent

predictor of all-cause mortality in women (RR = 2.2; 95% CI: 1.5-3.2) and men

(RR = 1.5; 95% CI: 1.2-2.2). However, lone atrial fibrillation (which occurred in

15 subjects) was not associated with a statistically significant increase in, either

cardiovascular events (RR = 1.5; 95% CI: 0.6-3.6) or mortality (RR = 1.8; 95%

CI: 0.9-3.8). CONCLUSION: Atrial fibrillation is associated with an increased

long-term risk of stroke, heart failure, and all-cause mortality, especially in

women. (C) 2002 by Excerpta Medica, Inc



Keywords: age/aged/all-cause mortality/arrhythmia/atrial

fibrillation/CARDIOMYOPATHY/cardiovascular/cardiovascular

event/cardiovascular events/death/DISEASE/fibrillation/heart/heart

failure/HEART-FAILURE/hospitalization/men/morbidity/MORTALITY/NATU

RAL-HISTORY/NEW-YORK/population-based/PREVALENCE/PREVENTIO

N/PROGNOSIS/risk/SCOTLAND/STROKE/symptoms/women



Yusuf, S. (2002), From the Hope to the Ontarget and the Transcend Studies: Challenges

in Improving Prognosis. American Journal of Cardiology, 89 (2A), 18A-25A.



Abstract: The Heart Outcomes Prevention Evaluation (HOPE) study conclusively

demonstrated that ramipril, an angiotensin- converting enzyme (ACE) inhibitor,

reduces the risk of cardiovascular death, myocardial infarction (MI), and death in

patients at risk for cardiovascular events but without heart failure. The Study to

Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and

Vitamin E (SECURE) substudy demonstrated that ramipril also reduced

atherosclerosis. These results suggest that the renin-angiotensin system (RAS)

has a more important role in the development and progression of atherosclerosis

than previously believed, and they indicate the need for further clinical studies to

define the range of benefits available from modifying the RAS. Achieving

maximum benefit may require treatment with both an ACE inhibitor and an

angiotensin II type-1 receptor blocker (ARB). The Randomized Evaluation of

Strategies for Left Ventricular Dysfunction (RESOLVD) study indicated that

combining an ACE inhibitor with an ARB decreased blood pressure and

improved the ejection fraction more than treatment with either drug alone in

patients with congestive heart failure. The Valsartan in Heart Failure Trial

(Val-HeFT) showed that the combination of an ACE inhibitor and an ARB

reduced hospitalization for heart failure in patients with congestive heart failure

by 27.5%, although no decrease in all-cause mortality was observed. The

Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint

Trial (ONTARGET) is a large, long-term study (23,400 patients, 5.5 years). It

will compare the benefits of ACE inhibitor treatment, All treatment, and

treatment with an ACE inhibitor and All together, in a study population with

established coronary artery disease, stroke, peripheral vascular disease, or

diabetes with end-organ damage. Patients with congestive heart failure will be

excluded. In a parallel study, patients unable to tolerate an ACE inhibitor will be

randomized to receive telmisartan or placebo (the Telmisartan Randomized

Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease

[TRANSCEND]). The primary endpoint for both trials is a composite of

cardiovascular death, MI, stroke, and hospitalization for heart failure. Secondary

endpoints will investigate reductions in the development of diabetes mellitus,

nephropathy, dementia, and atrial fibrillation. These 2 trials are expected to

provide new insights into the optimal treatment of patients at high risk of

complications from atherosclerosis. (C) 2002 by Excerpta Medica, Inc



Keywords: ACE inhibitor/all-cause mortality/angiotensin/angiotensin

II/atherosclerosis/atrial/atrial fibrillation/benefits/blocker/blood

pressure/cardiovascular/cardiovascular events/clinical

studies/combination/complications/congestive heart failure/coronary artery

disease/death/dementia/development/diabetes/diabetes

mellitus/disease/drug/fibrillation/heart/heart failure/high

risk/hospitalization/infarction/mortality/myocardial/myocardial

infarction/nephropathy/NEW-YORK/peripheral vascular

disease/population/primary/progression/ramipril/randomized/renin angiotensin

system/renin-angiotensin system/risk/stroke/treatment/trials/vascular/vascular

disease



Morse, J.M. (2002), Enhancing the safety of hospitalization by reducing patient falls.

American Journal of Infection Control , 30 (6), 376-380.



Abstract: The iatrogenic nature of hospitalization places patients at risk of falling, injury

and death. In this article, the major principles of providing protective and

preventive interventions are outlined. The principles are the establishment of a

multifaceted fall prevention program that targets fall interventions according to

each etiologic factor; the recognition that fall protective and prevention

interventions are distinct and serve a different function; the use of the fall

monitoring system comprehensively; the creation of a clinical nurse specialist

position, responsible for fall intervention; and a conscious and individualized

approach to fall prevention. The process and problems of the varying nature of

providing fall protection and fall prevention are discussed: for example, use of a

side rail as a protective strategy may be successful with one patient but

considered a hazard when used with a different patient



Keywords: death/hospitalization/monitoring/OLDER

ADULTS/prevention/PRONE/protection/RISK/safety/STRENGTH/STROKE

REHABILITATION/use



Ruilope, L.M., Coca, A., Volpe, M. and Waeber, B. (2002), ACE inhibition and

cardiovascular mortality and morbidity in essential hypertension: The end of the

search or a need for further investigations? American Journal of Hypertension,

15 (4), 367-371.



Abstract: Scientific evidence currently available supports the concept that

renin-angiotensin blockade with angiotensin converting enzyme inhibitors as a

first-line treatment exhibits in arterial hypertension beneficial effects in the

prevention of mortality and morbidity comparable to those achieved with

diuretics and beta-blockers. In addition, the renin-angiotensin blockade has also

proved to be beneficial in the secondary prevention of several complications of

hypertensive disease such as after myocardial infarction and congestive heart

failure, as well as in the prevention of the incidence of type 2 diabetes, and the

progression of diabetic and nondiabetic nephropathy. In this later regard, recent

evidence with angiotensin II receptor antagonists in reducing the progression of

nephropathy in type 2 diabetes strongly confirms that antagonism of the

renin-angiotensin system is an effective approach to cardiovascular and renal

disease. Finally, the renin-angiotensin blockade in high-risk patients may reduce

cardiovascular mortality independently of the effect on blood pressure (BP). The

effect of other antihypertensive drugs on cardiovascular risk in patients with

high-normal BP should be investigated to establish whether they exhibit a

comparable effect or whether there is a class-related benefit of drugs blocking

the renin-angiotensin system. Such a strategy could also be encouraged to design

future interventional studies with the newer classes of compounds (angiotensin II

AT(1)-receptor antagonists, vasopeptidase inhibitors. endothelin antagonists),

which would have the additional potential advantage of providing information

more easily transferable to large-scale clinical practice. (C) 2002 American

Journal of Hypertension, Ltd



Keywords: ACE inhibition/angiotensin/angiotensin converting enzyme

inhibitors/angiotensin II/antihypertensive drugs/antihypertensive

therapy/arterial/arterial hypertension/beta-blockers/blood

pressure/BLOOD-PRESSURE/cardiovascular/cardiovascular

mortality/cardiovascular risk/clinical practice/complications/congestive heart

failure/CONVERTING-ENZYME-INHIBITION/design/diabetes/disease/diureti

cs/drugs/essential/heart/heart failure/high

risk/hypertension/incidence/infarction/LEFT-VENTRICULAR

HYPERTROPHY/METAANALYSIS/morbidity/mortality/myocardial/myocardi

al

infarction/MYOCARDIAL-INFARCTION/nephropathy/NEW-YORK/preventio

n/prevention of mortality/RANDOMIZED DOUBLE-BLIND/RATS/renal/renal

disease/renin angiotensin system/renin-angiotensin

system/risk/secondary/secondary

prevention/Spain/STROKE/SURVIVAL/treatment/TRIAL/trials/type 2 diabetes



Sumoza, A., de Bisotti, R., Sumoza, D. and Fairbanks, V. (2002), Hydroxyurea (HU) for

prevention of recurrent stroke in sickle cell anemia (SCA). American Journal of

Hematology, 71 (3), 161-165.



Abstract: Cerebrovascular accident (CVA) is a major cause of morbidity and death in

sickle cell anemia (SCA). Transfusion of packed erythrocytes is widely used to

prevent this complication. However, chronic transfusion may lead to iron

overload, alloimmunization, or infections. Cost and compliance may compromise

transfusion therapy. A possible alternative, the prophylactic use of hydroxyurea

(HU), has not been tried to determine whether it may prevent recurrent stroke.

We used HU in five children with SCA who had suffered stroke, in three of them

after a first episode and in the other two after a second CVA. Four had infarctive

stroke and one a transient ischemic attack (TIA). Four patients took HU at a dose

of 40 mg/kg/d, one patient at 30 mg/kg/d. None of the patients had recurrent

stroke during 42-112 months of observation. None experienced pain crises. In all,

HbF increased significantly. and was maintained above 14.7% during treatment.

The total Hb concentration increased 19.5 g/L (median) above the value before

treatment. HU was well tolerated. None of the five children had leukopenia or

thrombocytopenia during therapy. HU appears to prevent recurrence of stroke in

SCA without risk of major toxicity. (C) 2002 Wiley-Liss, Inc



Keywords: alloimmunization/anemia/cerebrovascular accident

(CVA)/CHILDREN/CVA/death/DISEASE/FETAL

HEMOGLOBIN/hemoglobin S (Hb S)/hydroxyurea (HU)/iron

overload/ischemic/morbidity/MORTALITY/NEW-YORK/pain/prevention/recur

rence/recurrent stroke/risk/RISK-FACTORS/sickle cell anemia/sickle cell

anemia/disease/stroke/THERAPY/TIA/toxicity/transfusion/TRANSFUSIONS/tr

ansient/transient ischemic attack/transient ischemic attack (TIA)/treatment/use



Matchar, D.B., Samsa, G.P., Cohen, S.J., Oddone, E.Z. and Jurgelski, A.E. (2002),

Improving the quality of anticoagulation of patients with atrial fibrillation in

managed care organizations: Results of the Managing Anticoagulation Services

Trial. American Journal of Medicine, 113 (1), 42-51.



Abstract: PURPOSE: Randomized trials have indicated that well-managed

anticoagulation with warfarin could prevent more than half of the strokes related

to atrial fibrillation. However, many patients with atrial fibrillation who are

eligible for this therapy either do not receive it or are not maintained within an

optimal prothrombin time-international normalized ratio (INR) range. We sought

to determine whether an anticoagulation service within a managed care

organization would be a feasible alternative for providing anticoagulation care.

SUBJECTS AND METHODS: We performed a multi-site randomized trial in

six large managed care organizations in the United States. Subjects were aged 65

years or older and had nonvalvular atrial fibrillation. At each site, physician

practices were divided into two geographically defined practice clusters; each

site was randomly assigned to have one intervention and one control cluster. The

intervention cluster received an anti-coagulation service that satisfied

specifications for high-quality anticoagulation care and was coordinated through

the managed care organization. Control clusters continued with their usual

provider-based care. We measured the proportion of time that warfarin-treated

patients in each of the clusters (intervention and control) were in the target range

for the INR at baseline, and again during a follow-up period. RESULTS: Five of

the Six Selected Site, succeeded at developing air anticoagulation service.

Patients in the intervention and control Clusters had Similar demographic

characteristics, contrain-dications to warfarin, and risk factors for stroke. Among

patient, (n = 144 in the intervention clusters; n = 118 in the control clusters) for

whom data were available during the baseline and follow-up periods, the changes

in percentages of time in the target range were similar for those in the

intervention clusters (baseline: 47.7%; follow-up: 55.6%) and in the control

clusters (baseline: 49.1%; follow-up: 52.3%; intervention effect: 5%; 95%

confidence interval: -5% to 14%; P = 0.32). CONCLUSION: Although it was

feasible in a managed care organization to implement anticoagulation services

that were tailored to local circumstances, provision of this service did not

improve anticoagulation care compared With usual care. The effect of the

anticoagulation service was limited by the utilization of the service, the degree to

which the referring physician supports Strict adherence to recommended target

ranges for the INR, and the ability of the anticoagulation service to identify and

to respond to out-of-range Values promptly. (C) 2002 by Excerpta Medica, Inc



Keywords: adherence/aged/anticoagulation/anticoagulation service/atrial/atrial

fibrillation/BLEEDING

COMPLICATIONS/control/fibrillation/INR/INTENSITY/managed care

organization/NEW-YORK/nonvalvular atrial

fibrillation/organizations/OUTCOMES/OUTPATIENTS/PROTHROMBIN

TIME/randomized/randomized trial/risk/risk factors/risk factors for

stroke/RISK-FACTORS/SELF-MANAGEMENT/stroke/STROKE

PREVENTION/THERAPY/trial/trials/United States/warfarin/WARFARIN USE



Wattigney, W.A., Mensah, G.A. and Croft, J.B. (2002), Increased atrial fibrillation

mortality: United States, 1980- 1998. American Journal of Epidemiology, 155 (9),

819-826.



Abstract: The authors used death certificate data to evaluate national trends in the

reporting of atrial fibrillation as an underlying or contributory cause of death for

groups defined by age (45 years or older), sex, and race (Black vs. White) and to

examine comorbidity. The multiple-causes mortality files from 1980 through

1998 were analyzed for decedents, with atrial fibrillation (International

Classification of Diseases, Ninth Revision, code 427.3) listed as one of up to 20

conditions causing death. The number of decedents with atrial fibrillation

increased from 18,947 in 1980 to 61,946 in 1998, and the proportion with atrial

fibrillation reported as the underlying cause of death rose from 8.3% in 1980 to

11.6% in 1998. Age- standardized death rates from 1980 to 1998 were

consistently highest among White men, followed (in descending order) by White

women, Black men, and Black women. Overall, the age- standardized rate (per

100,000) increased from 27.6 in 1980 to 69.8 in 1998 (an average annual

increase of 5.4%, p 325 mg daily, no antiplatelet

regimen is more effective than aspirin for long-term use. In primary prevention,

5 randomized trials have been published involving more than 60 000 apparently

healthy men and women. Persons randomized to receive aspirin in these trials

had significant reductions in risk of a first MI (32%) and important vascular

events (15%). Since the numbers of strokes and vascular deaths were insufficient

to distinguish between the benefits found in secondary prevention and no effect,

use of aspirin in primary prevention should be weighed in light of the

cardiovascular risk profile, the side effects of the drug, and its clear benefit in

reducing risk of a first MI. Aspirin should be an adjunct, not an alternative, to

managing other cardiovascular risk factors. Recently, the US Preventive Services

Task Force and the American Heart Association recommended aspirin use for all

men and women whose 10-year risks are > 6% and greater than or equal to10%,

respectively. In all these patient categories, including secondary prevention,

acute MI and acute occlusive stroke, as well as primary prevention, increased

and appropriate use of aspirin will prevent large numbers of premature deaths

and MIs



Keywords: acute/acute coronary syndromes/acute myocardial

infarction/angina/antiplatelet/antiplatelet drugs/antiplatelet

therapy/aspirin/benefits/bleeding/BRITISH/bypass/cardiovascular/cardiovascular

disease/cardiovascular risk/cardiovascular risk

factors/CARE/causes/clopidogrel/control/coronary artery

bypass/death/disease/drug/drugs/glycoprotein IIb/IIIa receptor

antagonist/HEALTH/high

risk/infarction/ischemic/men/mortality/myocardial/myocardial

infarction/prevention/primary/primary prevention/randomized/RANDOMIZED

TRIAL/randomized trials/research/risk/risk factors/risks/secondary/secondary

prevention/side effects/stroke/therapy/transient/transient ischemic

attacks/treatment/trials/US/USA/use/vascular/vascular events/women



Iwamoto, J., Takeda, T. and Ichimura, S. (2002), Beneficial effect of etidronate on bone

loss after cessation of exercise in postmenopausal osteoporotic women.

American Journal of Physical Medicine & Rehabilitation, 81 (6), 452-457.



Abstract: Objectives: To determine whether etidronate could prevent or restore bone loss

after cessation of exercise in postmenopausal osteoporotic women. Design:

Thirty-five postmenopausal osteoporotic women were studied. Exercise

consisted of daily brisk walking and gymnastic training. The changes in the

lumbar bone mineral density measured by dual energy x-ray absorptiometry were

assessed. Results: One or two years of exercise increased the bone mineral

density from the baseline. One year of cessation of exercise after 1 yr of exercise

resulted in the loss of the bone mineral density gained through exercise. Two

years of cyclical etidronate treatment from year 2 sustained the bone mineral

density during 2 yr of cessation of exercise in the preventative etidronate

treatment group and completely restored the loss of bone mineral density after 1

yr of cessation of exercise in the therapeutic etidronate treatment group.

Conclusions: Cyclical etidronate treatment, when exercise is discontinued, seems

to be beneficial for the prevention or restoration of bone loss after cessation of

exercise in postmenopausal osteoporotic women. Although the present study has

a small sample size, the results may be interesting, especially because they raise

additional questions that could stimulate further research



Keywords: bone mineral density/CALCITRIOL/CALCIUM/cessation of

exercise/etidronate/exercise/Japan/MASS/MINERAL

DENSITY/osteoporosis/postmenopausal

women/prevention/research/STROKE/THERAPY/treatment/WALKING/women

/xray/YOUNG



Nappi, J. and Talbert, R. (2002), Dual antiplatelet therapy for prevention of recurrent

ischemic events. American Journal of Health-System Pharmacy, 59 (18),

1723-1735.

Abstract: The advantages of dual antiplatelet therapy over monotherapy in preventing

recurrent ischemic events are examined. Atherosclerosis is an insidious systemic

process involving multiple vascular beds, including the cerebral, coronary, and

peripheral arteries. Atherosclerotic plaque rupture is one of the inciting events in

the progression of platelet activation, aggregation, and thrombus formation.

Patients with any clinical manifestation of atherosclerosis are vulnerable to

others in different vascular beds since the disease develops throughout the

vasculature, and different vascular events have common, predisposing risk

factors. Ischemic coronary heart disease and cerebrovascular disease are two of

the three most frequent causes of death in the United States. The efficacy of

aspirin in the secondary prevention of myocardial infarction (MI) and stroke has

been demonstrated in numerous trials. While dipyridamole has not been linked

with a greater odds reduction than aspirin in the development of MI, stroke, and

vascular death, ticlopidine and clopidogrel have been associated with a greater

reduction in the development of acute MI, stroke, and vascular death than aspirin.

Clinical trials evaluating the efficacy and safety of combination antiplatelet

therapy in the prevention,of recurrent ischemic events are ongoing. The rationale

for using a combination of two mechanistically different antiplatelet agents is

supported by ex vivo and clinical studies. Inhibition of platelet aggregation and

thrombus formation is enhanced with dual antiplatelet therapy. Combination

antiplatelet regimens with different mechanisms of action to inhibit multiple sites

in the thrombotic pathway may further improve long-term clinical outcomes.

Dual antiplatelet therapy may have advantages over monotherapy in the

prevention of recurrent ischemic events



Keywords: activation/acute/ACUTE CORONARY

SYNDROMES/aggregation/AMERICAN-HEART-ASSOCIATION/antiplatelet/

antiplatelet agents/antiplatelet therapy/ANTITHROMBOTIC

ACTIVITY/arteries/ARTERY

DISEASE/aspirin/atherosclerosis/ATHEROSCLEROTIC

PLAQUES/causes/cerebral/CEREBRAL-ISCHEMIA/cerebrovascular/cerebrova

scular disease/clinical studies/clopidogrel/combination/COMBINATION

THERAPY/combined therapy/coronary heart

disease/death/development/dipyridamole/disease/formation/heart/heart

disease/infarction/ischemia/ischemic/mechanism of

action/mechanisms/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/plaque/plaque

rupture/platelet/platelet activation/platelet aggregation/platelet aggregation

inhibitors/prevention/RECEPTOR ANTAGONIST/risk/risk

factors/safety/secondary/SECONDARY

PREVENTION/stroke/therapy/thrombus/ticlopidine/trials/United

States/vascular/vasculature



Hu, F.B. and Grodstein, F. (2002), Postmenopausal hormone therapy and the risk of

cardiovascular disease: The epidemiologic evidence. American Journal of

Cardiology, 90 (1), 26F-29F.

Abstract: The relation between hormone use in postmenopausal women and

cardiovascular disease remains controversial. Whereas epidemiologic studies and

clinical studies assessing several intermediate cardiovascular disease endpoints

indicate a clear benefit for the primary prevention of coronary artery disease

(CAD), secondary-prevention trials of relatively short duration do not support a

benefit. More recent epidemiologic studies continue to supply evidence that

long-term postmenopausal hormone therapy may reduce the risk for CAD in

healthy women. Adding progestin to the regimen does not appear to attenuate the

benefit. The Nurses' Health Study and studies from Europe, where estradiol is the

commonly prescribed form of estrogen, suggest that estrogen at lower doses may

confer similar benefit. However, remarkably consistent data from both

epidemiologic studies and a secondary-prevention trial indicate a significantly

increased risk of venous thromboembolism with hormone use. The data on stroke

are inconclusive, but there is little evidence to suggest a benefit of hormone use

on either ischemic or hemorrhagic stroke. Existing evidence indicates that the

various potential benefits and risks should be weighed carefully when

prescribing hormone therapy to a postmenopausal woman. (C) 2002 by Excerpta

Medica, Inc



Keywords: cardiovascular/cardiovascular disease/clinical studies/coronary artery

disease/CORONARY

HEART-DISEASE/DIET/disease/ESTROGEN/Europe/ischemic/LIFE-STYLE/

NEW-YORK/postmenopausal women/prevention/primary/primary

prevention/PROGESTIN/REPLACEMENT THERAPY/risk/SECONDARY

PREVENTION/STROKE/therapy/thromboembolism/trial/trials/use/venous

thromboembolism/WOMEN



Newman, N.J., Scherer, R., Langenberg, P., Kelman, S., Feldon, S., Kaufman, D. and

Dickersin, K. (2002), The fellow eye in NAION: Report from the ischemic optic

neuropathy decompression trial follow-up study. American Journal of

Ophthalmology, 134 (3), 317-328.



Abstract: PURPOSE: To examine the prevalence and incidence of second eye

nonarteritic anterior ischemic optic neuropathy (NAION) and associated patient

characteristics in patients enrolled in the Ischemic Optic Neuropathy

Decompression Trial (IONDT) Follow-up Study. DESIGN: Randomized clinical

trial with observational cohort. METHODS: Patients randomized to optic nerve

sheath decompression surgery or careful follow,up had a diagnosis of acute

unilateral NAION, visual acuity between 20/64 and light perception, and were

aged 50 years or older. Eligible patients who declined randomization or whose

visual acuity was better than 20/64 were not randomized but followed as part of

an observational cohort. Follow-up examinations took place at 3, 6, 12, 18, and

24 months and annually thereafter. RESULTS: Four hundred eighteen patients

were enrolled; 258 randomized and 160 observed. Previous NAION or other

optic neuropathy was present in the fellow eye of 21.1% (88/418) of patients at

baseline. Four patients developed optic neuropathy in the fellow eye at follow up

that could not be conclusively diagnosed as NAION. New NAION in the fellow

eye occurred in 14.7% (48/326) of patients at risk during a median follow up of

5.1 years. Randomized patients experienced a higher incidence (35/201; 17.4%)

than nonrandomized patients (13/125; 10.4%). A history of diabetes and baseline

visual acuity of 20/200 or worse in the study eye, but not age, sex, aspirin use, or

smoking were significantly associated with new NAION in the fellow eye. Final

fellow eye visual acuity was significantly worse in those patients with new

fellow eye NAION whose baseline study eye visual acuity was 20/200 or worse.

CONCLUSIONS: Follow-up data from the IONDT cohort provide evidence that

the incidence of fellow eye NAION is lower than expected: new NAION was

diagnosed in 14.7% of IONDT patients over approximately 5 years. Increased

incidence is associated with poor baseline visual acuity in the study eye and

diabetes, but not age, sex, smoking history, or aspirin use. (C) 2002 by Elsevier

Science Inc. All rights reserved



Keywords: acute/age/aged/ASPIRIN/CLINICAL PROFILE/clinical

trial/DESIGN/diabetes/diagnosis/history/incidence/ischemic/NATURAL-HISTO

RY/NEW-YORK/prevalence/PREVENTION/randomized/risk/RISK-FACTORS

/sex/SMOKING/STROKE/surgery/THERAPY/trial/use



Rubia, M., Marcos, I. and Muennig, P.A. (2002), Increased risk of heart disease and

stroke among foreign-born females residing in the United States. American

Journal of Preventive Medicine, 22 (1), 30-35.



Abstract: Background: Although the number of foreign-born people residing ill the

United States is at its highest point in 80 Nears, a mortality analysis of the

foreign born has not been conducted Since 1989. This article provides all update

Of mortality rates among the foreign burn in the United States and, in particular,

examines mortality rates from heart disease among foreign-born females.

Methods: We calculated mortality rates for U.S.-born and foreign-born people

for all causes ischemic heart disease. stroke, neoplastic disease, hypertensive

diseases, diabetes, accidents, infectious disease, and chronic obstructive

pulmonary disease-for 1997. Death data were obtained from the 1997 Multiple

Cause of Death data file, and population data were obtained from the 1997

Current Population Survey. Results: While all-cause, age-adjusted mortality rates

for foreign-born people are significantly lower than for native-born people,

deaths due to ischemic heart disease and stroke are significantly higher among

foreign-born females than native- born females (161.63) and 58.24 deaths,

espectively, per 100,000 foreign-born females vs 122.01 and 19.39 deaths per

100,000 native-born females). Conclusions: Foreign-born females appear to be at

greater risk of death from ischemic heart disease and stroke than native-born

females. Future research efforts are needed to determine which Foreign-born

groups are most at risk for heart disease and stroke so that targeted prevention

efforts can be initiated



Keywords: ACCULTURATION/BIRTH/causes/chronic/CORONARY-ARTERY

DISEASE/cross-sectional studies/death/diabetes/disease/diseases/emigration and

immigration/HEALTH/heart/heart disease/ischemic/ischemic heart

disease/MORTALITY/mortality/NATIVITY/NEW-YORK/NEW-YORK-CITY/

population/POPULATIONS/prevention/pulmonary/research/risk/stroke/United

States/WOMEN



Lew, H.L., Lee, E.H., Date, E.S. and Melnik, I. (2002), Rehabilitation of a patient with

heat stroke - A case report. American Journal of Physical Medicine &

Rehabilitation, 81 (8), 629-632.



Abstract: The recent death of a famous football player raised public awareness of the

fatal nature of heat stroke, which is actually the third leading cause of death

among American athletes. We present a typical case of heat stroke to illustrate its

clinical manifestation and recovery process; risk factors, treatment options, and

the importance of prevention are also discussed. Although heat stroke is not a

common admission diagnosis for inpatient rehabilitation, physiatrists need to be

aware of its pathophysiology, rehabilitation management, and prevention



Keywords: awareness/case report/cause of death/CLINICAL

CHARACTERISTICS/death/diagnosis/heat/heat

stroke/HEATSTROKE/management/pathophysiology/PILGRIMAGE/prevention

/rehabilitation/risk/risk factors/stroke/treatment



Djousse, L., Folsom, A.R., Province, M.A., Hunt, S.C. and Ellison, R.C. (2003), Dietary

linolenic acid and carotid atherosclerosis: the National Heart, Lung, and Blood

Institute Family Heart Study. American Journal of Clinical Nutrition, 77 (4),

819-825.



Abstract: Background: Dietary intake of linolenic acid is associated with a lower risk of

cardiovascular disease mortality. However, it is unknown whether linolenic acid

is associated with a lower risk of carotid atherosclerosis. Objective: The

objective was to examine the association between dietary linolenic acid and the

presence of atherosclerotic plaques and the intima-media thickness of the carotid

arteries. Design: In a cross-sectional design, we studied 1575 white participants

of the National Heart, Lung, and Blood Institute Family Heart Study who were

free of coronary artery disease, stroke, hypertension, and diabetes mellitus.

High-resolution ultrasound was used to assess intima-media thickness and the

presence of carotid plaques beginning 1 cm below to 1 cm above the carotid bulb.

We used logistic regression and a generalized linear model for the analyses.

Results: From the lowest to the highest quartile of linolenic acid intake, the

prevalence odds ratio (95% CI) of a carotid plaque was 1.0 (reference), 0.47

(0.30, 0.73), 0.38 (0.22, 0.66), and 0.49 (0.26, 0.94), respectively, in a model that

adjusted for age, sex, energy intake, waist-to-hip ratio, education, field center,

smoking, and the consumption of linoleic acid, saturated fat, fish, and vegetables.

Linoleic acid, fish long-chain fatty acids, and fish consumption were not

significantly related to carotid artery disease. Linolenic acid was inversely

related to thickness of the internal and bifurcation segments of the carotid

arteries but not to the common carotid artery. Conclusion: Higher consumption

of total linolenic acid is associated with a lower prevalence odds of carotid

plaques and with lesser thickness of segment-specific carotid intima-media

thickness



Keywords: age/and Blood Institute Family Heart

Study/arteries/atherosclerosis/cardiovascular/cardiovascular

disease/cardiovascular disease mortality/carotid/carotid arteries/carotid

artery/carotid artery disease/carotid atherosclerosis/coronary artery

disease/CORONARY-ARTERY DISEASE/DENSITY-LIPOPROTEIN

CHOLESTEROL/design/diabetes/diabetes mellitus/diet/disease/disease

mortality/education/energy intake/Family Heart Study/fat/fish/FOOD

FREQUENCY QUESTIONNAIRE/hypertension/internal/intima-media

thickness/linolenic acid/Lung/MEN/mortality/n-3 fatty acids/n-6 fatty

acids/National Heart/NUTRITION/plaque/POLYUNSATURATED

FATTY-ACIDS/prevalence/PREVENTION/REPRODUCIBILITY/RISK/sex/sm

oking/stroke/ultrasound/USA/VALIDITY/vegetables/WOMEN



Blake, G.J., Ridker, P.M. and Kuntz, K.M. (2003), Potential cost-effectiveness of

C-reactive protein screening followed by targeted statin therapy for the primary

prevention of cardiovascular disease among patients without overt

hyperlipidemia. American Journal of Medicine, 114 (6), 485-494.



Abstract: BACKGROUND: Evidence suggests that statin therapy reduces the rate of

cardiovascular events among patients with low lipid levels but elevated

C-reactive protein levels. However, no cost-effectiveness analyses have been

performed to assist in determining whether large-scale randomized trials are

merited to test this hypothesis. METHODS: We used a Markov model to

estimate the benefits, costs, and incremental cost- effectiveness of C-reactive

protein screening followed by targeted statin therapy for elevated C-reactive

protein levels, compared with dietary counseling alone, for the primary

prevention of cardiovascular events among patients with low- density lipoprotein

cholesterol levels 20 antihypertensive therapy outcome trials found

that the reduction in myocardial infarction risk with ramipril observed in HOPE

was consistent with the modest blood pressure reduction seen with that agent.

Nevertheless, there are convincing data for prevention of myocardial infarction

with ACE inhibitors in patients with heart failure, including those with heart

failure after myocardial infarction, as well as supportive evidence from studies in

patients with diabetes mellitus and cancomitant hypertension. On the other hand,

Dr. William B. White takes the position that ARBs are well-tolerated

antihypertensive agents that specifically antagonize the angiotensin II type 1

(AT(1)) receptor and provide a more complete block of the pathologic effects of

angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors.

The Evaluation of Losartan in the Elderly (ELITE) 11 study and the Valsartan

Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in

patients with congestive heart failure. The Losartan Intervention for Endpoint

(LIFE) Reduction in Hypertension trial also demonstrated beneficial effects of

ARBs in the prevention of stroke events. The Irbesartan in Patients with Diabetes

and Microalbuminuria (IRMA) study, the Irbesartan Diabetic Nephropathy Trial

(IDNT), and the Reduction of Endpoints in NIDDM with the Angiotensin II

Antagonist Losartan (RENAAL) study demonstrated significant reductions in the

rate of progression of renal disease in patients receiving ARBs, independent of

effects on blood pressure. These data support the use of ARBs, in addition to the

standard of care, in hypertensive patients with heart failure who are intolerant of

ACE inhibitors, and also provide compelling evidence for their use in patients

with hypertension and type 2 diabetes. (C) 2003 by Excerpta Medica, Inc



Keywords: ACE inhibitors/angiotensin/angiotensin II/ANTAGONISTS/antihypertensive

agents/antihypertensive therapy/blood pressure/BLOOD-PRESSURE

REDUCTION/cardiovascular/CARDIOVASCULAR

MORBIDITY/cerebrovascular/congestive heart failure/CT/diabetes/diabetes

mellitus/DIABETIC NEPHROPATHY/diastolic blood

pressure/disease/ELITE/heart/heart failure/HEART-FAILURE/high

risk/HYPERTENSION/incidence/infarction/INTERVENTION/LIFE/LOSARTA

N/MORTALITY/myocardial/myocardial

infarction/NEW-YORK/NIDDM/outcome/prevention/progression/ramipril/RAN

DOMIZED TRIAL/renal/renal disease/risk/stroke/systolic blood/systolic blood

pressure/therapy/treatment/trial/trials/type 2 diabetes/USA/use



Penado, S., Cano, M., Acha, O., Hernandez, J.L. and Riancho, J.A. (2003), Atrial

fibrillation as a risk factor for stroke recurrence. American Journal of Medicine,

114 (3), 206-210.



Abstract: BACKGROUND: Although atrial fibrillation is a well-known risk, factor for

ischemic stroke, the extent to which it increases the risk of stroke recurrence,

particularly in elderly patients, is less certain. METHODS: We performed a

retrospective cohort study of 915 patients aged 50 to 94 years who were admitted

with an ischemic stroke. The rates of recurrent strokes and recurrent severe

strokes were estimated with the Kaplan-Meier method. The effects of atrial

fibrillation on stroke risk were analyzed with proportional hazards models.

RESULTS: Of the 829 patients who survived the initial hospitalization, 163

(20%) had a stroke during follow- up. Of the 203 patients with-atrial fibrillation

during index hospitalization who were not anticoagulated, 54 (27%) had

recurrent strokes, compared with 18% (19/103) among those with atrial

fibrillation who were anticoagulated and 17% (90/523) among those without

atrial fibrillation. The age-adjusted hazard ratio for recurrent stroke among those

with atrial fibrillation who were not treated with anticoagulants was 2.1 (95%

confidence interval [Cl]: 1.4 to 2.9; P 3.1 cm(2) vs 14.4 +/- 3.3 cm(2), n = 42, P 4.4 cm2 vs 16.3 +/- 4.2 cm(2), n = 7,

P79 years old. The records

of all patients older than 79 years of age who underwent a CEA in a recent time

period from January 1988 to December 1996 were retrospectively reviewed.

Forty-one patients (31 men, 10 women) were identified by computer search. The

indication for operation included transient ischemic attack in 12 (29.3%),

amaurosis fugax in nine (22%), stroke in two (4.9%), and nonhemispheric

symptoms in three (7.3%). Fifteen patients (36.6%) were asymptomatic. Medical

risk factors included coronary artery disease in 26 (63.4%), hypertension in 22

(53.7%), and smoking in 12 (29.3%). The procedure was performed under EEG

monitoring in all patients. General anesthesia was administered in 37 (90%) and

regional anesthesia in four (10%). Shunts were used in four (10%) patients. The

internal carotid artery was patched in 16 patients (39%). One patient (2.4%)

developed a perioperative stroke and only one patient developed perioperative

myocardial infarction (MI). None of the patients died within 30 days of surgery.

In addition to the one MI case, five patients developed minor complications. The

average length of time for stay after CEA was 3.4 days. Patients were followed

up for an average of 20.7 months. Six patients died during follow-up. Four of

those died from an MI and two from a stroke. The authors conclude that with

proper selection of patients, CEA is safe in the octogenarian. Age alone should

not be a contraindication for CEA



Keywords: age/carotid/carotid endarterectomy/clinical trials/complications/coronary

artery disease/EEG/endarterectomy/HEAD/hypertension/infarction/myocardial

infarction/prevention/RISK/risk factors/smoking/stroke/stroke

prevention/SURGERY/transient/transient ischemic attack/trials/women

Wakita, M., Yasaka, M., Minematsu, K. and Yamaguchi, T. (2002), Effects of

anticoagulation on infarct size and clinical outcome in acute cardioembolic

stroke. Angiology, 53 (5), 551-556.



Abstract: Effects of anticoagulation on infarct size and outcome have not been fully

elucidated in patients with acute cardioembolic stroke, although the

anticoagulation therapy reduces both occurrence and recurrence of ischemic

stroke greatly. The authors retrospectively investigated the relationship of

anticoagulation intensity to infarct size and outcome. In 104 consecutive patients

(mean age 70.8 +/- 10.0 years) who had suffered acute supratentorial

cardioembolic infarction or transient ischemic attacks, they analyzed risk factors

for atherosclerosis, underlying heart diseases, the infarct size (maximal area) on

brain computed tomography, and modified Rankin scale score upon discharge,

They compared these clinical data between patients who had received warfarin

before the ictus and those who had not. In addition, they investigated the effects

of the international normalized ratio (INR) on infarct size and outcome in 19

patients who had been receiving anticoagulant therapy and had measurement of

INR within 24 hours after stroke onset. There were 25 patients who had received

anticoagulation before the stroke (A/C group) and 79 patients who had not

(non-A/C group). The infarct size in the A/C group tended to be smaller than that

in the non-A/C group (p = 0.081, Mann-Whitney U test). In the 19 patients who

had prior anticoagulation and measurement of INR within 24 hours of stroke

onset, large infarcts were seen in 6 of 13 patients with INR 12 vs. less than or equal to 12 (odds ratio [OR] = 0.4, 95%

confidence interval [CI] = 0.2-0.8); smoking greater than or equal to 20

cigarettes/day vs. nonsmokers (OR = 2.8, 95% CI = 1.1-7.3); and the regular use

of multivitamins (OR = 0.4, 95% CI = 0.2-0.9). CONCLUSIONS: These results

suggest that a substantial proportion of healthy young premenopausal women

have tHcy levels that increase their risk for vascular disease. A number of

potentially modifiable behavioral and environmental factors appear to be

significantly related to elevated tHcy levels in young women



Keywords: age/aged/alcohol/blacks/cholesterol/COMMON

MUTATION/CORONARY-ARTERY

DISEASE/correlates/DETERMINANTS/education/FOLATE/FOLIC-ACID/hom

ocyst(e)ine/homocysteine/HORDALAND

HOMOCYSTEINE/METHYLENETETRAHYDROFOLATE

REDUCTASE/NEW-YORK/PLASMA HOMOCYSTEINE

CONCENTRATIONS/population/population-based/race/risk/RISK

FACTOR/risk factors/risk factors for stroke/smoking/stroke/vascular/vascular

disease/VASCULAR- DISEASE/women



Williams, R.R., Rao, D.C., Ellison, R.C., Arnett, D.K., Heiss, G., Oberman, A., Eckfeldt,

J.H., Leppert, M.F., Province, M.A., Mokrin, S.C. and Hunt, S.C. (2000),

NHLBI Family Blood Pressure Program: Methodology and recruitment in the

HyperGEN network. Annals of Epidemiology, 10 (6), 389-400.



Abstract: PURPOSE: Hypertension is a common precursor of serious disorders

including stroke, myocardial infarction, congestive heart failure, and renal failure

in whites and to a greater extent in African Americans. Large

genetic-epidemiological studies of hypertension are needed to gain information

that will improve future methods for diagnosis, treatment, and prevention of

hypertension, a major contributor to cardiovascular morbidity and mortality.

METHODS: We report successful implementation of a new structure of research

collaboration involving four NHLBI "Networks," coordinated under the Family

Blood Pressure Program. The Hypertension Genetic Epidemiology Network

(HyperGEN) involves scientists from six universities and the NHLBI who seek

to identify and characterize genes promoting hypertension. Blood samples and

clinical data were projected to be collected from a sample of 2244 hypertensive

siblings diagnosed before age 60 from 960 sibships (half African-American) with

two or more affected persons. Nonparametric sibship linkage analysis of over

one million genotype determinations (20 candidate loci and 387 anonymous

marker loci) was projected to have sufficient power for detecting genetic loci

promoting hypertension. For loci showing evidence for linkage in this study and

for loci reported linked or associated with hypertension by other groups,

genotypes are compared in hypertensive cases Versus population-based controls

to identify or confirm genetic variants associated with hypertension. For some of

these genetic variants associated with hypertension, detailed physiological and

biochemical characterization of untreated adult offspring carriers versus

non-carriers may help elucidate the pathophysiological mechanisms that promote

hypertension. RESULTS: The projected sample size of 2244 hypertensive

participants was surpassed, as 2407 hypertensive individuals (1262 African

Americans and 1145 whites) from 917 sibships were examined. Detailed consent

forms were designed to offer participants several options for DNA testing; 94%

of participants gave permission for DNA testing now or in the future for any

confidential medical research, with only 6% requesting restrictions for tests

performed on their DNA. Since this is a family study, participants also are asked

to list all first degree relatives (along with names, addresses, and phone numbers)

and to indicate for each relative whether they were willing to allow study staff to

make a contact. Seventy percent gave permission to contact some relatives; about

30% gave permission to contact all first degree relatives; and less than 1% asked

that no relatives be contacted. Successes after the first four years of this study

include: 1) productive collaboration of eight centers from six different locations;

2) early achievement of recruitment goals for study participants including

African-Americans; 3) an encouraging rate of consent for DNA testing

(including future testing) and relative contacting; 4) completed analyses of

genetic linkage and association for several candidate gene markers and

polymorphisms; 5) completed genotyping of random markers for over half of the

full sample; and 6) early sharing of results among the four Family Blood

Pressure Program networks for candidate and genome search analyses.

CONCLUSIONS: Experience after four years of this five-year program

(1995-2000) suggests that the newly initiated NHLBI Network Program

mechanism is fulfilling many of the expectations for which it was designed. It

may serve as a paradigm for future genetic research that can benefit from large

sample sizes, frequent sharing of ideas among laboratories, and prompt

independent confirmation of early findings, which are required in the search for

common genes with relatively small effects such as those that predispose to

human hypertension. Ann Epidemiol 2000;10:389- 400. Published by Elsevier

Science inc



Keywords: African Americans/age/ANGIOTENSINOGEN/ASSOCIATIONS/blood

pressure/cardiovascular/cardiovascular morbidity/CARDIOVASCULAR

RISK-FACTORS/congestive heart

failure/consent/diagnosis/DNA/DYSLIPIDEMIC

HYPERTENSION/epidemiology/EXTENSIVE

INFORMATION/FRENCH-CANADIAN

POPULATION/GENE/genes/genetic/genetics/heart/heart

failure/human/hypertension/infarction/linkage/linkage

analysis/markers/morbidity/mortality/myocardial/myocardial

infarction/NEW-YORK/pathophysiology/population-based/prevention/recruitme

nt/renal/SODIUM-LITHIUM

COUNTERTRANSPORT/stroke/treatment/TWINS/UTAH PEDIGREES



Du, X.L., McNamee, R. and Cruickshank, K. (2000), Stroke risk from multiple risk

factors combined with hypertension: A primary care based case control study in

a defined population of northwest England. Annals of Epidemiology, 10 (6),

380-388.



Abstract: PURPOSE: To examine how hypertension interacts with ether known risk

factors in affecting the rick of stroke in a primary care based setting. METHODS:

Cases were patients with first-ever stroke identified from the community-based

stroke register in 1994-95 in northwest England. Two controls per case wore

randomly selected from the same primary care site and matched by age and sex.

Information on predefined risk factors was extracted from medical records.

RESULTS: 267 cases and 534 controls were included. Adjusted odds ratio (OR)

for stroke from hypertension was 2.6 (95%, confidence interval: 1.7-3.9). In

hypertensives who were current smokers, risk of stroke was increased 6 fold (OR

= 6.1 (2.7-13.7)) as compared to non- smokers without hypertension.

Hypertensives who had a preexisting history of myocardial infarction or obesity

or diabetes had 3 fold higher risks of stroke. Subjects with hypertension and with

a history of transient ischemic attack or atrial fibrillation had greater than or

equal to 8 fold excess risk of stroke. Among them, the risk was greater in those

with poorly controlled or untreated hypertension (OR = 13.2 (2.6- 67.0)) and in

those with well or moderately controlled (OR = 5.2 (1.6-17.2)) as compared to

subjects without both risk factors. There appeared to be a steady increase in rick

of stroke according to the number of risk factors present, particularly in

hypertensive subjects. CONCLUSIONS: Stroke risks in hypertensives associated

with combinations of other risk factors appeared to follow an additive model.

Subjects with multiple risk factors should he targeted in order to reduce the

overall risk for stroke. Ann Epidemiol 2000;10:380- 388. (C) 2000 Elsevier

Science Inc. All rights reserved



Keywords: age/ALCOHOL/atrial

fibrillation/BLOOD-PRESSURE/CARDIOVASCULAR-DISEASE/case-control

study/CEREBROVASCULAR-

DISEASE/COMMUNITY/control/diabetes/England/fibrillation/FRAMINGHA

M/HEALTH/history/hypertension/infarction/ischemic/MANAGEMENT/myocar

dial/myocardial

infarction/NEW-YORK/obesity/population/PREVENTION/primary/primary

care/risk/risk factors/sex/stroke/transient/transient ischemic attack/WEST

ENGLAND



Schreiner, P.J., Wu, K.K., Malinow, M.R., Stinson, V.L., Szklo, M., Nieto, J. and Heiss,

G. (2002), Hyperhomocyst(e)inemia and hemostatic factors: The atherosclerosis

risk in communities study. Annals of Epidemiology, 12 (4), 228-236.



Abstract: PURPOSE: To determine whether homocyst(e)ine (H(e)) is related to

hemostatic factors in a population-based sample without evidence of

cardiovascular disease. METHODS: A subsample of 660 participants-67

African-American women, 53 African-American men, 201 white women, and

339 white men-was selected from the Atherosclerosis Risk in Communities

Study baseline cohort. This was based on carotid intimal-medial wall thickness

above the 90th percentile or below the 75th percentile of the population

distribution, assessed by B-mode ultrasonography. Unadjusted and

multivariable-adjusted associations between fasting plasma H(e) and the

hemostatic factors fibrinogen, factor VII:c, factor VIII:c, protein C antigen,

hematocrit, platelet count, beta-thromboglobulin ( beta-TG), tissue plasminogen

activator (tPA), PAI-1, D-dimer, and lipoprotein[a] were examined. RESULTS:

Mean age-adjusted H(e) was positively, albeit weakly, correlated with beta-TG,

tPA, hematocrit, D-dimer and PAI-1; inversely cot-related with protein C; and

was higher in smokers, men and African-Americans. In multivariable regression,

beta-TG, tPA, and factor VII:c were positively associated with H(e), as well as

age, black race, male sex, and current cigarette smoking. CONCLUSIONS:

These cross-sectional data for a biracial group of middle-aged individuals

suggest that H(e) levels falling below values consistent with homocyst(e)inemia

are associated with several prothrom boric factors after adjustment for

sociodemographic factors. If H(e) change is antecedent to altered hemostasis,

FDA-mandated fortification of grain products with folic acid for prevention of

fetal neural tube defects may lead to both reduced plasma H(e) levels and

improved hemostatic profiles. (C) 2002 Elsevier Science Inc. All rights reserved



Keywords: African American/African Americans/African-American

women/age/atherosclerosis/cardiovascular/cardiovascular

disease/carotid/cigarette smoking/CORONARY-ARTERY

DISEASE/disease/fibrinogen/folic acid/HEART-

DISEASE/hematocrit/hemostasis/homocyst(e)ine/homocysteine/LIPOPROTEIN

(A)/men/MYOCARDIAL-INFARCTION/NEW-YORK/PLASMA

HOMOCYST(E)INE/plasminogen

activator/platelet/population/population-based/prevention/PROTEIN-C

ACTIVATION/race/risk/SERUM TOTAL

HOMOCYSTEINE/sex/smoking/STROKE/TISSUE-PLASMINOGEN-ACTIV

ATOR/tPA/ultrasonography/VASCULAR-DISEASE/women



Yeh, S.P., Hsueh, E.J., Wu, H. and Wang, Y.C. (1998), Ticlopidine-associated aplastic

anemia - A case report and review of literature. Annals of Hematology, 76 (2),

87-90.



Abstract: Serious hematologic complications associated with ticlopidine have been

reported, including aplastic anemia. We report here an additional case of fatal

aplastic anemia due to ticlopidine. A 66-year-old male patient developed fever

and pancytopenia 2 months after ticlopidine was started. Despite the

administration of granulocyte colony-stimulating factor (G-CSF) and

broad-spectrum antibiotics, as well as aggressive red cell and platelet

transfusions, the patient died 16 days after admission due to septic shock.

Eighteen other cases of ticlopidine-induced aplastic anemia published in the

English literature are also reviewed and presented here. Eight of the total 19

patients (including the one reported here) have died, mostly due to infection. Of

the seven who received supportive treatment only, four had spontaneous

recovery. Nine cases were treated with G-CSF or granulocyte-macrophage

colony-stimulating factor (GM-CSF), and response was observed in only four of

them. Several other cases were treated with high-dose corticosteroids or

androgens; however, it was not possible to evaluate the efficacy of these

treatments because of the limited number of cases. In the absence of satisfactory

treatment for ticlopidine-induced aplastic anemia at present, it may be reasonable

to try antilymphocyte globulin or cyclosporine. Also, great efforts should be

made in the prevention and management of infection accompanying this disease



Keywords: administration/antilymphocyte globulin/aplastic

anemia/complications/corticosteroid/cyclosporine/growth

factor/MECHANISM/NEW-YORK/PATIENT/PREVENTION/STROKE/THER

APY/ticlopidine/treatment



Yasaka, M., Oomura, M., Ikeno, K., Naritomi, H. and Minematsu, K. (2003), Effect of

prothrombin complex concentrate on INR and blood coagulation system in

emergency patients treated with warfarin overdose. Annals of Hematology, 82 (2),

121-123.



Abstract: We investigated the effect of prothrombin complex concentrate (PCC) on the

international normalized ratio (INR) and blood coagulation system in two

emergent patients treated with warfarin for secondary prevention of

cardioembolic stroke due to nonvalvular atrial fibrillation. An 80-year-old

woman developed massive subcutaneous hemorrhage and swelling on her right

upper extremity with weak pulsation of the right radial artery and had an INR

above 10. An 83-year-old man had pleural effusion with an INR value of 6.69

and pleural puncture was immediately required. We administered 500 IU of PCC

to the two patients (17.2 IU/kg and 12.5 IU/kg) with 10 mg of vitamin K. The

INR decreased to 1.12 and 1.85, respectively, with an increase of plasma levels

of protein C and coagulant factors IIa, VIIa, IXa, and Xa 10 min after

administration. The plasma levels of the thrombin-antithrombin III complex

increased (from 4.0 to 12.0 mug/l and from 0.5 to 28.9 mug/l, respectively,

normal value 0.2). The

incidence of hemorrhage was 2% in both groups. Conclusion: Low-

molecular-weight heparinoid, given in a fixed dose of 750 anti- factor Xa units

subcutaneously twice daily, is more effective than subcutaneous low-dose

heparin for the prevention of deep vein thrombosis in patients with acute

ischemic stroke



Keywords: CEREBROVASCULAR DISORDERS/CONTROLLED

TRIAL/ENOXAPARIN/HEPARIN/HEPARINOID/HIP-

SURGERY/LEG/LOW-DOSE

HEPARIN/ORG-10172/PROPHYLAXIS/THROMBOEMBOLISM/VENOUS

THROMBOSIS



Anderson, D.C., Asinger, R.W., Newburg, S.M., Farmer, C.C., Wang, K., Bundlie, S.R.,

Koller, R.L., Jagiella, W.M., Kreher, S., Jorgensen, C.R., Sharkey, S.W., Flaker,

G.C., Webel, R., Nolte, B., Stevenson, P., Byer, J., Wright, W., Chesebro, J.H.,

Wiebers, D.O., Holland, A.E., Miller, D.M., Bardsley, W.T., Litin, S.C.,

Meissner, I., Zerbe, D.M., Mcanulty, J.H., Marchant, C., Coull, B.M., Feldman,

G., Hayward, A., Gandara, E., Macmillan, K., Blank, N., Leonard, A.D., Kanter,

M.C., Isensee, L.M., Quiroga, E.S., Presti, C.H., Tegeler, C.H., Logan, W.R.,

Hamilton, W.P., Green, B.J., Bacon, R.S., Redd, R.M., Cadell, D.J., Gomez,

C.R., Janosik, D.L., Labovitz, A.J., Kelley, R.E., Chahine, R., Cristo, L.,

Palermo, M., Perez, O., Feinberg, W.M., Vold, B.K., Kern, K.B., Appleton, C.,

Miller, V.T., Hockersmith, C.J., Cohen, B.A., Martin, G.J., Pawlow, A.J.,

Halperin, J.L., Rothlauf, E.B., Weinberger, J.M., Goldman, M.E., Fuster, V.,

Dittrich, H.C., Rothrock, J.F., Hagenhoff, C., Helgason, C.M., Kondos, G.T.,

Hoff, J., Kaufmann, L., Rabjohns, R.R., Mcrae, R.P., Ghali, J., Adams, H.P.,

Theilen, E.O., Biller, J., Brown, D.D., Marsh, E.E., Sirna, S.J., Mitchell, V.L.,

Rothbart, R.M., Bailey, G.H., Burkhardt, C., Blackshear, J.L., Weaver, L., Lee,

G., Lane, G., Rubino, F., Safford, R., Kronmal, R.A., Mcbride, R., Athearn,

M.W., Pearce, L.A., Nasco, E., Hart, R.G., Sherman, C.P., Sherman, D.G.,

Talbert, R.L., Dacy, T.L. and Heberling, P.A. (1992), Predictors of

Thromboembolism in Atrial-Fibrillation .1. Clinical-Features of Patients at Risk.

Annals of Internal Medicine, 116 (1), 1-5.



Abstract: Objective: To identify those patients with nonrheumatic atrial fibrillation who

are at high risk and those at low risk for arterial thromboembolism. Design:

Cohort study of patients assigned to placebo in a randomized clinical trial.

Setting: Five hundred sixty-eight inpatients and outpatients with nonrheumatic

atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from

1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study. Patients were

followed for a mean of 1.3 years. Measurements: Clinical variables were

assessed at study entry and correlated with subsequent ischemic stroke and

systemic embolism by multivariate analysis. Main Results: Recent (within 3

months) congestive heart failure, a history of hypertension, and previous arterial

thromboembolism were each significantly and independently associated with a

substantial risk for thromboembolism (> 7% per year; P less- than-or-equal-to

0.05). The presence of these three independent clinical predictors (recent

congestive heart failure, history of hypertension, previous thromboembolism)

defined patients with rates of thromboembolism of 2.5% per year (no risk

factors), 7.2% per year (one risk factor), and 17.6% per year (two or three risk

factors). Nondiabetic patients without these risk factors, comprising 38% of the

cohort, had a low risk for thromboembolism (1.4% per year; 95% Cl, 0.05% to

3.7%). Patients without clinical risk factors who were under 60 years of age had

no thromboembolic events. Conclusion: Patients with atrial fibrillation at high

risk (> 7% per year) and low risk ( 0.2). The risk ratios for nonfatal and fatal stroke

with fibrates, resins, and dietary interventions were all close to 1.0, and the

difference between the HMGcoA reductase inhibitor effect and the pooled

estimate for all other interventions would, under the null hypothesis, be unlikely

to occur by chance (P = 0.01). Trials with HMGcoA reductase inhibitors also

showed reductions in rates of death from coronary heart disease and overall

mortality. Conclusion: This meta-analysis of randomized, controlled trials

suggests that in hyperlipidemic patients who have not previously had stroke,

HMGcoA reductase inhibitors reduce the incidence of stroke



Keywords: ARTERY

DISEASE/cerebrovascular/cholesterol/CHOLESTEROL-LOWERING

TRIALS/control/coronary heart disease/CORONARY

HEART-DISEASE/heart/HMGcoA

inhibitors/hypercholesterolemia/incidence/meta-analysis/MIDDLE-AGED

MEN/MORTALITY/MYOCARDIAL-INFARCTION/PHYSICIANS/PRIMAR

Y- PREVENTION TRIAL/RACE/randomized/RISK/SECONDARY

PREVENTION/SERUM-CHOLESTEROL/stroke/treatment/trials



Lewis, S.J., Moye, L.A., Sacks, F.M., Johnstone, D.E., Timmis, G., Mitchell, J.,

Limacher, M., Kell, S., Glasser, S.P., Grant, J., Davis, B.R., Pfeffer, M.A. and

Braunwald, E. (1998), Effect of pravastatin on cardiovascular events in older

patients with myocardial infarction and cholesterol levels in the average range -

Results of the cholesterol and recurrent events (CARE) trial. Annals of Internal

Medicine, 129 (9), 681-+.



Abstract: Background: A majority of all myocardial infarctions occur in patients who are

65 years of age or older and have average cholesterol levels, but little

information is available on whether cholesterol lowering in such patients reduces

the rate of recurrent cardiovascular disease. Objective: To determine whether

pravastatin reduces the rate of recurrent cardiovascular events in older patients.

Design: Subset analysis of a randomized, controlled trial. Setting: 80 hospitals

and affiliates in the United States and Canada. Patients: 1283 patients aged 65 to

75 years who had had myocardial infarction and had a plasma total cholesterol

level less than 6.2 mmol/L (240 mg/dL) and a low-density lipoprotein cholesterol

level of 3.0 to 4.5 mmol/L (115 to 174 mg/dL). Intervention: Pravastatin, 40

mg/d, or placebo. Measurements: Five-year event rates of major coronary events

(coronary death, nonfatal myocardial infarction, angioplasty, or bypass surgery)

and stroke. Results: Major coronary events occurred in 28.1% of placebo

recipients and 19.7% of pravastatin recipients (difference, 9.0 percentage points

[95% CI, 4 to 13 percentage points]; relative risk reduction, 32%; P 0.2 for the

difference). Conclusions: In patients who had preexisting vascular disease or

diabetes combined with an additional cardiovascular risk factor, mild renal

insufficiency significantly increased the risk for subsequent cardiovascular

events. Ramipril reduced cardiovascular risk without increasing adverse effects



Keywords: adverse effects/angiotensin converting enzyme

inhibitors/angiotensin-converting enzyme

inhibitors/cardiovascular/cardiovascular events/cardiovascular

risk/death/diabetes/DISEASE/FAILURE/incidence/infarction/KIDNEY/MILD/

MORTALITY/myocardial/myocardial

infarction/outcome/PHYSICIAN/PHYSICIANS/primary/RACE/ramipril/random

ized/randomized trial/renal/risk/risk factor/serum/SERUM

CREATININE/stroke/treatment/trial/use/vascular/vascular disease



Berg, A.O., Allan, J.D., Frame, P., Homer, C.J., Johnson, M.S., Klein, J.D., Lieu, T.A.,

Orleans, C.T., Peipert, J.F., Pender, N.J., Siu, A.L., Teutsch, S.M. and Woolf,

S.H. (2002), Postmenopausal hormone replacement therapy for primary

prevention of chronic conditions: Recommendations and rationale. Annals of

Internal Medicine, 137 (10), 834-839.

Abstract: This statement summarizes the U.S. Preventive Services Task Force (USPSTF)

recommendations for use of hormone replacement therapy for the primary

prevention of chronic conditions in postmenopausal women and updates the

1996 USPSTF recommendations on this topic. The complete information on

which this statement is based, including evidence tables and references, is

available through the USPSTF Web site (www.preventiveservices.ahrq.gov) and

through the National Guideline Clearinghouse (www.guideline.gov) The

USPSTF reviewed the evidence on the use of postmenopausal hormone

replacement therapy and the following outcomes: cardiovascular disease,

including CHD and stroke; osteoporosis and fractures; thromboembolism;

dementia and cognitive function; breast, colon, ovarian, and endometrial cancer;

and cholecystitis. The USPSTF also reviewed evidence of the effects of hormone

replacement therapy on phytoestrogens and osteoporosis and cardiovascular

disease. The use of hormone replacement therapy for relieving active symptoms

of menopause, such as hot flashes, urogenital symptoms, and mood and sleep

disturbances, among others, is outside the scope of these USPSTF

recommendations, and literature on this topic was not reviewed. Sources for

estimates of benefits and harms cited in this Recommendation statement are

described in the summary of the evidence available from the Agency for

Healthcare Research and Quality



Keywords: BREAST-CANCER/cancer/cardiovascular/cardiovascular

disease/CHD/cognitive function/dementia/DISEASE/ESTROGEN-PROGESTIN

REPLACEMENT/fractures/HEART/hormone replacement

therapy/menopause/METAANALYSIS/MORTALITY/osteoporosis/PHYSICIA

N/PHYSICIANS/postmenopausal hormone replacement/postmenopausal

women/prevention/primary/primary

prevention/RACE/RISK/sleep/STROKE/symptoms/therapy/thromboembolism/U

S/use/WOMEN



Tonelli, M., Moye, L., Sacks, F.M., Kiberd, B. and Curhan, G. (2003), Pravastatin for

secondary prevention of cardiovascular events in persons with mild chronic renal

insufficiency. Annals of Internal Medicine, 138 (2), 98-104.



Abstract: Background: Cardiovascular disease is a common cause of morbidity and

death in persons with renal insufficiency. Although 3-hydroxy-3methylglutaryl

coenzyme A reductase inhibitors (statins) are effective for secondary prevention

of cardiovascular events in the general population, they have not been

specifically studied in chronic renal insufficiency. Objective: To determine

whether pravastatin is effective and safe for secondary prevention of

cardiovascular events in persons with chronic renal insufficiency. Design: Post

hoc subgroup analysis of a randomized, double-blind, placebo- controlled trial.

Setting: The Cholesterol and Recurrent Events (CARE) study, a randomized trial

of pravastatin versus placebo in 4159 participants with previous myocardial

infarction and total plasma cholesterol levels less than 6.21 mmol/L (130 mg/dL or

untreated total cholesterol concentrations >200 mg/dL were included. The

median duration of follow-up after the first MI was 3.3 years. Medical record

review was used to collect information on cardiovascular risk factors.

Computerized pharmacy records were used to assess antihyperlipidemic drug use

during the first 6 months after hospitalization. RESULTS: Compared with 1263

subjects who did not receive lipid-lowering drug treatment, 373 subjects who

received statins had a lower risk of recurrent coronary events (relative risk [RR]

0.59; 95% Cl 0.39 to 0.89), stroke (RR 0.82; 95% Cl 0.35 to 1.95),

atherosclerotic cardiovascular mortality (RR 0.49; 95% Cl 0.21 to 1.13), and any

atherosclerotic cardiovascular event (RR 0.63; 95% Cl 0.40 to 0.98). Among 320

subjects who used non-statin drug therapies, the RRs were 0.66 (95% Cl 0.45 to

0.97) for recurrent coronary events, 0.95 (95% Cl 0.46 to 1.95) for stroke, 0.68

(95% Cl 0.35 to 1.32) for cardiovascular mortality, and 0.77 (95% Cl 0.53 to

1.11) for any atherosclerotic cardiovascular event, compared with untreated

hyperlipidemic patients. CONCLUSIONS: In this study of MI survivors, the use

of lipid-lowering drug therapies after hospitalization was associated with a

reduced risk of cardiovascular events. These results emphasize the importance of

lipid-lowering drug treatment in patients with hyperlipidemia who survive a first

MI



Keywords: cardiovascular/cardiovascular event/cardiovascular events/cardiovascular

mortality/cardiovascular risk/cardiovascular risk factors/cholesterol/clinical

practice/coronary heart disease/DEATH/disease/drug/drugs/heart/heart

disease/hospital/hospitalization/hydroxymethylglutaryl coenzyme

A/hyperlipidemia/infarction/ISCHEMIC-HEART-DISEASE/lipid

lowering/lipid-lowering/METAANALYSIS/MORTALITY/myocardial/myocardi

al

infarction/Netherlands/pharmacy/prevention/randomized/REDUCTION/relative

risk/review/RISK/risk factors/secondary/secondary

prevention/SERUM-CHOLESTEROL/statins/stroke/treatment/TREATMENT

ADHERENCE/TRIALS/use/WOMEN



McKenney, J.M. (2003), Potential nontraditional applications of statins. Annals of

Pharmacotherapy, 37 (7-8), 1063-1071.



Abstract: OBJECTIVE: To review the current evidence for use of

hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) in

nontraditional lipid-related applications, including acute coronary syndromes,

peripheral arterial disease, stroke, and renal disease, and to describe ongoing

trials evaluating the role of statins in these conditions. DATA SOURCES:

Clinical literature was identified by a MEDLINE search (1990-November 2002)

using 1 of the following search terms: acute coronary syndrome(s), angina

pectoris, atherosclerosis, atorvastatin, clinical trials, diabetes mellitus, end-stage

renal disease, fluvastatin, lovastatin, myocardial infarction, peripheral arterial

disease, pravastatin, simvastatin, statins, and stroke. Treatment guidelines issued

by professional and governmental organizations, such as the American Diabetes

Association, American Heart Association, National Cholesterol Education

Program, National Kidney Foundation, and National Stroke Foundation, were

reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles

identified from the data sources were included if they pertained to the conditions

described in the objectives and provided unique information concerning use of

statins. DATA SYNTHESIS: Substantial evidence exists for the use of statins in

acute coronary syndromes. Meta-analyses of data from major clinical trials

indicate that statins prevent first and recurrent stroke, and large-scale trials are

underway to evaluate the efficacy of statins in this setting. Accumulating

evidence suggests that statins may be beneficial in reducing the morbidity and

mortality associated with peripheral arterial disease and end-stage renal disease,

and results from ongoing trials may confirm these benefits. Statins may also have

a future role in amelioration of other conditions associated with atherosclerosis,

such as diabetes mellitus. CONCLUSIONS: A large body of evidence supports

the evaluation of statins in clinical settings beyond primary and secondary

prevention of morbidity and mortality associated with coronary atherosclerosis

Keywords: acute/ACUTE CORONARY SYNDROMES/acute coronary

syndromes/angina/angina pectoris/arterial/arterial

disease/atherosclerosis/ATHEROSCLEROSIS

PROGRESSION/atorvastatin/AVERAGE CHOLESTEROL

LEVELS/benefits/clinical trials/diabetes/diabetes mellitus/disease/end-stage

renal

disease/evaluation/fluvastatin/guidelines/HEART-DISEASE/hydroxymethylglut

aryl coenzyme A/infarction/morbidity/morbidity and

mortality/mortality/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/organizations/peripheral arterial

disease/PERIPHERAL

ARTERIAL-DISEASE/pravastatin/prevention/primary/primary and secondary

prevention/RANDOMIZED CONTROLLED TRIAL/recurrent stroke/renal/renal

disease/RENAL- TRANSPLANT

PATIENTS/results/review/SCANDINAVIAN-SIMVASTATIN-SURVIVAL/sec

ondary/secondary prevention/SELECTION/simvastatin/ST- SEGMENT

ELEVATION/statins/stroke/trials/USA/use



Carroll, C.A., Coen, M.M. and Piepho, R.W. (2003), Economic impact of ramipril on

hospitalization of high-risk cardiovascular patients. Annals of

Pharmacotherapy, 37 (3), 327-331.



Abstract: OBJECTIVE: To estimate differences in direct costs attributable to avoided

hospitalizations. and procedures during the years of the HOPE (Heart Outcomes

Prevention Evaluation). study after the cost of treatment with ramipril or

alternative angiotensin- converting enzyme inhibitor therapy was taken into

account. METHODS: A decision analytical model was developed to estimate the.

economic impact of reductions in hospitalizations and/or procedures both at

annual increments and over the first 4 years of the HOPE study. The analysis

compared the number of cardiovascular events per endpoint per year in the..

intervention and placebo group with hospitalization and procedural costs. Cost

data were derived from the literature and inflated,to the appropriate index year

using the consumer- price index. RESULTS: For approximately 9000 patients

studied, the gross estimated savings in direct costs for 297 events avoided were

more than $5 million over 4 years. After the cost of treatment was,deducted for

both groups, the. net estimated savings were $871000 over 4 years.

CONCLUSIONS: The results demonstrate that the use of ramipril provides

cost-effective treatment for high-risk cardiovascular patients with an ejection

fraction >40%



Keywords: AIRE/angiotensin/angiotensin converting enzyme

inhibitor/cardiovascular/cardiovascular disease/cardiovascular

events/cost/COST-EFFECTIVENESS/costs/EVENTS/HEART-FAILURE/high

risk/hospitalization/INHIBITOR/LEFT-VENTRICULAR

DYSFUNCTION/MYOCARDIAL-

INFARCTION/ramipril/results/STROKE/SURVIVAL/therapy/treatment/USA/u

se

Skurnik, Y.D., Tchemiak, A., Edlan, K. and Sthoeger, Z. (2003), Ticlopidine-induced

cholestatic hepatitis. Annals of Pharmacotherapy, 37 (3), 371-375.



Abstract: OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis,

investigate its mechanism, and compare the observed main characteristics with

those of the published cases. CASE SUMMARIES: Two patients developed

prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous

coronary angioplasty, with complete remission during the follow-up period.

T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated

in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic

hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases

have been reported but few in the English literature. Our patients developed

jaundice following treatment with ticlopidine and showed the clinical and

laboratory characteristics of cholestatic hepatitis, which resolved after

discontinuation of the drug. Hepatitis may develop weeks after discontinuation of

the drug and may run a prolonged course, but complete remission was observed

in all reported cases. An objective causality assessment revealed that the adverse

drug event was probably related to the use of ticlopidine. The mechanisms of this

ticlopidine-induced cholestasis are unclear. Immune mechanisms may be

involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation

study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse

effect of ticlopidine that may be immune mediated. Patients receiving the drug

should be monitored with liver function tests along with complete blood cell

counts. This complication will be observed even less often in the future as

ticlopidine is being replaced by the newer antiplatelet agent clopidogrel



Keywords:

angioplasty/antiplatelet/APLASTIC-ANEMIA/ASPIRIN/cholestasis/cholestatic/

cholestatic hepatitis/CLOPIDOGREL/complication/coronary

angioplasty/drug/hepatitis/HEPATOTOXICITY/IMMUNE-RESPONSE/Israel/ja

undice/mechanisms/PREVENTION/stimulation/STROKE/ticlopidine/treatment/

TRIAL/USA/use



Albunyan, M. (1993), Binswanger-Disease - the King-Khalid-University-Hospital

Experience. Annals of Saudi Medicine, 13 (5), 429-431.



Abstract: Two hundred and twenty-one Saudi patients admitted for stroke in King

Khalid University Hospital between 1982 and 1987 were evaluated clinically and

by laboratory and radiological investigations. Twelve patients were found to

have leukoaraiosis on brain CT and a clinical picture compatible with

Binswanger disease (subcortical arteriosclerotic encephalopathy). Arterial

hypertension was present in all cases, seizure disorders in 25%, and dementia in

83%. The features of these cases are compared with similar cases reported from

other places. The importance of control of hypertension in prevention of

Binswanger disease is emphasized

AlShammari, S.A., Khoja, T.A. and AlMaatouq, M.A. (1996), The prevalence of obesity

among Saudi males in the Riyadh region. Annals of Saudi Medicine, 16 (3),

269-273.



Abstract: Attendees of 15 health centers in urban and rural areas in the Riyadh region

were screened for obesity during May and June 1994. Systemic selection yielded

1580 Saudi males for analysis. The mean age was 33.6 +/- 13.5 years and body

mass index (BMI) was 26.9 +/- 5.7 kg/m(2). Only 36.6% of subjects were their

ideal weight (BMI 40 kg/m(2)). Middle age, lower education and

joblessness predicted a higher risk for obesity. Patients living in rural areas had

greater BMIs than those living in urban areas (P 120 (OR 1.19, 95% Cl 1.02-1.40, p 70% or occlusion) was found in 20% of the patients. Of

the total, 12% were reviewed in the out-patient clinic following which no action

was taken, 2% had angiography but no surgery, while 5% had angiography and

surgery. 1% were lost to follow-up. The mean delay from scan to operation was

36 days. Conclusion: Fast track scanning has led to early detection of surgically

relevant carotid lesions and avoidance of delay in surgical intervention. It is an

efficient and cost-effective practice



Keywords: age/carotid/carotid duplex scanning/carotid

stenosis/CVA/detection/disease/district general hospital/duplex/duplex

scanning/ENDARTERECTOMY/ENGLAND/hospital/MANAGEMENT/outco

me/review/stenosis/STROKE/stroke prevention/surgery/TIA/transient ischaemic

attack

Qayumi, A.K., Jamieson, W.R.E. and Poostizadeh, A. (1991), Effects of

Platelet-Activating-Factor Antagonist Cv-3988 in Preservation of Heart and

Lung for Transplantation. Annals of Thoracic Surgery, 52 (4), 1026-1032.



Abstract: The preservation of heart and lung for transplantation remains a major concern

in extended ischemic intervals. This experiment evaluated the effect of high

molecular weight deferoxamine and a platelet-activating factor antagonist

(CV-3988) in ischemic reperfused tissue. Heart-lung transplantation was

performed in a swine model after 4 hours 45 minutes of ischemia. Animals were

divided into three groups. Group A was a control without pharmacological

intervention. In group B, high molecular weight deferoxamine, 50 mg/kg, was

used, and in group C, platelet- activating factor antagonist CV-3988, 10 mg/kg,

was used. The results of functional variables (cardiac index, stroke index, lung

water, oxygen and carbon dioxide tensions, alveolar- arterial gradient, and

alveolar-arterial ratio) demonstrated superior heart and lung function for groups

B and C compared with the control group. These alterations of heart and lung

function were significantly less (p 0.99)

were similar in aspirin users and nonaspirin users. We found no significant

difference between blood product requirements for the two groups. Similarly, we

found no significant difference in the incidence of the secondary outcomes.

Conclusions. Preoperative aspirin did not increase bleeding-related

complications, mortality rate, or other morbidities in patients who had off-pump

coronary artery operation. (C) 2003 by The Society of Thoracic Surgeons



Keywords: ANTIPLATELET

THERAPY/aspirin/bleeding/bypass/complications/coronary artery

bypass/DIPYRIDAMOLE/DISEASE/England/IMMEDIATE

POSTOPERATIVE ASPIRIN/in-hospital

mortality/incidence/infarction/intensive care/morbidity/MORTALITY/mortality

rate/myocardial/myocardial infarction/NEW-YORK/outcome/outcome

measures/outcomes/postoperative/PREVENTION/primary/REEXPLORATION/

risks/secondary/stroke/SURGERY/therapy/TRIAL/USA/use/VEIN-GRAFT

PATENCY



Albert, A.A., Beller, C.J., Walter, J.A., Arnrich, B., Rosendahl, U.P., Priss, H. and

Ennker, J. (2003), Preoperative high leukocyte count: A novel risk factor for

stroke after cardiac surgery. Annals of Thoracic Surgery, 75 (5), 1550-1557.



Abstract: Background. Stroke after cardiac surgery is a devastating complication. The

relationship between white blood cell count (WBC) and perioperative

cerebrovascular accident (CVA) has not been investigated. An effort was made

to identify how preoperative WBC may relate to CVA development during or

after cardiac surgery. Methods. Prospective data were collected from 7,483

patients who underwent coronary artery bypass grafting or valvular surgery or

both. WBC was determined preoperatively and postoperatively. Differentiation

of WBC was examined only preoperatively. Results. There were a total of 125

CVAs (10 transient ischemic attacks [TIAs], 115 strokes). WBC was

significantly higher preoperatively and directly postoperatively in patients with

stroke. Qualitative changes in preoperative WBC were also found in these

patients (chi(2); p 240

mg/dl, HDL cholesterol 180 mg/dl, fibrinogen > 450

mg/dl, hematocrit > 45 %, hypertension, diabetes mellitus, cigarette smoking,

familial ischemic events, previous ischemic CVD, ischemic cardiac disease,

embolic cardiopathy. In males with ischemic stroke the most frequent risk factors

were: hypertension (43 %), fibrinogen > 450 mg/dl (37.9 %), diabetes mellitus.

cigarette smoking and previous ischemic CVD (25.8 %). in females with

ischemic stroke a clear prevalence of hypertension (69.8 %), ischemic

cardiopathy and previous ischemic CVD (47 %) and diabetes mellitus (41.5 %)

were observed. In males with RIA hypertension (50 %) and cigarette smoking

(38 %). Females with RIA presented a high prevalence of reduced HDL

cholesterol, lower than 35 mg/dl (77.7 %), hypertension (63.6 %) and ischemic

cardiopathy (54.5 %). The results indicate that there are no highly significant

differences between the data reported by other authors on the most important

acute ischemic CVD risk factors in Italy and elsewhere. Arterial hypertension

and diabetes mellitus are the most important risk factors of cerebral ischemic

events in both sexes. The diffusion of cigarette smoking among women in the

last thirty years must be taken into consideration. Although it does not represent

a risk factor for elderly women today, it may do in the future. Therefore,

antismoking campaigns must be more decisive and targeted at both sexes



Keywords: cerebrovascular disease/cholesterol/diabetes

mellitus/elderly/fibrinogen/HIGH-DENSITY-LIPOPROTEIN/hypertension/INT

ERNAL/ischemic stroke/prevention/reversible ischemic attack/risk

factors/secondary prevention/smoking/STROKE/stroke/triglycerides



Cozzolino, D., Salvatore, T. and Torella, R. (1996), Diabetic non ketotic hyperosmolar

state: A special care in aged patients. Archives of Gerontology and Geriatrics,

245-253.



Abstract: The hyperosmolar hyperglycemic nonketotic state (HHNS) is an acute

metabolic complication occurring characteristically in elderly type-2 diabetic

patients. It may account for 10 up to 47 % of cases of severe hyperglycemia with

or without ketoacidosis. Many factors associated with advanced age may explain

the predilection of both elderly subjects in general and older diabetics in

particular to develop hyperosmolar coma, including reduced glomerular filtration

rate and elevated renal threshold for glucose [which fall to correct hyperglycemia

by osmotic diuresis), lack of thirst appropriate to the state of hydratation and

some iatrogenic factors. In HHNS the age of the patients is the best known

prognostic indicator. The increased mortality rate in the elderly diabetics depends

on the severity of precipitating acute diseases (gastrointestinal hemorrhage.

cardiovascular accident, pneumonia, pancreatitis, etc.], but the frequent

compromises of the hemodynamic state and renal function of aged subjects

substantially contributes. However, the role of erroneous management is not

negligible and difficulties may be encountered in conciliating correction of

metabolic disorder with treatment of precipitating illness. Insulin. water and

electrolytes are the most important therapeutical tools for the treatment of

hyperglycemic emergencies. In HHNS, the aggressive fluid replacement with

isotonic or hypotonic NaCl solutions have first priority. Such a type of strategy is

difficult to perform in patients suffering from cerebral stroke (which needs of

anti-edema therapy) or congestive heart failure (necessitating to avoid fluid

excess). According to the literary data, in our experience these two precipitating

factors are frequent causes of death. We outline the validity of prefixed protocols

of management; on the other hand, we think that the pathophysiological

understanding of HHNS in the single patient is essential to decide the proper

corrections and to permit a successful outcome. The primary way aiming at

diminishing mortality by HHNS is its prevention; it is fundamental to warrant an

appropriate fluid intake and to utilize with caution some drugs (thiazides.

steroids, phenytoin, etc.) in aged diabetics, especially when nephropathic or

unable, or living in nursing homes



Keywords: ACUTE STROKE/aged/CEREBRAL EDEMA/COMA/diabetes

mellitus/diseases/elderly/GLUCOSE/heart/HYPERGLYCEMIA/hyperosmolar

hyperglycemic nonketotic

state/INSULIN/KETOACIDOSIS/mortality/PRESSURE/prevention/RABBITS/s

everity/stroke/THERAPY/treatment



Alletto, M., Burgio, A., Fulco, G., Paradiso, R., Piangiamore, M. and Vancheri, F.

(1996), A marked increase of ischemic stroke incidence between 1980 and 1994

in S Caterina, Sicily. Archives of Gerontology and Geriatrics, 167-172.



Abstract: Stroke death rates have been declining for some decades in most of the

industrialized countries. It is not clear, whether this has been associated with a

decrease in stroke incidence. We studied temporal trends in stroke incidence in a

rural community in Sicily, during two periods 1980-84 and 1990-94. There was a

total of 231 patients (120 of them women). The diagnosis of stroke was based on

the clinical evaluation and CT scan since 1982 and onward. There were 109

ischemic strokes (51 women) mean age 72.7 years, in 1980-84 period; 122

ischemic strokes (69 women) mean age 75.1, in 1990-94 period. Cardiovascular

risk factor rates did not change in the two periods considered. The relative annual

stroke incidence rate increased 37.0 %; (2.7 in 1980-84 to 3.7/1000 inhabitants in

1990-94, p = 0.016). In the population older than 65 years, the same parameter

increased by 21.1 % between the two periods; (16.1 in 1980-84 to 19.5/1000

inhabitants in 1990-94, not significant). This increase was due mainly to a 45.3

% significant relative increase in women, from 7.5 to 11.0/1000 inhabitants (p =

0.039). These findings suggest a need of the reconsideration of effective

strategics for the prevention of stroke



Keywords: absolute stroke incidence/CT/DECLINING

INCIDENCE/INTERNAL/ischemic

stroke/MEN/MORTALITY/prevention/relative stroke incidence/stroke/TRENDS

Acanfora, D., Trojano, L., Iannuzzi, G.L., Furgi, G., Picone, C., Rengo, C., Abete, P.

and Rengo, F. (1996), The brain in congestive heart failure. Archives of

Gerontology and Geriatrics, 23 (3), 247-256.



Abstract: In the present paper we discuss two issues about relationships between

congestive heart failure and the brain. First, major acute cerebrovascular events

are very frequent among elderly people, but stroke does not appear io be

frequently associated with congestive heart failure. Second, some cardiovascular

conditions may determine progressive damage of cerebral tissue, with

consequent impairment of cognitive functions. The association of cognitive

impairment and cardiovascular diseases may dramatically increase morbility and

mortality risks in the elderly. Recent studies seem to show that hypotension and

congestive heart failure are risk factors for dementia in elderly people. In view of

this data, an Italian multicentric study on congestive heart failure in hospitalized

elderly patients (CHF Italian Study I) included a brief screening of cognitive

abilities (MMSE)I The presence of congestive heart failure induced a significant

decrease of MMSE scores: mean MMSE score after statistical adjustment for the

other variables was about one point lower in patients with congestive heart

failure respect to elderly patients affected by heart disease but without congestive

heart failure. A novel multicentric study (CHF Italian Study II) has been

performed to identify cognitive functions more specifically impaired during

congestive heart failure in the elderly. Preliminary data relative to 385 patients,

confined that congestive heart failure may induce a generalized impairment of

cognitive functions. These data have relevant implications because they

demonstrate that a multidisciplinary approach is necessary in these patients, both

for prevention and rehabilitation therapy. Copyright (C) 1996 Elsevier Science

Ireland Ltd



Keywords: acute/ALZHEIMERS-DISEASE/brain/cardiovascular

diseases/CARE/cerebral/CEREBRAL

BLOOD-FLOW/cerebrovascular/cognitive function/cognitive

impairment/COGNITIVE PERFORMANCE/congestive heart

failure/dementia/diseases/elderly/heart/heart failure/HYPERTENSIVE

PATIENTS/LEUKO-ARAIOSIS/MINI-MENTAL-STATE/MMSE/mortality/N

ORMS/POPULATION/prevention/rehabilitation/risk/risk factors/SENILE

DEMENTIA/stroke/SURVIVAL/therapy



Vasishta, S., Toor, F., Johansen, A. and Hasan, M. (2001), Stroke prevention in atrial

fibrillation: physicians' attitudes to anticoagulation in older people. Archives of

Gerontology and Geriatrics, 33 (3), 219-226.



Abstract: The increased prevalence of atrial fibrillation (AF) in older people contributes

to an increased risk of stroke. Although clear guidelines exist, there is

considerable variation in physicians' approaches to the selection of patients

appropriate for warfarin treatment as stroke prevention. We compared attitudes

to the anticoagulation of elderly patients with AF, in a postal study of

geriatricians and specialist physicians (general physicians with specialist

interests in Cardiology, Gastroenterology, Diabetes and Endocrinology,

Nephrology and Neurology). A structured questionnaire was mailed to all 108

consultant physicians and geriatricians in South East Wales. This explored their

attitude to their patients' age and comorbidity when considering the benefits and

risks of warfarin prophylaxis for AF. About 25/30 geriatricians (83%) and 43/78

specialist physicians (55%) responded; an overall response rate of 63%. About

94% of the respondents agreed that patients aged over 75 with atrial fibrillation

were at a greater risk of stroke than younger patients. About 68% considered

warfarin related bleeds more likely in this age group, despite which most thought

that the benefits of warfarin outweighed the risks. In people aged above 75, only

13/25 (52%) geriatricians and 17/43 (40%) specialist physicians viewed lone AF

(AF with no underlying risk factor) as an indication for anticoagulation. When

considering the use of warfarin, geriatricians' appeared more likely to be

influenced by coexisting problems such as disability, falls, cerebrovascular

disease and limited life expectancy. Only a history of falls (96% geriatricians vs.

86% specialist physicians) and cerebrovascular disease (79% geriatricians vs.

51% specialist physicians) had a significant influence on prescribing practice (P

2 mg of hemoglobin per gram of stool) were detected in 11%

and values greater than 4 mg of hemoglobin per gram of stool were found in 8%,

Mean (+/-SD) values were more for those randomly assigned to receive

combined therapy (1.7+/-3.3 mg of hemoglobin per gram of stool vs

adjusted-dose warfarin therapy, 1.0+/-1.9 mg/g; P=.003), The 54 nonrandomized

patients with low risk of stroke receiving aspirin alone had a mean (+/-SD)

HemoQuant value of 0.8+/-0.7 mg of hemoglobin per gram of stool 1 month

after entry in the study. Conclusions: Abnormal levels of fecal hemoglobin

excretion were common in elderly patients with high risk of atrial fibrillation 1

month after randomization to prophylactic antithrombotic therapy. Combined

warfarin and aspirin therapy was associated with greater fecal hemoglobin

excretion than standard warfarin therapy, suggesting the potential for increased

gastrointestinal hemorrhage



Keywords: aspirin/atrial fibrillation/clinical

trials/elderly/fibrillation/hemorrhage/PREDICTION/prophylaxis/risk/stroke/trial

s/warfarin



[Anon]. (1997), The efficacy of aspirin in patients with atrial fibrillation - Analysis of

pooled data from 3 randomized trials. Archives of Internal Medicine, 157 (11),

1237-1240.

Abstract: Background: Atrial fibrillation (AF) is associated with an increased risk of

stroke. Six randomized studies of the use of oral anticoagulation therapy have

demonstrated that the relative risk of stroke is decreased by approximately 68%.

Three of these studies also compared aspirin with placebo use in a double-blind

design. We pooled individual patient data from these 3 studies. Objectives: To

determine if there were subgroups of patients who were particularly responsive

to aspirin use and to determine the efficacy of aspirin compared with placebo use

in the broad spectrum of patients with AF. Methods: There were 1985

patient-years assigned to the aspirin and 1867 patient-years assigned to the

placebo groups in the analysis. The daily dose of aspirin was 75 mg in the Atrial

Fibrillation, Aspirin, Anticoagulation Study, 325 mg in the Stroke Prevention in

Atrial Fibrillation 1 Study, and 300 mg in the European Atrial Fibrillation Trial.

The European Atrial Fibrillation Trial was a secondary prevention trial, while the

other 2 were primary prevention studies. The primary end point in this analysis

was ischemic stroke. Results: At the time of randomization, the patients' mean

age was 70 years and the mean blood pressure was 145/83 mm Hg. Sixty-two

percent of patients were male, 46% had a history of hypertension, 35% had a

previous transient ischemic attack or stroke, and 19% had intermittent AF.

Although aspirin use seemed particularly effective in younger patients and in

those with hypertension in the Stroke Prevention in Atrial Fibrillation 1 Study,

this was not the case in the other studies. No other subgroups particularly

responsive to aspirin therapy were identified. When patients from all the studies

were combined, the relative risk reduction with aspirin therapy was 21% (95%

confidence interval, 0%-38%; P=.05). Conclusions: A subgroup of patients with

AF that has a particularly large reduction in stroke incidence from aspirin

therapy was not convincingly identified. The data from the combined analysis of

these 3 randomized trials suggest a small effect of aspirin use in preventing

stroke in patients with AF



Keywords: AF/age/anticoagulation/aspirin/atrial fibrillation/blood

pressure/design/fibrillation/history/hypertension/incidence/ischemic/ischemic

stroke/oral anticoagulation/PREVENTION/primary

prevention/randomized/randomized trials/relative risk/risk/secondary

prevention/STROKE/therapy/transient/transient ischemic

attack/trials/WARFARIN



Crouse, J.R., Byington, R.P., Hoen, H.M. and Furberg, C.D. (1997), Reductase inhibitor

monotherapy and stroke prevention. Archives of Internal Medicine, 157 (12),

1305-1310.



Abstract: Background: Epidemiologic evidence and meta-analyses of data from early

clinical trials suggest that lowering the levels of cholesterol does not reduce the

events of stroke. These analyses have not included more recent clinical trials

using reductase inhibitors. Objective: To conduct a meta-analysis of the effect of

reducing cholesterol levels on stroke in all reported clinical trials of primary (n=4)

and secondary (n=8) prevention of coronary heart disease that used reductase

inhibitor monotherapy and provided information on incident stroke. Results:

Analysis of combined data from primary and secondary prevention trials showed

a highly statistically significant reduction of stroke associated with the use of

reductase inhibitor monotherapy (27% reduction in stroke; P=.001). Analysis of

secondary prevention trials alone disclosed a similar statistically significant

effect (32% reduction in stroke; P=.001). A smaller nonsignificant reduction in

stroke was noted in the primary prevention trials (15% reduction in stroke;

P=.48). Conclusions: Reductase inhibitors now in use for lowering cholesterol

levels are more potent and have fewer side effects than the cholesterol- lowering

agents previously available. They appear to reduce stroke, most notably in

patients with prevalent coronary artery disease, which may be partly due to the

effects of lowering the levels of cholesterol on the progression and plaque

stability of extracranial care tid atherosclerosis or the marked reduction of

incident coronary heart disease associated with treatment



Keywords: ARTERY

DISEASE/atherosclerosis/BLOOD-PRESSURE/CARDIOVASCULAR

EVENTS/CAROTID ATHEROSCLEROSIS/cholesterol/CLINICAL

EVENTS/clinical trials/coronary artery disease/coronary heart

disease/CORONARY HEART-DISEASE/EASTERN

FINLAND/heart/INTERVENTION

TRIAL/meta-analysis/MYOCARDIAL-INFARCTION/plaque/prevention/primar

y prevention/secondary prevention/SERUM-CHOLESTEROL

LEVELS/stroke/stroke prevention/treatment/trials



Whittle, J., Wickenheiser, L. and Venditti, L.N. (1997), Is warfarin underused in the

treatment of elderly persons with atrial fibrillation? Archives of Internal

Medicine, 157 (4), 441-445.



Abstract: Background: Several randomized clinical trials have shown that among

patients with atrial fibrillation, warfarin sodium use protects against stroke.

Recently, experts have voiced concern about possible underuse of warfarin by

practicing physicians. Few studies, however, have quantitated the amount of

warfarin underuse. Methods: We randomly sampled 65 Medicare beneficiaries

discharged alive from each of 5 small Pennsylvania hospitals between July 1,

1993, and June 30, 1994, with a discharge diagnosis code for atrial fibrillation.

Trained abstractors verified that atrial fibrillation was present at some time

during the hospitalization, determined the presence of contraindications to

anticoagulation, and identified warfarin or aspirin use at discharge for each

patient. An internist used implicit criteria to identify the reason for warfarin

nonuse in patients who had none of the explicit contraindications to warfarin and

did not receive it. Results: Of 322 charts reviewed, 48 patients were not in atrial

fibrillation during the hospitalization, 79 had contraindications to warfarin use,

21 either died or were transferred to another hospital, and 2 were admitted with a

complication of warfarin. Of the 172 remaining patients, 76 (44%) underwent

anticoagulation. On implicit review of the 96 patients who did not undergo

anticoagulation, the internist judged that warfarin would not have been

appropriate in 54. After excluding those patient's, 76 (64%) of the remaining 118

patients underwent anticoagulation. Patients not receiving warfarin were slightly

older (81.6 vs 78.3 years old), but this was not statistically significant after

stratifying by hospital. Rates of warfarin use at the 5 hospitals varied widely

(32%, 57%, 79%, 82%, 94%; P1 to 75 years old) compared with a younger control group (between 60

and 69 years) and to assess the quality of anticoagulant control and incidence of

hemorrhagic complications in those patients who recently commenced receiving

warfarin therapy (first year of therapy). Patients and Methods: In this

retrospective follow-up study, anticoagulant control and the incidence of

hemorrhagic complications and stroke were assessed in an elderly population (>

75 years old) compared with a younger control group (between 60 and 69 years),

all with atrial fibrillation(target international normalized ratio [INR] 2.5) and

attending a hospital outpatient anticoagulant clinic. Results: A total of 328

patients were studied over a 21-month period. There were 204 patients in the

control group providing 288 patient-years of follow-up and 124 patients in the

elderly group providing 170 patient-years of follow-up. The percentage of INR

results in the target range was not statistically significantly different between the

elderly and control groups (71.5% vs 66.1%) and the occurrences of incidences

of INR greater than 7 were 4.2% in the control group and 4.7% in the elderly

group (P=.96). The incidences of major hemorrhage were 2.8% per year in the

elderly group and 2.9% per year in the control group (P=.96); overall incidence

was 2.8% (95% confidence interval, 1.3%-4.4%). One hundred one of the 328

patients studied commenced warfarin therapy during or within 3 months of the

start of the study. In this induction group, 62.1% of INRs were within the target

range compared with 70.9% of INRs in patients who had been receiving warfarin

therapy for more than 3 months at the start of the study (P=.002). The incidences

of INR greater than 7 and major hemorrhage were 7.9% per year and 6.9% per

year, respectively, in the cohort who recently began warfarin therapy compared

with 3.4% per year and 1.7% per year in the group who were receiving warfarin

therapy for more than 3 months. Conclusion: While it was impossible to consider

any selection bias at the level of referral to the clinic, these findings suggest that

the elderly population attending our anticoagulant clinic did not have poorer

anticoagulant control or an increased incidence of hemorrhage while receiving

warfarin therapy



Keywords: anticoagulant/anticoagulation/ARCH/atrial

fibrillation/CHICAGO/complications/control/elderly/elderly

patients/fibrillation/hemorrhage/hospital/incidence/incidences/INR/international

normalized ratio/population/risk/sodium/stroke/STROKE

PREVENTION/THERAPY/TRIAL/WARFARIN



Seshadri, S., Wolf, P.A., Beiser, A., Vasan, R.S., Wilson, P.W.F., Kase, C.S.,

Kelly-Hayes, M., Kannel, W.B. and D'Agostino, R.B. (2001), Elevated midlife

blood pressure increases stroke risk in elderly persons - The framingham study.

Archives of Internal Medicine, 161 (19), 2343-2350.



Abstract: Background: Stroke risk predictions are traditionally based on current blood

pressure (13P). The potential impact of a subject's past BP experience

(antecedent BP) is unknown. We assessed the incremental impact of antecedent

BP on the risk of ischemic stroke. Methods: A total of 5197 stroke-free subjects

(2330 men) in the community-based Framingham Study cohort were enrolled

from September 29, 1948, to April 25, 1953, and followed up to December 31,

1998. We determined the 10-year risk of completed initial ischemic stroke for

60-, 70-, and 80- year-old subjects as a function of their current BP (at baseline),

recent antecedent BP (average of readings at biennial examinations 1-9 years

before baseline), and remote antecedent BP (average at biennial examinations

10-19 years earlier), with adjustment for smoking and diabetes mellitus. Models

incorporating antecedent BP were also adjusted for baseline BP. The effect of

each BP component (systolic 13P, diastolic BP, and pulse pressure) was assessed

separately. Results: Four hundred ninety-one ischemic strokes (209 in men) were

observed in eligible subjects. The antecedent BP influenced the 10-year stroke

risk at the age of 60 years (relative risk per SD increment of recent antecedent

systolic BP: women, 1.68 [95% confidence interval, 1.25-2.25]; and men, 1.92

[95% confidence interval, 1.39-2.66]) and at the age of 70 years (relative risk per

SD increment of recent antecedent systolic BP: women, 1.66 [95% confidence

interval, 1.28-2.14]; and men, 1.30 [95% confidence interval, 0.97-1.75]). This

effect was evident for recent and remote antecedent BP, consistent in

hypertensive and nonhypertensive subjects, and demonstrable for all BP

components. Conclusions: Antecedent BP contributes to the future risk of

ischemic stroke. Optimal prevention of late-life stroke will likely require control

of midlife BP



Keywords: age/ARCH/blood

pressure/CARDIOVASCULAR-DISEASE/CHICAGO/COHORT/control/diabet

es/diabetes

mellitus/elderly/HEART-DISEASE/HYPERTENSION/ischemic/ischemic

stroke/men/MORTALITY/prevention/PROFILE/pulse pressure/REGRESSION

DILUTION/relative risk/risk/smoking/stroke/TRENDS/women



McCormick, D., Gurwitz, J.H., Goldberg, R.J., Becker, R., Tate, J.P., Elwell, A. and

Radford, M.J. (2001), Prevalence and quality of warfarin use for patients with

atrial fibrillation in the long-term care setting. Archives of Internal Medicine, 161

(20), 2458-2463.



Abstract: Background: Evidence-based clinical practice guidelines recommend the use

of warfarin sodium for stroke prevention in most patients with atrial fibrillation

(AF) who do not have risk factors for hemorrhagic complications, irrespective of

age. Methods: The medical records of all residents of a convenience sample of

long-term care facilities in Connecticut (n=21) were reviewed. The percentages

of all patients with AF (AF patients) and ideal candidates for warfarin therapy (ie,

AF patients with no risk factors for hemorrhage) who received warfarin were

determined; for patients receiving warfarin, the percentage of days spent in the

therapeutic range of international normalized ratio (INR) values (2.0-3.0) was

also assessed. The relationship between receipt of warfarin and the presence of

stroke and bleeding risk factors was assessed in multivariate models. Results:

Atrial fibrillation was present in 429 (17%) of the 2587 long-term care residents.

Overall, 42% of AF patients were receiving warfarin. However, only 44 (53%) of

83 ideal candidates were receiving this therapy. In residents who received

warfarin therapy, the therapeutic range of INR values was maintained only 51%

of the time. The odds of receiving warfarin in the study sample decreased with

increasing number of risk factors for bleeding and increased (nonsignificant

trend) with increasing number of stroke risk factors present. Conclusions: Atrial

fibrillation is very common among residents of long-term care facilities. Even

among apparently ideal candidates, warfarin therapy is underused for stroke

prevention in patients with AF. Prescribing decisions and monitoring related to

warfarin therapy in the long-term care setting warrant improvement



Keywords: AF/age/ANTITHROMBOTIC THERAPY/ARCH/atrial

fibrillation/bleeding/CHICAGO/clinical

practice/COMPLICATIONS/ELDERLY

PATIENTS/fibrillation/GUIDELINES/hemorrhage/INR/international normalized

ratio/medical/monitoring/NATIONAL PATTERNS/ORAL

ANTICOAGULANT-THERAPY/PHYSICIAN ATTITUDES/practice

guidelines/prevention/risk/risk

factors/RISK-FACTORS/sodium/stroke/STROKE

PREVENTION/therapy/UNDERUTILIZATION/use/warfarin/warfarin sodium



Qureshi, A.I., Suri, M.F.K., Guterman, L.R. and Hopkins, L.N. (2001), Ineffective

secondary prevention in survivors of cardiovascular events in the US population

- Report from the Third National Health and Nutrition Examination Survey.

Archives of Internal Medicine, 161 (13), 1621-1628.

Abstract: Background: Survivors of myocardial infarction (MI) or stroke are at high risk

for subsequent cardiovascular events. There is limited assessment of the

effectiveness of risk factor modification through current secondary preventive

strategies in the US population. We determined the adequacy of risk factor

modification in 1252 survivors of MI, stroke, or both in a nationally

representative sample of US adults and identified factors related to inadequate

control of risk factors. Methods: The adequacy of control for hypertension,

diabetes mellitus, cigarette smoking, alcohol use, and hypercholesterolemia was

assessed by personal interview, blood pressure measurements, and serum

glycosylated hemoglobin and cholesterol levels in 17752 US adults who

participated in the Third National Health and Nutrition Examination Survey

between 1988 and 1994. We also evaluated the role of potentially related factors,

including age, sex, race/ethnicity, educational attainment, socioeconomic status,

and medical insurance status using multivariate logistic regression analysis.

Results: Of 738 known hypertensive persons, hypertension was uncontrolled in

388 (53%). Previously undiagnosed hypertension was detected in 138 others

(11%). Of 289 diabetic persons, serum glucose control was inadequate in 141. Of

1252 survivors, 225 (18%) were currently smoking, and heavy alcohol use was

observed in 56 persons. Hypercholesterolemia was poorly controlled in 185

(46%) of 405 persons with known hypercholesterolemia. Undetected

hypercholesterolemia was observed in 160 persons (13%). In the multivariate

analysis, high-risk profiles were more likely to be observed in persons aged 46 to

65 years, women, and African Americans. Conclusions: High prevalence of

inadequate secondary prevention was found in a subset of the US population at

highest risk for stroke and MI. Considerable efforts are required to effectively

implement risk factor modification strategies after MI or stroke, particularly in

middle-aged persons, African Americans, and women



Keywords: adults/African Americans/age/aged/alcohol/ARCH/ARTERY

DISEASE/blood pressure/cardiovascular/cardiovascular

events/CHICAGO/cholesterol/CHOLESTEROL-EDUCATION-PROGRAM/cig

arette smoking/control/CORONARY HEART-DISEASE/diabetes/diabetes

mellitus/DRUG PROJECT/FOLLOW-UP/glucose/hemoglobin/high

risk/hypercholesterolemia/hypertension/infarction/medical/multivariate

analysis/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/population/prevalence/prevention/ris

k/risk factor/risk factors/RISK- FACTORS/secondary/secondary

prevention/serum/sex/smoking/SMOKING CESSATION/socioeconomic

status/status/STROKE/UNITED- STATES ADULTS/use/women



Koffman, D.M., Bazzarre, T., Mosca, L., Redberg, R., Schmid, T. and Wattigney, W.A.

(2001), An evaluation of choose to move 1999 - An American Heart Association

physical activity program for women. Archives of Internal Medicine, 161 (18),

2193-2199.



Abstract: Background: Rates of physical inactivity and poor nutrition, which are 2 of the

most important modifiable risk factors for cardiovascular disease in women, are

substantial. Even so, studies of interventions designed to improve lifestyle

behaviors in women have been limited and often confined to particular

geographical areas. Objective: To evaluate the effect of Choose to Move on

increasing women's physical activity, improving their knowledge of heart disease

and stroke, and improving their nutrition. Participants and Methods: A

prospective, nonrandomized, 12-week educational intervention designed by the

American Heart Association for women across the United States. Participants

received a welcome kit and manual with weekly information about how to

manage cardiovascular disease risk factors and how to build a support system for

lifestyle change. Women (N = 23171) aged 25 years or older were recruited by

direct mail, the media, health care providers, and other means. Follow-up

evaluations were returned from 6389 women at 2 weeks, 5338 at 4 weeks, 4209

at 8 weeks, 3916 at 10 weeks, and 3775 at 12 weeks. Participants self- reported

their physical activity, diet, and knowledge about heart disease, stroke, and

related symptoms. Results: Ninety percent of the participants were white and

56% were aged between 35 and 54 years. Among the participants who completed

the week 12 follow-up evaluation, the percentage who reported being active (at

least moderate exercise greater than or equal to5 times per week or > 21/2 hours

per week for the past 1 to 6 months) increased from 32% at baseline to 67% at

the program's end (P=.001). Participants currently limiting excess calories or fat

increased from 72% to 91% at week 10 follow-up evaluation (P=.001). The

proportion correctly identifying heart disease as the leading cause of death

increased from 84% to 91% at week 10 follow-up evaluation (P 30 days but 80%) classified by Doppler criteria was twice

as frequent in men (2.4%) as in women (1.1%). Age and sex were found to be

particularly strong and independent predictors of asymptomatic carotid artery

disease. Accordingly, separate logistic regression models were developed for

both men and women in the elderly (65-79 years) and middle-aged (50-64 years)

groups. Systolic blood pressure turned out to be the only attribute with

independent significance in all subgroups examined. Cigarette smoking, recorded

as pack-years, emerged as the leading risk factor of carotid atherosclerosis in

men. Serum fibrinogen levels were found to be highly indicative of carotid artery

disease in elderly men and women. For apolipoprotein B predictive significance

was observed in the middle-aged populations, whereas apolipoprotein A-I had a

protective effect in elderly women. Diabetes mellitus completed the risk factor

profile for elderly men. In summary, the relation between cardiovascular risk

factors and asymptomatic carotid artery disease showed a dynamic dependence

on sex and age. These findings may help to improve the efficacy of risk

prediction in the general population and facilitate well-directed preventive

measures



Keywords: APOLIPOPROTEIN-B/B-MODE

ULTRASOUND/BLOOD-PRESSURE/CAROTID

ATHEROSCLEROSIS/CIGARETTE- SMOKING/DENSITY-LIPOPROTEIN

CHOLESTEROL/DISEASE/EPIDEMIOLOGY/HEART/MYOCARDIAL-INF

ARCTION/PLASMA-FIBRINOGEN/RISK

FACTORS/STENOSIS/STROKE/ULTRASOUND



Benderly, M., Graff, E., ReicherReiss, H., Behar, S., Brunner, D. and Goldbourt, U.

(1996), Fibrinogen is a predictor of mortality in coronary heart disease patients.

Arteriosclerosis Thrombosis and Vascular Biology, 16 (3), 351-356.

Abstract: Results of epidemiological studies have indicated that fibrinogen is an

important primary cardiovascular risk factor. The role of fibrinogen as a

predictor of mortality in coronary heart disease (CHD) patients is unclear. We

investigated the association between fibrinogen and mortality in a large cohort of

CHD patients screened for participation in a secondary prevention clinical trial.

Of the total investigated, 3092 men who were not included in the trial and for

whom vital status was known were followed up for a mean period of 3.2 years.

In 54.4% of the 111 men who died, mortality was attributed to CHD. Mean

baseline plasma fibrinogen levels were 29.4 mg/dL higher in patients who died

than in the survivors. All-cause and CHD mortality rates increased with

increasing fibrinogen levels. This relationship was also demonstrated within

categories of the primary variables predicting mortality in these patients. The

contribution of fibrinogen to CHD and all-cause mortality was assessed by

multivariate analysis adjusting for age, CHD severity, and comorbidity. Risks of

CHD and all-cause mortality for patients in the highest fibrinogen tertile were

1.67 and 1.75, respectively, relative to patients in the lowest tertile, and an

increase of about 1 SD of plasma fibrinogen level (75 mg/dL) was found to

increase risk of CHD and all-cause mortality by 29% and 31%, respectively.

These results indicate clearly that fibrinogen level is associated with significantly

increased mortality in CHD patients. Implementation of a standardized

measuring method is required to allow assessment of risk in CHD patients on the

basis of fibrinogen levels



Keywords: comorbidity/coronary disease/coronary heart

disease/DENSITY-LIPOPROTEIN

CHOLESTEROL/fibrinogen/heart/HEMOSTATIC

FUNCTION/mortality/MYOCARDIAL-INFARCTION/prevention/prospective

study/risk/risk factors/RISK-FACTORS/secondary prevention/severity/STROKE



Schmidt, H., Schmidt, R., Niederkorn, K., Horner, S., Becsagh, P., Reinhart, B.,

Schumacher, M., Weinrauch, V. and Kostner, G.M. (1998), beta-fibrinogen gene

polymorphism (C-148 -> T) is associated with carotid atherosclerosis - Results

of the Austrian Stroke Prevention Study. Arteriosclerosis Thrombosis and

Vascular Biology, 18 (3), 487-492.



Abstract: Polymorphisms at the beta-fibrinogen locus have been shown to be associated

with plasma concentration of fibrinogen and coronary heart disease. The effect of

the genetic heterogeneity of fibrinogen on carotid atherosclerosis has not been

determined so far. We examined the: influence of the C-148 --> T polymorphism

on carotid disease in a large cohort of middle- aged to elderly subjects without

evidence of neuropsychiatric disease. This polymorphism is located close to the

consensus sequence of the interleukin-6 element and may represent a functional

sequence variant. The genotype of 399 randomly selected, neurologically

asymptomatic individuals, aged 45 to 75 years, was determined by denaturing

gradient gel electrophoresis. Carotid atherosclerosis was assessed by color-

coded duplex scanning and was graded on a five-point scale ranging from 0

(=normal) to 5 (=complete luminal obstruction). The C/C, C/T, and T/T

genotypes were noted in 226 (56.6%), 148 (37.1%), and 25 (6.3%) individuals,

respectively. The T/T genotype soup demonstrated higher grades of carotid

atherosclerosis than did the C/C and C/T genotypes (P=.003). Logistic regression

analysis created a model of independent predictors of carotid atherosclerosis that

included apolipoprotein B (odds ratio [OR], 1.17/10 mg/dL), age (OR, 2.46/10

years), lifetime tobacco consumption (OR, 1.03/1000 g), presence of the

beta-fibrinogen promoter T/T genotype (OR, 6.17), plasma fibrinogen

concentration (OR, 1.05/10 mg/dL), and cardiac disease (OR, 1.80). These data

suggest that the beta- fibrinogen promoter T/T148 genotype represents a genetic

risk factor for carotid atherosclerosis in the middle-aged to elderly



Keywords: age/aged/ARTERY

ATHEROSCLEROSIS/atherosclerosis/CARDIOVASCULAR

RISK-FACTORS/carotid/carotid arteries/consensus/coronary heart

disease/DETERMINANTS/duplex

scanning/elderly/fibrinogen/genetic/genetics/heart/ISCHEMIC-HEART-DISEAS

E/LOCUS/MYOCARDIAL-INFARCTION/PLASMA-

FIBRINOGEN/POPULATION/predictors/PREVALENCE/risk/tobacco/VARIA

BILITY



Schmidt, R., Schmidt, H., Fazekas, F., Kapeller, P., Roob, G., Lechner, A., Kostner,

G.M. and Hartung, H.P. (2000), MRI cerebral white matter lesions and

paraoxonase PON1 polymorphisms - Three-year follow-up of the Austrian stroke

prevention study. Arteriosclerosis Thrombosis and Vascular Biology, 20 (7),

1811-1816.



Abstract: White matter lesions (WMLs) on magnetic resonance imaging (MRI) scans of

older persons are thought to be caused by cerebral small-vessel disease. As they

progress, these brain abnormalities frequently result in cognitive decline and gait

disturbances, and their predictors are incompletely understood. Genetic risk

factors have been implicated but remain undetermined so far. We examined

whether 2 common polymorphisms of the paraoxonase (PON1) gene leading to a

methionine (M allele)-leucine (L allele) interchange at position 54 and an

arginine (B allele)-glutamine (A allele) interchange at position 191 are associated

with the presence and progression of WMLs. We studied 264

community-dwelling subjects without neuropsychiatric disease (ages 44 to 75

years). All underwent vascular risk factor assessment, brain MRI, and PON1

genotyping. MRI scanning was repeated after 3 years. The extent and number of

WMLs were recorded by 3 independent readers. Progression of WMLs was

assessed by direct scan comparison. The final rating relied on the majority

judgment of the 3 readers. The LL, LM, and MM genotypes were noted in 111

(42.0%), 118 (44.7%), and 35 (13.3%) subjects, respectively; the AA, AB, and

BE genotypes occurred in 146 (55.3%), 98 (37.1%), and 20 (7.8%) individuals,

respectively. Carriers of the LL genotype showed a nonsignificant trend toward

more extensive WMLs and more frequently demonstrated lesion progression

over the 3-year observation period (P = 0.03), The polymorphism at position 191

had no effect. Logistic regression analysis yielded age (odds ratio, 1.08/y),

diastolic blood pressure (odds ratio, 1.05/mm Hg), and LL paraoxonase genotype

(odds ratio, 2.65) to be significant predictors of WML progression. These data

suggest that the LL PON1 genotype at position 54 influences the extent and

progression of WMLs in elderly subjects



Keywords: ABNORMALITIES/age/ATHEROSCLEROSIS/Austria/blood

pressure/brain/CARDIOVASCULAR-DISEASE/cerebral/cerebral small-vessel

disease/CORONARY HEART-DISEASE/diastolic blood

pressure/disease/elderly/GENE/genetics/HYPERINTENSITIES/LOW-DENSIT

Y-LIPOPROTEIN/magnetic resonance imaging/MRI/OLDER

ADULTS/paraoxonase/predictors/prevention/risk/risk factor/risk factors/RISK-

FACTORS/SERUM PARAOXONASE/stroke/stroke prevention/vascular/white

matter/white matter lesions



Leppala, J.M., Virtamo, J., Fogelholm, R., Huttunen, J.K., Albanes, D., Taylor, P.R. and

Heinonen, O.P. (2000), Controlled trial of alpha-tocopherol and beta-carotene

supplements on stroke incidence and mortality in male smokers. Arteriosclerosis

Thrombosis and Vascular Biology, 20 (1), 230-235.



Abstract: Observational data suggest that diets rich in fruits and vegetables and with

high serum levels of antioxidants are associated with decreased incidence and

mortality of stroke. We studied the effects of alpha-tocopherol and beta-carotene

supplementation. The incidence and mortality of stroke were examined in 28 519

male cigarette smokers aged 50 to 69 years without history of stroke who

participated in the Alpha- Tocopherol, Beta-Carotene Cancer Prevention Study

(ATBC Study). The daily supplementation was 50 mg alpha-tocopherol, 20 mg

beta-carotene, bath, or placebo. The median follow-up was 6.0 years. A total of

1057 men suffered from incident stroke: 85 men had subarachnoid hemorrhage;

112, intracerebral hemorrhage; 807, cerebral infarction; and 53, unspecified

stroke. Deaths due to stroke within 3 months numbered 38, 50, 65, and 7,

respectively (total 160). alpha-Tocopherol supplementation increased the risk of

subarachnoid hemorrhage 50% (95% CI - 3% to 132%, P = 0.07) but decreased

that of cerebral infarction 14% (95% CI -25% to - 1%, P = 0.03), whereas

beta-carotene supplementation increased the risk of intracerebral hemorrhage

62% (95% CI 10% to 136%, P = 0.01). alpha-Tocopherol supplementation also

increased the risk of fatal subarachnoid hemorrhage 181% (95% CI 37% to

479%, P = 0.01). The overall net effects of either supplementation on the

incidence and mortality from total stroke were nonsignificant. alpha- Tocopherol

supplementation increases the risk of fatal hemorrhagic strokes but prevents

cerebral infarction. The effects may be due to the antiplatelet actions of alpha-

tocopherol. beta-Carotene supplementation increases the risk of intracerebral

hemorrhage, but no obvious mechanism is available



Keywords: aged/alpha-tocopherol/antioxidants/antiplatelet/ATHEROSCLEROTIC

PLAQUE/beta

carotene/beta-carotene/CARDIOVASCULAR-DISEASE/cerebral/cerebral

infarction/Finland/hemorrhage/history/incidence/infarction/intracerebral/intracer

ebral hemorrhage/LASER/MEN/mortality/PLASMA/PLATELET-

FUNCTION/risk/serum/stroke/stroke incidence/subarachnoid

hemorrhage/trial/VITAMIN-C



Durrington, P.N., Mackness, B. and Mackness, M.I. (2001), Paraoxonase and

atherosclerosis. Arteriosclerosis Thrombosis and Vascular Biology, 21 (4),

473-480.



Abstract: There is considerable evidence that the antioxidant activity of high density

lipoprotein (HDL) is largely due to the paraoxonase-1(PON1) located on it.

Experiments with transgenic PON1 knockout mice indicate the potential for

PON1 to protect against atherogenesis. This protective effect of HDL against low

density lipoprotein (LDL) lipid peroxidation is maintained longer than is the

protective effect of antioxidant vitamins and could thus be more important. There

is evidence that the genetic polymorphisms of PON1 least able to protect LDL

against lipid peroxidation are overrepresented in coronary heart disease,

particularly in association with diabetes. However, these polymorphisms explain

only part of the variation in serum PON1 activity; thus, a more critical test of the

hypothesis is likely to be whether low serum PON1 activity is associated with

coronary heart disease. Preliminary case-control evidence suggests that this is

indeed the case and, thus, that the quest for dietary and pharmacological means

of modifying serum PON1 activity may allow the oxidant model of

atherosclerosis to be tested in clinical trials



Keywords: ACUTE-PHASE RESPONSE/antioxidant/antioxidant

vitamins/APOLIPOPROTEIN-A-I/atherogenesis/atherosclerosis/AUSTRIAN

STROKE PREVENTION/BINDING CASSETTE

TRANSPORTER-1/CHOLESTERYL ESTER

TRANSFER/CHRONIC-RENAL-FAILURE/clinical trials/coronary heart

disease/CORONARY-ARTERY DISEASE/DEPENDENT

DIABETES-MELLITUS/diabetes/disease/England/genetic/GULF-WAR

VETERANS/HDL/heart/heart disease/high density lipoprotein/high density

lipoproteins/HIGH-DENSITY-LIPOPROTEIN/LDL/lipid peroxidation/low

density lipoprotein/paraoxonase/serum/trials/vitamins



Herrington, D.M., Vittinghoff, E., Howard, T.D., Major, D.A., Owen, J., Reboussin,

D.M., Bowden, D., Bittner, V., Simon, J.A., Grady, D. and Hulley, S.B. (2002),

Factor V Leiden, hormone replacement therapy, and risk of venous

thromboembolic events in women with coronary disease. Arteriosclerosis

Thrombosis and Vascular Biology, 22 (6), 1012-1017.



Abstract: Oral contraceptive use in women with factor V Leiden is associated with

increased rates of venous thromboembolic events (VTEs). However, the effects

of hormone replacement therapy (HRT) in postmenopausal women with factor V

Leiden are not known. A nested case-control study was conducted among

women with established coronary disease enrolled in 2 randomized clinical trials

of HRT, the Heart and Estrogen/Progestin Replacement Study (HERS) and the

Estrogen Replacement and Atherosclerosis (ERA) trial. The Leiden mutation

was present in 8 (16.7%) of 48 cases with VTE compared with only 7 (6.3%) of

112 controls (odds ratio [OR](Leiden) 3.3, 95% Cl 1.1 to 9.8; P=0.03). In women

without the factor V Leiden mutation, risk associated with HRT use was

significantly increased (ORHRT 3.7, 95% Cl 1.4 to 9.4; P5

such lesions), MRS showed relative reduction of NA peaks, Although no patient

was studied when acutely ill, prior neurologic involvement was related to

abnormal findings. Conclusion. MRI and MRS are helpful in the investigation of

cerebral complications of SLE, There are chronic changes which may be

ischemic in nature, Their precise cause, consequences, and prevention are current

challenges



Keywords: ACUTE

STROKE/ARTHRITIS/brain/cerebral/CHOLINE/complications/control/CRANI

AL COMPUTERIZED-TOMOGRAPHY/DISEASE/HIV-

INFECTION/INVIVO/ischemic/LESIONS/magnetic resonance

imaging/MANIFESTATIONS/METABOLITES/MR/MRI/NEUROPSYCHIAT

RIC LUPUS/prevention/white matter/women



Goodman, T.A., Merkel, P.A., Perlmutter, G., Doyle, M.K., Krane, S.M. and Polisson,

R.P. (1997), Heterotopic ossification in the setting of neuromuscular blockade.

Arthritis and Rheumatism, 40 (9), 1619-1627.



Abstract: Objective, Heterotopic ossification (HO) is a disorder characterized by the

formation of new bone in tissue that does not ossify under normal conditions, We

report a series of 6 cases in which HO occurred in the setting of adult respiratory

distress syndrome (ARDS). We wished to show that HO can occur after

neuromuscular blockade and that these cases might provide additional evidence

that HO is influenced by neural mechanisms, Methods, Cases of HO were

selected from the consultation services at the Massachusetts General Hospital

and the Brigham and Women's Hospital, Affected patients all had ARDS and had

been treated vith a neuromuscular blocking agent. Patients with a history of

stroke, burn, head trauma, spinal cord injury, or joint replacement were excluded

from this study, Results. Heterotopic bone appeared around large joints in a

pattern identical to that seen in patients with paralysis, traumatic brain injury,

severe burns, or trauma, New bone formation was self-limited over a period of

1-2 years, Alkaline phosphatase and technetium bone scan were sensitive ways

of detecting early disease and monitoring disease activity, Medical therapies had

limited benefit, Surgical excision of mature new bone appeared to be the only

definitive therapy. Conclusion. Neuromuscular blockade in the setting of ARDS

appears to be an important risk factor for the development of HO, The similarity

of these cases of HO occurring in patients with brain or spinal cord injury raises

the possibility that neural mechanisms may be important in the pathogenesis of

this disease. Whether the type of neuromuscular blocking agent and the duration

of use are important determinants of disease severity remains to be determined



Keywords:

ARTHRITIS/BONE-FORMATION/brain/development/DIFFERENTIATION/D

ISODIUM

ETIDRONATE/formation/FRUIT/GROWTH/history/INJURY/MYOSITIS-OSS

IFICANS/PREVENTION/risk/severity/spinal cord injury/stroke/therapy

Barnett, H.J.M. (1991), Clinical-Trials in Stroke Prevention.

Arzneimittel-Forschung/Drug Research, 41-1 (3A), 340-344.



Abstract: The randomized clinical trial has no satisfactory substitute in the evaluation of

preventive treatment for stroke-threatened patients, and is the gold standard also

in studies designed to test strategies which may reduce the impact of brain

damage after ischemic stroke has occurred. Stroke data banks and contemporary

non-randomized comparisons are imperfect or flawed as bench-marks against

which to judge treatments for these types of patients. Flaws in the design,

execution and analysis of randomized clinical trials have been eliminated

gradually over the past 35 years. On the basis of the existing trials in stroke

prevention it may be stated that anticoagulants are effective in patients with

non-rheumatic atrial fibrillation and after myocardial infarction. No other uses of

anticoagulants in preventing ischemic stroke have been proven. Acetylsalicylic

acid between 325-1300 mg/d will prevent stroke; lower doses have not been

proven of value. Ticlopidine is effective. Benefit for dipyridamole, suloctidil or

sulfinpyrazone has not been shown. Cerebral by-pass surgery has not been

shown to have any role in stroke prevention in arteriosclerotic cerebral vascular

disease. Carotid endarterectomy is still undergoing careful evaluation



Keywords: ASPIRIN/CAROTID

ENDARTERECTOMY/CEREBRAL/CEREBRAL-ISCHEMIA/CLINICAL

TRIALS/INTRACRANIAL ARTERIAL BYPASS/ISCHEMIA/ISCHEMIC

STROKE/PREVENTION/PROGRESSION/RANDOMIZED

TRIAL/RISK/SECONDARY PREVENTION/THROMBOEMBOLIC

STROKE/TICLOPIDINE



Laragh, J.H. (1993), The Renin System and New Understanding of the Complications of

Hypertension and Their Treatment. Arzneimittel-Forschung/Drug Research, 43-1

(2A), 247-254.



Abstract: The renin-angiotensin-aldosterone hormonal axis is the major long-term

servocontrol for regulation of both arterial blood pressure and sodium balance. It

supports normotension or hypertension via angiotensin vasoconstriction and

angiotensin plus aldosterone-induced renal sodium retention. Normally, in the

presence of hypertension or sodium-volume excess, plasma renin activity

promptly falls to zero. Accordingly, any renal secretion of renin in the face of

high blood pressure is abnormal. In established essential hypertension varying

degrees of abnormal plasma renin activity operate to cause or sustain the

hypertension; only very low plasma renin values reflect a normal renal response.

Human hypertensive disorders comprise a spectrum of abnormal plasma

renin-sodium volume products. High renin, intensely vasoconstricted,

hypovolemic forms (e.g., malignant, renovascular) are one extreme of the

spectrum, ''wet''-volume-excess low-renin forms are the other extreme (eg,

primary aldosteronism, low-renin essential hypertension). These varying, but

abnormal renin-sodium products are caused by a renal lesion in which a

subpopulation of ischemic nephrons hypersecretes renin and retains sodium

despite systemic hypertension and sodium excess. Thus, hypertensive patients

cannot suppress their renin secrection normally. The hypertension from this renal

lesion is correctable by agents that reduce renin secretion or block its effect (beta

blockade, CEI, renin inhibition, or angiotensin II antagonism). None of these

agents lower blood pressure after binephrectomy, verifying the renal origin of

renin in the cardiovascular control system. In essential hypertension, the plasma

renin level appears as a continuous variable associated with greater risk of

ischemic injury. With higher renin levels, vascular injury to heart, brain and

kidneys occurs in humans and is readily produced in animal models. Conversely,

patients with lower plasma renin values are protected from heart attack and

stroke despite even higher pressures and greater age. The near future holds

considerable potentials for the ultimate goal of prevention of cardiovascular

injury (heart attack and stroke), utilizing explicit strategies to contain

inappropriate plasma renin activity. In this light the modern evaluation of the

hypertensive patient includes a baseline plasma renin assay among ten important

tests. This accurate test reliably screens for curable forms of hypertension,

evaluates the risk of morbid events (i. e., heart attack) and guides more specific

drug therapies



Keywords: ALDOSTERONE/ALDOSTERONE

SYSTEM/ANGIOTENSIN/BLOCKADE/COMPLICATIONS/CONVERTING-

ENZYME-INHIBITOR/HEART

ATTACK/HYPERTENSION/MYOCARDIAL-INFARCTION/PRAZOSIN/RE

NIN/RENIN-MEDIATED/RENIN-SODIUM

RECIPROCALITY/RENINANGIOTENSIN

SYSTEM/SARALASIN/SECRETION/STROKE/VASCULAR DAMAGE



Heyden, S. (1988), Risk Factor Detection and Intervention in the Prevention of

Cardiovascular-Diseases - No Influence of Cholesterol Reduction on the Stroke

Rate and No Influence of Isolated Treatment of Hypertension on the Chd Rate.

Arztliche Laboratorium, 34 (12), 341-344



Keywords: COMMUNITY/FAMILY



Kieu, N.T.M., Yasugi, E., Lien, D.T.K., Anh, N.T.L., Do, T.T., Khoi, H.H., Kido, T.,

Kondo, K., Itakura, H., Van Chuyen, N., Yamamoto, S. and Oshima, M. (2000),

Serum fatty acids, lipoprotein(a) and apolipoprotein composition of rural,

suburban and urban populations in North Vietnam. Asia Pacific Journal of

Clinical Nutrition, 9 (2), 62-66.



Abstract: This study was conducted to investigate the concentrations of serum fatty acids,

lipoprotein(a) and apolipoprotein of three populations in North Vietnam: rural

area with low income (n = 101), suburban with average income (n = 97), and

urban with high income (n = 95). The results showed the suburban and urban

populations had higher fat intake than the rural. The fat intake in quality was

different in these three populations. The suburban had the highest consumption

of fatty foods rich in n-6 polyunsaturated fatty acid (PUFA). The rural consumed

more fatty foods rich in monounsaturated fatty acid (MUFA), but less fatty foods

rich in n-3 PUFA than the two other populations. The high index of

thrombogenicity (IT) of the Vietnamese diet may result from their low intake of

fish and vegetable oils. Risk factors for premature cardiovascular disease (CVD)

assessed by serum Lipoprotein(a) and apolipoprotein levels were not observed in

all three populations. However, coronary heart disease (CHD) and stroke are

problems that should be monitored because the increase of CVD morbidity has

been reported in Vietnamese people. From a nutritional point of view, the

increase of fish and vegetable oils consumption is necessary for the prevention of

CVD and CHD in these Vietnamese populations



Keywords: apolipoprotein/AUSTRALIA/cardiovascular/cardiovascular disease/coronary

heart disease/CORONARY HEART-DISEASE/diet/dietary pattern/fat

consumption/fatty acid/heart/heart

disease/lipoprotein(a)/morbidity/prevention/serum/stroke/urban/vegetable



McBurney, M.I. (2001), Candidate foods in the Asia-Pacific region for cardiovascular

protection: relevance of grains and grain-based foods to corollary heart disease.

Asia Pacific Journal of Clinical Nutrition, 10 (2), 123-127.



Abstract: This review elucidates the importance of healthy dietary and lifestyle habits to

reduce morbidity and mortality associated with coronary heart disease (CHD),

stroke and cardiovascular diseases. Given published evidence of the poor

compliance, increased cost, and decreased benefit/risk ratios of medical therapies,

individuals (and populations) are encouraged to adopt healthy life habits. The

three most atherogenic dietary risk factors are saturated fat, cholesterol and

obesity. Dietary patterns associated with the consumption of grains and grain

based foods predict risk of CHD independently of other life habits.

Epidemiological and intervention studies elucidating the strong protective

associations of grains, cereal fibers and anti-oxidant vitamins on CHD are

reviewed. In summary, the consumption of grains and grain-based cereals is

repeatedly associated with the ingestion of many nutrients, e.g., dietary fiber and

anti-oxidants, that alter energy balance and nutrient intakes to positively affect

cardiovascular health, especially when combined with healthy life habits



Keywords: ALPHA-TOCOPHEROL/antioxidant/antioxidant

vitamins/antioxidants/AUSTRALIA/BREAKFAST

CEREAL/cardiovascular/cardiovascular disease/cardiovascular

diseases/cardiovascular health/CAROTENE CANCER

PREVENTION/cereal/CHD/cholesterol/CHOLESTEROL-LOWERING

THERAPY/coronary heart disease/cost/dietary fiber/disease/diseases/EVENT

RATES/fiber/folic acid/health/heart/heart disease/homocysteine/intervention

studies/lifestyle/medical/MONICA PROJECT

POPULATIONS/morbidity/mortality/MYOCARDIAL-INFARCTION/obesity/P

LASMA HOMOCYST(E)INE/protection/review/risk/risk factors/RISK

REDUCTION/SERUM- CHOLESTEROL/stroke/vitamins

Newnham, J.P., Moss, T.J., Nitsos, I., Sloboda, D.M. and Challis, J.R. (2002), Nutrition

and the early origins of adult disease. Asia Pacific Journal of Clinical Nutrition,

11 S537-S542.



Abstract: There is now overwhelming evidence that much of our predisposition to adult

illness is determined by the time of birth. These diseases appear to result from

interactions between our genes, our intrauterine environment and our postnatal

lifestyle. Those at greatest risk are individuals in communities making a rapid

transition from lives of 'thrift' to a lives of 'plenty'. From a global perspective,

such origins of diabetes, coronary heart disease and stroke, should render

research in these fields as one of the highest priorities in human health care.

Prevention will be enhanced by elucidation of the mechanisms by which the

fetus is programmed by the mother for the life she expects it to live. At the

present time, there is evidence that fetal nutrition and premature exposure to

cortisol are effective intrauterine triggers, but a multitude of alternative pathways

require investigation. It is also likely that programming extends across

generations, and may involve the embryo and perhaps the oocyte. An oocyte that

becomes an adult human develops in the uterus of its grandmother, so further

research is required to describe the role of environments of grandmothers and

mothers in predisposing offspring to health or illness in adult life



Keywords: 11-BETA-HYDROXYSTEROID

DEHYDROGENASE/Australia/BLOOD-PRESSURE/cardiovascular

disease/coronary heart disease/diabetes/diabetes

mellitus/disease/diseases/EARLY ATHEROSCLEROTIC

LESIONS/environment/FETAL/fetus/genes/GLUCOCORTICOID

EXPOSURE/GROWTH-FACTOR (IGF)-I/health/health care/heart/heart

disease/human/INSULIN/LATE-GESTATION/LATER

LIFE/lifestyle/MATERNAL

HYPERCHOLESTEROLEMIA/mechanisms/nutrition/pregnancy/research/risk/s

troke/triggers



Serfatylacrosniere, C., Civeira, F., Lanzberg, A., Isaia, P., Berg, J., Janus, E.D., Smith,

M.P., Pritchard, P.H., Frohlich, J., Lees, R.S., Barnard, G.F., Ordovas, J.M. and

Schaefer, E.J. (1994), Homozygous Tangier-Disease and Cardiovascular-Disease.

Atherosclerosis, 107 (1), 85-98.



Abstract: Decreased levels of plasma high density lipoprotein (HDL) cholesterol have

been associated with premature cardiovascular disease (CVD). Tangier disease is

an autosomal co-dominant disorder in which homozygotes have a marked

deficiency of HDL cholesterol and apolipoprotein (ape) A-I levels (both .008, Fisher exact test). A

correlation exists between MCA(large-vessel) and conjunctival (small-vessel)

flow velocities. CAIM is a noninvasive quantitative technique that might

contribute to the identification of SCD patients at high risk of stroke. Small-

vessel vasculopathy might be an important pathological indicator and should be

further explored in a large-scale study. (Blood. 2001;97:3401-3404) (C) 2001 by

The American Society of Hematology



Keywords: ANEMIA/BLOOD/cerebral/cerebral

artery/CHILDREN/disease/Doppler/Doppler ultrasonography/high risk/middle

cerebral artery/RISK/sickle cell disease/STROKE/TCD/transcranial/transcranial

Doppler/transcranial Doppler ultrasonography/ultrasonography/vessels



Pegelow, C.H., Macklin, E.A., Moser, F.G., Wang, W.C., Bello, J.A., Miller, S.T.,

Vichinsky, E.P., Debaun, M.R., Guarini, L., Zimmerman, R.A., Younkin, D.P.,

Gallagher, D.M. and Kinney, T.R. (2002), Longitudinal changes in brain

magnetic resonance imaging findings in children with sickle cell disease. Blood,

99 (8), 3014-3018.



Abstract: Children with sickle cell anemia (HbSS) are at high risk for neurologically

overt cerebral infarcts associated with stroke and neurologically silent cerebral

infarcts correlated with neuropsychometric deficit. We used complete magnetic

resonance imaging (MRI) histories from 266 HbSS children, aged 6 through 19

years, who were enrolled in the Cooperative Study of Sickle Cell Disease

(CSSCD) to examine silent infarct prevalence, localization, recurrence, and

progression. We report a baseline prevalence of 21.8%, marginally higher than

previously reported due to improved imaging technologies. Although we

observed no overall sex difference in prevalence, most lesions in girls occurred

before age 6, whereas boys remained at risk until age 10. Silent infarcts were

significantly smaller and less likely to be found in the frontal or parietal cortex

than were infarcts associated with stroke. Children with silent infarct had an

increased incidence of new stroke (1.03/100 patient years) and new or more

extensive silent infarct (7.06/100 patient-years) relative to stroke incidence

among all children in our cohort (0.54/100 patient-years). Both events were

substantially less frequent than the risk of stroke recurrence among children not

provided chronic transfusion therapy. Although chronic transfusion is known to

decrease occurrence of new silent infarcts and strokes in children with elevated

cerebral arterial blood flow velocity, further study is required to determine its

risk-benefit ratio in children with silent infarct and normal velocities. Until safe

and effective preventive strategies against infarct recurrence are discovered, MRI

studies are best reserved for children with neurologic symptoms,

neuropsychometric deficits, or elevated cerebral artery velocities. (Blood.

2002;99: 3014-3018). (C) 2002 by The American Society of Hematology



Keywords: age/aged/ANEMIA/arterial/BLOOD/blood flow/brain/brain magnetic

resonance imaging/cerebral/cerebral artery/children/chronic/chronic

transfusion/disease/flow velocity/high

risk/imaging/incidence/INFARCTION/magnetic resonance

imaging/MRI/prevalence/PREVENTION/progression/recurrence/RECURRENT

STROKE/RISK/sex/sickle cell anemia/sickle cell disease/stroke/stroke

incidence/stroke recurrence/symptoms/therapy/TRANSCRANIAL DOPPLER

ULTRASONOGRAPHY/transfusion/TRANSFUSIONS



Shibata, J., Hasegawa, J., Siemens, H.J., Wolber, E., Dibbelt, L., Li, D.C., Katschinski,

D.M., Fandrey, J., Jelkmann, W., Gassmann, M., Wenger, R.H. and Wagner, K.F.

(2003), Hemostasis and coagulation at a hematocrit level of 0.85: functional

consequences of erythrocytosis. Blood, 101 (11), 4416-4422.



Abstract: We have generated a transgenic mouse line that reaches a hematocrit

concentration of 0.85 due to constitutive overexpression of human erythropoietin

in an oxygen-independent manner. Unexpectedly, this excessive erythrocytosis

did not lead to thrombembolic complications in all investigated organs at any age.

Thus, we investigated the mechanisms preventing thrombembolism in this mouse

model. Blood analysis revealed an age-dependent elevation of reticulocyte

numbers and a marked thrombocytopenia that matched. the reduced

megakaryocyte numbers in the bone marrow. However, platelet counts were not

different from wild-type controls, when calculations were based on the

distribution (eg, plasma) volume, thereby explaining why thrombopoietin levels

did not increase in transgenic mice. Nevertheless, bleeding time was significantly

in creased in transgenic animals. A longitudinal investigation using computerized

thromboelastography revealed that thrombus formation was reduced with

increasing age from 1 to 8 months in transgenic animals. We observed that

increasing erythrocyte concentrations inhibited profoundly and reversibly

thrombus formation and prolonged the time of clot development, most likely due

to mechanical interference of red blood, cells with clot-forming platelets,

Transgenic animals showed in-creased nitric oxide levels in the blood that could

inhibit vasoconstriction and platelet activation. Finally, we observed that

plasmatic coagulation activity in transgenic animals was significantly decreased.

Taken together, our findings suggest that prevention of thrombembolic disease in

these erythrocytotic transgenic mice was due to functional consequences inherent

to increased eryhrocyte concentrations and a reduction of plasmatic coagulation

activity, the cause of which remains to be elucidated. (C) 2003 by The American

Society of Hematology



Keywords: activation/age/ALTITUDE/bleeding/bleeding

time/BLOOD/coagulation/complications/CONGENITAL

HEART-DISEASE/development/disease/EXPRESSION/formation/GENE/Germ

any/hematocrit/human/mechanisms/MICE OVEREXPRESSING

ERYTHROPOIETIN/nitric oxide/NITRIC-OXIDE/platelet/platelet

activation/platelets/POLYCYTHEMIA/prevention/RISK/STROKE/thrombus/tra

nsgenic mice/USA



Lind, S.E., Pearce, L.A., Feinberg, W.M. and Bovill, E.G. (1999), Clinically significant

differences in the International Normalized Ratio measured with reagents of

different sensitivities. Blood Coagulation & Fibrinolysis, 10 (5), 215-227.



Abstract: `The International Normalized Ratio (INR) system was introduced a decade

ago as a way of standardizing the results of prothrombin time testing for patients

taking oral anticoagulants. A strong emphasis has been placed upon using

thromboplastin reagents that are very sensitive to the effects of oral

anticoagulants upon the prothrombin time [i.e. reagents with low International

Sensitivity Index (ISI)]. In order to assess how well the INR system functions as

currently used in clinical laboratories, we compared the INRs determined using

thromboplastins of differing ISIs in samples collected during a large clinical trial

of oral anticoagulation for atrial fibrillation (Stroke Prevention in Atrial

Fibrillation III trial). Frozen plasma was subjected to prothrombin time testing

using thromboplastins with ISIs ranging from 0.97 to 2.49. INRs were calculated

using machine-specific ISIs and Westgard's rules were followed to maintain

quality control. An unanticipated coagulometer failure allowed a determination

of the effect of machine recalibration upon the INR of control plasmas. The

correlation between each pair of INRs obtained from 1181 plasmas was high (>

0.9), but the differences between reagents were statistically different from zero

(P(I)/alcohol/alpha-tocopherol/antioxidants/ATHEROGENESIS/atheroscl

erosis/BRAIN/CALCIUM/cerebral/cerebral

hemorrhage/CONTRACTION/coronary

disease/disease/ENGLAND/ETHANOL-INDUCED

ELEVATION/hemorrhage/intracellular free Mg2+

([Mg2+](i))/MAGNESIUM/MG2+/muscle/NEURONAL

LOSS/prevention/pyrrolidine dithiocarbamate (PDTC)/RAPID

DEPLETION/RAT- BRAIN/serum/smooth/stroke/vascular



Dubois-Dauphin, M., Pfister, Y., Vallet, P.G. and Savioz, A. (2001), Prevention of

apoptotic neuronal death by controlling procaspases? A point of view. Brain

Research Reviews, 36 (2-3), 196-203.



Abstract: In various animal models of neurodegenerative diseases the long-lasting

control of cell death by anti-apoptotic therapies is not successful. We present

here our view on the control of procaspase expression in a model of cerebral

stroke. We have investigated how Hu-Bcl-2 overexpression modifies cell death

protein activation in a model of cerebral ischemia induced by permanent middle

cerebral artery occlusion (MCAO). In wild type mice MCAO induced release of

cytochrome c from the mitochondria, and activation of caspases 9 and 3. In

parallel with caspases activation, procaspase 9 and procaspase 3 were,

respectively, increased and decreased. In Hu-Bcl-2 transgenic mice cytochrome c

release and caspases 9 and 3 activation were blocked. However procaspase 9

increased, like in wt mice, but procaspase 3 remained unchanged. By 2 weeks

after MCAO caspases were no longer blocked in Hu-Bcl-2 transgenic mice.

Procaspase 9 increase could represent a time bomb in Hu-Bcl-2 mice where

caspase 9 activation is blocked. Indeed, cellular accumulation of procaspase 9 is

a potentially harmful event able to overcome anti-apoptotic protection by Bcl-2

and threaten cells with rapid destruction. Through understanding of the upstream

regulation of procaspase 9, early targets for the pharmacological control of

apoptotic cell death may be revealed. (C) 2001 Elsevier Science B.V. All rights

reserved



Keywords:

activation/AMYOTROPHIC-LATERAL-SCLEROSIS/animal/apoptosis/Bcl-2/B

RAIN/caspase/CASPASE-9 ACTIVATION/CELL-DEATH/cerebral/cerebral

artery/cerebral

ischemia/control/CYTOCHROME-C/death/diseases/INTERLEUKIN-1-BETA

CONVERTING-ENZYME/ischemia/ISCHEMIC BRAIN

INJURY/MESSENGER-RNA/middle cerebral artery/middle cerebral artery

occlusion/MIDDLE CEREBRAL-ARTERY/NERVOUS-

SYSTEM/NETHERLANDS/protection/stroke/Switzerland/transgenic

mice/TRANSGENIC MOUSE MODEL



Shah, D., Azhar, M., Oakley, C.M., Cleland, J.G.F. and Nihoyannopoulos, P. (1994),

Natural-History of Secundum Atrial Septal-Defect in Adults After Medical Or

Surgical-Treatment - A Historical Prospective- Study. British Heart Journal, 71

(3), 224-227.



Abstract: Objective-To compare outcome in patients with medically treated secundum

atrial septal defect (ASD) first diagnosed after the age of 25 with the long-term

outcome in a similar group of patients after surgical closure. Design-A historical,

prospective, unrandomised study. Setting-A tertiary referral centre. Patients-All

patients with ASD followed up since 1955 who fulfilled the entry criteria and

had reached a current age of over 45 years-that is, 34 medical and 48 surgical

patients with a mean follow up of 25 years. Main outcome measures- Survival,

symptoms, and complications. Results-There was no difference in survival or

symptoms between the two groups and no difference in the incidence of new

arrhythmias, stroke or other embolic phenomena, or cardiac failure. No patient in

either group developed progressive pulmonary vascular disease.

Conclusion-Outcome in adults with ASD was not improved by surgical closure.

because progressive pulmonary vascular disease did not develop in any of these

patients its prevention is not a reason for advising closure of ASD in adults



Keywords:

adults/BRITISH/complications/ENGLAND/HEART/incidence/OLDER/preventi

on/stroke/vascular/vascular disease



Wilson, S.L. and Poulter, N.R. (2001), Cardiovascular risk: its assessment in clinical

practice. British Journal of Biomedical Science, 58 (4), 248-251.



Abstract: Cardiovascular disease is one of the major causes of mortality and morbidity in

Western industrialised countries. Many factors impact on the likelihood of an

individual suffering a stroke or heart attack. One of the greatest challenges facing

clinicians today is how best to identify those individuals at increased risk, to

prevent them becoming tomorrow's patients. Risk assessment tools can provide

useful frameworks to support the identification of individuals who may benefit

from therapeutic intervention: however, such tools should be used with care, as

they do not include all the factors that contribute to future disease risk, and they

are subject to an age bias. Nonetheless, they provide a systematic,

evidence-based approach to the delivery of preventative healthcare services

Keywords: age/BLOOD-PRESSURE/cardiovascular system/causes/clinical

practice/CORONARY HEART-DISEASE/disease/disease

risk/England/Framingham

equation/heart/HYPERTENSION/LONDON/MEDICINE/morbidity/mortality/P

REDICTION/PREVENTION/risk/risk assessment/risk factors/STROKE



King, D., Davies, K.N., Slee, A. and Silas, J.H. (1995), Atrial-Fibrillation in the Elderly

- Physicians Attitudes to Anticoagulation. British Journal of Clinical Practice,

49 (3), 123-125.



Abstract: The use of warfarin and aspirin for the primary prevention of stroke in elderly

patients with atrial fibrillation (AF) is controversial. To establish current practice

we circulated a questionnaire to 300 geriatricians (G) and 300 cardiologists (C).

The response rates were 47% G and 51% C. Most physicians prescribed warfarin

in AF associated with mitral stenosis (G vs C, 86% vs 89%, NS). Cardiologists

were more likely to prescribe warfarin in AF associated with dilated

cardiomyopathy (G vs C, 52% vs 86%, P0.001) in the practice where all patients received dosing through DSS. In the

practice where patients were randomized to either DSS or hospital dosing,

logistic regression showed a significant trend for improvement in intervention

patients which was not apparent in the hospital-dosed patients (P 1225 mg/week spread over at least three

doses) yielded an odds ratio of 3.05 (1.02 to 9.14, P= 0.047). There was no

evidence of an increased risk among subgroups defined by age, sex, Mood

pressure status, alcohol intake, smoking, and the presence or absence of previous

cardiovascular disease. Conclusions No increase in risk of intracerebral

haemorrhage was found among aspirin users overall or among those who took

low doses of the drug or other non-steroidal anti-inflammatory drugs. These data

provide evidence that doses of aspirin usually used for prophylaxis against

vascular disease produce no substantial increase in risk of intracerebral

haemorrhage



Keywords: age/alcohol/aspirin/Australia/BRITISH/cardiovascular/cardiovascular

disease/CEREBRAL-ISCHEMIA/COMMUNITY STROKE/computed

tomography/control/CONTROLLED

TRIAL/DISEASE/drugs/ENGLAND/HEMORRHAGE/hospitals/INFARCTION

/intracerebral

haemorrhage/PERTH/PREVENTION/primary/prophylaxis/risk/sex/smoking/stro

ke/vascular/vascular disease/WOMEN



Hingorani, A.D. and Vallance, P. (1999), A simple computer program for guiding

management of cardiovascular risk factors and prescribing. British Medical

Journal, 318 (7176), 101-105.



Abstract: Objective To describe, and to test against trial data, a simple and flexible

computer program for calculating cardiovascular risk in individual patients as an

aid to managing risk factors and prescribing drugs to lower cholesterol

concentration and blood pressure. Design Descriptive comparison of actual

cardiovascular risk in randomised controlled trials of cholesterol reduction with

risk predicted by a computer program based on the Framingham risk equation.

Comparison of the program's performance with that of tables and guidelines by

means of hypothetical case examples. Main outcome measures Average risk of

coronary heart disease and myocardial infarction. Results The computer program

accurately predicted baseline absolute risk in a UK population as well as the

relative and absolute reduction in risk from cholesterol lowering for primary

prevention of coronary heart disease. The program also allowed a more refined

estimate of absolute risk of coronary heart disease than some existing tables and

enabled the impact of prescribing decisions to be quantified and costed.

Conclusions This simple computer program to estimate individuals'

cardiovascular disease risk and display the benefits of intervention should help

clinicians and patients decide on the most effective packages of risk reduction

and identify those most likely to benefit from modulation of risk factors



Keywords: absolute risk/blood

pressure/BLOOD-PRESSURE/BRITISH/cardiovascular/cardiovascular

disease/cardiovascular risk/cardiovascular risk

factors/cholesterol/cholesterol-lowering/coronary heart disease/CORONARY

HEART-DISEASE/disease

risk/drugs/England/guidelines/heart/HYPERTENSION/infarction/myocardial/my

ocardial infarction/MYOCARDIAL-

INFARCTION/population/PRAVASTATIN/prevention/primary/PRIMARY

PREVENTION/PROFILE/risk/risk factors/STROKE/TABLE/trials



Meade, T.W. and Brennan, P.J. (2000), Determination of who may derive most benefit

from aspirin in primary prevention: subgroup results from a randomised

controlled trial. British Medical Journal, 321 (7252), 13-17.



Abstract: Objective To determine which groups of patients may derive particular benefit

or experience harm from the use of low dose aspirin for the primary prevention

of coronary heart disease. Design Randomised controlled trial. Setting 108 group

practices in the Medical Research Council's general practice research framework

who were taking part in the thrombosis prevention trial. Participants 5499 men

aged between 45 and 69 years at entry who were at increased risk of coronary

heart disease. Main outcome measures Myocardial infarction, coronary death,

and stroke. Results Aspirin reduced coronary events by 20%. This benefit,

mainly for non-fatal events, was significantly greater the lower the systolic blood

pressure at entry (interaction P = 0.0015), the relative risk at pressures 130 mm

Hg being 0.55 compared with 0.94 at pressures > 145 mm Hg. Aspirin also

reduced strokes at low but not high pressures, the relative risks being 0.41 and

1.42 (P = 0.006) respectively. The relative risk of all major cardiovascular

events-that is, the sum of coronary heart disease and stroke-was 0.59 at pressures

145 mm Hg (P = 0.0001).

Conclusion Even with the limitations of subgroup analyses the evidence suggests

that the benefit of low dose aspirin in primary prevention may occur mainly in

those with lower systolic blood pressures, although it is not clear even in these

men that the benefit outweighs the potential hazards. Men with higher pressures

may be exposed to the risks of bleeding while deriving no benefit through

reductions in coronary heart disease and stroke



Keywords: aged/aspirin/bleeding/blood pressure/BRITISH/cardiovascular/coronary

heart disease/death/disease/England/heart/heart

disease/HYPERTENSION/infarction/ISCHEMIC

HEART-DISEASE/LOW-DOSE

ASPIRIN/men/outcome/prevention/primary/primary prevention/relative

risk/RISK/SEVERITY/stroke/systolic blood pressure/thrombosis/use



Kalra, L., Yu, G., Perez, I., Lakhani, A. and Donaldson, N. (2000), Prospective cohort

study to determine if trial efficacy of anticoagulation for stroke prevention in

atrial fibrillation translates into clinical effectiveness. British Medical Journal,

320 (7244), 1236-1239.



Abstract: Objective To determine whether trial efficacy of prophylaxis with warfarin for

patients with atrial fibrillation at high risk of stroke translates into effectiveness

in clinical practice. Design Two year prospective cohort study. Setting District

general hospital. Participants 167 patients with atrial fibrillation and at high

stroke risk who were eligible for anticoagulation. Interventions Long term

anticoagulation with warfarin at adjusted doses to maintain an international

normalised ratio of 2.0-3.0. Main outcome measures Comparison of patient

characteristics, comorbidity, anticoagulation control, stroke rate, and

haemorrhagic complications with pooled data from five randomised controlled

trials. Results Patients in the study group were seven years older (95%

confidence interval 4 to 10) and comprised 33%, more women than patients in

the pooled trials. The inter national normalised ratio was in the target range for

61% of the time (range 37%- 85%), below for 26% of the time (range 8%-32%),

and above for 13% of the time (range 6%-26%). The time that patients in the

study group spent in the target range was significantly less than in the pooled

analysis. The incidence of stroke in the study group (2.0% per rear, 0.7% to 4.4%)

was comparable to that of patients receiving warfarin in pooled studies (1.4%,

0.8% to 2.3%). Per year the incidence of major (1.7% v 1.6%) and minor (5.4% v

9.2%) bleeding complications was also similar. Conclusion Rates of stroke and

major haemorrhage after anticoagulation in clinical practice were comparable to

those obtained from pooled data from randomised controlled studies for patients

with atrial fibrillation at high risk of stroke



Keywords: anticoagulation/ASPIRIN/atrial fibrillation/bleeding/BRITISH/clinical

practice/cohort

study/comorbidity/complications/control/England/fibrillation/haemorrhage/high

risk/hospital/incidence/outcome/prevention/prophylaxis/prospective cohort

study/risk/stroke/stroke prevention/trials/WARFARIN/women



Taylor, F.C., Cohen, H. and Ebrahim, S. (2001), Systematic review of long term

anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial

fibrillation. British Medical Journal, 322 (7282), 321-326.



Abstract: Objective To examine the benefits and risks of long term anticoagulation

(warfarin) compared with antiplatelet treatment (aspirin/indoprofen) in patients

with non-rheumatic atrial fibrillation. Methods Meta-analysis of randomised

controlled trials from Cochrane library, Medline, Embase, Cinhal, and Sigle fr

am 1966 to December 1999. Odds ratios (95% confidence intervals) calculated to

estimate treatment effects. Outcome measures Fatal and non-fatal cardiovascular

events, reductions of which were classified as benefits. Fatal and major non-fatal

bleeding events classified as risks. Results No trials were found from before

1989. There were five randomised controlled trials published between 1989-99.

There were no significant differences in mortality between the two treatment

options (fixed effects model: odd ratio 0.14 (95% confidence interval 0.39 to

1.40) for stroke deaths; 0.86 (0.63 to 1.17) for vascular deaths). There was a

borderline significant difference in non-fatal stroke in favour of anticoagulation

(0.68 (0.46 to 0.99)); and 0.15 (0.50 to 1.13) after exclusion of one trial with

weak methodological design. A random effects model showed no significant

difference in combined fatal and non-fatal events (odds ratio 0.79 (0.61 to 1.02)),

There were more major bleeding events among patients on anticoagulation than

on antiplatelet treatment (odds ratio 1.45 (0.93 to 2.27)). One trial was stopped

prematurely after a significant difference in favour of anticoagulation was

observed, The only trial to show a significant difference in effect (favouring

anticoagulation) was methodologically weaker in design than the others.

Conclusions The heterogeneity between the trials and the limited data result in

considerable uncertainty about the value of long term anticoagulation compared

with antiplatelet treatment The risks of bleeding and the higher cost of

anticoagulation make it an even less convincing treatment option



Keywords: anticoagulation/antiplatelet/antiplatelet treatment/ANTITHROMBOTIC

THERAPY/ASPIRIN/atrial

fibrillation/BIAS/bleeding/BRITISH/cardiovascular/cardiovascular

events/cost/design/England/fibrillation/LONDON/METAANALYSIS/mortality/

non-rheumatic atrial fibrillation/nonrheumatic/review/SERVICE/stroke/stroke

deaths/STROKE

PREVENTION/THROMBOEMBOLISM/treatment/trial/TRIALS/vascular/WA

RFARIN



Cappuccio, F.P., Oakeshott, P., Strazzullo, P. and Kerry, S.M. (2002), Application of

Framingham risk estimates to ethnic minorities in United Kingdom and

implications for primary prevention of heart disease in general practice: cross

sectional population based study. British Medical Journal, 325 (7375),

1271-1274B.



Abstract: Objective To compare the 10 year risk of coronary heart disease (CHD), stroke,

and combined cardiovascular disease (CVD) estimated from the Framingham

equations. Design Population based cross sectional survey. Setting Nine general

practices in south London. Population 1386 men and women, age 40-59 years,

with no history of CVD (475 white people, 447 south Asian people, and 464

people of African origin), and a subgroup of 1069 without known diabetes, left

ventricular hypertrophy, peripheral vascular disease, renal impairment, or target

organ damage. Main outcome measures 10 year risk estimates. Results People of

African origin had the lowest 10 year risk estimate of CHD adjusted for age and

sex (7.0%, 95% confidence interval 6.5 to 7.5.) compared with white people

(8.8%, 8.2 to 9.5) and south Asians (9.2%, 8.6 to 9.9) and the highest estimated

risk of stroke (1.7% (1.5 to 1.9),1.4% (1.3 to 1.6),1.6% (1.5 to 1.8), respectively).

The estimate risk of combined CVD, however, was highest in south Asians

(12.5%, 11.6 to 13.4) compared with white people (11.9%, 11.0 to 12.7) and

people of African origin (10.5%, 9.7 to 11.2). In the subgroup of 1069, the

probability that a risk of CHD greater than or equal to 15% would identify risk of

combined CVD greater than or equal to 20% was 91% in white people and 81%

in both south Asians and people of African origin. The use of thresholds for risk

of CHD of 12% in south Asians and 10% in people of African origin would

increase the probability of identifying those at risk to 100% and 97%,

respectively. Conclusion Primary care doctors should use a lower threshold of

CHD risk when treating mild uncomplicated hypertension in people of African or

south Asian origin



Keywords:

age/BLOOD-PRESSURE/BRITISH/BRITISH-HYPERTENSION-SOCIETY/ca

rdiovascular/cardiovascular disease/CARDIOVASCULAR

RISK/CHD/CLINICAL-PRACTICE/coronary heart disease/CORONARY

RISK/diabetes/disease/England/EUROPEAN POPULATIONS/general

practice/GUIDELINES/HEALTH SURVEY/heart/heart

disease/history/hypertension/hypertrophy/left ventricular/left ventricular

hypertrophy/LONDON/MANAGEMENT/men/minorities/outcome/peripheral

vascular disease/population/population-based/prevention/primary/primary

prevention/renal/risk/sex/stroke/survey/United

Kingdom/use/VALIDATION/vascular/vascular disease/women



Marshall, T. and Rouse, A. (2002), Resource implications and health benefits of primary

prevention strategies for cardiovascular disease in people aged 30 to 74:

mathematical modelling study. British Medical Journal, 325 (7357), 197-199.



Abstract: Objective To develop a model to determine the resource costs and health

benefits of implementing guidelines for the prevention of cardiovascular disease

in primary care, Design Modelling of data from six strategies for prevention of

cardiovascular disease. Strategies incorporated two ways of identifying patients

for assessment: traditional (assessment of all adults) and novel (preselection of

patients For assessment using a prior estimate of their risk of cardiovascular

disease). Three treatment strategies were modelled in conjunction with each

identification strategy. Setting England. Subjects Patients aged 30 to 74 eligible

for primary prevention strategies for cardiovascular disease who were selected

from a hypothetical population of 2000. Main outcome measures Resource costs

of assessing eligible adults, providing treatment and follow up and number of

cardiovascular events this should prevent. Results Novel strategies prevented

more cardiovascular disease, at lower cost, than traditional strategies. Some

treatment strategies prevent more cardiovascular disease with fewer resources

than others. The findings were robust across a range of different assumptions

about workload. Conclusion Preselecting patients for assessment makes better

use of staff time than assessing all adults. Treating many patients with low cost

drugs is more efficient than prescribing a few patients intensive

antihypertensives and statins. Authors of guidelines should model workload

implications and health benefits of following their recommendations



Keywords: adults/aged/BLOOD- PRESSURE/BRITISH/cardiovascular/cardiovascular

disease/cardiovascular events/CHOLESTEROL/CORONARY

HEART-DISEASE/cost/costs/disease/drugs/England/guidelines/health/LONDO

N/METAANALYSIS/outcome/population/prevention/primary/primary

care/primary prevention/RANDOMIZED CONTROLLED TRIALS/risk/RISK

PROFILE/STATINS/STROKE/treatment/use

Meade, T., Zuhrie, R., Cook, C. and Cooper, J. (2002), Bezafibrate in men with lower

extremity arterial disease: randomised controlled trial. British Medical Journal,

325 (7373), 1139-1141.



Abstract: Objective To assess the effect of bezafibrate on the risk of coronary heart

disease and stroke in men with lower extremity arterial disease. Design Double

blind placebo controlled randomised trial. Setting 85 general practices and nine

hospital vascular clinics. Participants 1568 men, mean age 68.2 years (range 35

to 92) at recruitment. Interventions Bezafibrate 400 mg daily (783 men) or

placebo (785 men). Main outcome measures Combination of coronary heart

disease and of stroke. All coronary events, fatal and non-fatal coronary events

separately, and strokes alone (secondary end points). Results Bezafibrate did not

reduce the incidence of coronary heart disease and stroke. There were 150 and

160 events in the active and placebo groups respectively (relative risk 0.96, 95%

confidence interval 0.76 to 1.21). There were 90 and 111 major coronary events

in the active and placebo groups respectively (0.81, 0.60 to 1.08), of which 64

and 65 were fatal (0.95, 0.66 to 1.37) and 26 and 46 non-fatal (0.60, 0.36 to 0.99).

Beneficial effects on non-fatal events were greatest in men aged 70% symptomatic stenosis were

considered appropriate, those for 50%-69% symptomatic and > 60%

asymptomatic stenosis were considered uncertain and all others, including those

in medically or neurologically unstable patients, were designated inappropriate.

In part 4, the referral source and nature of the patients was also determined.

Results: Part I (April 1994 - September 1995) found that of 291 CEAs performed

33% were appropriate, 48% were uncertain and 18% were inappropriate, and

40% of patients who underwent CEA were asymptomatic. In part 2 (September

1996 - September 1997) appropriate indications significantly improved to 49%

of 184 CEAs (P=0.005), uncertain indications remained nearly the same at 47%,

inappropriate indications fell to 4% (P=0.00002), and asymptomatic patients

remained at 40%. The results of part 3 (October 1997 - October 1998) remained

nearly the same as part 2 (249 CEAs, 47% appropriate, 51% uncertain, 2%

inappropriate, 45% asymptomatic). Part 4 (October 1999 - October 2000) results

were significantly better than part 3, appropriate indications increasing from 47%

to 58% of 222 CEAs (P=0.02), and an elimination of inappropriate operations

(P=0.03). Stroke and death complications declined over the study period from an

overall rate of 5.2% in part 1 to 2.3% in part 4. In part 4 the majority of patients

(69%) were referred to surgeons directly from general practitioners, including 58

(73%) of the 80 asymptomatic patients who underwent CEA. Interpretation:

Regular auditing and feedback of results and information to surgeons has

resulted in significant and continued improvements in the surgical performance

of CEA in our region. Since the majority of patients are referred directly to

surgeons by general practitioners, it is important that this group of physicians be

familiar with current CEA guidelines



Keywords: AD-HOC-COMMITTEE/AMERICAN-HEART-ASSOCIATION/ARTERY

STENOSIS/asymptomatic/asymptomatic stenosis/ASYMPTOMATIC

ULCERATIVE LESIONS/CANADA/carotid/carotid

endarterectomy/complications/death/endarterectomy/GUIDELINES/LARGE

METROPOLITAN AREA/MEDICARE

BENEFICIARIES/MULTIDISCIPLINARY CONSENSUS

STATEMENT/NATURAL-HISTORY/prevention/randomized/randomized

controlled trials/randomized trials/stenosis/stroke/STROKE COUNCIL/stroke

prevention/symptomatic stenosis/trials/use

Chang, E., Holroyd, B.R., Kochanski, P., Kelly, K.D., Shuaib, A. and Rowe, B.H.

(2002), Adherence to practice guidelines for transient ischemic attacks in an

emergency department. Canadian Journal of Neurological Sciences, 29 (4),

358-363.



Abstract: Objective: To evaluate the investigation and treatment of patients with a

diagnosis of transient ischemic attacks (TIA) in the emergency department (ED)

a tertiary care teaching hospital with a neuroscience referral program. Methods:

A chart review was conducted in the hospital. Consecutive ED charts with a

diagnosis of TIA were included; each was reviewed by independent coders using

a standardized data form. Results: Two hundred and ninety-three TIA charts

were reviewed; the gender ratio was 1: 1 with a mean age of 66 years. Most

patients (75%; 95% CI: 70, 80) were evaluated by ED physicians; the remaining

patients were seen directly by referral services. The median time from symptom

onset to ED arrival was 2.9 hours and the duration of symptoms was 4.6 hours.

Most patients received CT scans (81%; 95% CI: 73, 85), complete blood counts

(74%; 95% CI: 68, 79), and electrocardiograms (75%; 95% CI: 70, 80) in the ED.

In 16% (95% CI: 13, 22) a carotid doppler was performed and in 26% (95% CI:

21, 31) an outpatient doppler was booked. Among those who were discharged

(75%; 95% CI: 70, 80), antithrombotic medications were not prescribed to 28%

(95% CI: 22, 34). Conclusion: Practice variation exists with respect to the

investigation and treatment of TIAs in this tertiary-care teaching hospital.

Carotid doppler investigation and use of anti-platelet therapy for patients with

TIA are suboptimal. Clinical practice guidelines and rapid assessment TIA

clinics may change these results



Keywords:

AD-HOC-COMMITTEE/age/AMERICAN-HEART-ASSOCIATION/antiplatele

t/antiplatelet therapy/antithrombotic/ASPIRIN/CANADA/carotid/CT/CT

scans/diagnosis/gender/guidelines/hospital/ischemic/MANAGEMENT/practice

guidelines/PREVENTION/PROGNOSIS/review/STATEMENT/STROKE-COU

NCIL/symptoms/therapy/TIA/transient/transient ischemic attacks/treatment/use



Bungard, T.J., Ghali, W.A., McAlister, F.A., Buchan, A.M., Cave, A.J., Hamilton, P.G.,

Mitchell, L.B., Shuaib, A., Teo, K.K. and Tsuyuki, R.T. (2003), The relative

importance of barriers to the prescription of warfarin for nonvalvular atrial

fibrillation. Canadian Journal of Cardiology, 19 (3), 280-284.



Abstract: BACKGROUND AND PURPOSE: Despite the publication of a number of

randomized, controlled trials demonstrating a substantial reduction in stroke with

anticoagulation in patients with nonvalvular atrial fibrillation, the 'real world' use

of warfarin is sub-optimal. Previous surveys have attempted to explain this

problem but have significant limitations. The purpose of this study was to assess

the relative importance of various barriers that may influence the prescription of

warfarin in patients with nonvalvular atrial fibrillation. METHODS: This

cross-sectional survey was mailed to all practising cardiologists, neurologists and

internists, as well as a random sample of family physicians within Alberta.

Physicians caring for patients with NVAF rated the relative importance of

potential barriers using a Likert scale. RESULTS: Sixty-seven per cent of all

physicians returned the survey. Overall, barriers pertaining to the patient's

clinical characteristics were rated to be more important than those pertaining to

the physician or to the organization required when prescribing these therapies.

Specifically, an ongoing history of falls, a history of bleeding within the previous

year and an inability to comply with therapy were rated as important barriers by

64%, 55% and 53% of physicians, respectively. Most physicians strongly

believed that patients should receive information on the benefits and risks of

warfarin (96%) and that patients should have a say in whether warfarin is

prescribed (86%). IMPLICATIONS: This study suggests that most of the barriers

to warfarin use pertain to patient clinical characteristics and the need for patients

to be involved in the decision to initiate therapy. The use of decision support

technologies would facilitate involvement of the patient and serve to educate

both the patient and physician on the risks and benefits of warfarin therapy



Keywords: ANTICOAGULATION/ANTITHROMBOTIC THERAPY/atrial/atrial

fibrillation/barriers/benefits/bleeding/CANADA/CARE/ELDERLY

PATIENTS/falls/fibrillation/history/international normalized

ratio/MANAGEMENT/nonvalvular atrial fibrillation/PATTERNS/PHYSICIAN

ATTITUDES/prescribing/randomized/risks/stroke/STROKE

PREVENTION/survey/therapy/TRIAL/trials/use/warfarin



Hittelet, A. and Deviere, J. (2003), Management of anticoagulants before and after

endoscopy. Canadian Journal of Gastroenterology, 17 (5), 329-332.



Abstract: The risk of procedure-related bleeding while taking anticoagulants needs to be

weighed against the risk of thromboembolism from discontinuing these drugs. It

is not necessary to adjust anticoagulation for low-risk procedures, such as upper

endoscopy with biopsy, colonoscopy with biopsy or endoscopic retrograde

cholangiopancreatography with stent insertion (but without sphincterotomy).

Procedures that incur a high risk of bleeding include polypectomy, endoscopic

sphincterotomy, laser therapy, mucosal ablation and treatment of varices. For

these procedures, warfarin should be discontinued four to five days beforehand.

Depending on the risk of thromboembolism, that is based on the nature of the

underlying condition, the patient may require vitamin K and/or fresh frozen

plasma (to ensure that coagulation parameters are within the normal range) or

heparin infusions (to ensure that some degree of anticoagulation is maintained).

Low molecular weight heparin is an alternative to unfractionated heparin for

select cases with a high risk of thromboembolism. Warfarin therapy may

generally be resumed on the night of the procedure and may be supplemented by

heparin in patients with a high risk of thromboembolism. It is not necessary to

discontinue acetylsalicylic acid or nonsteroidal anti-inflammatory drugs, when

used in standard doses, for endoscopic procedures. There are insufficient data to

make recommendations regarding newer antiplatelet drugs, such as ticlopidine or

clopidogrel, but it is prudent to discontinue these medications seven to 10 days

before a high-risk procedure

Keywords: acetylsalicylic

acid/anticoagulant/anticoagulants/anticoagulation/antiplatelet/antiplatelet

drugs/bleeding/BLEEDING

COMPLICATIONS/CANADA/clopidogrel/coagulation/DEEP-VEIN

THROMBOSIS/drugs/endoscopy/HEPARIN/high

risk/LOW-MOLECULAR-WEIGHT/NSAID/PREVENTION/risk/SPHINCTER

OTOMY/stent/STROKE/SURGERY/therapy/thromboembolism/ticlopidine/treat

ment/unfractionated heparin/VENOUS

THROMBOEMBOLISM/vitamin/warfarin/WARFARIN THERAPY/weight



McLellan, C.S., Abdollah, H., Brennan, F.J. and Simpson, C.S. (2003), Atrial fibrillation

in the pacemaker clinic. Canadian Journal of Cardiology, 19 (5), 492-494.



Abstract: BACKGROUND: Electrocardiographic (ECG) recognition of the underlying

rhythm in patients with ventricular pacing can be difficult. Atrial fibrillation (AF)

in particular may go unreported. OBJECTIVES: To compare the underlying

atrial rhythm determined in the pacemaker clinic with the 12-lead ECG

interpretation of the atrial rhythm in those who were continuously paced in the

ventricle. It was intended to determine whether long term anticoagulation therapy

was related to whether AF was diagnosed before or after pacemaker implantation.

METHODS: Pacemaker clinic patients were enrolled if they had a 100% paced

ventricular rhythm. The underlying rhythm was determined using pacemaker

programming manoeuvres. A 12-lead ECG was recorded on all patients within

10 min of their pacemaker assessment and interpreted by one of the several

geographic full-time cardiologists at the centre. All cardiologists were blinded to

the results of pacemaker assessment and to the clinical history. RESULTS:

Fifty-six patients were enrolled. At the pacemaker clinic, 37 were determined to

be in AF and three were in atrial flutter (AFL). Of these 40 patients with

AF/AFL, 28 were correctly identified as such on the 12-lead ECG interpretation.

Twelve of the 40 were interpreted only as having an 'electronic ventricular

pacemaker' (EVP). Sixteen of the 40 patients (40.0%) with AF or AFL were not

taking warfarin. Twenty-two of 25 patients with an AF/AFL diagnosis before

pacemaker implantation were taking warfarin, compared with two of 15 patients

with AF/AFL diagnosis after pacemaker implantation (P 50% carotid stenosis, 16 with previously unknown cardiac

arrhythmias and 104 had hypertension, It was concluded that this protocol

provides an accurate, rapid and cost-effective means of screening for the three

immediate causes of stroke and can on broad application result in significant

stroke reduction. (C) 1998 The International Society for Cardiovascular Surgery,

Published by Elsevier Science Ltd. All rights reserved



Keywords: arrhythmias/atrial fibrillation/carotid/carotid artery/carotid artery

disease/CAROTID ENDARTERECTOMY/carotid

stenosis/cholesterol/cost/detection/ENGLAND/fibrillation/hypertension/new

protocol/prevention/protocols/screening/STENOSIS/stroke/stroke

prevention/trials/ultrasound



Kim, G.E., Kwon, T.W., Cho, Y.P., Kim, D.K. and Kim, H.S. (2001), Carotid

endarterectomy with bovine patch angioplasty: A preliminary report.

Cardiovascular Surgery, 9 (5), 458-462.



Abstract: Carotid endarterectomy with patch angioplasty is a durable procedure for

prevention of recurrent neurological symptoms and stroke. However, no

definitive study has demonstrated a clear benefit of one class of the patch

material over another. The aim of this study was to evaluate the clinical outcome

of carotid endarterectomy with bovine pericardium patch in comparison with

autologous vein patch. One hundred and twenty- two carotid endarterectomies

were performed using patch closure of the arteriotomy with bovine pericardium

(61 cases) and autologous vein (61 cases) between September 1995 and June

1999. Though this is not a double-blind type randomized comparative study,

effort was made to achieve a 1:1 ratio in sequence with a few exceptions such as

non-availabie veins at time of surgery or for future use. In bovine pericardium

patch closure group, the mean total operating time was significantly shorter than

autologous vein closure group (P

0.05). The octogenarians' Kaplan- Meier 6-year overall and free-stroke survival

rates were 86 and 76% respectively. CEA can be performed in selected

octogenarian patients with low early and late mortality and neurologic morbidity

rates. (C) 2003 The International Society for Cardiovascular Surgery. Published

by Elsevier Science Ltd. All rights reserved



Keywords: AGE/ASYMPTOMATIC PATIENTS/carotid/carotid

endarterectomy/CIGARETTE-SMOKING/death/DISEASE/elderly/endarterecto

my/ENGLAND/MODERATE/morbidity/mortality/NATURAL-HISTORY/octog

enarian/outcomes/RISK FACTOR/safety/STENOSIS/STROKE/stroke

prevention/SURGERY/survival



White, C.J., Gomez, C.R., Iyer, S.S., Wholey, M. and Yadav, J.S. (2000), Carotid stent

placement for extracranial carotid artery disease: Current state of the art.

Catheterization and Cardiovascular Interventions, 51 (3), 339-346.



Abstract: Percutaneous revascularization techniques have dramatically altered traditional

approaches to the management of both coronary and peripheral vascular disease.

Their major advantage is that they are less invasive than conventional surgical

procedures, offering revascularization without the risk of general anesthesia and

with lesser procedural morbidity and mortality, shorter hospital stay, and lower

cost. In patients with comorbidities that increase their risk of surgical

complications, percutaneous revascularization techniques are the procedures of

choice. The Achilles heel of balloon angioplasty, the higher risk of lesion

recurrence, restenosis, has been markedly reduced with the use of endovascular

stents. Over the past 20 years, percutaneous angioplasty and stenting have

become accepted alternatives to surgical revascularization of aortoiliac, renal,

femoropopliteal, subclavian, brachiocephalic, and dialysis access lesions. The

most recent application of percutaneous intervention has been to explore its

clinical utility and safety for stroke prevention in stenotic extracranial carotid

arteries. Cathet. Cardiovasc. Intervent. 51:339-346, 2000. (C) 2000 Wiley-Liss,

Inc



Keywords:

AD-HOC-COMMITTEE/AMERICAN-HEART-ASSOCIATION/ANGIOPLAS

TY/arteries/balloon angioplasty/carotid/carotid arteries/carotid artery/carotid

artery disease/CATHETER/cerebrovascular

circulation/complications/cost/ENDARTERECTOMY/GUIDELINES/hospital/m

orbidity/mortality/NEW-YORK/peripheral vascular

disease/prevention/PROFESSIONALS/recurrence/renal/revascularization/risk/RI

SKS/safety/STENOSIS/stenting/stents/stroke/STROKE COUNCIL/stroke

prevention/vascular/vascular disease



Velianou, J.L., Strauss, B.H., Kreatsoulas, C., Pericak, D. and Natarajan, M.K. (2000),

Evaluation of the role of abciximab (Reopro) as a rescue agent during

percutaneous coronary interventions: In-hospital and six-month outcomes.

Catheterization and Cardiovascular Interventions, 51 (2), 138-144.

Abstract: Abciximab is effective for the prevention of complications when administered

prior to percutaneous coronary intervention (PCI). The efficacy and safety of

abciximab as an unplanned or rescue agent for complications of PCI is unknown.

Rescue versus planned use was compared in 186 consecutive patients. Primary or

rescue PCI for acute myocardial infarction (MI) and shock were excluded.

Rescue abciximab use was undertaken in 101 patients (54.3%) and planned

abciximab was used in 85 (45.7%). The rescue abciximab patients had a lower

incidence of previous MI, preprocedural thrombus, multivessel, and vein graft

intervention. In-hospital endpoints in the rescue versus planned abciximab

patients were death (1.0% vs. 1.2%, P = 1.0), Q-wave MI (2.0% vs. 2.4%, P =

1.0), any MI (14.9% vs. 9.4%, P = 0.3), target vessel revascularization (TVR; 0%

vs. 1.2%, P = 1.0), and composite (15.8% vs. 10.6%, P = 0.3). At 6 months,

events were death (4.0% vs. 2.3%, P = 0.69), MI (14.9% vs. 9.4%, P = 0.26),

TVR (20.8% vs. 4.7%, P = 0.001), and composite (30.7% vs. 15.3%, P = 0.01).

In-hospital complications between the rescue and planned abciximab patients of

major bleed (1.0% vs. 1.8%, P = NS), stroke (0% vs. 1.8%, P = NS), and

thrombocytopenia (3.0% vs. 1.8%, P = NS) were similar. There was a

significantly higher procedural time (99.6 min vs. 86.1 min, P = 0.02), contrast

volume (278.8 ml vs. 223.5 ml, P = 0.04), and heparin use (8984 u vs. 6003 u, P

= 0.0006) in the rescue group. In this nonrandomized comparison, rescue

abciximab allowed for the safe discharge from hospital in the majority of patients.

However, during a 6-month follow-up, more patients treated with rescue

abciximab required TVR with either repeat PCI or CABG. Further studies are

warranted to evaluate the overall strategy of rescue abciximab use in PCI. Cathet

Cardiovasc. Intervent 51:138-144, 2000. 2000 Wiley-Liss, Inc



Keywords: abciximab/ABRUPT CLOSURE/acute/acute myocardial

infarction/ANGIOPLASTY/angioplasty/ANTIPLATELET/CABG/CATHETER/

COMPLICATIONS/coronary artery

disease/heparin/hospital/incidence/infarction/myocardial/myocardial

infarction/NEW-YORK/PREVENTION/REVASCULARIZATION/RISK/safety

/stroke/THERAPY/thrombus/UNSTABLE ANGINA/VESSEL CLOSURE



Du, Z.D., Cao, Q.L., Joseph, A., Koenig, P., Heischmidt, M., Waight, D.J., Rhodes, J.,

Brorson, J. and Hijazi, Z.M. (2002), Transcatheter closure of patent foramen

ovale in patients with paradoxical embolism: Intermediate-term risk of recurrent

neurological events. Catheterization and Cardiovascular Interventions, 55 (2),

189-194.



Abstract: Closure of patent foramen ovale (PFO) has been proposed as an alternative to

anticoagulation in patients with presumed paradoxical emboli. We report our

preliminary intermediate results of patients who underwent transcatheter PFO

closure for paradoxical embolism using DAS-Angel Wings occluder or

Amplatzer devices. Eighteen patients (8 male/10 female) underwent catheter

closure of their PFOs at a median age of 42 years. The complete closure rate was

67% immediately after the procedure and 100% at a mean follow-up interval of

2.2 +/- 1.8 years. The mean fluoroscopy time and procedure time in the

Amplatzer group were 8.5 +/- 3.2 min and 65 +/- 21 min, respectively, which

were significantly shorter than those of DAS-Angel Wings group (18.9 +/- 4.7

min and 137 +/- 28 min, respectively). There were no recurrent embolic

neurological events following device placement in this subset of patients. No

complications were encountered either during or after the closure procedure. In

conclusion, transcatheter closure of PFO seems to be an effective alternative

therapy in the prevention of presumed paradoxical emboli. Further study is

needed to identify patients most likely to benefit from this intervention. (C) 2002

Wiley-Liss, Inc



Keywords: age/anticoagulation/ATRIAL

SEPTAL-DEFECT/CATHETER/complications/CRYPTOGENIC

STROKE/DEVICE/device closure/emboli/embolism/foramen

ovale/HEART-DISEASE/NEW-YORK/paradoxical embolism/patent/patent

foramen ovale/PFO/prevention/risk/stroke/therapy/transcatheter

closure/TRANSESOPHAGEAL ECHOCARDIOGRAPHY/transient ischemic

attack



Wilentz, J.R., Chati, Z., Krafft, V. and Amor, M. (2002), Retinal embolization during

carotid angioplasty and stenting: Mechanisms and role of cerebral protection

systems. Catheterization and Cardiovascular Interventions, 56 (3), 320-327.



Abstract: Carotid stenting has become an accepted alternative to endarterectomy, but

fear of embolic stroke has impeded its generalized application. The retina

provides a unique observatory for the study of emboli, which may occur either

directly or indirectly via collaterals to the ophthalmic artery. Systems under

development for cerebral protection differ in their capacity to trap small emboli

and in their protection of the collateral circulation. We evaluated 118 sequential

patients undergoing carotid stenting using fundoscopy, fluorescein retinal

angiography, and visual field examination. The site and size of emboli was

assessed, and degree of edema estimated. All patients were treated using distal

protection during carotid stent implantation: 38 patients with the Theron system

(using routine flushing toward the external carotid) and 80 patients with the

Percusurge(R) system (aspiration only). Retinal embolization occurred in 6 of the

118 patients (4%), of whom 2 were symptomatic (1.7%). Using the Theron

system, 5 of 38 patients (13.2%) had emboli while 1 of 80 (1.25%) had emboli

using the Percusurge system (P = 0.019). Symptoms occurred only with emboli

>20 mum. Symptomatic retinal embolization is uncommon during carotid

stenting, but is more likely when external to internal carotid collaterals are not

protected. Cerebral protection system designs should take into consideration the

existence of collaterals and the need to protect against smaller sized emboli,

which may cause blindness in the retinal circulation



Keywords: amaurosis fugax/angiography/angioplasty/ARTERY

DISEASE/aspiration/blindness/carotid/carotid angioplasty/carotid artery/carotid

circulation/carotid endarterectomy/carotid stenosis/carotid stent/carotid

stenting/CATHETER/cerebral/cerebral protection/development/distal

protection/EFFICACY/emboli/EMBOLIC

EVENTS/embolization/ENDARTERECTOMY/FLOW/internal/NEW-YORK/op

hthalmic artery/PREVENTION/protection/retina/retinal

artery/RISK/stent/stenting/stents/stroke/transient ischemic attack/USA



Fayed, A.M., White, C.J., Ramee, S.R., Jenkins, J.S. and Collins, T.J. (2002), Carotid

and cerebral angiography performed by cardiologists: Cerebrovascular

complications. Catheterization and Cardiovascular Interventions, 55 (3),

277-280.



Abstract: The management of extracranial carotid artery disease is primarily concerned

with the prevention of acute stroke. In order to understand the current risks of

carotid angiography performed by interventional cardiologists, we undertook a

retrospective study to determine the neurologic complications in patients who

underwent selective cerebral angiography. All patients undergoing studies that

were limited to diagnostic aortic arch angiography and selective four-vessel

cerebral angiography in the cardiac catheterization laboratories during the past 6

years were included in this study. Hospital records were reviewed to determine

any in-hospital cerebrovascular complications following carotid angiography,

ranging from transient ischemic attack to major disabling stroke or death. A total

of 189 consecutive patients underwent 191 diagnostic studies limited to aortic

arch and four-vessel cerebral angiography in the cardiac catheterization

laboratories between 1 January 1995 and 31 December 2000. Only one (0.52%)

neurological complication, a minor stroke, occurred in our study population.

There were no transient ischemic attacks, major strokes, or death. We have

shown that experienced interventional cardiologists can perform diagnostic aortic

arch and selective carotid and vertebral angiography in a cardiac catheterization

laboratory with a very low complication rate. Because the risks of angiography

add to those of revascularization of the carotid artery, the most highly skilled

angiographer, regardless of primary specialty, should perform these studies. (C)

2002 Wiley-Liss, Inc



Keywords: acute/acute stroke/angiography/ANGIOPLASTY/aortic arch

angiography/cardiac/carotid/carotid artery/carotid artery

disease/CATHETER/catheterization/catheterization

complications/cerebral/cerebral

angiography/cerebrovascular/complication/complications/death/diagnostic/DISE

ASE/ENDARTERECTOMY/ISCHEMIA/ischemic/management/neurologic

complications/neurological

complication/NEW-YORK/population/prevention/primary/revascularization/RIS

K/STROKE/transient/transient ischemic attack/transient ischemic

attacks/ULTRASOUND



Grube, E., Colombo, A., Hauptmann, E., Londero, H., Reifart, N., Gerckens, U. and

Stone, G.W. (2003), Initial multicenter experience with a novel distal protection

filter during carotid artery stent implantation. Catheterization and

Cardiovascular Interventions, 58 (2), 139-146.

Abstract: Atheroembolization resulting in transient or permanent neurologic impairment

is the most common complication of catheter-based percutaneous carotid artery

intervention. Protection of the distal cerebral vasculature during carotid stent

implantation may enhance procedural safety. Carotid stent implantation with

distal cerebral protection using the FilterWire EX was performed in 35

consecutive patients undergoing 36 procedures at six centers. The FilterWire was

delivered and deployed successfully in all 36 cases, and embolic material was

retrieved from 74% of procedures. The 30- day rate of major adverse events

(death, major or minor stroke) was 0%. Transient ipsilateral periprocedural

neurologic ischemia developed in two patients (5.7%), both resolving within 30

min. Distal cerebral protection with the FilterWire during carotid stenting is

feasible and safe, results in capture and extraction of atheroembolic debris in the

majority of patients while affording uninterrupted cerebral perfusion, and in this

initial multicenter experience was associated with a high rate of procedural

success without major complications



Keywords: adverse events/ANGIOPLASTY/carotid/carotid artery/carotid

disease/carotid stent/carotid stenting/CATHETER/cerebral/cerebral

perfusion/CEREBRAL

PROTECTION/complication/COMPLICATIONS/death/distal

protection/EFFICACY/emboli/ENDARTERECTOMY/filters/ischemia/NEW-Y

ORK/OCCLUSION/PREVENTION/protection/results/safety/STENOSIS/stent/st

enting/STROKE/SYSTEM/transient/USA/vasculature



Biousse, V., Woimant, F., Amarenco, P., Touboul, P.J. and Bousser, M.G. (1992), Pain

As the Only Manifestation of Internal Carotid-Artery Dissection. Cephalalgia,

12 (5), 314-317.



Abstract: Internal carotid artery dissection is a major cause of ischemic stroke in the

young. Pain is the leading symptom and is associated with other focal signs such

as Homer's syndrome and painful tinnitus or with signs of cerebral or retinal

ischemia. We report two patients with angiographically confirmed extracranial

internal carotid artery dissection presenting with cephalic pain as the only

manifestation. The first patient had a diffuse headache and a latero-cervical pain

lasting for 12 days, reminiscent of carotidynia. The second patient experienced

an exploding headache suggestive of subarachnoid hemorrhage, which was ruled

out by computed tomography of the head and cerebrospinal fluid study. These

patients demonstrate that recognition of carotid artery dissection as a cause of

carotidynia and headache suggestive of subarachnoid hemorrhage may permit an

earlier diagnosis and possibly the prevention of a stroke through the use of

anticoagulation



Keywords: CAROTIDYNIA/HEADACHE/INTERNAL CAROTID ARTERY

DISSECTION/MIGRAINE



Giroud, M., Gras, P. and Dumas, R. (1991), Usefulness of A Population-Based Stroke

Registry. Cerebrovascular Diseases, 1 45-49.

Abstract: Stroke registries can supply eminent informations concerning epidemiological,

clinical and socio-economical data providing they are reliable, i.e. compliant

with Malmgren's criteria and the Oxford registration model. The collection must

include a well-defined population. It must be exhaustive, specific and

prospective in order to prevent omissions and to facilitate the elimination of

other diagnoses. Only the first stroke has to be taken into account for each patient

and the clinical reports have to be complete (usefulness of a simplified but

flexible work file). Finally, the rate of diagnoses either doubtful or based on

death certificate has to be low. A CT scan should be performed for each patient

and a maximum number of information sources is required. Consequently, a

stroke registy (1) provides descriptive epidemiological stroke studies. They are

based on the estimation of incidence and mechanisms of stroke. Their main value

is to appreciate the extent of the health problem, to forecast the expected number

of patients and to assess the quality of data collection by controlling their

consistency from one year to the next. These studies can determine the

distribution of stroke among the 3 traditional health care procedures (hospitals,

private clinics and home care). This information is of major importance when

undertaking clinical or prevention trials. Finally, the collection of survival data

from the studies is important to state the natural history of stroke and therefore to

appreciate their alteration following a special treatment or new preventive

procedures. (2) A stroke registry allows some contribution to clinical research by

providing the distribution ratio of different stroke subtypes and mechanisms, the

clinical data for semiological analyses and the adjusted prognosis criteria

according to data trom nonhospitalized cases. (3) It also allows the development

of analytic epidemiological studies. Such a registry avoids some bias. Analysis of

etiological factors is done on case-control and cohort studies. These registries are

of great methodological help to the analyses of drug trials. (4) The registry leads

to experimental epidemiological studies. It is a good tool for controlling health

care quality and confirming the role of a factor underscored by an analytic

epidemiological study: the consequences of the risk factor reduction or eviction

(e.g. smoking, alcohol, high blood pressure, dyslipidemia) provide additional

evidence towards its etiological role. (5) It provides sanitary information. The

diffusion of these results to clinicians, searchers and sanitary authorities is of

great importance. All these advantages do not abolish the relevance of hospital

registries, which despite recruitment bias, provide much more accurate clinical

studies, CT scans in almost 100% of the patients, and a better follow-up, such as

in Lausanne



Keywords: ACUTE

CEREBROVASCULAR-DISEASE/AREA/COMMUNITY/CT/DATA-BANK/

DECLINE/EPIDEMIOLOGY/HISTORY/INCIDENCE

RATES/INFARCTION/PROJECT 1981- 86/REGISTRY/STROKE



Barnett, H.J.M. (1991), 35 Years of Stroke Prevention - Challenges, Disappointments

and Successes. Cerebrovascular Diseases, 1 (2), 61-70.

Abstract: Thirty-five years have demonstrated conclusively that stroke is a preventable

disease. Clinical trials have determined that: anticoagulants prevent stroke when

thrombi are in the left side of the heart and are of benefit in the presence of atrial

fibrillation. Aspirin and ticlopidine reduce the risk of stroke in symptomatic

patients. No other platelet-inhibiting drugs alone or in combination have a

proven value. Primary stroke prevention trials remain to be done in the

population most likely to benefit from aspirin. Bypass surgery has failed to

prevent stroke; patients should not be subjected to this procedure except in an

experimental setting. The appropriate indications and benefits from carotid

endarterectomy in symptomatic and asymptomatic patients remain uncertain;

present studies will give definitive answers to this 35-year-old question



Keywords: ASPIRIN/ATRIAL- FIBRILLATION/BYPASS SURGERY/CAROTID

ENDARTERECTOMY/DECLINE/EXTRACRANIAL-INTRACRANIAL

BYPASS/INTERNATIONAL RANDOMIZED TRIAL/MIDDLE

CEREBRAL-ARTERY/OCCLUSION/PLATELET

INHIBITORS/SECONDARY PREVENTION/STROKE/STROKE

PREVENTION/THROMBOEMBOLIC STROKE/UNSTABLE ANGINA



Hacke, W., Krieger, D. and Hirschberg, M. (1991), General-Principles in the Treatment

of Acute Ischemic Stroke. Cerebrovascular Diseases, 1 93-99.



Abstract: Currently, therapy of acute ischemic stroke includes general treatment, such as

pulmonary function and airway protection, cardiac care and blood pressure

management, fluid and electrolyte balance, treatment of elevated intracranial

pressure due to brain edema and specific treatment, such as restitution of

perfusion, maintenance of perfusion and increase of diminished blood flow, as

well as prevention of ischemic cellular damage. In this article, the rationale for

these therapeutic strategies is discussed and appropriate approaches to different

subgroups of strokes are proposed. These include dissection of the carotid and

vertebral arteries, basilar occlusion, middle cerebral artery occlusion, multiple

transient ischemic attacks or slowly progressive stroke due to high-grade internal

carotid artery stenosis and space-occupying cerebellar infarction. Despite the

lack of generally accepted and scientifically proven therapies, many approaches

seem promising. Individual concepts for defined stroke subgroups need to be

verified in controlled prospective multicenter trials



Keywords: ACUTE NONHEMORRHAGIC STROKE/CEREBRAL

INFARCTION/DAMAGE/DISEASE/DOUBLE-BLIND TRIAL/GENERAL

THERAPY/HEMODILUTION/ISCHEMIC STROKE/NIMODIPINE/SPECIFIC

MEDICAL AND SURGICAL THERAPY/SUBARACHNOID HEMORRHAGE



Sherman, D.G. (1992), Stroke Prevention Trials in Atrial-Fibrillation. Cerebrovascular

Diseases, 2 14-17.



Abstract: Four randomized, controlled clinical trials have been reported comparing

warfarin or aspirin to placebo for the primary prevention of stroke or systemic

embolism in patients with atrial fibrillation. Two trials studied aspirin. Control

patients in the warfarin eligible studies had stroke event rates of 4.5% per year

(3.0-7.0) compared to 1.7% per year (0.2-3.4) in the patients treated with

warfarin. One of the two studies examining aspirin found a significant reduction

in stroke whereas the other did not. Annual rates of major bleeding in the patients

treated with warfarin were less than 2%. These studies conclude that all patients

with atrial fibrillation should be treated with antithrombotic therapy to prevent

cerebral infarction. Warfarin reduces the risk of stroke by about two thirds with

an acceptable risk of bleeding



Keywords: ANTICOAGULATION/ATRIAL FIBRILLATION/CARDIOGENIC

EMBOLUS/STROKE



Anderson, D.C., Asinger, R.W., Newburg, S.M., Bundlie, S.R., Farmer, C.C., Koller,

R.L., Haugland, J.M., Nance, M.A., Tarrel, R.M., Dunbar, D.N., Jorgensen, C.R.,

Sharkey, S.W., Flaker, G.C., Webel, R., Nolte, B., Stevenson, P., Byer, J.,

Wright, W., Chesebro, J.H., Wiebers, D.O., Holland, A.E., Lee, S., Bardsley,

W.T., Kopecky, S., Litin, S.C., Meissner, I., Zerbe, D.M., Mcanulty, J.H.,

Marchant, C., Coull, B.M., Feldman, G., Hayward, A., Macmillan, K., Gandara,

E., Blank, N., Leonard, A.D., Kanter, M.C., Solomon, D., Zabalgoitia, M., Logan,

W.R., Hamilton, W.P., Green, B.J., Bacon, R.S., Janosik, D.L., Cadell, D.J.,

Kellerman, L., Gomez, C.R., Labovitz, A.J., Kelley, R.E., Chahine, R., Palermo,

M., Teixeiro, P., Feinberg, W.M., Vold, B.K., Kern, K.B., Appleton, C., Miller,

V.T., Hockersmith, C.J., Cohen, B.A., Halperin, J.L., Rothlauf, E.B., Weinberger,

J.M., Goldman, M.E., Dittrich, H.C., Rothrock, J.F., Hagenhoff, C., Helgason,

C.M., Kondos, G.T., Hoff, J., Rabjohns, R.R., Mcrae, R.P., Ghali, J., Rothbart,

R.M., Bailey, G.H., Burkhardt, C., Horwitz, L., Blackshear, J.L., Weaver, L.,

Baker, V., Lee, G., Lane, G., Rubino, F., Stafford, R., Mcbride, R., Pearce, L.,

Fossum, K., Nasco, E., Hart, R.G., Sherman, D.G., Talbert, R.L., Dacy, T.L.,

Heberling, P.A., Anderson, D.C., Halperin, J.L., Hart, R.G., Mcanulty, J.H.,

Mcbride, R., Pearce, L.A., Colton, T., Levy, D.E., Marsh, J.D., Welch, K.M.A.,

Marler, J.R. and Walker, M.D. (1992), Warfarin Compared to Aspirin for

Prevention of Arterial Thromboembolism in Atrial-Fibrillation - Design and

Patient Characteristics of the Stroke Prevention in Atrial Fibrillation-Ii Study.

Cerebrovascular Diseases, 2 (6), 332-341.



Abstract: Recent clinical trials have established that warfarin is highly effective in

reducing ischemic stroke in patients with nonvalvular atrial fibrillation, but the

relative value of aspirin compared to warfarin is less clear. We report the

rationale and design of the second phase of the Stroke Prevention in Atrial

Fibrillation (SPAF II) Study. The SPAF II Study compares warfarin (adjusted to

prolong the prothrombin time ratio 1.3-1.8 times control or INR 2-4.5) to aspirin

(325 mg/day) in a randomized clinical trial involving 1,100 patients at 16 centers.

Medications are not administered in a blind fashion; primary events (all ischemic

strokes and systemic emboli) are verified by an Events Verification Committee

who has no knowledge of treatment allocation. We hypothesize that aspirin may

be inadequately effective in patients over age 75 years and that warfarin may be

more toxic in these elderly patients. Consequently, the primary analyses of the

SPAF II Study compare the effect of antithrombotic therapies separately in

patients less-than-or-equal-to 75 years old (n = 715) and in patients > 75 years

old (n = 385). All patients have been entered and final results are expected in

1993. The mean patient age is 64 years in the younger group and 80 years in the

older group. Patients over age 75 years are more often women (p 1,900 patients, enough to

detect a 30% reduction in the frequency of stroke and death in the warfarin group

compared with aspirin if differences this large exist



Keywords: ASPIRIN/DOUBLE-BLIND/INTERNATIONAL NORMALIZED

RATION/NEW-YORK/prevention/PROTHROMBIN

TIME/RANDOMIZED/RECURRENT STROKE/stroke/TRIAL/WARFARIN



Adams, H.P., Byington, R.P., Hoen, H., Dempsey, R. and Furberg, C.D. (1995), Effect

of Cholesterol-Lowering Medications on Progression of Mild Atherosclerotic

Lesions of the Carotid Arteries and on the Risk of Stroke. Cerebrovascular

Diseases, 5 (3), 171-177.



Abstract: The Asymptomatic Carotid Artery Progression Study (ACAPS) compared the

usefulness of lovastatin alone or in combination with warfarin in the prevention

of 3-year progression of mean maximum intimal-medial thickness (IMT), which

is a measure of early atherosclerosis. The factorally desgined, placebo-

controlled study enrolled 919 men and women aged 40-79 who had moderately

elevated low-density-lipoprotein (LDL) cholesterol and a single maximum IMT

of 1.5-3.5 mm in the carotid arteries. Lovastatin significantly reduced LDL

cholesterol. The mean maximum IMT declined at an annual rate of 0.009 mm

among those persons taking lovastatin while the mean maximum IMT increased

by 0.006 mm in the controls (p = 0.001). In addition, deaths and the combined

frequency of coronary deaths, nonfatal myocardial infarctions and strokes were

significantly lowered among the lovastatin-treated groups. Only 5 strokes (3

hemorrhages) were detected in the study; all occurred among those persons who

were receiving lovastatin placebo. Our study suggests that early administration of

lipid-lowering drugs halts the progression of early atherosclerosis in the carotid

artery. In turn, such early primary preventive treatment may lessen the risk of

important ischemic vascular events including stroke



Keywords: aged/ASSOCIATIONS/ATHEROSCLEROSIS/B-MODE

ULTRASOUND/carotid/carotid arteries/CAROTID

ARTERY/cholesterol/CORONARY HEART-DISEASE/EXPANDED

CLINICAL-EVALUATION/HYPERCHOLESTEROLEMIA/HYPERLIPIDEM

IA/INTIMAL-MEDIAL

THICKNESS/LIPOPROTEINS/LOVASTATIN/LOVASTATIN

EXCEL/POPULATIONS/prevention/REGRESSION/risk/stroke/THERAPY/trea

tment/vascular/warfarin/women



Adams, H.P. and Love, B.B. (1995), Transesophageal Echocardiography in the

Evaluation of Young- Adults with Ischemic Stroke - Promises and Concerns.

Cerebrovascular Diseases, 5 (5), 323-327.



Abstract: Transesophageal echocardiography (TEE) is a valuable and sensitive test to

screen for embolic cardiac lesions. This procedure is recommended for the

evaluation of most young adults with ischemic stroke. However, several

questions about the role of TEE need to be addressed. Large studies that clarify

the influence of the results of TEE on management are needed. Additional data

about the importance of some of the findings are also needed. The prevalence

and significance of TEE-detected abnormalities such as atrial septal aneurysm,

patent foramen ovale, left atrial turbulence, left atrial appendage thrombi,

Lambl's excrescence, or a Chiari network among young adults require definition.

Thereafter, clinical trials can test interventions for primary or secondary

prevention of stroke in these cohorts



Keywords: adults/atrial septal aneurysm/ATTACKS/CARDIAC

EVALUATION/clinical

trials/DISEASE/echocardiography/evaluation/FIBRILLATION/FOCAL

CEREBRAL-ISCHEMIA/ISCHEMIC STROKE/LEFT ATRIAL

THROMBI/PATENT FORAMEN OVALE/PATIENT/prevention/secondary

prevention/stroke/SYSTEMIC EMBOLISM/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/trials/TWO-DIMENSIONAL

ECHOCARDIOGRAPHY/YOUNG ADULTS

Eriksson, S., Olofsson, B.O. and Wester, P.O. (1995), Atenolol in Secondary Prevention

After Stroke. Cerebrovascular Diseases, 5 (1), 21-25.



Abstract: This study investigated the effect of 50 mg atenolol in reducing the risk of

death, stroke and myocardial infarction after stroke and transient ischaemic

attacks (TIA). The study was designed as a Swedish multicentre, randomised,

double- blind, parallel group study with randomisation stratified according to age

and prognostic score. Seven hundred and twenty patients aged over 40 years who

had no contraindications to beta-blockers were included within 3 weeks of a

stroke or TIA, with 372 patients (mean age 70.7 years) randomised to the

treatment and 348 patients (mean age 70.1 years) to the placebo group. Major

strokes made up the index events in 81% of patients in the treatment and 79% of

those in the placebo group. The two groups were similar in respect to baseline

characteristics. The index event was classified as an ischaemic stroke in 86.8 and

86.3% of patients in the treatment and placebo groups, respectively. Side effects

of atenolol and placebo caused 17 and 10% of patients to withdraw from

allocated treatment. During the follow-up period (mean 28 months) 51 patients in

the treatment group died compared to 60 in the placebo group [relative risk with

95% confidence interval 0.79 (0.54-1.16)] and 74 patients in the treatment group

suffered a further major stroke compared to 69 in the placebo group. Twenty-six

and 29 patients, respectively, suffered an acute myocardial infarction.

Calculations using survival techniques and Cox's proportional hazard model

indicated a reduced risk of death (21%) and myocardial infarction (7%) in the

treatment group with no reduction in the risk of further stroke. None of these

reductions was statistically significant. Thus the study failed to confirm a

statistically significant reduction in death, stroke or myocardial infarction after

major stroke or TIA by 50 mg atenolol. However, the results do not exclude a

possible secondary prophylactic effect of atenolol in secondary prophylaxis after

stroke and TIA



Keywords: acute myocardial

infarction/aged/BETA-BLOCKADE/beta-blockers/CEREBROVASCULAR

DISORDER/INTERNAL/myocardial

infarction/MYOCARDIAL-INFARCTION/PROGNOSIS/PROJECT/prophylaxi

s/risk/RISK- FACTORS/SECONDARY

PROPHYLAXIS/stroke/TIA/transient/TRANSIENT ISCHEMIC

ATTACK/TRANSIENT ISCHEMIC ATTACKS/treatment



Rastenyte, D., Tuomilehto, J., Sarti, C., Cepaitis, Z. and Bluzhas, J. (1996), Trends in

the incidence and mortality of stroke in Kaunas, Lithuania, 1986-1993.

Cerebrovascular Diseases, 6 (1), 13-20.



Abstract: The trends in incidence, 28-day mortality and 28-day case fatality of stroke

during the period 1986-1993 were assessed in the population aged 35-64 years in

Kaunas, Lithuania. The Kaunas community-based stroke register was the source

of data. During the study period the incidence of stroke increased by 14% in men

and remained stable in women. The overall mortality from stroke increased by

34% in men and by 10% in women. The case fatality of all strokes as well as that

of first ever strokes increased during the study period approximately by 20%.

These results suggest that the increase in mortality from stroke in Kaunas is

mostly due to an increase in the severity of the disease, especially among men. In

addition, also the number of new stroke events increased in men, partly

explaining the larger increase in mortality from stroke observed among men than

among women. Appropriate strategies for the primary prevention of stroke are

required in Lithuania. To achieve this aim, future studies are also needed to

estimate relative and population-attributable risks for various risk factors of

stroke



Keywords: aged/ANTIHYPERTENSIVE TREATMENT/attack rate/case

fatality/COMMUNITY/DECLINE/DISEASE/FATALITY

RATES/FINLAND/incidence/INCIDENCE

RATES/Lithuania/mortality/NORTH KARELIA/prevention/primary

prevention/PROJECT/risk/risk factors/severity/stroke/women



Bogousslavsky, J., Brott, T., Diener, H.C., Fieschi, C., Hacke, W., Kaste, M., Orgogozo,

J.M. and Wahlgren, N.G. (1996), European strategies for early intervention in

stroke - A report of an Ad Hoc Consensus Group meeting. Cerebrovascular

Diseases, 6 (5), 315-324.



Abstract: Stroke is a major cause of death and disability in industrialized countries, but

stroke awareness is still generally poor and treatment often ill-defined. At a

meeting of a European Ad Hoc Consensus Group, the following

recommendations for acute stroke management were made. Need for education:

There is a clear need for stroke awareness to be increased. Use of the terms 'brain

attack' and 'brain infarction', appropriately translated into the major European

languages, can aid this process. The major target groups for educational

programmes should be the public, particularly those at risk and their spouses and

relatives, and paramedical staff. Media campaigns that inform the public what to

do and where to go/contact if a stroke occurs could significantly reduce the time

to presentation. Acute stroke care should not be promoted too aggressively or

prematurely before an adequate infrastructure is in place to successfully

administer modern evidence-based therapies. Organization of acute stroke care:

Stroke is a medical emergency. A stroke unit offers the most effective acute

stroke care in terms of both mortality and short- and long-term morbidity, and

may thereby both improve outcome and lower costs. A stroke team is an

acceptable alternative in areas where a dedicated stroke unit is not available.

Optimal acute stroke care: General guidelines should be provided on the flow of

decision-making and urgent care, with specific instructions for each stage and

event in acute stroke. It is essential that all stroke patients are admitted to

hospital quickly, ideally within the first 1-2 h. Ways must be established to

reduce transition times within the local setting when patients and/or emergency

services contact a variety of different physicians and hospitals. The minimum

emergency investigations necessary for differential diagnosis of stroke are

computed tomography (CT), Doppler ultrasonography, electrocardiography

(ECG) and blood tests. These must be available 24 h/day and be performed

without delay. General medical measures should be instituted as necessary, even

before CT scanning, with reference to the potential particular complications of

acute stroke. Acute stroke patients should be monitored continuously or at

frequent intermittent intervals throughout the first 24 h with respect to blood

pressure, ECG, respiration, temperature and oxygen saturation. In carefully

selected patients, thrombolysis with recombinant tissue plasminogen activator

(rt-PA) may be indicated (if approved by regional registration agencies). This

must be administered under specialist supervision, and on a dedicated intensive

care or intensive stroke care unit. Careful selection of eligible patients is

paramount. Thrombolysis with streptokinase is not recommended, due to the

excessive risk of haemorrhage. If these measures and early secondary prevention

are implemented, it will be possible to improve stroke outcome and reduce the

cost of acute and chronic stroke care. New agents for acute stroke treatment, e.g.

the neuroprotectants currently being evaluated in phase III trials, should also

contribute to improved outcomes



Keywords: ACUTE ISCHEMIC STROKE/CT/DIAGNOSIS/DOUBLE-BLIND/early

intervention/education/future therapeutic

opportunities/HYPERTENSION/INTENSIVE-CARE/INTRAVENOUS

GLYCEROL/MANAGEMENT/morbidity/mortality/PREVENTION/RANDOMI

ZED TRIAL/secondary prevention/stroke/stroke management/stroke

outcome/stroke treatment/stroke units/THERAPY/thrombolysis/thrombolytic

therapy/treatment/trials



Bath, P.M.W., Soo, J., Butterworth, R.J. and Kerr, J.E. (1996), Do acute stroke units

improve care? Cerebrovascular Diseases , 6 (6), 346-349.



Abstract: Background and Purpose: Stroke rehabilitation units have been shown to

improve mortality and reduce morbidity and hospital length of stay as compared

with conventional medical ward care. In contrast, the effectiveness of acute

stroke units (ASUs), which only provide early in-patient care, is unknomn. We

have compared ASU care with that administered on a general medical or

geriatric ward. Methods: Historical comparison of 116 consecutive patients

admitted to a new ASU during the 6-month period from February to July 1994

with 128 consecutive patients admitted to general medical or geriatric wards

during the previous 6-month period (August 1993 to January 1994). Results:

Admission baseline characteristics were similar between the two groups, As

compared with conventional general ward care, patients admitted to the ASU had

a shorter stay in casualty, 6 h (4-6) versus 7 h (4-11; 2p = 0.03); reduced length

of stay in hospital, 20 days (10-55) versus 31 days (13-80; 2p = 0.09); increased

carotid Doppler investigation, 40/94 versus 25/101 (2p = 0.013) increased

prescription of secondary prevention measures, aspirin 49/94 versus 33/101 (2p

= 0.009) or treatment of hypertension 19/50 versus 5/47 (2p = 0.004); improved

outcome, home: institution:death, 69:11:18 versus 63:13:32 (2p = 0.049).

Conclusion: ASUs appear to contribute to improved care (investigations,

secondary prevention) and outcome following stroke whilst patients spend less

time in hospital



Keywords: acute stroke

unit/aspirin/hypertension/INTENSIVE-CARE/morbidity/mortality/secondary

prevention/stroke/stroke intensive-care unit/stroke management



Rudd, A. and Wolfe, C.D.A. (1996), Developing a district stroke service.

Cerebrovascular Diseases, 6 (2), 89-96.



Abstract: Stroke is responsible for a significant proportion of acute admissions to

hospital and for long-term disability. Large amounts of money are spent on

prevention and treatment, but many of the components of management are of

unproven value. Effective organisation of care, as with other chronic diseases,

may significantly improve outcome. This paper describes the components

necessary for a stroke service, based on published evidence and practical

experience in developing such a service in an inner-city district



Keywords: CARE/CASE FATALITY/COMMUNITY/CONTROLLED

TRIAL/DISEASE/diseases/organisation of

care/PHYSIOTHERAPY/prevention/REHABILITATION/SOUTHERN

ENGLAND/stroke/treatment



Mant, J., Hicks, N., Rosenberg, W. and Sackett, D. (1996), How to use overviews of

prevention trials to treat individual patients. Cerebrovascular Diseases, 6 34-39



Keywords:

ATRIAL-FIBRILLATION/CLINICAL-TRIALS/IMPACT/MYOCARDIAL-IN

FARCTION/prevention/STROKE/trials



Easton, J.D. (1997), Epidemiology of stroke recurrence. Cerebrovascular Diseases, 7

2-4



Keywords:

ASPIRIN/CEREBRAL-ISCHEMIA/CEREBROVASCULAR-DISEASE/COM

MUNITY/epidemiology/EVENTS/INFARCTION/recurrence/recurrent

stroke/RISK/risk factors/SECONDARY

PREVENTION/stroke/TICLOPIDINE/TRANSIENT ISCHEMIC ATTACK



Sandercock, P. and Tangkanakul, C. (1997), Very early prevention of stroke recurrence.

Cerebrovascular Diseases, 7 10-15



Keywords: ACUTE ISCHEMIC STROKE/ANTICOAGULATION/CEREBRAL

INFARCTION/COMMUNITY/DISEASE/EMBOLISM/MORTALITY/NONVA

LVULAR

ATRIAL-FIBRILLATION/prevention/PROGNOSIS/recurrence/recurrent

stroke/stroke/stroke prevention/TRIAL/TRIALS

vanGijn, J. and Algra, A. (1997), Secondary stroke prevention with antithrombotic drugs:

What to do next? Cerebrovascular Diseases, 7 30-32



Keywords:

AORTIC-ARCH/ASPIRIN/CEREBRAL-ISCHEMIA/DIPYRIDAMOLE/drugs/

INTENSITY/prevention/RISK/stroke/stroke prevention/TRIAL/WARFARIN



Dyken, M.L. (1997), Aspirin with and without dipyridamole. Cerebrovascular Diseases,

7 10-16



Keywords:

ACETYLSALICYLIC-ACID/ATHEROSCLEROSIS/CEREBRAL-ISCHEMIA/

CONTROLLED TRIAL/dipyridamole/GENERATION/INDUCED

PLATELET-AGGREGATION/LOW-DOSE ASPIRIN/PERIPHERAL

VASCULAR-DISEASE/SECONDARY PREVENTION/STROKE



Butterworth, R.J., Marshall, W.J. and Bath, P.M.W. (1997), Changes in serum lipid

measurements following acute ischaemic stroke. Cerebrovascular Diseases, 7

(1), 10-13.



Abstract: Strong observational and interventional evidence exists linking

hypercholesterolaemia terolaemia and coronary heart disease, such that lowering

total cholesterol significantly reduces cardiovascular morbidity and mortality.

Increasingly, data LDL cholesterol suggest that hypercholesterolaemia is also an

important factor in cerebrovascular atherosclerosis, and possibly for subsequent

ischaemic stroke. Measurement of serum cholesterol fractions following acute

myocardial infarction must be performed within the first 48 h or delayed for 3

months because serum cholesterol levels significantly fall during the first week.

We have studied the temporal changes in serum cholesterol fractions and

triglycerides following ischaemic stroke in 72 patients. Significant falls in total

cholesterol (TC) as well as HDL and LDL cholesterol were seen during the first

week whilst levels normalised by 3 months; TC mean (SD in parentheses)

mmol/l, admission vs. 1 week, 5.54 (1.32) vs. 5.13 (1.07), n = 72, 2p 220

mm Hg, or mean arterial blood pressure (MABP) > 140 mm Hg]. As a general

guide, MABP should be lowered by decrements no larger than 15 mm Hg.

Antihypertensive agents should be chosen appropriately to avoid increases in

cerebrovascular blood volume or ICP. An antipyretic and/or an antibiotic should

be given immediately for raised temperature, possibly with a cooling blanket,

and subcutaneous or intravenous insulin should be used for markedly elevated

blood glucose levels. Prophylaxis against deep vein thrombosis and pulmonary

embolism is indicated in all acute stroke patients, but anticoagulation should be

avoided in those with large intracranial haemorrhage and in selected

neurosurgical patients. Physiotherapy as well as speech and occupational therapy

should be started as early as possible. The Need for Neurological Intensive Care:

Neurological ICUs can improve the survival and outcome of those acute stroke

patients who require intensive care. Aggressive approaches to acute stroke

therapy, e.g. hypervolaemic- hypertensive therapy, ventricular drainage,

decompressive surgery, or experimental use of thrombolytic agents, require

management in a specialized neurological ICU. About 10% of hospitalized acute

stroke patients require ICU care, which is best provided by staff with specialized

training in neurological care. The minimum requirements for optimal

neurological intensive care are a 24-hour neurologist or neurointensivist shift

sei-vice, 1 nurse per patient in attendance at all times, and facilities for advanced

haemodynamic, neurological and ICP monitoring



Keywords: ACUTE ISCHEMIC STROKE/acute stroke

management/anticoagulation/blood

pressure/cerebral/cerebrovascular/complications/computed

tomography/costs/education/embolism/EMERGENCY/emergency care

organization/evaluation/glucose/HEMISPHERIC

INFARCTION/hospital/HYPERTENSION/incidence/infarction/intracranial

pressure/INTRACRANIAL-

PRESSURE/MANAGEMENT/monitoring/mortality/myocardial/myocardial

infarction/neurointensive care/prevention/prognosis/protocols/pulmonary

embolism/RANDOMIZED CONTROLLED TRIAL/rehabilitation/risk/risk

factor/secondary prevention/stroke/stroke intensive care/stroke

units/surgery/therapy/thrombolytic

agents/thrombosis/TISSUE-PLASMINOGEN-ACTIVATOR/treatment/UNIT/U

RGENT THERAPY



Hankey, G.J. (1998), One year after CAPRIE, IST and ESPS 2 - Any changes in

concepts? Cerebrovascular Diseases, 8 1-7.



Abstract: The IST, CAPRIE and ESPS-2 have shown that large collaborative

randomised trials can be conducted in stroke medicine and can provide

statistically and clinically significant results. They, and other concurrent studies,

have highlighted the potential hazards of early anticoagulation, and the

effectiveness and safety of early (and continuous) antiplatelet therapy in limiting

early stroke recurrence and its consequences. In addition, they have shown that

antiplatelet agents with differing mechanisms of action can have different effects,

and perhaps additive effects when combined. The ESPRIT trial should delineate

the roles of oral anticoagulant therapy, and the combination of aspirin and

dipyridamole, in the prevention of stroke due to arterial disease. Future trials will

hopefully determine the role in secondary stroke prevention of inhibitors of the

platelet GPIIb/IIIa complex (the final common pathway of platelet aggregation),

the combination of anitplatelet agents with different mechanisms of action (e.g.

aspirin and clopidogrel, aspirin and IIb/IIIa inhibitors), the combination of

antiplatelet agents and oral anticoagulants (which may simultaneously modify

platelet function and fibrin production), and the combination of antithrombotic

and cholesterol-lowering (statin) medications



Keywords:

aggregation/anticoagulant/ANTICOAGULANTS/anticoagulation/ANTIPLATE

LET/antiplatelet agents/antiplatelet therapy/antithrombotic

therapy/ASPIRIN/Australia/CEREBRAL- ISCHEMIA/clinical

trials/clopidogrel/DIPYRIDAMOLE/fibrin/new concepts/platelet

aggregation/PLATELET-AGGREGATION/prevention/recurrence/safety/stroke/

STROKE PREVENTION/stroke

prevention/THERAPY/TICLOPIDINE/TRANSIENT ISCHEMIC

ATTACKS/trials



Auburger, G. (1998), New genetic concepts and stroke prevention. Cerebrovascular

Diseases, 8 28-32.



Abstract: So far, stroke genetics has the reputation of daunting complexity and

heterogeneity. However, progress through efforts at studying the human genome

has provided novel technologies and focus, and 12 stroke genes or loci have

already been identified in the last years, usually through the study of large

pedigrees. However, particularly little is known about the ischemic form of

stroke, and only recently could one chromosomal locus be shown to exert a

major effect on stroke latency and outcome - through QTL studies in mouse

strains. Whether the outstanding role of this one gene locus is also true in

humans should be tested in linkage analyses of large pedigrees. The

characterization of such families will probably be essential for progress in

molecular genetics of ischemic stroke as well as being a challenge for clinical

stroke centers



Keywords: ADULT-ONSET/BLOOD-PRESSURE/CEREBRAL CAVERNOUS

MALFORMATION/CEREBROVASCULAR-DISEASE/FAMILIAL

HEMIPLEGIC MIGRAINE/genes/genetic/HEMORRHAGE/HUMAN

HYPERTENSION/ischemic stroke/linkage/LOCUS/MISSENSE

MUTATION/NOTCH3 MUTATIONS/prevention/QTL/stroke/stroke prevention



Al Rajeh, S., Larbi, E.B., Bademosi, O., Awada, A., Yousef, A., Al Freihi, H. and

Miniawi, H. (1998), Stroke register: Experience from the Eastern Province of

Saudi Arabia. Cerebrovascular Diseases, 8 (2), 86-89.



Abstract: A stroke registry was established in the Eastern Province of Saudi Arabia with

an estimated population of 750,000 inhabitants of whom 545,000 are Saudi

citizens. The register started in July 1989 and ended in July 1993. The Gulf war

led to its interruption from August 1990 to August 1991. Four hundred

eighty-eight cases (314 males, 174 females) of first- ever strokes affecting Saudi

nationals were registered over the 3-year period. The crude incidence rate for

first-ever strokes was 29.8/100,000/year (95% CI: 25.2-34.3/100,000 year).

When standardized to the 1976 US population, it rose up to 125.8/100,000/year.

Ischemic strokes (69%) predominated as in other studies but subarachnoid

hemorrhage (SAH) was extremely rare (1.4%). The important risk factors were:

systemic hypertension (38%), diabetes mellitus (37%), heart disease (27%),

smoking (19%) and family history of stroke (14%), Previous transient ischemic

attacks (3%) and carotid bruits (1%) were uncommon. The 30-day case fatality

rate was 15%, The study showed that the age-adjusted stroke incidence rate for

Saudis in this region is lower than the rates reported in developed countries but

within the range reported worldwide. The pattern of stroke in Saudi Arabia is not

different from that reported in other communities with the exception of the low

Incidence of SAH. The risk factors are similar to findings in other studies except

for the high frequency of diabetes mellitus in our cases, The lower mortality rate

was probably due to the younger age of the population and the availability of free

medical services for management of cases



Keywords: age/carotid/case fatality/cerebrovascular

disease/CEREBROVASCULAR-DISEASE/COMMUNITY/diabetes/diabetes

mellitus/epidemiology/heart/hemorrhage/history/hypertension/incidence/mortalit

y/OXFORDSHIRE/PATTERN/PREVENTION/risk/risk factors/Saudi

Arabia/smoking/stroke/subarachnoid hemorrhage/transient



Dyken, M.L. (1998), Reply - Aspirin dose in secondary prevention of stroke.

Cerebrovascular Diseases, 8 (6), 361-362



Keywords: DIPYRIDAMOLE/prevention/secondary prevention/stroke/TRIAL

Meyer, B.J. (1998), Antithrombotic drugs: Insights from cardiology. Cerebrovascular

Diseases, 8 19-27.



Abstract: The primary purpose of this overview is to provide an update on the newer

antiplatelet drugs evaluated in clinical trials and introduced in clinical practice of

modern cardiology. Despite the remarkable clinical developments with the use of

new antiplatelet drugs, several fundamental issues remain unresolved. Some of

the observed safety/efficacy problems in major clinical trials can be directly

attributed to the lack of careful phase II studies where issues such as monitoring,

pharmacological profiles, and individual response variations were not considered

sufficiently. Nevertheless, none of the available antiplatelet agents meet all the

criteria of an ideal antiplatelet agent. Aspirin has been the standard reference

agent in cardiovascular disease. However, it is a weak and nonselective

antiplatelet compound and is unable to interfere substantially with the

thrombogenic activity of a fresh mural thrombus of a stenosed vessel. The newer

antiplatelet drug classes such as the ADP receptor blockers (ticlopidine,

clopidogrel) and the platelet glycoprotein IIb/IIIa receptor inhibitors produce

their therapeutic effects by distinct mechanisms which differ from aspirin. Large

clinical trials have documented their efficacy in acute coronary syndromes

associated with intracoronary thrombus formation. The future challenge is to

evaluate long-term treatment strategies which are equally safe but distinctly more

effective than aspirin, e.g. a combination therapy with aspirin and clopidogrel or

oral GP IIb/IIIa receptor antagonists



Keywords: ABCIXIMAB/acute coronary syndromes/ADP/antiplatelet

agents/antiplatelet drugs/aspirin/C7E3 FAB/cardiovascular disease/clinical

trials/clopidogrel/coronary artery disease/CORONARY

INTERVENTION/DISEASE/formation/GLYCOPROTEIN IIB/IIIA

ANTAGONIST/MYOCARDIAL-INFARCTION/platelet glycoprotein IIb/IIIa

receptor inhibitors/PREVENTION/RANDOMIZED

TRIAL/STROKE/thienopyridines/thrombus/ticlopidine/treatment/trials/UNSTA

BLE ANGINA



Devuyst, G., Paciaroni, M. and Bogousslavsky, J. (1999), Secondary stroke prevention:

A European perspective. Cerebrovascular Diseases, 9 29-36



Keywords: ATRIAL-FIBRILLATION/CAROTID

ENDARTERECTOMY/CHOLESTEROL/EVENTS/METAANALYSIS/PATEN

T FORAMEN OVALE/prevention/RECURRENCE/RISK/stroke/stroke

prevention/THERAPY/TICLOPIDINE ASPIRIN STROKE



[Anon]. (1999), Antiplatelets, therapy for stroke prevention. Cerebrovascular Diseases,

9 41-45



Keywords: prevention/stroke/stroke prevention/therapy



[Anon]. (1999), Anticoagulant therapy and stroke prevention. Cerebrovascular Diseases,

9 47-52

Keywords: prevention/stroke/stroke prevention/therapy



Cheung, R.T.F., Li, L.S.W., Mak, W., Tsang, K.L., Lauder, I.J., Chan, K.H. and Fong,

G.C.Y. (1999), Knowledge of stroke in Hong Kong Chinese. Cerebrovascular

Diseases, 9 (2), 119-123.



Abstract: A random telephone survey on knowledge of stroke was conducted in 1,238

Hong Kong Chinese. Most respondents realized that effective treatment was

available, that stroke was preventable and that it could be fatal or disabling.

Sudden unilateral limb weakness, sudden speech and language disturbances, and

sudden vertigo and clumsiness were better recognized than other warning

symptoms of stroke. A slightly better recognition of symptoms of stroke was

seen in those with a belief of knowing about stroke, providing a correct

description of stroke, those with a positive household history of stroke and those

with a better knowledge of potential risk factors. Most respondents would choose

desirable actions if stroke was suspected in their family members or themselves.

Friends and relatives, newspapers and magazines, and mass media provided the

major sources of their knowledge



Keywords: Chinese/history/Hong Kong/knowledge/PREVENTION/risk/risk

factors/stroke/survey/THROMBOLYSIS/treatment



[Anon]. (1999), Stroke prevention in atrial fibrillation and other cardiac sources of

embolism. Cerebrovascular Diseases, 9 53-61



Keywords: ANTICOAGULANT-THERAPY/ANTITHROMBOTIC

TREATMENT/ASPIRIN/atrial

fibrillation/embolism/fibrillation/MANAGEMENT/prevention/RANDOMIZED

TRIALS/TRANSIENT ISCHEMIC ATTACKS/WARFARIN



van Gijn, J. and Algra, A. (1999), Secondary stroke prevention with drugs: Single or

combined therapy? Cerebrovascular Diseases, 9 24-28



Keywords:

ACETYLSALICYLIC-ACID/ANTICOAGULANT-THERAPY/CEREBRAL-IS

CHEMIA/CONTROLLED TRIAL/DIPYRIDAMOLE/drugs/LOW-DOSE

ASPIRIN/Netherlands/prevention/stroke/stroke

prevention/therapy/TICLOPIDINE/WARFARIN



Sacco, R.L. (1999), Secondary prevention of ischemic stroke: A 1998 US perspective.

Cerebrovascular Diseases, 9 37-44



Keywords: ASPIRIN/CAROTID

ENDARTERECTOMY/INFARCTION/ischemic/ischemic

stroke/LEHIGH-VALLEY/MORTALITY/prevention/RECURRENCE/RISK-FA

CTORS/STENOSIS/stroke/TICLOPIDINE/WARFARIN

Bornstein, N.M., Gur, A.Y., Fainshtein, P. and Korczyn, A.D. (1999), Stroke during

sleep: Epidemiological and clinical features. Cerebrovascular Diseases, 9 (6),

320-322.



Abstract: Stroke during sleep is an unexplored area of vascular neurology and its

pathogenesis; clinical significance and prevention still remain uncertain. The aim

of our study was to determine the epidemiological and clinical patterns of

ischemic stroke occurring during sleep. Consecutive patients (n = 1822) with

acute ischemic stroke recorded in the Tel Aviv Stroke Register were studied.

Stroke during sleep was determined whenever focal neurological deficit was

verified to have occurred while the patient had been asleep. The comparisons

between patients with stroke during sleep and while awake were performed using

the t test with Bonferroni correction and the chi(2) test for age, sex, vascular risk

factors (i.e. ischemic heart disease, myocardial infarction, atrial fibrillation,

arterial hypertension, hyperlipidemia, diabetes mellitus, peripheral vascular

disease, smoking), vascular distribution (carotid versus vertebrobasilar) and

severity of stroke (mild, moderate or severe). Data regarding the onset of stroke

(during sleep or while awake) were available for 1,671 patients. A minority of

strokes occurred during sleep (n = 311, 18.6%), and stroke during sleep was

severer (chi(2) = 11.9, p 30 mu mol/l) and 20.2% in the other group (log- rank test

7.5; p = 0.0062). After adjustment for age, sex, high blood pressure, diabetes,

heart disease, previous cerebrovascular disease, smoking and serum cholesterol,

the relative risk of vascular event for patients above compared with those below

the 75th percentile of serum homocyst(e)ine was 2.8 (Cl 95% 1.3-6; p = 0.01).

Conclusion: Hyperhomocyst(e)inemia is a significant risk factor for vascular

events after ischemic stroke. This finding is independent of other risk factors

such as hypertension, and may have therapeutic relevance in the secondary

prevention of vascular diseases in stroke patients, Copyright (C) 2001 S. Karger

AG, Basel



Keywords: age/arterial/blood pressure/BRITISH MEN/cerebrovascular/cerebrovascular

disease/cholesterol/deep venous

thrombosis/DETERMINANTS/diabetes/DISEASE/diseases/ELEVATED

PLASMA HOMOCYST(E)INE/heart/heart disease/high blood

pressure/homocyst(e)ine/HOMOCYSTEINE LEVELS/HORDALAND

HOMOCYSTEINE/HYPERHOMOCYSTEINEMIA/hypertension/ischemic/isch

emic heart disease/ISCHEMIC STROKE/peripheral arterial

disease/prevention/recurrence/relative risk/risk/risk factor/risk

factors/secondary/secondary prevention/serum/sex/smoking/Spain/stroke/stroke

recurrence/thrombosis/vascular/vascular event/VENOUS

THROMBOSIS/VITAMIN STATUS



Lechat, P., Lardoux, H., Mallet, A., Sanchez, P., Derumeaux, G., Lecompte, T., Maillard,

L., Mas, J.L., Mentre, F., Pousset, F., Lacomblez, I., Pisica, G., Solbes-Latourette,

S., Raynaud, P. and Chaumet-Riffaud, P. (2001), Anticoagulant

(fluindione)-aspirin combination in patients with high-risk atrial fibrillation - A

randomized trial (fluindione, fibrillation auriculaire, aspirin et contraste spontane;

FFAACS). Cerebrovascular Diseases, 12 (3), 245-252.



Abstract: Background: A combination of low-dose aspirin with anticoagulants may

provide better protection against thromboembolic events compared to

anticoagulants alone in high- risk patients with atrial fibrillation. Objective:

Evaluation of the preventive efficacy against nonfatal thromboembolic events

and vascular deaths of the combination of the oral anticoagulant fluindione and

aspirin (100 mg) in patients with high-risk atrial fibrillation. Methods: A

multicenter, placebo- controlled, double-blind, randomized trial was conducted at

49 investigating centers in France. Atrial fibrillation patients with a previous

thromboembolic event or older than 65 years and with either a history of

hypertension, a recent episode of heart failure or decreased left ventricular

function were included in the study. Patients were treated with fluindione plus

placebo (i.e. anticoagulant alone) or fluindione plus aspirin (i.e. combination

therapy), with an international normalized ratio target of between 2 and 2.6. The

combined primary endpoint was stroke (ischemic or hemorrhagic), myocardial

infarction, systemic arterial emboli or vascular death. The secondary endpoint

was the incidence of hemorrhagic complications. Results: The 157 participants

(average age 74 years; 52% women; 42% with paroxysmal atria[ fibrillation)

were followed for an average of 0.84 years. Three nonfatal thromboembolic

events were observed (1 in the anticoagulation group, 2 in the combination group)

and 6 patients died (3 in the anticoagulation group, 3 in the combination group),

none of them from a thromboembolic complication. However, 3 deaths were

secondary to severe hemorrhagic complications (1 in the anticoagulation group, 2

in the combination group). Nonfatal hemorrhagic complications occurred more

often in the combination group (n = 10, 13.1%) compared to the anticoagulation

group (n = 1, 1.2%) (p = 0.003). Conclusion:The combination of aspirin with

anticoagulant is associated with increased bleeding in elderly atrial fibrillation

patients. The effect on thromboembolism and the overall balance of benefit to

risk could not be accurately assessed in this study due to the limited number of

ischemic events. Copyright(C) 2001 S. Karger AG, Basel



Keywords: age/anticoagulant/anticoagulants/anticoagulation/aspirin/atrial

fibrillation/bleeding/bleeding complications/combination/combination

therapy/complications/death/elderly/emboli/fibrillation/fluindione/heart/heart

failure/high risk/history/hypertension/incidence/infarction/international

normalized ratio/ischemic/left

ventricular/METAANALYSIS/myocardial/myocardial

infarction/PLACEBO/PREVENTION/primary/protection/randomized/randomize

d trial/risk/secondary/SPONTANEOUS ECHO

CONTRAST/STROKE/THERAPY/thromboembolic

complications/thromboembolic

events/THROMBOEMBOLISM/trial/vascular/WARFARIN/women



Bogousslavsky, J. (2001), Benefit of ADP receptor antagonists in atherothrombotic

patients: New evidence. Cerebrovascular Diseases, 11 5-10.



Abstract: In the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events

(CAPRIE) trial, clopidogrel showed a statistically significant superiority over

aspirin in the prevention of ischaemic stroke, myocardial infarction and vascular

death in patients with symptomatic atherosclerosis. More recently, post-hoc

analysis of the data also showed that repeat hospitalization for ischaemic or

bleeding events was decreased with clopidogrel compared with aspirin.

Complementary analyses show that the benefit of clopidogrel over aspirin is

amplified in a large population at very high risk of further atherothrombotic

events (diabetics, patients with high cholesterol, and patients with previous

manifestations of atherothrombosis). A potential clinically useful advantage of

clopidogrel is its low propensity for adverse interaction with

angiotensin-converting enzyme (ACE) inhibitors, contrary to what may be seen

with aspirin, as observed in a post-hoc CAPRIE analysis. The putative

aspirin-ACE inhibitor interaction is being tested prospectively in the Warfarin

and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial - a

randomized comparison of warfarin, clopidogrel and aspirin in patients with

chronic heart failure. The good gastrointestinal tolerance of clopidogrel seen in

CAPRIE has been further demonstrated in a study in healthy volunteers where

there was a markedly lower gastroduodenal erosion score after 8 days'

administration of clopidogrel 75 mg/day compared with aspirin 325 mg/day (p 70% by angiogram) stenosis should receive carotid

endarterectomy, provided the operative risk is 2.0) for at least 3 weeks before and 4 weeks after successful CV. In all

patients, exclusion of internal carotid artery stenosis and atrial thrombus was

performed prior to CV. Five unilateral 1-hour transcranial Doppler ME

monitorings over the middle cerebral artery were performed (1) before CV, and

(2) immediately, (3) 4-6 h, (4) 24 h, and (5) 2-4 weeks after CV. Total absence of

circulating ME was found before CV as well as during a cumulative monitoring

time of 115 h after successful CV. Electrical CV of AF after at least 3 weeks of

effective anticoagulation is not associated with occurrence of cerebral circulating

ME. This finding requires further investigation including high-risk patients with

AF undergoing CV based on different treatment protocols. Copyright (C) 2001 S.

Karger AG, Basel

Keywords: AF/aged/ANTICOAGULATION/APPENDAGE

FUNCTION/ASYMPTOMATIC EMBOLIZATION/atrial

fibrillation/cardioversion/carotid/carotid artery/carotid artery

stenosis/CAROTID-ARTERY STENOSIS/cerebral/cerebral artery/CEREBRAL

MICROEMBOLISM/diagnostic/Doppler/embolism/fibrillation/formation/Germa

ny/high risk/INR/INTENSITY TRANSIENT SIGNALS/internal carotid

artery/men/microemboli/middle cerebral artery/monitoring/oral

anticoagulation/prevention/protocols/RISK/stenosis/stroke/THERAPY/thrombus

/transcranial/TRANSCRANIAL DOPPLER/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/treatment/ultrasonography



Diez-Tejedor, E. and Fuentes, B. (2001), Acute care in stroke: Do stroke units make the

difference? Cerebrovascular Diseases , 11 31-39.



Abstract: The consideration of stroke as a medical emergency and the development of

new specific treatments to be applied in a narrow therapeutic window have

shown the need to establish an adequate organization system for the management

of stroke. It should be considered as an integral process both outside and inside

the hospital. General care is essential and must already start outside the hospital,

and comprises respiratory and cardiac care, fluid and metabolic management,

especially blood glucose control, avoiding the administration of glucose

solutions, blood pressure control, early treatment of hyperthermia and prevention

and treatment of neurologic and systemic complications. In the early 70s, the

first stroke units (SU) were established as intensive-care SU, but failed to show

improvement in terms of reduction of mortality-morbidity. Nowadays, the

concept has changed to a non-intensive-ca re SU. The benefit of these SU has

been amply demonstrated in terms of reduction in mortality and in long

institutionalization, as well as better functional outcome compared with general

wards, and the efficacy of a neurology ward compared to a general medicine

department has also been shown, but at the moment there are no studies

analyzing the differences between a stroke team (ST) in a department of

neurology and a SU. In this regard, we have performed a sequential analysis

comparing both SU and ST and demonstrated a reduction in length of stay,

complications and acute care costs with an improvement in functional state at

hospital discharge, a reduction in the discharge to nursing homes with an

increase in patients translated into rehabilitation wards. With these data, we can

conclude that SU, not ST are the most effective organizational model for acute

stroke management. Definitely, the SU make the difference. Copyright (C) 2001

S. Karger AG, Basel



Keywords: acute/acute stroke/acute stroke care/acute stroke

management/administration/ADMISSION/BENEFITS/blood pressure/blood

pressure control/cardiac/cerebral

infarction/complications/control/COSTS/development/essential/glucose/hospital/

hyperthermia/intensive care/INTENSIVE-CARE/ISCHEMIC STROKE/length

of stay/MANAGEMENT/medical/MORTALITY/neurology/nursing/nursing

homes/outcome/prevention/RANDOMIZED CONTROLLED

TRIAL/REHABILITATION/Spain/stroke/stroke management/stroke team/stroke

unit/stroke units/treatment



Hacke, W. (2002), From CURE to MATCH: ADP receptor antagonists as the treatment

of choice for high-risk atherothrombotic patients. Cerebrovascular Diseases, 13

22-26.



Abstract: Patients with a clinical manifestation of atherothrombosis such as a recent

ischaemic cerebrovascular event are at high risk of subsequent events.

Atherothrombosis often reflects disseminated disease; thus, further events may

occur not only in the same arterial distribution but also in other vascular beds. To

achieve adequate secondary prevention in these patients, long- term antiplatelet

therapy with consistent benefit across the atherothrombosis spectrum is required.

In the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic

Events) Trial, clopidogrel (clopidogrel bisulphate) was superior to acetylsalicylic

acid (ASA) in reducing the combined risk of ischaemic stroke (IS), myocardial

infarction (MI) or vascular death in patients with symptomatic atherosclerosis.

Post hoc analyses demonstrated that the benefit of clopidogrel was amplified in

high-risk patients, including patients with a history of previous ischaemic events,

diabetic patients and patients with hypercholesterolaemia. The synergistic

antiplatelet effect produced by using clopidogrel on top of ASA may be

beneficial in high-risk patients. The benefit of dual antiplatelet therapy was

recently examined in the CURE (Clopidogrel in Unstable Angina to Prevent

Recurrent Events) Study, which demonstrated that long-term treatment with

clopidogrel on top of standard therapy including ASA was superior to standard

therapy alone in the prevention of major vascular ischaemic events in patients

with unstable angina or non-Q-wave MI. The ongoing MATCH (Management of

Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient

Ischaemic Attack or Ischaemic Stroke) trial will evaluate the efficacy and safety

of clopidogrel plus ASA versus clopidogrel alone in patients with recent transient

ischaemic attack (TIA) or IS and with at least one additional risk factor.

Approximately 7,600 patients will be enroled, with treatment and follow-up for

each patient lasting 18 months. The primary combined efficacy endpoint will be

the first occurrence of an event in the composite of IS, MI, vascular death or

rehospitalization for an acute ischaemic event during the follow-up period.

MATCH will explore the potential benefit of clopidogrel in high-risk stroke/TIA

patients and together with CAPRIE and CURE could provide further evidence of

the long-term benefit of clopidogrel in patients with major atherothrombotic

manifestations. Copyright (C) 2002 S. Karger AG, Basel



Keywords: acetylsalicylic acid/acute/ADP/ADP receptor/angina/antiplatelet/antiplatelet

therapy/arterial/ASPIRIN/atherosclerosis/atherothrombosis/cerebrovascular/cere

brovascular

event/clopidogrel/CLOPIDOGREL/COMBINATION/death/disease/Germany/hi

gh

risk/history/hypercholesterolaemia/infarction/INHIBITION/ischaemic/ischaemic

stroke/myocardial/myocardial infarction/prevention/primary/risk/risk factor/risk

of ischaemic stroke/safety/secondary/secondary

prevention/STENT/stroke/THERAPY/THROMBOGENESIS/TIA/TICLOPIDIN

E/transient/transient ischaemic attack/treatment/trial/unstable angina/vascular



Alberts, M.J. (2002), Secondary prevention of stroke and the expanding role of the

neurologist. Cerebrovascular Diseases, 13 12-16.



Abstract: Stroke is the leading cause of adult disability and dependency in western

society. Following stroke, the risk of myocardial infarction (MI) is increased by a

factor of around 2-3 compared with baseline. Indeed, after the first 30 days,

stroke survivors are more likely to die from a cardiac event than from a

cerebrovascular event. In patients with atherothrombotic stroke, preventing

subsequent manifestations of the underlying disease is therefore an important

therapeutic goal. A number of options have been shown to reduce the risk of

stroke. Aggressively controlling stroke risk factors, such as hypertension,

diabetes and smoking, should provide significant benefit in reducing stroke risk;

however, it is difficult to realize the full potential of these approaches in routine

clinical practice. A number of classes of medication can reduce the risk of stroke

and other vascular events, including antiplatelet agents, anticoagulants,

angiotensin-converting enzyme inhibitors and statins. Several antiplatelet agents

are approved to reduce the risk of recurrent stroke, although only clopidogrel and

acetylsalicylic acid (ASA) are approved for the reduction of both stroke and MI

in such patients. In the CAPRIE study, clopidogrel showed a statistically

significant relative risk reduction of 8.7% (p = 0.043) compared with ASA for

the composite endpoint of ischaemic stroke, MI or vascular death. Evidence from

animal studies, ex vivo models in humans, and patients undergoing coronary

stent insertion or patients with unstable angina/non-Q-wave MI clearly

demonstrates the synergistic antiplatelet effect of using clopidogrel with ASA. In

summary, most patients with an ischaemic stroke should be treated with an

antiplatelet agent to reduce their risk of recurrent stroke, MI, or vascular death.

The use of aggressive antiplatelet therapy has the potential to become a new

paradigm for managing patients with vascular disease due to atherothrombosis.

Copyright (C) 2002 S. KargerAG, Basel



Keywords: acetylsalicylic acid/angiotensin converting enzyme

inhibitors/angiotensin-converting enzyme

inhibitors/animal/anticoagulants/antiplatelet/antiplatelet agents/antiplatelet

therapy/ASPIRIN/atherothrombosis/BENEFIT/CAPRIE

study/cardiac/CAROTID

ENDARTERECTOMY/cerebrovascular/cerebrovascular event/clinical

practice/CLOPIDOGREL/coronary

stent/death/dependency/diabetes/DIPYRIDAMOLE/disability/disability and

dependency/DISEASE/humans/hypertension/infarction/ischaemic/ischaemic

stroke/myocardial/myocardial infarction/neurologist/prevention/recurrent

stroke/relative risk/RISK/risk

factors/smoking/statins/STENT/stroke/therapy/TICLOPIDINE/use/vascular/vasc

ular disease/vascular events

Schmidt, R., Schmidt, H., Kapeller, P., Lechner, A. and Fazekas, F. (2002), Evolution of

white matter lesions. Cerebrovascular Diseases, 13 16-20.



Abstract: A 3-year follow-up of 273 participants (mean age 60 years) of the Austrian

Stroke Prevention Study provides first information on the rate, clinical predictors

and cognitive consequences of MRI white matter lesions (WML) in elderly

individuals without neuropsychiatric disease. Lesion progression was found in

17.9% of individuals over a time period of 3 years. Diastolic blood pressure and

early confluent or confluent white matter hyperintensities at baseline were the

only significant predictors of white matter hyperintensity progression. Genetic

association studies in the setting of the Austrian Stroke Prevention Study provide

first evidence for genetic susceptibility factors for progression of WML. We

observed associations with the paraoxonase Leu-->Met 54 polymorphism and

with the M235T polymorphism of the angiotensinogen gene. Lesion progression

had no influence on the course of neuropsychologic test performance over the

observational period, but the statistical power of this analysis was low. Copyright

(C) 2002 S. Karger AG, Basel



Keywords: 3-YEAR

FOLLOW-UP/ABNORMALITIES/age/angiotensinogen/Austria/AUSTRIAN

STROKE PREVENTION/blood

pressure/cognition/disease/elderly/gene/genetic/genetics/HYPERINTENSITIES/

INDIVIDUALS/MRI/PARAOXONASE/polymorphism/predictors/progression/s

tatistical/vascular risk factors/white matter/white matter lesions



Chang, Y.J., Ryu, S.J. and Lin, S.K. (2002), Carotid artery stenosis in ischemic stroke

patients with nonvalvular atrial fibrillation. Cerebrovascular Diseases, 13 (1),

16-20.



Abstract: Purpose: To study the prevalence, severity and clinical relevance of carotid

atherosclerosis in ischemic stroke patients with nonvalvular atrial fibrillation

(NVAF). Material and Methods: We reviewed carotid duplex sonography,

computed tomography (CT) and clinical features in 103 consecutive ischemic

stroke patients with NVAF. Both sonography and CT were performed within 3-7

days after stroke. There were 64 men and 39 women with a mean age at stroke

onset of 69 years. Results: Highgrade (greater than or equal to50%) stenosis of

the extracranial carotid artery was detected in 25 patients (24.3%), including 11

patients (10.6%) with internal carotid artery (ICA) occlusion. In 15 (66.7%) of

the patients who had high-grade carotid stenosis; the lesion was ipsilateral to the

infarct, including 8 ICA occlusions. Patients with high-grade stenosis smoked

more cigarettes (p 1.1 relative value units)

were 1.29 (95% Cl, 0.69-2.47) for IgG and 1.31 (95% Cl, 0.69-2.55) for IgA by

matched-pair analyses, and 1.42 (95% Cl, 0.69-2.98) for IgG and 1.57 (95% Cl,

0.76-3.35) for IgA after adjustments for conventional risk factors and the

inflammatory marker, soluble intercellular adhesion molecule-1. We explored

the possibility that the risk of ischemic stroke may increase in parallel to

increasing antibody titers, but did not demonstrate any significant association.

Conclusions: Serological evidence for prior infection with C. pneumoniae did not

emerge as an independent risk factor for incident ischemic stroke among patients

at high risk due to pre-existing vascular disease. Copyright (C) 2003 S. Karger

AG, Basel



Keywords: age/antibodies/antibody/atherosclerosis/ATHEROSCLEROTIC

PLAQUE/CAROTID-ARTERY/Chlamydia pneumoniae/coronary heart

disease/CORONARY-ARTERY DISEASE/disease/heart/heart

disease/HEART-DISEASE/HELICOBACTER-PYLORI/high

risk/infarction/INFARCTION PREVENTION

BIP/infection/INFECTION/ischemic/ischemic

stroke/Israel/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/NESTED

CASE-CONTROL/prevention/risk/risk factor/risk

factors/secondary/SECONDARY PREVENTION/stroke/trial/vascular/vascular

disease



Rothwell, P.M. (2003), Incidence, risk factors and prognosis of stroke and TIA: The

need for high-quality, large-scale epidemiological studies and meta-analyses.

Cerebrovascular Diseases, 16 2-10.



Abstract: Stroke is a considerable clinical, social and economic burden. In recent clinical

trials, a number of strategies have been shown to reduce the risk of stroke and

transient ischaemic attack (TIA) in both primary and secondary prevention

settings. Whether these treatments are leading to a significant reduction in the

incidence of first and recurrent stroke in the clinic, however, remains unclear due

to a paucity of high-quality epidemiological data. A similar lack of reliable

epidemiological studies has undermined our understanding of the relationship

between many potentially important vascular risk factors and stroke risk.

Improvement in our knowledge of stroke epidemiology is a prerequisite for the

planning of stroke services, the effective application of current stroke prevention

strategies, the development of new strategies, and our understanding of the

mechanisms of stroke. Future studies must take into account the clinical and

pathological heterogeneity of TIA and stroke, and must be powered to allow

subtype differences in risk factor relationships and prognosis to be determined

reliably. In many cases, this will require meta-analysis of detailed individual

patient data from multiple independent studies. Copyright (C) 2003 S. Karger

AG, Basel



Keywords: ATRIAL- FIBRILLATION/BLOOD-PRESSURE/CASE- FATALITY

RATES/CEREBRAL

INFARCTION/CEREBROVASCULAR-DISEASE/cholesterol/clinical

trials/COMMUNITY-STROKE/development/England/epidemiology/hypertensio

n/incidence/ischaemic/knowledge/mechanisms/meta-analysis/NATURAL-

HISTORY/prevention/primary/primary and secondary

prevention/prognosis/recurrent stroke/risk/risk factor/risk

factors/secondary/secondary prevention/SECULAR TRENDS/stroke/stroke

prevention/SYMPTOMATIC CAROTID STENOSIS/TIA/transient/transient

ischaemic attack/TRANSIENT ISCHEMIC ATTACKS/trials/vascular/vascular

risk/vascular risk factors



Ferro, J.M., Correia, M., Rosas, M.J., Pinto, A.N. and Neves, G. (2003), Seizures in

cerebral vein and dural sinus thrombosis. Cerebrovascular Diseases, 15 (1-2),

78-83.



Abstract: To describe early symptomatic and late seizures in a cohort of patients with

acute cerebral vein and dural sinus thrombosis (CVDST) and to identify their

determinants, we performed a prospective registry and follow-up study of

CVDST patients admitted to 20 Portuguese hospitals, from June 1995 to June

1998. Of 91 registered patients, 31 (34%) had early symptomatic seizures; 29

(31.9%) as a presenting feature and 2 (2.1%) after admission. Early symptomatic

seizures were more frequent in patients with motor and sensory deficits and in

those with focal oedema/ischaemic infarcts or haemorrhages on admission

CT/MR. On multivariate logistic regression analysis, sensory defects (OR = 7.8;

95% CI = 0.8-74.8) and a parenchymal lesion on admission CT/MR (OR = 3.7,

95% CI = 1.4-9.4) were found to be significant predictors of early symptomatic

seizures. Seizures were directly related to acute death in 2 patients. Eight (9.5%)

patients had late seizures, which were multiple in 4 (4.8%). Late seizures were

more frequent in patients with early symptomatic seizures and with haemorrhage

on admission CT/MR. Neither early symptomatic seizures nor late seizures were

related to functional prognosis at the last follow-up (median = 1 year). There is a

moderate risk of seizure recurrence early in the course and during the first year

after CVDST. Seizures can be a cause of acute death, but might not have an

independent influence on functional outcome. Pharmacological prevention of

seizures after CVDST should probably be limited to patients with early

symptomatic seizures and cerebral lesions on admission CT/MR. Copyright (C)

2003 S. Karger AG, Basel



Keywords: acute/ADULTS/cerebral/cerebral vein/death/dural

sinus/EPILEPSY/epilepsy/focal/haemorrhage/hospitals/outcome/predictors/preve

ntion/prognosis/recurrence/registry/risk/RISK-FACTORS/seizure/STROKE/thro

mbosis/VENOUS THROMBOSIS



Ringleb, P.A. and Hacke, W. (2003), Antiplatelet therapy in stroke prevention.

Cerebrovascular Diseases, 15 43-48



Keywords: ASPIRIN/CLOPIDOGREL/CORONARY-ARTERY

STENTS/DISEASE/HIGH-RISK/ISCHEMIC

EVENTS/MYOCARDIAL-INFARCTION/PLACEMENT/prevention/RANDO

MIZED- TRIALS/stroke/stroke prevention/therapy/TICLOPIDINE



Musolino, R., La Spina, P., Granata, A., Gallitto, G., Leggiadro, N., Carerj, S.,

Manganaro, A., Tripodi, F., Epifanio, A., Gangemi, S. and Di Perri, R. (2003),

Ischaemic stroke in young people: A prospective and long-term follow-up study.

Cerebrovascular Diseases, 15 (1-2), 121-128.



Abstract: Background: A few studies have comprehensively assessed the epidemiology,

aetiology, prognosis, and secondary prevention of ischaemic stroke in young

adults. To gain further information on this field, we have prospectively studied a

hospital-based series of young adults with a first-ever episode of cerebral

ischaemia (CI). Methods: Sixty consecutive patients aged 17-45 with ischaemic

stroke (55 patients) or transient ischaemic attack within 24 h before hospital

admission were recruited and investigated by a standardized rigorous protocol.

The patients were followed up for greater than or equal to 1 year after hospital

discharge. Arbitrary doses of aspirin 100 mg/d or ticlopidine 250 mg b.i.d. in

case of intolerance to aspirin were given for the secondary prevention.

Adjusted-dose oral anticoagulation (INR target 2.5) was used in the presence of

cardioembolism or hypercoagulable states. Endpoints included the residual

disability, rated by modified Rankin Scale (RS) and Barthel Index (BI), and

post-stroke recurrence. Results: CI was associated with two or more risk factors

in 61.6% of patients. Cigarette smoking was more frequently associated with

male gender (p 3) in 11% of the patients, slight to moderate (1 greater than or equal

to RS less than or equal to 3) in 59% and absent in 30% (RS = 0). Functional

disability was relatively low with 50% of the patients independent (BI greater

than or equal to 95), 38.9% partially dependent (BI 60 to 86), and 11.1% fully

dependent (BI 0.50 (OR, 1.403; p

= 0.0001) predicted an increased risk of experiencing SVT, Left ventricular

ejection fraction, New York Heart Association functional class, and treatment

with digoxin vs placebo were not related to the occurrence of SVT. After

adjustment for other risk factors, development of SVT predicted a greater risk of

subsequent total mortality (risk ratio [RR] = 2.451; p = 0.0001), stroke (RR =

2.352; p = 0.0001), and hospitalization for worsening CHF (RR = 3.004; p =

0.0001). Conclusion: In CHF patients in sinus rhythm, older age, male sex,

longer duration of CHF, and increased cardiothoracic ratio predict an increased

risk for experiencing SVT. Development of SVT is a strong independent

predictor of mortality, stroke, and hospitalization for CHF in this population.

Prevention of SVT may prolong survival and reduce morbidity in CHF patients



Keywords: age/atrial fibrillation/CHRONIC ATRIAL-FIBRILLATION/congestive heart

failure/development/digoxin/heart/heart

failure/hospitalization/incidence/LEFT-VENTRICULAR

DYSFUNCTION/morbidity/MORTALITY/MYOCARDIAL-INFARCTION/PH

YSICIAN/PHYSICIANS/population/PROGRESSION/RISK/risk

factors/sex/sinus rhythm/stroke/supraventricular arrhythmia/SYSTOLIC

DYSFUNCTION/THERAPY/treatment/TRIALS



Shinokawa, N., Hirai, T., Takashima, S., Kameyama, T., Nakagawa, K., Asanoi, H. and

Inoue, H. (2001), A transesophageal echocardiographic study on risk factors for

stroke in elderly patients with atrial fibrillation - A comparison with younger

patients. Chest, 120 (3), 840-846.



Abstract: Study objectives: Atrial fibrillation (AF) becomes an increasingly important

cause of stroke as patients get older. The aim of the study was to determine

whether risk factors of cerebral embolism among elderly patients with AF

differed from those of younger patients by using transesophageal

echocardiography (TEE). Design and setting: Cross-sectional study at a

university hospital. Methods: Cardiovascular lesions with the potential for

thromboembolism in patients with AF were investigated using TEE. Left atrial

spontaneous echocardiographic contrast (SEC), peak flow velocity in the left

atrial appendage (LAA-flow), and aortic atherosclerosis of the thoracic aorta

were assessed in 67 elderly (greater than or equal to 70 years old) and 135

younger (94% by ASA administration in all patients.

Importantly, platelet recruitment followed one of three distinct patterns. In group

A (n=32; 39%), platelet recruitment was blocked by ASA both in the presence

and absence of erythrocytes. In group B (n=37; 45%), recruitment was abolished

when platelets were evaluated alone but continued in the presence of

erythrocytes, indicating a suboptimal effect of ASA on erythrocytes of this

patient group. In group C (n=13; 16%), detectable recruitment in stimulated

platelets alone persisted and was markedly enhanced by the presence of

erythrocytes. Conclusions-In two thirds of a group of patients with vascular

disease, 200 to 300 mg ASA was insufficient to block platelet reactivity in the

presence of erythrocytes despite abolishing thromboxane A, synthesis. Platelet

activation in the presence of erythrocytes can induce the release reaction and

generate biologically active products that reemit additional platelets into a

developing thrombus. Insufficient blockade of this proaggregatory property oi

erythrocytes can lead to development of additional ischemic complications



Keywords: acetylsalicylic

acid/ACTIVATION/ADENOSINE-DIPHOSPHATE/administration/aspirin/bloo

d cells/cardiovascular diseases/cerebrovascular

disorders/CIRCULATION/COLLAGEN/complications/development/heart/ische

mic heart disease/ischemic

stroke/NEUTROPHILS/platelets/prevention/PROSTACYCLIN/RECRUITMEN

T/RED-BLOOD-CELLS/secondary prevention/stroke/THROMBOXANE

PRODUCTION/thrombus/treatment/vascular/vascular disease



Moinuddeen, K., Quin, J., Shaw, R., Dewar, M., Tellides, G., Kopf, G. and Elefteriades,

J. (1998), Anticoagulation is unnecessary after biological aortic valve

replacement. Circulation, 98 (19), II95-II98.



Abstract: Background-Opinion differs as to whether anticoagulation is beneficial in

preventing ischemic stroke in the early postoperative period after biological

aortic valve replacement (AVR), The purpose of this study was to determine

whether early anticoagulation with heparin and warfarin confers any significant

advantage for patients undergoing such replacement. Methods and

Results-Patients undergoing biological AVR between 1987 and 1996 were

divided retrospectively into 2 groups based on their postoperative anticoagulation.

Group A (109 patients) received heparin followed by warfarin for 3 months

(prothrombin time, 20 to 25 seconds). Group B (76 patients) received no

postoperative anticoagulation. Patients were followed for cerebral ischemic

events, bleeding, repeat operation, hospital stay, and survival. There were 5

(4.6%), 3 (2.8%), and 12 (11%) postoperative cerebral ischemic events for group

A at time points of 3 months, respectively;

for group B patients, 3 (3.9%), 2 (2.6%), and 9 (11.8%) events were seen during

the same respective time periods. There were no statistically significant

differences for ischemic events during any of these time periods for the 2 groups.

Bleeding complications occurred in 10 (9.2%) group A and 7 (9.2%) group B

patients. Mean hospital stay was 12 days for both groups. Repeat operative AVR

was required in 6 (5.5%) group A and 7 (9.2%) group B patients. A comparison

of Kaplan- Meier survival rates between groups A and B (mean follow-up,

47+/-26 and 59+/-30 months, for groups A and B, respectively) was not

statistically significant (P=0.60). Survival rates were 93%, 84%, and 62% at 1, 5,

and 7 years for group A and 87%, 74%, and 67% for group B, respectively.

Conclusions-Early anticoagulation after AVR confers no advantage in the

prevention of early cerebral ischemic events after biological AVR. No

disadvantage in terms of bleeding or prolonged hospital stay was incurred by

early anticoagulation, Long-term valve function and survival were not adversely

affected by withholding early anticoagulation. We conclude that early

anticoagulation after biological AVR is unnecessary



Keywords:

anticoagulants/anticoagulation/CIRCULATION/complications/CT/embolism/FO

LLOW-UP/heparin/ischemic stroke/PORCINE

BIOPROSTHESIS/prevention/prosthesis/prothrombin

time/RISK/stroke/valves/warfarin



Molloy, J., Martin, J.F., Baskerville, P.A., Fraser, S.C.A. and Markus, H.S. (1998),

S-nitrosoglutathione reduces the rate of embolization in humans. Circulation, 98

(14), 1372-1375.



Abstract: Background-Antiplatelet agents presently used in the secondary prevention of

cardiovascular disease fail to prevent the majority of cases of recurrent stroke

and systemic embolization. An evaluation of the efficacy of new agents is

hampered by a lack of in vivo models in humans. Asymptomatic cerebral

embolic signals (ES) may be detected with the use of transcranial Doppler

ultrasonography. These signals an particularly common after carotid

endarterectomy, and this provides a situation in which new antiplatelet agents

can be evaluated. With this model, we determined the effectiveness of

S-nitrosoglutathione (GSNO), a nitric oxide donor with relative platelet

specificity, in reducing cerebral embolization. Methods and Results-Transcranial

Doppler ultrasound recordings from the ipsilateral middle cerebral artery were

made after carotid endarterectomy in 12 control patients and 12 patients

receiving intravenous GSNO from the induction of anesthesia until 2 hours after

skin closure. Recording times were 0.5 to 3.5, 6 to 7, and 24 to 25 hours after

skin closure. The Doppler signal was recorded onto tape, and analysis for ES was

performed, with the investigators blinded to treatment group. All patients

received aspirin 300 mg/d before surgery and 5000 IU of heparin during surgery.

The median (range) number of ES detected during the initial 3-hour

postoperative recording was markedly reduced in the GSNO group compared

with the control group: 7.5 (0 to 61) versus 38.5 (1 to 219) (P=0.018). This

difference persisted until 6 hours after surgery. Conclusions- Despite the

administration of aspirin and heparin, frequent embolization occurred and was

markedly reduced after the administration of GSNO. This demonstrates the

potential use of platelet-specific nitric oxide donors in the treatment of

thromboembolic disease. This model of cerebral embolism may allow

determination of the effectiveness of new antiplatelet agents in humans

Keywords: ADHESION/ANGIOPLASTY/antiplatelet agents/aspirin/cardiovascular

disease/carotid/CAROTID ENDARTERECTOMY/cerebral

embolism/CIRCULATION/drugs/EMBOLIC

SIGNALS/embolism/endarterectomy/endothelium-derived

factors/evaluation/heparin/INHIBITION/INVITRO/MODEL/NITROSO-GLUT

ATHIONE/PLATELET ACTIVATION/platelet aggregation

inhibitors/prevention/secondary prevention/stroke/surgery/TRANSCRANIAL

DOPPLER ULTRASONOGRAPHY/treatment/ultrasonics



Berger, P.B., Bell, M.R., Hasdai, D., Grill, D.E., Melby, S. and Holmes, D.R. (1999),

Safety and efficacy of ticlopidine for only 2 weeks after successful intracoronary

stent placement. Circulation, 99 (2), 248-253.



Abstract: Background-In patients receiving intracoronary stents, stent thrombosis is

reduced when ticlopidine therapy is combined with aspirin after the procedure.

However, ticlopidine causes neutropenia in 1% of patients when administered for

>2 weeks, and little is known about the duration that ticlopidine needs be

administered to prevent stent thrombosis. Methods and Results-We analyzed 827

patients undergoing successful stent placement in 1061 coronary segments at

Mayo Clinic who were treated between May 1, 1996, and October 31, 1997.

Chronic warfarin therapy, cardiogenic shock, and enrollment in research

protocols requiring 4 weeks of ticlopidine were exclusion criteria; ticlopidine

was discontinued after 14 days in all remaining patients. The mean age of the

study population was 64 +/- 11 years; 49% had suffered a prior infarction, 20%

had undergone coronary artery bypass surgery, and 65% had multivessel disease.

The indication for stent placement was dissection or abrupt closure in 31% of

patients and suboptimal results from balloon angioplasty in 18%. Placement was

elective in 51% of patients, and 10.3% of patients were treated within 12 hours

of an acute myocardial infarction. Mean nominal stent size was 3.3 +/- 0.5 mm.

High-pressure inflations (greater than or equal to 12 atm) were performed in all

patients (mean, 17 +/- 4 atm). Intravascular ultrasound was used to facilitate stent

placement in 8.8% of patients. Abciximab was administered to 38% of patients;

11% of patients who were at increased risk of stent thrombosis were treated with

enoxaparin for 10 to 14 days. Adverse cardiovascular events in the 14 days after

stent placement occurred in II patients (1.3%). Two patients died of nonischemic

causes (sepsis and renal failure) in the 15th through 30th days after ticlopidine

was stopped. However, there were no cardiovascular deaths, myocardial

infarctions, coronary artery bypass operations, or repeat angioplasty procedures

between the 15th and 30th days; stent thrombosis did not occur in any patient

after ticropidine had been stopped. No patient developed neutropenia, although

1.8% of the first 489 patients who were closely monitored for side effects from

ticlopidine developed side effects requiring its discontinuation, and milder side

effects occurred in 4.7%. Conclusions-In patients receiving intracoronary stents,

the discontinuation of ticlopidine therapy 14 days after stent placement is

associated with a very low frequency of stent thrombosis and other adverse

events

Keywords: acute/acute myocardial infarction/adverse

events/age/angioplasty/ANGIOPLASTY/ANGIOSCOPY/ANTIPLATELET/aspi

rin/balloon angioplasty/bypass surgery/cardiovascular/cardiovascular

events/CIRCULATION/COMPLICATIONS/CORONARY/dissection/infarction/

low frequency/myocardial/myocardial infarction/neutropenia/platelet aggregation

inhibitors/population/PREVENTION/protocols/RANDOMIZED

TRIAL/renal/RESTENOSIS/risk/stents/STROKE/surgery/therapy/THROMBOS

IS/thrombosis/ticlopidine/ultrasound/warfarin



Dearani, J.A., Ugurlu, B.S., Danielson, G.K., Daly, R.C., McGregor, C.G.A., Mullany,

C.J., Puga, F.J., Orszulak, T.A., Anderson, B.J., Brown, R.D. and Schaff, H.V.

(1999), Surgical patent foramen ovale closure for prevention of paradoxical

embolism-related cerebrovascular ischemic events. Circulation, 100 (19),

171-175.



Abstract: Background-The role of surgical closure of patent foramen ovale (PFO) for

cerebral infarction (CI) or transient ischemic attack (TIA) resulting from

paradoxical embolism is unclear, and its effect on recurrence is unknown. Our

objective was to determine the outcome of surgical closure of PFO in patients

with a prior ischemic neurological event, define the rate of CI or TIA recurrence

after PFO closure, and identify risk factors for these recurrences. Methods and

Results-We retrospectively analyzed 91 patients (58 men, 33 women) with

greater than or equal to 1 previous cerebrovascular ischemic events who

underwent surgical PFO closure between April 1982 and March 1998. The

presence of a PFO with a right-to-left shunt was confirmed with transesophageal

echocardiography. Mean age was 44.2 +/- 12.2 years. The index event was a CI

in 59 and a TIA in 32; a Valsalva-like episode preceded the event in 15 patients.

Deep venous thrombosis was documented in 9 patients, and a hypercoagulable

state was identified in 10. Surgical closure was performed with extracorporeal

circulation by either direct suture (n=82) or patch closure (n=9), Limited

incisions were used in 18.7% of patients. There was no operative mortality.

Morbidity included transient atrial fibrillation (n=11), pericardial drainage for

effusion (n=4), exploration for bleeding (n=3), and superficial wound infection

(n=1). Follow-up totaled 176.3 patient-years, and mean follow-up was 2.0 years.

No one had a CI, and 8 had a TIA during follow-up, with I caused by temporal

arteritis, Transesophageal echocardiography demonstrated all closures to be

intact in these patients. The overall freedom from TIA recurrence during

follow-up was 92.5+/-3.2% at 1 year and 83.4+/-6.0% at 4 years. Having

multiple neurological events before PFO closure was the only significant risk

factor for TIA or CI recurrence after closure by univariate analysis (P=0.05); the

small number of post-PFO closure cerebral ischemic events precluded

multivariate analysis. Conclusions-Surgical closure of PFO can be performed

with minimal morbidity and mortality. PFO closure may decrease the risk of

recurrent stroke or TIA and may avoid lifelong anticoagulation in the young

adult if there is no other indication. Recurrent cerebrovascular ischemic events

after surgery should prompt further evaluation to identify causes other than

paradoxical embolism

Keywords: age/anticoagulation/atrial fibrillation/ATRIAL SEPTAL

ANEURYSM/cerebral/cerebral

infarction/cerebrovascular/CIRCULATION/CRYPTOGENIC

STROKE/echocardiography/embolism/evaluation/extracorporeal

circulation/fibrillation/foramen ovale/heart septal

defects/infarction/infection/ischemic/men/morbidity/mortality/paradoxical

embolism/patent/patent foramen ovale/prevention/recurrence/recurrent

stroke/risk/risk factor/risk factors/shunt/stroke/STROKE

RECURRENCE/surgery/thrombosis/TIA/transesophageal

echocardiography/transient/transient ischemic attack/venous thrombosis/women



Plehn, J.F., Davis, B.R., Sacks, F.M., Rouleau, J.L., Pfeffer, M.A., Bernstein, V., Cuddy,

T.E., Moye, L.A., Piller, L.B., Rutherford, J., Simpson, L.M. and Braunwald, E.

(1999), Reduction of stroke incidence after myocardial infarction with

pravastatin - The cholesterol and recurrent events (CARE) study. Circulation, 99

(2), 216-223.



Abstract: Background-The role of lipid modification in stroke prevention is

controversial, although increasing evidence suggests that HMG-CoA reductase

inhibition may reduce cerebrovascular events in patients with prevalent coronary

artery disease. Methods and Results-To test the hypothesis that cholesterol

reduction with pravastatin may reduce stroke incidence after myocardial

infarction, we followed 4159 subjects with average total and LDL serum

cholesterol levels (mean, 209 and 139 mg/dL, respectively) who had sustained an

infarction an average of 10 months before study entry and who were randomized

to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events

(CARE) trial. Using prospectively defined criteria, we assessed the incidence of

stroke, a prespecified secondary end point, and transient ischemic attack (TIA)

over a median 5-year follow-up period. Patients were well matched for stroke

risk factors and the use of antiplatelet agents (85% of subjects in each group).

Compared with placebo, pravastatin lowered total serum cholesterol by 20%,

LDL cholesterol by 32%, and triglycerides by 14% and raised HDL cholesterol

by 5% over the course of the trial. A total of 128 strokes (52 on pravastatin, 76

on placebo) and 216 strokes or TIAs (92 on pravastatin, 124 on placebo) were

observed, representing a 32% reduction (95% CI, 4% to 52%, P=0.03) in

all-cause stroke and 27% reduction in stroke or TIA (95% CI, 4% to 44%,

P=0.02). All categories of strokes were reduced, and treatment effect was similar

when adjusted for age, sex, history of hypertension, cigarette smoking, diabetes,

left ventricular ejection fraction, and baseline total, HDL, and LDL cholesterol

and triglyceride levels. There was no increase in hemorrhagic stroke in patients

on pravastatin compared with placebo (2 versus 6, respectively).

Conclusions-Pravastatin significantly reduced stroke and stroke or TIA incidence

after myocardial infarction in patients with average serum cholesterol levels

despite the high concurrent use of antiplatelet therapy



Keywords: age/antiplatelet/antiplatelet agents/antiplatelet

therapy/arteriosclerosis/CARDIOVASCULAR EVENTS/CARE/CAROTID

ATHEROSCLEROSIS/cerebrovascular/cholesterol/cigarette

smoking/CIRCULATION/coronary artery disease/diabetes/DISEASE/FACTOR

INTERVENTION TRIAL/HDL/HDL

cholesterol/history/hypertension/incidence/infarction/ischemic/LDL/LDL

cholesterol/LDL-cholesterol/LIPIDS/lipids/MEN/MORTALITY/myocardial/my

ocardial infarction/pravastatin/PREVENTION/randomized/risk/risk

factors/RISK-FACTORS/serum/SERUM-CHOLESTEROL/sex/smoking/stroke/

stroke incidence/stroke prevention/therapy/TIA/transient/transient ischemic

attack/treatment/triglycerides



de Lorgeril, M., Salen, P., Martin, J.L., Monjaud, I., Delaye, J. and Mamelle, N. (1999),

Mediterranean diet, traditional risk factors, and the rate of cardiovascular

complications after myocardial infarction - Final report of the Lyon Diet Heart

Study. Circulation, 99 (6), 779-785.



Abstract: Background-The Lyon Diet Heart Study is a randomized secondary prevention

trial aimed at testing whether a Mediterranean-type diet may reduce the rate of

recurrence after a first myocardial infarction. An intermediate analysis showed a

striking protective effect after 27 months of follow-up. This report presents

results of an extended follow-up (with a mean of 46 months per patient) and

deals with the relationships of dietary patterns and traditional risk factors with

recurrence. Methods and Results-Three composite outcomes (COs) combining

either cardiac death and nonfatal myocardial infarction (CO 1), or the preceding

plus major secondary end points (unstable angina, stroke, heart failure,

pulmonary or peripheral embolism) (CO 2), or the preceding plus minor events

requiring hospital admission (CO 3) were studied. In the Mediterranean diet

group, CO 1 was reduced (14 events versus 44 in the prudent Western- type diet

group, P=0.0001), as were CO 2 (27 events versus 90, P=0.0001) and CO 3 (95

events versus 180, P=0.0002). Adjusted risk ratios ranged from 0.28 to 0.53,

Among the traditional risk factors, total cholesterol (1 mmol/L being associated

with an increased risk of 18% to 28%), systolic blood pressure (1 mm Hg being

associated with an increased risk of 1% to 2%), leukocyte count (adjusted risk

ratios ranging from 1.64 to 2.86 with count >9x10(9)/L), female sex (adjusted

risk ratios, 0.27 to 0.46), and aspirin use (adjusted risk ratios, 0.59 to 0.82) were

each significantly and independently associated with recurrence.

Conclusions-The protective effect of the Mediterranean dietary pattern was

maintained up to 4 years after the first infarction, confirming previous

intermediate analyses. Major traditional risk factors, such as high blood

cholesterol and blood pressure, were shown to be independent and joint

predictors of recurrence, indicating that the Mediterranean dietary pattern did not

alter, at least qualitatively, the usual relationships between major risk factors and

recurrence. Thus, a comprehensive strategy to decrease cardiovascular morbidity

and mortality should include primarily a cardioprotective diet. It should be

associated with other (pharmacological?) means aimed at reducing modifiable

risk factors. Further trials combining the 2 approaches are warranted

Keywords: angina/aspirin/blood pressure/cardiovascular/cardiovascular

morbidity/CHOLESTEROL/CIRCULATION/complications/coronary

disease/diet/DISEASE/embolism/FISH/FOLLOW-UP/HEALTH/heart/heart

failure/hospital/infarction/INSIGHTS/morbidity/MORTALITY/myocardial/myo

cardial infarction/predictors/PREVENTION/randomized/recurrence/risk/risk

factors/secondary prevention/sex/stroke/systolic blood

pressure/TRIAL/trials/unstable angina/VENTRICULAR-FIBRILLATION



Agmon, Y., Khandheria, B.K., Meissner, I., Gentile, F., Whisnant, J.P., Sicks, J.D.,

O'Fallon, W.M., Covalt, J.L., Wiebers, D.O. and Seward, J.B. (1999), Frequency

of atrial septal aneurysms in patients with cerebral ischemic events. Circulation,

99 (15), 1942-1944.



Abstract: Background-Atrial septal aneurysm (ASA) is a putative risk factor for

cardioembolism. However, the frequency of ASA in the general population has

not been adequately determined. Therefore, the frequency in patients with

cerebral ischemic events, compared with the frequency in the general population,

is poorly defined. We sought to determine the frequency of ASA in the general

population and to compare the frequency of ASA in patients with cerebral

ischemic events with the frequency in the general population. Methods and

Results -The frequency of ASA in the population was determined in 363 subjects,

a sample of the participants in the stroke Prevention: Assessment of Risk in a

Community study (control subjects), and was compared with the frequency in

355 age- and sex-matched patients undergoing transesophageal

echocardiography in search of a cardiac source of embolism after a focal cerebral

ischemic event. The proportion with ASA was 7.9% in patients versus 2.2% in

control subjects (P=0.002; odds ratio of ASA, 3.65; 95% CI, 1.64 to 8.13, in

patients versus control subjects). Patent foramen ovale (PFO) was detected with

contrast injections in 56% of subjects with ASA. The presence of-ASA predicted

the presence of PFO (odds ratio of PFO, 4.57; 95% CI, 2.18 to 9.57, in subjects

with versus those without ASA). In 86% of subjects with ASA and cerebral

ischemia, transesophageal echocardiography did not detect an alternative source

of cardioembolism other than an associated PFO. Conclusions-The prevalence of

ASA based on this population-based study is 2.2%. The frequency of ASA is

relatively higher in patients evaluated with transesophageal echocardiography

after a cerebral ischemic event. ASA is frequently associated with PFO,

suggesting paradoxical embolism as a mechanism of cardioembolism. In patients

with cerebral ischemia and ASA, ASA (with or without PFO) commonly is the

only potential cardioembolic source detected with transesophageal

echocardiography



Keywords: ADULTS/age/aneurysm/cerebral/cerebral

ischemia/CIRCULATION/CLASSIFICATION/control/echocardiography/emboli

sm/focal/foramen ovale/ischemia/ischemic/MULTICENTER/paradoxical

embolism/POPULATION/population-based/PREVALENCE/RISK/risk

factor/STROKE/TRANSESOPHAGEAL ECHOCARDIOGRAPHY

Go, A.S., Hylek, E.M., Phillips, K.A., Borowsky, L.H., Henault, L.E., Chang, Y.C.,

Selby, J.V. and Singer, D.E. (2000), Implications of stroke risk criteria on the

anticoagulation decision in nonvalvular atrial fibrillation - The anticoagulation

and risk factors in atrial fibrillation (ATRIA) study. Circulation, 102 (1), 11-13.



Abstract: Background-Warfarin dramatically reduces the risk of stroke in patients with

nonvalvular atrial fibrillation (NVAF) but increases the likelihood of bleeding,

Accurately identifying patients who need anticoagulation is critical. We assessed

the potential impact of prominent stroke risk classification schemes on this

decision in a large sample of patients with NVAF. Methods and Results-We used

clinical and electrocardiographic databases to identify 13559 ambulatory patients

with NVAF from July 1996 through December 1997, We compared the

proportion of patients classified as having a low enough stroke risk to receive

aspirin using published criteria from the Atrial Fibrillation Investigators (AFI),

American College of Chest Physicians (ACCP), and the Stroke Prevention in

Atrial Fibrillation Investigators (SPAF), In this cohort, AFI criteria classified

11% as having a low stroke risk, compared with 23% for ACCP and 29% for

SPAF (kappa range, 0.44 to 0.85). This 2- to-3-fold increase in low stroke risk

patients by ACCP and SPAF criteria primarily resulted from the inclusion of

many older subjects (65 to 75 years +/- men >75 years) with no additional

clinical stroke risk factors. Conclusions-The age threshold for assigning an

increased stroke risk has a dramatic impact on whether to recommend warfarin in

populations of patients with NVAF, Large, prospective studies with many stroke

events are needed to precisely determine the relationship of age to stroke risk in

AF and to identify which AF subgroups are at a sufficiently low stroke risk to

forego anticoagulation



Keywords: AF/age/anticoagulants/anticoagulation/aspirin/atrial

fibrillation/bleeding/CIRCULATION/fibrillation/men/nonvalvular atrial

fibrillation/prospective studies/risk/risk factors/stroke/warfarin



Cooper, R., Cutler, J., Desvigne-Nickens, P., Fortmann, S.P., Friedman, L., Havlik, R.,

Hogelin, G., Marler, J., McGovern, P., Morosco, G., Mosca, L., Pearson, T.,

Stamler, J., Stryer, D. and Thom, T. (2000), Trends and disparities in coronary

heart disease, stroke, and other cardiovascular diseases in the United States -

Findings of the National Conference on Cardiovascular Disease Prevention.

Circulation, 102 (25), 3137-3147.



Abstract: A workshop was held September 27 through 29, 1999: to address issues

relating to national trends in mortality and morbidity from cardiovascular

diseases; the apparent slowing of declines in mortality from cardiovascular

diseases; levels and trends in risk factors for cardiovascular diseases; disparities

in cardiovascular diseases by race/ethnicity, socioeconomic status, and

geography; trends in cardiovascular disease preventive and treatment services;

and strategies for efforts to reduce cardiovascular diseases overall and to reduce

disparities among subpopulations. The conference concluded that coronary heart

disease mortality is still declining in the United States as a whole, although

perhaps at a slower rate than in the 1980s; that stroke mortality rates have

declined little, if at all, since 1990; and that there are striking differences in

cardiovascular death rates by race/ethnicity, socioeconomic status, and

geography. Trends in risk factors are consistent with a slowing of the decline in

mortality; there has been little recent progress in risk factors such as smoking,

physical inactivity, and hypertension control. There are increasing levels of

obesity and type 2 diabetes, with major differences among subpopulations. There

is considerable activity in population-wide prevention, primary prevention for

higher risk people, and secondary prevention, but wide disparities exist among

groups on the basis of socioeconomic status and geography, pointing to major

gaps in efforts to use available, proven approaches to control cardiovascular

diseases. Recommendations for strategies to attain the year 2010 health

objectives were made



Keywords: ACE-INHIBITORS/ACUTE

MYOCARDIAL-INFARCTION/ATRIAL-FIBRILLATION/cardiovascular/card

iovascular disease/cardiovascular diseases/CIRCULATION/control/coronary

heart disease/death/diabetes/DIABETES- MELLITUS/disease/disease

mortality/diseases/epidemiology/FAILURE/geography/HEALTH/heart/heart

disease/hypertension/morbidity/MORTALITY/obesity/PATTERNS/PHYSICIA

NS/PREVALENCE/prevention/primary/primary prevention/risk/risk

factors/secondary/secondary prevention/smoking/socioeconomic

status/status/stroke/stroke mortality/treatment/trends/type 2 diabetes/United

States/use



Muller, C., Buttner, H.J., Petersen, J. and Roskamm, H. (2000), A randomized

comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the

placement of coronary-artery stents. Circulation , 101 (6), 590-593.



Abstract: Background-The introduction of an effective antiplatelet therapy with aspirin

and ticlopidine after the placement of coronary-artery stents has decreased the

risk of thrombotic stent occlusions (TSO) and hemorrhagic complications.

However, the use of ticlopidine is limited by hematological and gastrointestinal

adverse effects. The safety and efficacy of clopidogrel after stenting remains to

be established. Methods and Results-After successful coronary stenting during

elective or emergency percutaneous transluminal coronary angioplasty, 700

patients with 899 lesions were randomly assigned to receive a 4-week course of

either 500 mg ticlopidine (n=345) or 75 mg clopidogrel (n=355), in addition to

100 mg aspirin. All the following clinical events reflecting TSO were included in

the prespecified primary cardiac endpoint: cardiac death, urgent target vessel

revascularization, angiographically documented TSO, or nonfatal myocardial

infarction within 30 days. The primary noncardiac endpoint was defined as

noncardiac death, stroke, severe peripheral vascular or hemorrhagic events, or

any adverse event resulting in discontinuation of study medication. Cardiac

events occurred in 17 patients [11 (3.1%) with clopidogrel and 6 (1.7%) with

ticlopidine (P=0.24)]. The primary noncardiac endpoint was observed in 16

patients (4.5%) assigned to receive clopidogrel versus 33 patients (9.6%)

assigned to receive ticlopidine (P=0.01). Conclusions-After the placement of

coronary-artery stents in unselected patients, antiplatelet therapy with aspirin and

clopidogrel seems to be comparably safe and effective as aspirin and ticlopidine.

Noncardiac events were significantly reduced with clopidogrel



Keywords: adverse effects/angioplasty/ANTIPLATELET/antiplatelet

therapy/aspirin/cardiac/CIRCULATION/clopidogrel/complications/coronary

angioplasty/death/Germany/IMPLANTATION/infarction/myocardial/myocardial

infarction/prevention/primary/randomized/revascularization/risk/safety/stenting/s

tents/stroke/THERAPY/thrombosis/ticlopidine/use/vascular



Agmon, Y., Khandheria, B.K., Meissner, I., Schwartz, G.L., Petterson, T.M., O'Fallon,

W.M., Gentile, F., Whisnant, J.P., Wiebers, D.O. and Seward, J.B. (2000),

Independent association of high blood pressure and aortic atherosclerosis - A

population-based study. Circulation, 102 (17), 2087-2093.



Abstract: Background-Atherosclerosis of the thoracic aorta is associated with stroke.

The association between hypertension, a major risk factor for stroke, and aortic

atherosclerosis has not been determined in the general population. Methods and

Results- Transesophageal echocardiography was performed in 581 subjects, a

random sample of the Olmsted County (Minnesota) population aged greater than

or equal to 45 years participating in the Stroke Prevention: Assessment of Risk in

a Community (SPARC) study. Blood pressure was assessed by multiple office

measurements and 24-hour ambulatory blood pressure monitoring. The

association between blood pressure variables and aortic atherosclerosis was

evaluated by multiple logistic regression, adjusting for other associated variables.

Among subjects with atherosclerosis, blood pressure variables associated with

complex aortic atherosclerosis (protruding plaques greater than or equal to4 mm

thick, mobile debris, or ulceration) were determined. Age and smoking history

were independently associated with aortic atherosclerosis of any degree (P less

than or equal to0.001) and with complex atherosclerosis (P=0.002), whereas sex,

diabetes mellitus, and body mass index were not, Multiple systolic and pulse

pressure variables (office and ambulatory), but none of the diastolic blood

pressure variables, were associated with atherosclerosis and complex

atherosclerosis, adjusting for age and smoking. Among subjects with

atherosclerosis, the odds of complex atherosclerosis increased as ambulatory

out-of-bed systolic blood pressure increased (odds ratio 1.43 per 10 mm Hg

increase, 95% CI 1.10 to 1.87) and with hypertension treatment, adjusting for age

and smoking history. Conclusions-High blood pressure is independently

associated with aortic atherosclerosis. Among subjects with atherosclerosis, high

blood pressure is associated with complex atherosclerosis



Keywords: age/aged/aorta/atherosclerosis/blood pressure/body mass

index/CARDIOVASCULAR

RISK-FACTORS/CIRCULATION/diabetes/diabetes mellitus/diastolic blood

pressure/DISEASE/echocardiography/high blood

pressure/history/HYPERTENSION/hypertension/monitoring/PLAQUE/populati

on/population-based/PREVALENCE/risk/risk

factor/sex/smoking/STROKE/systolic blood pressure/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/treatment



Muhlestein, J.B., Anderson, J.L., Carlquist, J.F., Salunkhe, K., Horne, B.D., Pearson,

R.R., Bunch, T.J., Allen, A., Trehan, S. and Nielson, C. (2000), Randomized

secondary prevention trial of azithromycin in patients with coronary artery

disease - Primary clinical results of the ACADEMIC study. Circulation, 102 (15),

1755-1760.



Abstract: Background-Chlamydia pneumoniae is associated with coronary artery disease

(CAD), although its causal role is uncertain. A small preliminary study reported

a >50% reduction in ischemic events by azithromycin, an antibiotic effective

against C pneumoniae, in seropositive CAD patients. We tested this

prospectively in a larger, randomized, double-blind study. Methods and

Results-CAD patients (n=302) seropositive to C pneumoniae (IgG titers greater

than or equal to 1:16) were randomized to placebo or azithromycin 500 mg/d for

3 days and then 500 mg/wk for 3 months. The primary clinical end point

included cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial

infarction (MI), stroke, unstable angina, and unplanned coronary

revascularization at 2 years. Treatment groups were balanced, and azithromycin

was generally well tolerated. During the trial, 47 first primary events occurred

(cardiovascular death, 9; resuscitated cardiac arrest, 1; MI, 11; stroke, 3; unstable

angina, 4; and unplanned coronary revascularization, 19), with 22 events in the

azithromycin group and 25 in the placebo group. There was no significant

difference in the 1 primary end point between the 2 groups (hazard ratio for

azithromycin, 0.89; 95% CI, 0.51 to 1.61; P=0.74). Events included 9 versus 7

occurring within 6 months and 13 versus 18 between 6 and 24 months in the

azithromycin and placebo groups, respectively. Conclusions-This study suggests

that antibiotic therapy with azithromycin is not associated with marked early

reductions (greater than or equal to 50%) in ischemic events as suggested by an

initial published report. However, a clinically worthwhile benefit (ie, 20% to

30%) is still possible, although it may be delayed. Larger (several thousand

patient), longer-term (greater than or equal to 3 to 5 years) antibiotic studies are

therefore indicated



Keywords: angina/antibiotics/ATHEROSCLEROSIS/cardiovascular/Chlamydia

pneumoniae/CHLAMYDIA-PNEUMONIAE

INFECTION/CIRCULATION/coronary artery disease/coronary

disease/coronary

revascularization/delayed/HEART-DISEASE/infarction/ischemic/myocardial/my

ocardial

infarction/MYOCARDIAL-INFARCTION/prevention/primary/PROTEIN/RAB

BIT MODEL/randomized/revascularization/ROXITHROMYCIN/secondary

prevention/SEROLOGICAL EVIDENCE/SMOOTH-MUSCLE

CELLS/STRAIN TWAR/stroke/therapy/unstable angina

Eto, Y., Yonekura, K., Sonoda, M., Arai, N., Sata, M., Sugiura, S., Takenaka, K.,

Gualberto, A., Hixon, M.L., Wagner, M.W. and Aoyagi, T. (2000), Calcineurin

is activated in rat hearts with physiological left ventricular hypertrophy induced

by voluntary exercise training. Circulation , 101 (18), 2134-2137.



Abstract: Background-Calcineurin may play a pivotal role in the signaling of cardiac

hypertrophy; since this hypothesis was first put forward, controversial reports

have been published using various experimental models. This study was

designed to compare the physiological left ventricular hyper-trophy (LVH)

induced by voluntary exercise with LVH induced by aortic constriction and to

determine whether calcineurin participates in the signaling of exercise-induced

LVH. Methods and Results-Wistar rats were assigned to 1 of the following 5

groups: 10 weeks of voluntary exercise (EX), a sedentary regimen, a 1-week

(AC1) or l-week (AC4) ascending aortic constriction period, or a sham operation,

EX rats ran 2.4+/-0.7 km/day voluntarily in specially manufactured cages; this

was associated with an increase of LV diastolic dimension and stroke volume.

Myocardial calcineurin activity markedly increased in EX rats (46.4+/-8.3 versus

18.4+/-0.5 pmol.min(-1).mg(-1) in sedentary rats; P155 ms (odds ratio, 5.37; 95% CI,

3.10 to 9.30; P155 ms predicted AF with positive and negative predictive accuracy of 49%

and 84%, respectively. Conclusions-A combination of prolonged

SAPD,;advanced age, and male sex identifies patients at high risk for

development of AF after CABG



Keywords: AF/age/aging/arrhythmia/ARRHYTHMIAS/bypass

surgery/CABG/CIRCULATION/combination/CONDUCTION/development/EF

FICACY/fibrillation/FLUTTER/high risk/men/OPERATIONS/P-WAVE

DURATION/PREDICTOR/PREVENTION/prospective study/risk/risk

stratification/sex/STROKE/SUPRAVENTRICULAR

TACHYARRHYTHMIAS/surgery/therapy



Maron, B.J., Olivotto, I., Spirito, P., Casey, S.A., Bellone, P., Gohman, T.E., Graham,

K.J., Burton, D.A. and Cecchi, F. (2000), Epidemiology of hypertrophic

cardiomyopathy-related death - Revisited in a large non-referral-based patient

population. Circulation, 102 (8), 858-864.



Abstract: Background-Death resulting from hypertrophic cardiomyopathy (HCM),

particularly when sudden, has been reported to be largely confined to young

persons. These data emanated from tertiary HCM centers with highly selected

referral patterns skewed toward high risk patients. Methods and Results-The

present analysis was undertaken in an international population of 744

consecutively enrolled and largely unselected patients more representative of the

overall HCM spectrum. HCM-related death occurred in 86 patients (12%) over

8+/-7 years (mean+/- SD). Three distinctive modes of death were as follows: (1)

sudden and unexpected (51%; age, 45+/-20 years); (2) progressive heart failure

(36%; age, 56+/-19 years); and (3) HCM-related stroke associated with atrial

fibrillation (13%; age, 73+/-14 years). Sudden death was most common in young

patients, whereas heart failure- and stroke-related deaths occurred more

frequently in midlife and beyond. However, neither sudden nor heart

failure-related death showed a statistically significant, disproportionate age

distribution (P=0.06 and 0.5, respectively). Stroke related deaths did occur

disproportionately in older patients (P=0.002). Of the 45 patients who died

suddenly, most (71%) had no or mild symptoms, and 7 (16%) participated in

moderate to severe physical activities at the time of death.

Conclusions-HCM-related cardiovascular death occurred suddenly, or as a result

of heart failure or stroke, largely during different phases of life in a prospectively

assembled, regionally based, and predominantly unselected patient cohort.

Although most sudden deaths occurred in adolescents and young adults, such

catastrophes were not confined to patients of these ages and extended to later

phases of life. This revised clinical profile suggests that generally held

epidemiological tenants for HCM have been influenced considerably by skewed

reporting from highly selected populations. These data are likely to importantly

affect risk stratification and treatment strategies importantly for the prevention of

sudden death in HCM



Keywords: adolescents/adults/age/atrial

fibrillation/cardiomyopathy/cardiovascular/CIRCULATION/CLINICAL

COURSE/death/ECHOCARDIOGRAPHY/fibrillation/heart/heart failure/high

risk/HIGH-RISK/IMPROVED SURVIVAL/LEFT-VENTRICULAR

HYPERTROPHY/NATURAL- HISTORY/OBSTRUCTIVE

CARDIOMYOPATHY/population/prevention/PROGNOSIS/risk/risk

stratification/stroke/sudden/SUDDEN CARDIAC

DEATH/treatment/YOUNG/young adults



Fan, K., Lee, K.L., Chiu, C.S.W., Lee, J.W.T., He, G.W., Cheung, D., Sun, M.P. and

Lau, C.P. (2000), Effects of biatrial pacing in prevention of postoperative atrial

fibrillation after coronary artery bypass surgery. Circulation, 102 (7), 755-760.



Abstract: Background-Atrial fibrillation (AF) is common after coronary artery bypass

surgery (CABC) and results in prolonged hospitalization. The purpose of this

study was to evaluate the efficacy of biatrial pacing in preventing post-CABG

AF compared with single-site atrial pacing. Methods and Results-A total of 132

patients who had no history of AF and who underwent CABG were randomized

to 1 of the following 4 groups: biatrial pacing (BiA), left atrial pacing (LA), right

atrial pacing (RA), or no pacing (control) in postoperative period. Overdrive

atrial pacing was performed for 5 days. The incidence of AF was significantly

reduced in the BiA group (12.5%) compared with the other 3 groups (LA, 36.4%;

RA, 33.3%; control, 41.9%; P 200 mg/dL and 0.87 (95% CI 0.78 to 0.97) associated with a 5%

decrease in %HDL. The increased risk associated with high triglycerides was

found across subgroups of age, sex, patient characteristics, and cholesterol

fractions. Conclusions-High triglycerides constitute an independent risk factor

for ischemic stroke/TIA across subgroups, of age, sex, patient characteristics,

and cholesterol fractions. whereas high %HDL was an independent protective

factor among patients with CHD. These findings support the role of blood lipids,

including triglycerides, as important modifiable stroke risk factors



Keywords: age/brain/cerebrovascular/cerebrovascular disease/cerebrovascular

disorders/CEREBROVASCULAR-DISEASE/cholesterol/CIRCULATION/coro

nary heart disease/CORONARY

HEART-DISEASE/CT/DENSITY-LIPOPROTEIN

CHOLESTEROL/disease/FOLLOW-UP/HDL/HDL cholesterol/heart/heart

disease/history/ischemic/ischemic

stroke/Israel/lipids/lipoproteins/MEN/MORTALITY/MYOCARDIAL-INFARC

TION/PRAVASTATIN/risk/risk factor/risk factors/SECONDARY

PREVENTION/sex/STROKE/TIA/transient/transient ischemic

attack/triglycerides



Mathew, J., Sleight, P., Lonn, E., Johnstone, D., Pogue, J., Yi, Q.L., Bosch, J., Sussex,

B., Probstfield, J. and Yusuf, S. (2001), Reduction of cardiovascular risk by

regression of electrocardiographic markers of left ventricular hypertrophy by the

angiotensin-converting enzyme inhibitor ramipril. Circulation, 104 (14),

1615-1621.



Abstract: Background-Electrocardiographic markers of left ventricular hypertrophy

(LVH) predict poor prognosis. We determined whether the ACE inhibitor

ramipril prevents the development and causes regression of ECG-LVH and

whether these changes are associated with improved prognosis independent of

blood pressure reduction. Methods and Results-In the Heart Outcomes

Prevention Evaluation (HOPE) study, patients at high risk were randomly

assigned to ramipril or placebo and followed for 4.5years. ECGs were recorded

at baseline and at study end. We compared prevention/regression and

development/persistence of ECG-LVH in the two groups and related these

changes to outcomes. At baseline, 676 patients had LVH (321 in the ramipril

group and 355 in the placebo group) and 7605 patients did not have LVH (3814

in the ramipril group and 3791 in the placebo group). By study end, 336 patients

in the ramipril group (8.1%) compared with 406 in the placebo group (9.8%) had

development/persistence of LVH; in contrast, 3799 patients in the ramipril group

(91.9%) compared with 3740 in the placebo group (90.2%) had

regression/prevention of LVH (P=0.007). The effect of ramipril on LVH was

independent of blood pressure changes. Patients who had regression/prevention

of LVH had a lower risk of the predefined primary outcome (cardiovascular

death, myocardial infarction, or stroke) compared with those who had

development/persistence of LVH (12.3% versus 15.8%, P=0.006) and of

congestive heart failure (9.3% versus 15.4%, P 220 bpm for 10 consecutive beats. Analysis was confined to patients with at

least 1 AHRE duration exceeding 5 minutes. The 312 patients were median age

74 years, 55% female, and 60% had a history of SVT. 160 of 312 (51.3%)

patients enrolled had at least 1 AHRE >5 minutes duration over median

follow-up of 27 months. Cox proportional hazards analysis assessed the

relationship of AHREs with clinical events, adjusting for prognostic variables

and baseline covariates. The presence of any AHRE was an independent

predictor of the following: total mortality (hazard ratio AHRE versus no AHRE

and 95% confidence intervals=2.48 [1.25, 4.91], P=0.0092); death or nonfatal

stroke (2.79 [1.51, 5.15], P=0.0011); and atrial fibrillation (5.93 [2.88, 12.2],

P=0.0001). There was no significant effect of pacing mode on the presence or

absence of AHREs. Conclusions-AHRE detected by pacemakers in patients with

SND identify patients that are more than twice as likely to die or have a stroke,

and 6 times as likely to develop atrial fibrillation as similar patients without

AHRE



Keywords: age/arrhythmia detection/ARRHYTHMIAS/asymptomatic/atrial/atrial

fibrillation/CIRCULATION/clinical

trials/death/DESIGN/diagnostics/FIBRILLATION/fibrillation/history/IMPLAN

TATION/MANAGEMENT/mortality/outcomes/pacemaker/pacemaker

diagnostics/pacemakers/pacing/pacing

mode/PREVENTION/randomized/randomized trial/RISK/SINUS-NODE

DYSFUNCTION/stroke/trial/USA



Sasaki, S., Nakagawa, M., Nakata, T., Azuma, A., Sawada, S., Takeda, K. and Asayama,

J. (2002), Effects of pravastatin on exercise electrocardiography test performance

and cardiovascular mortality and morbidity in patients with hypercholesterolemia

- Lipid intervention study in Kyoto. Circulation Journal, 66 (1), 47-52.



Abstract: The long-term effects of the 3-hydoxy-3-methyl-glutaryl coenzyme A

reductase inhibitor, pravastatin, on exercise electrocardiography (ECG) test

performance and cardiovascular mortality and morbidity were compared with

those of conventional lipid-lowering drugs in hypercholesterolemic patients with

no history of myocardial infarction or stroke. One thousand two hundred and

seventeen patients were randomly assigned with mean serum cholesterol,

triglyceride, high- density lipoprotein (HDL) cholesterol, and low-density

lipoprotein (LDL) cholesterol levels of 6.98+/-0.91 mmol/L, 2.08+/-1.87 mmol/L,

1.38+/-0.44 mmol/L, and 5.07+/-1.14 mmol/L, respectively, and received either

pravastatin at a dose of 10- 20 mg/day (group P) or one of the conventional

lipid-lowering drugs such as fibrates, nicotinic acid, and probucol (group Q. The

numbers of patients available for analysis in groups P and C were 305 and 278 at

year 1, 261 and 216 at year 2, 206 and 184 at year 3, 159 and 122 at year 4, and

103 and 81 at year 5. Over the 3.2 year mean follow-up period, the reduction in

serum LDL cholesterol levels was significantly greater (p 130 ms in both leads II and Vi

and the other 14 patients (IIIa). The duration of the intrinsic P wave in leads II

and Vi was significantly greater in group III than in group I + II (119 20 vs 108

21 ms, p = 0.0417, 106 16 vs 95 21 ms, p = 0.0258, respectively). During the

follow-up of 40 21 months, AF recurrence was significantly higher in group IIIb

than in groups IIIa and I + II (17/20 vs 5/14 vs 2/23 p 1,500 x

10(9)/L, history of major thrombosis (myocardial infarction, stroke, peripheral

occlusive vascular disease), or presence of vascular disease (e.g., arteriosclerosis);

(b) history or presence of spontaneous or major bleedings, bleedings elicited by

low-dose aspirin for the secondary prevention of vascular complications in

essential thrombocythemia at platelet counts 65

years is recommended



Keywords: age/aged/arteriosclerosis/aspirin/aspirin

treatment/asymptomatic/complications/COUNT/ERYTHROMELALGIA/history

/HYDROXYUREA/infarction/ischemic/life

expectancy/MANIFESTATIONS/MYELOPROLIFERATIVE

DISORDERS/myocardial/myocardial

infarction/Netherlands/PLASMA/platelets/POLYCYTHEMIA-VERA/preventio

n/prophylaxis/randomized/RISK/risk factor/risk factors/secondary

prevention/stroke/therapy/thrombosis/THROMBOTIC

COMPLICATIONS/transient/transient ischemic

attacks/treatment/vascular/vascular disease



Syrbe, G., Redlich, H., Weidlich, B., Ludwig, J., Kopitzsch, S., Gockeritz, A. and

Herzog, K. (2001), Individual dosing of ASA prophylaxis by controlling platelet

aggregation. Clinical and Applied Thrombosis-Hemostasis, 7 (3), 209-213.

Abstract: Acetylsalicylic acid is widely used in the primary and secondary prevention of

cardiovascular diseases. In the current study, we used platelet aggregation ex

vivo in platelet-rich plasma induced with arachidonic acid as a routine method

for the determination of the individual dose of acetylsalicylic acid necessary to

inhibit platelet aggregation in 108 patients with cardiovascular diseases. In 40%

of all patients studied, a dose of 30 mg/day was sufficient to block the

arachidonic acid- induced platelet aggregation nearly completely. In 50% of all

patients, a dose of 100 mg/day was necessary. In 10% of all patients, the dose

had to be further increased to 300 mg/day or even to 500 mg/day to inhibit

platelet aggregation nearly completely. These results demonstrate that platelet

aggregation can be used as a simple routine laboratory method to control

acetylsalicylic acid treatment in patients with cardiovascular diseases and to

determine individual doses of acetylsalicylic acid for a nearly complete

inhibition of platelet aggregation. With a standard dose of 100 mg/day, 10% of

the patients were nonresponders



Keywords: ACETYLATION/acetylsalicyclic acid/acetylsalicylic acid/ACUTE

MYOCARDIAL-INFARCTION/aggregation/AMERICAN-HEART-ASSOCIA

TION/ASPIRIN/cardiovascular/cardiovascular diseases/control/diabetes

mellitus/diseases/Germany/HEALTH-CARE

PROFESSIONALS/INHIBITION/MECHANISM/platelet/platelet

aggregation/prevention/primary/primary and secondary

prevention/prophylaxis/secondary/secondary

prevention/slope/STATEMENT/STROKE COUNCIL/treatment/TRIAL



Ertorer, M.E., Gokcel, A., Savas, L. and Kocak, R. (2002), Ticlopidine-induced marrow

aplasia treated with cyclosporine. Clinical and Applied Thrombosis-Hemostasis,

8 (2), 183-185.



Abstract: A 50-year-old diabetic and hypertensive male patient is reported who had

ticlopidine-induced marrow aplasia partially responsive to colony-stimulating

factors and corticosteroids, but experienced complete recovery with cyclosporine.

There is no consensus on the treatment of ticlopidine-induced marrow aplasia.

Although many cases are reported to recover with colony-stimulating factors and

corticosteroids, others are unresponsive or partially responsive. Our patient also

did not completely respond to these medications, but was successfully treated

with cyclosporine alone. Alone or in combination with corticosteroids,

cyclosporine is an effective drug of choice for the resistant patients



Keywords:

AGRANULOCYTOSIS/ANEMIA/combination/consensus/cyclosporine/drug/H

EAD/marrow aplasia/PREVENTION/STROKE/ticlopidine/treatment/TRIAL



Kawashima, K., Watanabe, T.X., Sokabe, H. and Saito, K. (1987), Prevention of Renal

Damage and Decrease of Urinary Kinins Excretion by Chronic Treatments with

Enalapril and Captopril in Stroke-Prone Spontaneously Hypertensive Rats.

Clinical and Experimental Hypertension Part A-Theory and Practice, 9 (2-3),

409-413



Yamori, Y. (1991), Studies on Spontaneous Hypertension - Development from Animal-

Models Toward Man - Overview. Clinical and Experimental Hypertension Part

A-Theory and Practice, 13 (5), 631-644.



Abstract: The development of genetic rat models for research on hypertension, stroke

and other cardiovascular diseases (CVD) such as spontaneously hypertensive rats

(SHR) and stroke-prone SHR (SHRSP) have contributed not only to the

elucidation of the pathogenesis of hypertension-related CVD but also to their

prediction and prevention. Since both generic and environmental factors are

involved in the pathogenesis of CVD as extensively studied so far on these

models, the detection of the early pathogenic mechanisms related to the genetic

factors and the control of environmental factors such as dietary improvement are

useful as predictive and preventive measures against CVD. Sympathetic

overresponsiveness, early development of cardiovascular hypertrophy, increased

salt sensitivity and membrane or transport abnormalities in vascular smooth

muscle cells (VSMC) from SHR and SHRSP, possibly related to the

pathogenesis of hypertension, are so far regarded as predictors for hypertension

partly applicable to human hypertension. Genetic pathogenic mechanisms of

stroke in SHRSP which have been proven to be greatly influenced also by dietary

factors are hypertension-induced VSMC degeneration and necrosis of

intracerebral arteries due to local nutritional disturbance. One of predictors of

stroke related to the pathogenic mechanisms is reduction of regional cerebral

blood flow. On the other hand, the control of environmental factors, especially

nutrition and diets such as intakes of animal and vegetable proteins, some amino

acids and fatty acids, potassium, calcium, magnesium, dietary fibers, etc., have

been experimentally demonstrated to be effective for the prevention of CVD in

these genetic models, and the applicability of these experimental findings to the

CVD prevention in man is now supported from our world-wide epidemiological

studies (WHO CARDIAC Study)



Keywords: CARDIOVASCULAR-DISEASES/CEREBRAL BLOOD

FLOW/HYPERTENSION/MECHANISMS/NUTRITION/POTASSIUM/PROT

EIN/RATS/SALT/SHR/SHRSP/SPONTANEOUSLY HYPERTENSIVE RATS

(SHR)/STROKE/STROKE-PRONE/STROKE-PRONE SHR

(SHRSP)/VASCULAR SMOOTH MUSCLE CELLS



Miyagishi, A., Maniwa, T., Noguchi, T. and Hara, Y. (1991), Prevention of Cerebral

Stroke by Arotinolol in Salt-Loaded Shrsp. Clinical and Experimental

Hypertension Part A-Theory and Practice, 13 (5), 1077-1089.



Abstract: The preventive effects of long-term treatment with arotinolol on the

development of cerebral stroke were examined in SHRSP fed a high salt diet.

Arotinolol (4.87 mg/kg per day for 20 weeks) prevented cerebral lesions, reduced

signs of stroke and delayed early mortality but did not alter blood pressure from

control SHRSP, when the administration of the drug was started before the onset

of hypertension. At dosage levels similar to arotinolol, both pindolol and

labetalol were less effective in preventing cerebral lesions despite lower blood

pressure. Propranolol produced no detectable effect on blood pressure or

frequency of cerebral lesions. Furthermore, arotinolol (4.27 mg/kg per day)

markedly inhibited the development of stroke without blood pressure reduction,

when the administration was started after the onset of severe hypertension. These

results suggest that arotinolol is more effective in preventing cerebral stroke than

pindolol, labetalol and propranolol, and that factors other than blood pressure

reduction may be involved in this preventive effect



Keywords: A-ADRENOCEPTOR AND B-ADRENOCEPTOR BLOCKING

DRUG/ADRENOCEPTOR BLOCKING-AGENT/AROTINOLOL/CEREBRAL

STROKE/S-596/SALT LOADING DIET/SHRSP/SPONTANEOUSLY

HYPERTENSIVE RATS



Isles, C.G. and Hole, D.J. (1992), Is There A-J-Curve Distribution for Diastolic

Blood-Pressure. Clinical and Experimental Hypertension Part A-Theory and

Practice, 14 (1-2), 139-149.



Abstract: The question whether there is a level of diastolic pressure during treatment

below which further reduction of pressure may be harmful rather than beneficial

is of great interest. If, as the proponents of this hypothesis maintain, death from

CHD among treated hypertensives becomes more rather than less common at

very low diastolic pressure, this might explain at least in part why most primary

prevention trials of hypertension have failed to show a reduction in CHD

mortality. However, as the sceptics have pointed out, the evidence that drug

induced lowering of blood pressure is harmful is not of the highest quality, and

alternative explanations for excess cardiovascular mortality at low diastolic

pressure exist. In the following review of this hotly contested debate it is

concluded that both proponents and sceptics may be correct, but that the presence

of a J curve should not divert attention from the main benefit of treating

hypertension which is a reduction in the risk of fatal and non fatal stroke



Keywords: DEATH/DIASTOLIC BLOOD PRESSURE/ELDERLY

PATIENTS/HYPERTENSION/J-CURVE/MORTALITY/MYOCARDIAL-INF

ARCTION/REDUCTION/TRIAL



Liu, L.S. (1993), Hypertension Studies in China. Clinical and Experimental

Hypertension, 15 (6), 1015-1024.



Abstract: In China, hypertension (HT) prevalence increased from 7.7% in 1980 to over

11% in 1991. The higher prevalence of HT in the north and among urban

populations may be due in part to higher body mass index (BMI) levels and

dietary composition. Community control of HT has been organized since 1969.

Reports from centers with a history of community control for over 10 years have

indicated a 40% and 34% decrease respectively in the incidence of stroke and

acute myocardial infarction (AMI). Sino-Monica Beijing Project shows that

morbidity and mortality of stroke and coronary heart disease are higher in north

China and urban centers, stroke is 4-8 times higher than coronary events. The

trend from 1985-1989 was relatively steady. Although the mortality of stroke and

AMI was decreasing, the case fatality rate remained high, and the rapid increase

in the proportion of older population points to an urgent need for a nationwide

prevention and control program



Keywords: CARDIOVASCULAR EPIDEMIOLOGY/COMMUNITY

CONTROL/HYPERTENSION



Sleight, P. (1993), Smoking and Hypertension. Clinical and Experimental Hypertension,

15 (6), 1181-1192.



Abstract: Coronary heart disease is the most common cause of death in hypertensives -

about twice as common as stroke. Smoking increases this raised risk of

hypertension by some 2 to 3 times. Surprisingly perhaps, this increased risk from

smoking declines rapidly on quitting - within 2-3 years. Smoking increases the

risks of vascular damage by increasing sympathetic tone, platelet stickiness and

reactivity, free radical production, damage to endotherlium, and by surges in

arterial pressure. The latter may interfere with the action of some hypotensive

agents. Persuading hypertensive patients not to smoke is the single most effective

measure we can take to reduce their risk



Keywords: BLOOD-PRESSURE/CARDIOVASCULAR

RISK-FACTORS/CIGARETTE- SMOKING/CORONARY

HEART-DISEASE/FIBRINOGEN/HYPERTENSION/MEN/MORTALITY/PO

PULATION/PRIMARY PREVENTION/SMOKERS



Okada, M., Kobayashi, M., Maruyama, H., Takahashi, R., Ikemoto, F., Yano, M. and

Nishikibe, M. (1995), Effects of A Selective Endothelin A-Receptor Antagonist,

Bq- 123, in Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats.

Clinical and Experimental Pharmacology and Physiology, 22 (10), 763-768.



Abstract: 1. We examined the effects of a selective endothelin A (ET(A))- receptor

antagonist, BQ-123, on the development of hypertension and organ damage in

stroke-prone spontaneously hypertensive rats (SHRSP) given 1% NaCl for 6

weeks. 2. BQ-123 at doses of 0.7, 2.1 and 7.1 mg/day was continuously

administered for 6 weeks to 8 week old salt-loaded SHRSP, who were given

water containing 1% NaCl for the following 6 weeks, via a subcutaneous osmotic

minipump. 3. Development of high blood pressure was accelerated in salt-loaded

SHRSP compared with that in non-salt-loaded SHRSP. After 6 weeks of

salt-loading, incidence of cerebral infarction, renal sclerosis and renal fibrosis

were greater in salt-loaded than non-salt-loaded SHRSP. 4. BQ-123 attenuated

the age-related rise in blood pressure in a dose-dependent manner. The effect

coincided with reduction in the incidence of cerebral infarction and prevention of

renal sclerosis and fibrosis. Kidney function was improved as observed by an

increase in glomerular filtration rate and decreases in urinary protein excretion,

blood urea nitrogen and fractional sodium excretion. Furthermore, BQ-123

prevented increases in the heart weight/bodyweight ratio and aortic wall

thickness in salt-loaded SHRSP. 5. These results suggest that endogenous

endothelin-1 (ET-1) and ET(A)-receptors maybe, at least in part, involved in the

pathogenesis of hypertension and organ damage in salt-loaded SHRSP



Keywords: blood

pressure/BQ-123/C-FOS/development/DNA-SYNTHESIS/ET(A)-RECEPTOR

ANTAGONIST/EXPRESSION/FIBROBLASTS/heart/high blood

pressure/HYPERTENSION/HYPERTROPHY/incidence/KIDNEY/MITOGENE

SIS/ORGAN DAMAGE/POTENT/prevention/rats/RENIN/SALT-LOADED

SHRSP/SHRSP/SMOOTH-MUSCLE CELLS



Langer, R.D. (1995), The Epidemiology of Hypertension Control in Populations.

Clinical and Experimental Hypertension, 17 (7), 1127-1144.



Abstract: Despite an aging population, prevalence rates for hypertension in the U.S.

remain stable due to a decrease in rates in women but a corresponding increase in

rates for men. Epidemiological factors which may contribute to these rates are

discussed. The lack of a threshold for the association between blood pressure and

disease events means that the majority of events occur in the larger number of

people with mild disease. Because the efficacy and cost-effectiveness of medical

therapy to lower mildly elevated blood pressure remains controversial,

population-based strategies to effect behavior change are the most prudent course

for this, the largest group at risk. Targeted, resource-intensive medical

intervention for those at high risk combined with hygienic measures for the

population with mildly elevated blood pressure form the basis for an effective

public health strategy



Keywords: ALCOHOL-CONSUMPTION/behavior/blood pressure/CORONARY

HEART-DISEASE/cost

effectiveness/cost-effectiveness/DECLINE/EPIDEMIOLOGY/FAMILY/FOLL

OW-UP/health/HIGH BLOOD-PRESSURE/HIGH RISK

STRATEGY/HYPERTENSION/ISOLATED SYSTOLIC

HYPERTENSION/MILD HYPERTENSION/PARADOXICAL

SURVIVAL/PRIMARY PREVENTION/risk/RISK FACTORS/STROKE

MORTALITY/UNITED-STATES/women



Vaux, D.L. and Hacker, G. (1995), Hypothesis - Apoptosis Caused by Cytotoxins

Represents A Defensive Response That Evolved to Combat Intracellular

Pathogens. Clinical and Experimental Pharmacology and Physiology, 22 (11),

861-863.



Abstract: 1. Over 100 different agents have been shown, under certain circumstances, to

cause apoptosis, a form of cell death with characteristic morphology, In most

cases, the mechanism of cell death is likely to be the same, as expression of the

cell death inhibitory gene bcl-2 can frequently prevent apoptotic changes and/or

delay cell death. 2. These observations raise the question of how and why cells

detect these agents and why they respond by implementing the suicide

mechanism that bcl-2 can control, Our hypothesis is that apoptosis is used as an

anti- viral strategy, and that cells interpret any metabolic disturbance as evidence

of infection by a virus and thereby kill themselves in response to these toxins

before they are killed by the action of the toxin itself. 3. Experiments on the

effect of sodium azide upon growth factor-dependent cells support this idea.

Bcl-2 can delay cell death caused by azide, and inhibit apoptotic changes seen by

electron microscopy, but cannot prevent the eventual death of the cells. 4. These

ideas suggest that drugs designed to regulate cell death may be useful for the

treatment of ischaemic or neoplastic diseases, For example, human cells may

activate a suicide pathway in response to sub-lethal amounts of anoxia following

a stroke or heart attack and so blocking apoptosis may be a useful therapy to

limit tissue damage, On the other hand, increasing the propensity of cells to

activate their physiological cell death mechanisms may enhance the effectiveness

of toxins designed to kill tumour cells



Keywords: anoxia/APOPTOSIS/BACULOVIRUS

GENE/BCL-2/C-ELEGANS/CED-3/CELL

DEATH/diseases/ENZYME/heart/INSECT

CELLS/MECHANISMS/PREVENTION/PROGRAMMED

CELL-DEATH/stroke/SURVIVAL/TOXIN/treatment



Whelton, P.K., Williamson, J.D., Louis, G.T., Davis, B.R. and Cutler, J.A. (1996),

Experimental approaches to determining the choice of first-step therapy for

patients with hypertension. Clinical and Experimental Hypertension, 18 (3-4),

569-579.



Abstract: Detection, treatment and control of hypertension is one of the best proven

approaches to prevention of cardiovascular disease. Antihypertensive treatment

trials have convincingly demonstrated that diuretics and beta-blockers reduce the

risk of stroke and coronary heart disease. Corresponding information is not yet

available for newer classes of antihypertensive drug therapy such as calcium

channel blockers, angiotensin converting enzyme inhibitors and alpha, receptor

blockers. Several experimental studies are now addressing this question. The

largest such trial (n=40,000) is the Antihypertensive and Lipid-Lowering

Treatment to Prevent Heart Attack Trial (ALLHAT). This manuscript describes

two studies (TOMHS and the VA study on antihypertensive agents) that

compared several classes of antihypertensive drugs with regard to blood pressure

outcomes and ALLHAT, which is comparing the effect of four first-step

approaches to antihypertensive therapy on combined incidence of fatal coronary

heart disease and non-fatal myocardial infarction



Keywords: ANGINA/angiotensin/angiotensin converting enzyme

inhibitors/beta-blockers/blood pressure/cardiovascular disease/clinical

trials/coronary heart disease/DRUG-THERAPY/epidemiology/heart/high blood

pressure/hypertension/incidence/MILD/myocardial

infarction/MYOCARDIAL-INFARCTION/pharmacology/prevention/risk/stroke

/treatment/trials



Hobbs, L.M., Rayner, T.E. and Howe, P.R.C. (1996), Dietary fish oil prevents the

development of renal damage in salt-loaded stroke-prone spontaneously

hypertensive rats. Clinical and Experimental Pharmacology and Physiology, 23

(6-7), 508-513.



Abstract: 1. Stroke-prone spontaneously hypertensive rats (SHRSP) fed a high salt diet

rapidly develop proteinuria, a marker of renal damage, We have recently shown

that supplementing the diet of these rats with pure omega-3 fatty acids can inhibit

the development of proteinuria. The aim of the present study was to examine the

underlying renal pathology and to see whether a similar benefit could be

obtained with fish oil or canola oil. 2. Diets containing sodium (2% by weight)

and 5% fish oil, canola oil, olive oil or safflower oil (the latter two serving as

controls) were fed to groups of eight young SHRSP and the development of

hypertension and proteinuria was monitored. After 9 weeks, rats were killed and

their kidneys were taken for histological examination and fatty acid analysis.

Urinary protein was characterized electrophoretically. 3. Patterns of protein

excretion were consistent with the appearance of pathological changes in both

glomeruli and tubules. Fish oil inhibited the elevation of blood pressure,

prevented the development of proteinuria and minimized histological lesions,

However, in rats fed canola oil, hypertension and renal damage were equally

severe as in rats fed olive or safflower oil. 4. The prevention of hypertensive

renal damage by dietary fish oil may be attributable to increased incorporation of

long-chain omega-3 fatty acids in the kidney



Keywords: blood pressure/canola/development/diet/DISEASE/FATTY-ACIDS/fish

oil/hypertension/IMMUNE INJURY/INHIBITOR/omega-3 fatty

acids/prevention/proteinuria renal disease/rats/salt/SHRSP/URINARY

ALBUMIN EXCRETION



Pessina, A.C., Serena, L. and Semplicini, A. (1996), Hypertension, coronary artery and

cerebrovascular diseases in the population. Has epidemiology changed in the last

decades? Clinical and Experimental Hypertension, 18 (3-4), 363-370.



Abstract: Life expectancy has significantly increased in the last decades in many western

populations, due to the fall of total and cardiovascular death rate. However,

morbidity from cardiovascular diseases has decreased to a smaller extent. The

overall population risk profile has improved, but it is still unsatisfactory. This is

true for blood pressure control (with only 20% of hypertensive patients achieving

normotension with antihypertensive drugs), hypercholesterolemia (with

bordeline- high serum cholesterol levels in 50% of the population), and smoking

habits. Other potential causes of the poor cardiovascular prevention are: 1) a

limited knowledge of the optimal blood pressure goal with antihypertensive

treatment, 2) scanty information on the long term effects of antihypertensive

drugs on cerebral and coronary circulation. Finally, little is being done to

improve primary prevention in youth, when the slowly progressing

atherosclerotic plaque formation is already on the way. To improve the cost /

effectiveness of cardiovascular prevention, efforts must concentrate on the early

identification of the subjects at the highest risk and on health promotion among

youngsters. Large epidemiological trials conducted from the early 50s have

provided convincing evidence of the multifactorial origin of cardiovascular

diseases and encouraged the implementation of population based primary and

secondary preventive measures, including antihypertensive treatment, as well as

dietary and life-style modifications. It is now time to start asking ourselves

whether or not we are satisfied with the results obtained in terms of reduced

morbidity and mortality, whether these results are the direct consequence of

these measures and whether or not we can do even better. The present work

reviews some of the most recent comparative reports on the epidemiology of

cardiovascular diseases in different populations, and some intervention trials to

answer these questions and to help in identifying the most cost-effective

approach to cardiovascular disease prevention in the next few years



Keywords: arterial hypertension/blood pressure/cardiovascular disease/cardiovascular

diseases/cardiovascular risk factors/cerebrovascular diseases/cholesterol/cost

effectiveness/diseases/epidemiology/health/health

promotion/HYPERTENSION/lifestyle/morbidity/mortality/PRESSURE/preventi

on/primary prevention/secondary prevention/smoking/STROKE/treatment/trials



Borghi, C. and Ambrosioni, E. (1996), Primary and secondary prevention of myocardial

infarction. Clinical and Experimental Hypertension, 18 (3-4), 547-558.



Abstract: The prevention of coronary artery disease (CHD) and particularly of

myocardial infarction (MI) is based on some well designed strategies aimed at

treating both asymptomatic high-risk patients (primary prevention) and patients

with established CHD (secondary prevention). A positive impact from primary

prevention can be basically achieved trough a reduction in high blood pressure

and by correcting dyslipidemia. The benefit can be substantially increased by

smoking cessation, increasing physical exercise, reduction of body weight, use of

post-menopausal oestrogen, moderate alcohol consumption and use of high doses

of vitamin E in those patients who are compliant with the specific strategies.

Secondary prevention of MI can be again obtained by controlling blood pressure

and reducing serum cholesterol in patients surviving acute MI who can also

benefit from the administration of beta-blockers, aspirin and probably

ace-inhibitors particularly in presence of left ventricular dysfunction. We suggest

that in both arms of prevention, significant results can be achieved mainly by a

multifactorial approach capable of correcting all the modifiable risk factors that

contribute to the rather complex pathogenesis of CHD



Keywords: ace-inhibitors/aspirin/beta-blockers/blood

pressure/BLOOD-PRESSURE/CHOLESTEROL/cholesterol/CORONARY

HEART-DISEASE/exercise/hypertension/INTERNAL/MORBIDITY/MORTAL

ITY/myocardial infarction/prevention/primary prevention/risk/risk

factors/secondary prevention/smoking/STROKE/TRIALS/vitamin E



MacMahon, S. and Rodgers, A. (1996), Primary and secondary prevention of stroke.

Clinical and Experimental Hypertension, 18 (3-4), 537-546.



Abstract: Data from prospective observational studies indicate that usual levels of blood

pressure are directly and continuously related to the risk of stroke. a prolonged

difference in usual diastolic blood pressure levels of just 5 mmHg would

eventually confer about a one-third difference in stroke risk, with similar

proportional effects in hypertensives and non- hypertensives. The results of

randomised trials of blood pressure lowering drugs in hypertensive patients

suggest that much or all of this long-term potential stroke avoidance can be

achieved within just a few years of beginning treatment. Overall in 17

randomised trials of antihypertensive treatment, a net blood pressure reduction of

10-12 mmHg systolic and 5-6 mmHg diastolic, conferred a reduction in stroke

incidence of 38% SD 4, with similar reductions in fatal and non-fatal stroke.

Additionally, the sizes of the reductions were similar in trials in mild, moderate

or more severe hypertension, in trials in older or younger patients and in trials in

patients with or without a history of cerebrovascular disease. Because the

proportional effects of treatment were similar in all these groups, the absolute

effects of treatment on stroke varied in direct proportion to the background risk

of stroke. The greatest benefits were, therefore, observed among those with a

history of cerebrovascular disease, those above the age of 60 years, and those

with more severe hypertension



Keywords: antihypertensive treatment/blood

pressure/BLOOD-PRESSURE/cerebrovascular disease/CORONARY

HEART-DISEASE/epidemiology/history/HYPERTENSION/incidence/JAPAN/

MORBIDITY/MORTALITY/prevention/RISK-FACTORS/secondary

prevention/stroke/treatment/TRIAL/TRIALS



Whitlock, G., MacMahon, S., Anderson, C., Neal, B., Rodgers, A. and Chalmers, J.

(1997), Blood pressure lowering for the prevention of cognitive decline in

patients with cerebrovascular disease. Clinical and Experimental Hypertension,

19 (5-6), 843-855.



Abstract: Cerebrovascular disease and high blood pressure both appear to increase the

risk of vascular dementia. PROGRESS aims to investigate whether blood

pressure lowering with an angiotensin converting enzyme inhibitor-based

regimen will reduce the risk of cognitive impairment in patients with a history of

stroke or transient ischaemic attack. A total of at least 6000 patients will be

randomised to receive perindopril (+/- indapamide) or matching placebo(s), with

treatment and follow-up scheduled to continue for at least 4 years. Substudies

will investigate the effects of treatment on cognitive decline in subgroups defined

by apo-E genotype and on white matter lesions assessed by magnetic resonance

imaging. Final results from the study should be available in 2001

Keywords: ALZHEIMERS-DISEASE/angiotensin/blood

pressure/cerebrovascular/cerebrovascular disease/cognitive

impairment/dementia/FRAMINGHAM/high blood

pressure/history/HYPERTENSION/indapamide/magnetic resonance

imaging/MINI-MENTAL-STATE/NEW-YORK/PERFORMANCE/perindopril/

prevention/risk/stroke/transient/treatment/TRIAL/TRIALS/vascular/VASCULA

R DEMENTIA/white matter/WHITE MATTER LESIONS



Richer, C., Vacher, E., Fornes, P. and Giudicelli, J.F. (1997), Antihypertensive drugs in

the stroke-prone spontaneously hypertensive rat. Clinical and Experimental

Hypertension, 19 (5-6), 925-936.



Abstract: The stroke-prone spontaneously hypertensive rat (SHR-SP) is an experimental

model that has been widely used to investigate the potential preventive effects vs

stroke and mortality of numerous antihypertensive agents. Among the latter,

angiotensin I-converting enzyme inhibitors, angiotensin II AT1-receptor blockers

and calcium antagonists have proven to be very effective. The mechanisms

involved in their beneficial effects include limitation of the age-related

alterations of large cerebral arteries' functional parameters, prevention of

fibrinoid necrosis formation in cerebral arterioles and, to a lesser extent,

limitation of the blood pressure rise



Keywords: angiotensin/angiotensin II/antihypertensive drugs/blood pressure/calcium

antagonists/cerebral/CEREBRAL ARTERIOLES/cerebral

vessels/drugs/formation/HYPERTENSION/MECHANICS/mortality/necrosis/N

EW-YORK/prevention/PREVENTS

STROKE/rat/RENIN/SHRSP/stroke/stroke-prone spontaneously hypertensive

rat/TREATMENT WITHDRAWAL



Rodgers, A. and MacMahon, S. (1999), Blood pressure and the global burden of

cardiovascular disease. Clinical and Experimental Hypertension, 21 (5-6),

543-552.



Abstract: Cardiovascular disease is responsible for a large and increasing proportion of

death and disability worldwide. Half of this burden occurs in Asia. This study

assessed the possible effects of population-wide (2% lower DBP for all) and

targeted (7% lower DBP for those with usual DBP greater than or equal to 95

mmHg) BP interventions in Asia, using data from surveys of blood pressure

levels, the Global Burden of Disease Project, Eastern Asian cohort studies and

randomised trials of blood pressure lowering. Overall each of the two

interventions would be expected to avert about one million deaths per year

throughout Asia in 2020. These benefits would be approximately additive. About

half a million deaths might be averted annually by each intervention in China

alone, with about four-fifths of this benefit due to averted stroke. The relative

benefits of these two strategies are similar to estimates made for US and UK

populations. However, the absolute benefits are many times greater due to the

size of the predicted CVD burden in Asia

Keywords: antihypertensive drugs/blood pressure/cardiovascular/cardiovascular

disease/cohort studies/coronary heart

disease/epidemiology/HYPERTENSION/NEW-YORK/population/PREVENTIO

N/RISK-FACTORS/stroke/trials



Liu, L.S., Wang, J.G., Celis, H. and Staessen, J.A. (1999), Implications of the systolic

hypertension in China trial. Clinical and Experimental Hypertension, 21 (5-6),

499-505.



Abstract: In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group

started to investigate whether active treatment could reduce the incidence of

stroke and other cardiovascular complications of isolated systolic hypertension.

After stratification for center, sex and previous cardiovascular complications,

alternate patients (n = 1253) were assigned nitrendipine 10-40 mg daily, with the

possible addition of captopril 12.5-50.0 mg daily, or hydrochlorothiazide

12.5-50.0 mg daily, or both drugs. In 1141 control patients, matching placebos

were employed similarly. At entry, sitting blood pressure averaged 170 mm Hg

systolic and 86 mm Hg diastolic, age averaged 66 years, and total serum

cholesterol was 5.1 mmol/L. At 2 years, the between-group differences were 9.1

mm Hg systolic (95% confidence interval. 7.6-10.7 mm Hg) and 3.2 mm Hg

diastolic (2.4-4.0). Active treatment reduced total stroke by 38% (p=0.01),

all-cause mortality by 39% (p=0.003), cardiovascular mortality by 39% (p=0.03),

stroke mortality by 58% (p=0.02) and all fatal and nonfatal cardiovascular

endpoints by 37% (p=0.004). In conclusion, antihypertensive treatment prevents

stroke and other cardiovascular complications in older Chinese patients with

isolated systolic hypertension. Treatment of 1000 Chinese patients for 5 years

could prevent 55 deaths, 39 strokes, or 59 major cardiovascular endpoints



Keywords: age/antihypertensive treatment/blood pressure/calcium channel

blocker/captopril/cardiovascular/cardiovascular

mortality/Chinese/cholesterol/complications/control/dihydropyridine/drugs/hydr

ochlorothiazide/hypertension/incidence/isolated systolic

hypertension/mortality/NEW-YORK/prevention/REPUBLIC-OF-CHINA/RISK/

serum/sex/STROKE/stroke/treatment



Elliott, P., Nichols, R. and Chee, D. (1999), Quantifying risk of death and disability

associated with raised blood pressure. Clinical and Experimental Hypertension,

21 (5-6), 571-582.



Abstract: Raised blood pressure is one of the most important underlying risk factors for

morbidity and mortality in the world today, ranking alongside tobacco in

estimates of the worldwide attributable burden of mortality. It is a major risk

factor for coronary heart disease and the major risk factor for stroke. Taken

together, the cardiovascular diseases are estimated to account for some 28% of

all deaths in the world; Already many more of such deaths are occurring in the

developing than the developed world, and this burden of disease is set to worsen

as a result of demographic changes in the poorer countries, together with

adoption of Western lifestyle. The development of unfavourable blood pressure

patterns in populations is a key factor underlying this worldwide epidemic. Both

primary prevention (for example through improved diet) and secondary

prevention (through drug treatment and non-pharmacologic approaches) are

needed



Keywords: blood pressure/cardiovascular/cardiovascular diseases/cardiovascular

epidemiology/coronary heart

disease/development/diet/DISEASE/diseases/England/heart/high blood

pressure/hypertension/INTERSALT/lifestyle/morbidity/mortality/NEW-YORK/

POPULATIONS/prevention/primary/primary prevention/risk/risk factor/risk

factors/secondary prevention/stroke/tobacco/treatment



Yamori, Y. (1999), Implication of hypertensive rat models for primordial nutritional

prevention of cardiovascular diseases. Clinical and Experimental Pharmacology

and Physiology, 26 (7), 568-572.



Abstract: 1. Various substrains maintained during selective sib-mating contributed to the

establishment of spontaneously hypertensive rats (SHR) with a variety of clinical

features. 2. Stroke-prone SHR (SHRSP), developing haemorrhagic and/or

ischaemic stroke spontaneously, are regarded as a model for osteoporosis. 3. The

genetic mechanisms of spontaneous hypertension hale been attributed

pathophysiologically to neural and structural vascular alterations. 4. The

mechanisms of stroke are ascribed to the limited regional oxygen and nutrient

supplies to the brain areas fed by perforating arteries. 5. The genome-wide

Linkage analysis on the F2 obtained by crosses of SHRSP with normotensive

strains has demonstrated different gene loci contributing to the development and

maintenance of hypertension during the ageing process and also genes

influencing the susceptibility to stroke without any effect on blood pressure. 6.

Experimental studies in SHRSP revealed that stroke could be prevented by

protein, Ca- or Mg-supplemented diets, particularly if given in the early stage,

indicating the importance of primordial nutritional prevention of cardiovascular

diseases (CVD). 7. Experimental findings in SHRSP as well as epidemiological

studies on nutrition and CVD indicate the future avenue towards

'predictive-preventive medicine' for CVD



Keywords: arteries/AUSTRALIA/blood

pressure/BLOOD-PRESSURE/brain/cardiovascular/cardiovascular

diseases/development/diseases/gene/genes/genetic/hypertension/ischaemic

stroke/linkage

analysis/nutrition/osteoporosis/prevention/rat/rats/SHR/SHRSP/spontaneously

hypertensive rats/stroke/STROKE-PRONE/stroke-prone spontaneously

hypertensive rats/vascular



Fujishima, M. and Tsuchihashi, T. (1999), Hypertension and dementia. Clinical and

Experimental Hypertension, 21 (5-6), 927-935.

Abstract: Vascular dementia (VD) is more prevalent than Alzheimer's disease (AD) in

Japan, while AD is more common in Western countries. In the Hisayama study, a

community-based cohort study of Japan, the prevalence of VD decreased in men

during the 7-years (1985-1992) follow-up period, while the prevalence of AD

remained unchanged both in men and women. The incidence of dementia

increases with age,particularly AD aged 85 or older. Hypertension is a major risk

factor for VD. Other risk factors include age, prior stroke, diabetes, alcohol

intake, heart disease, and smoking. In contrast, age, a family history of dementia,

a low educational level, and low physical activity are risk factors for AD. The

role of hypertension in AD remains controversial; there,has been positive,

negative, or no association existed between blood pressure levels and AD. A

recent clinical trial has disclosed the potential preventive effect of

antihypertensive treatment on the incidence of dementia, especially of AD.

Although the role of vascular factors for the pathogenesis of AD is becoming

recognized, the effectiveness of antihypertensive treatment on-the prevention of

AD should be further clarified in the future studies



Keywords: age/aged/alcohol/Alzheimer's

disease/ALZHEIMERS-DISEASE/antihypertensive treatment/blood

pressure/BLOOD-PRESSURE/cohort

study/dementia/diabetes/epidemiology/heart/HISAYAMA/history/hypertension/i

ncidence/JAPANESE COMMUNITY/men/NEW-YORK/physical

activity/POPULATION/PREVALENCE/prevention/risk/risk factor/risk

factors/RISK-FACTORS/smoking/stroke/treatment/vascular/VASCULAR

DEMENTIA/women



Schmidt, D., Vaith, P. and Hetzel, A. (2000), Prevention of serious ophthalmic and

cerebral complications in temporal arteritis? Clinical and Experimental

Rheumatology, 18 (4), S61-S63.



Abstract: Patients Five patients (mean age 81.6 years) developed bilateral blindness and

3 additional patients suffered cerebral strokes (mean age 58 years) due to

temporal arteritis. Bilateral blindness and strokes occurred despite corticosteroid

treatment. Results In all patients with temporal arteritis, the diagnosis was made

too late. Patients with bilateral blindness were referred to the Eye Hospital when

one eye had already become blind. The delay between the fil st symptoms and

blindness in one eye was (average) 7 weeks. The interval between blindness of

the first and second eyes was (average) 5 days in 3 patients, and simultaneous

blindness in both eyes occurred in 2 patients. The other eye also became blind

despite mega-doses of prednisone in 3 patients. Three additionalpatients already

showed neurological signs and symptoms at the beginning of the temporal

headache. All 3 patients developed strokes after some weeks or months. The

wrong diagnosis was made in the first examination(s) by the physician with

patients having prodromal signs or symptoms, but who also showed signs of

other vascular diseases (diabetes mellitus, hypertension or occlusion of the

internal carotid artery) which masked the inflammatory disease of temporal

arteritis. Conclusions Early diagnosis is essential to prevent severe complications.

In patients with a cerebral stroke the early neurological deficits are warning signs

which means that one must observe the patient regularly at short intervals. After

the diagnosis has been settled, treatment of the patients for several months with a

high dosage of corticosteroids is mandatory



Keywords: age/blindness/carotid/carotid

artery/cerebral/complications/corticosteroid/diabetes/diabetes

mellitus/diagnosis/diseases/essential/Germany/giant cell arteritis/GIANT-CELL

ARTERITIS/headache/hypertension/internal carotid artery/intracranial

arteritis/INVOLVEMENT/stroke/temporal arteritis/treatment/vascular



Chalmers, J. and Chapman, N. (2001), Progress in reducing the burden of stroke.

Clinical and Experimental Pharmacology and Physiology, 28 (12), 1091-1095.



Abstract: 1. The burden of stroke worldwide is growing rapidly, driven by an ageing

population and by the rapid rate of urbanization and industrialization in the

developing world. There are approximately 5 million fatal and 15 million

non-fatal strokes each year and over 50 million survivors of stroke alive,

worldwide, today. 2. The most important determinant of stroke risk is blood

pressure, with a strong, continuous relationship between the level of the systolic

and diastolic pressures and the risk of initial and recurrent stroke, in both

Western and Asian populations. 3. Randomized clinical trials have clearly

demonstrated that blood pressure lowering reduces the risk of initial stroke by

35-40% in hypertensive patients; but, until recently, there was no conclusive

evidence that blood pressure lowering was effective in the secondary prevention

of stroke. 4. The Perindopril Protection Against Recurrent Stroke Study

(PROGRESS) has provided definitive evidence that blood pressure lowering in

patients with previous stroke or transient ischaemic attack (TIA) reduces the

incidence of secondary stroke by 28%, of major vascular events by 26% and of

major coronary events by 26%. These reductions were all magnified by

approximately 50% in a subgroup of patients in whom the

angiotensin-converting enzyme inhibitor perindopril was routinely combined

with the diuretic indapamide. 5. Successful global implementation of a treatment

with perindopril and indapamide in patients with a history of stroke or TIA

would markedly reduce the burden of stroke and could avert between 0.5 and one

million strokes each year, worldwide



Keywords: ageing/angiotensin converting enzyme inhibitor/angiotensin-converting

enzyme inhibitors/Australia/blood pressure/blood pressure

lowering/BLOOD-PRESSURE/CEREBROVASCULAR- DISEASE/clinical

trials/CORONARY HEART-DISEASE/dementia/disability and

dependency/diuretics/DOSE-RESPONSE/FAILURE/history/hypertension/HYPE

RTENSION/incidence/indapamide/ischaemic/major coronary

events/perindopril/PERINDOPRIL/PLACEBO/population/prevention/PROGRE

SS/recurrent stroke/RISK/secondary/secondary

prevention/stroke/THERAPY/TIA/transient/transient ischaemic

attack/treatment/trials/vascular/vascular events

Ledingham, J.M. and Laverty, R. (2002), Fluvastatin remodels resistance arteries in

genetically hypertensive rats, even in the absence of any effect on blood pressure.

Clinical and Experimental Pharmacology and Physiology, 29 (10), 931-934.



Abstract: 1. The aims of the present study were, first, to determine whether, in the

genetically hypertensive (GH) rat, fluvastatin would lower blood pressure and

remodel mesenteric resistance arteries (MRA) and the basilar artery and, second,

to see whether treatment with a combination of fluvastatin and the angiotensin

receptor antagonist valsartan would have any extra beneficial effect on blood

pressure and vascular remodelling. 2. Male GH rats had tail-cuff systolic blood

pressure (SBP) monitored weekly from the age of 7 to 12 weeks. Groups (n = 12-

14) were treated with fluvastatin (4 mg/kg per day), valsartan (5 mg/kg per day),

both mixed in with chow, or a combination of fluvastatin 4 mg/kg per day +

valsartan 5 mg/kg per day. Untreated GH and a group of normotensive Wistar (N)

rats served as control groups. 3. At 12 weeks of age, intra-arterial (i.a.) blood

pressure was measured by femoral cannulation and rats were then perfused (at

the SBP of the animal) with Tyrode's solution containing heparin and papaverine

followed by 2.5% glutaraldehyde in Tyrode's solution; MRA and basilar arteries

were embedded in Technovit. Serial sections were cut and Giemsa stained and

stereological methods used to obtain media width, lumen diameter, medial

cross-sectional area (CSA) and the ratio of media width to lumen diameter.

Hearts were weighed to determine left ventricular (LV) mass. 4. Fluvastatin had

no effect on blood pressure or LV mass, whereas valsartan given alone or with

fluvastatin significantly reduced both parameters. 5. In MRA, fluvastatin reduced

medial CSA, increased lumen size and, therefore, probably decreased vascular

resistance. The media/lumen ratio was reduced to a level below that seen with

the combination treatment and to below that of the N group. 6. In the basilar

artery, fluvastatin and valsartan showed similar outward remodelling of the

lumen and reduction in the media/lumen ratio. The combination treatment group

showed, in addition, a reduction in medial CSA and an even lower ratio than the

GH group on fluvastatin or valsartan alone or the N group. 7. Although

fluvastatin has no effect on blood pressure, it does cause significant remodelling

of MRA and the basilar artery. These beneficial structural changes in a peripheral

resistance artery bed and in an artery involved in regulating resistance in the

brain are worthy of further study



Keywords: age/angiotensin/animal/arteries/AUSTRALIA/basilar artery/blood

pressure/brain/CEREBRAL-ARTERIES/CHOLESTEROL/combination/control/

ENDOTHELIAL DYSFUNCTION/fluvastatin/genetically hypertensive

rat/heparin/left ventricular/LOVASTATIN/MRA/NITRIC-OXIDE

SYNTHASE/PREVENTION/rat/rats/REDUCTASE INHIBITORS/resistance

arteries/STATINS/STROKE/systolic blood/systolic blood

pressure/treatment/valsartan/VALSARTAN/vascular/vascular remodelling



Leys, D., Deplanque, D., Lucas, C. and Bordet, R. (2002), Hypolipemic agents for

stroke prevention. Clinical and Experimental Hypertension, 24 (7-8), 573-594.

Abstract: An important issue for stroke prevention is identification and treatment of risk

factors such as hypercholesterolemia. The four reasons to test hypolipidemic

agents in stroke prevention are: (i) a statistical link between elevated low-density

lipoprotein cholesterol (LDL-c) or decreased high-density lipoprotein cholesterol

(HDL-c) and ischemic stroke; (ii) a reduction in vascular risk in randomized

trials in patients with coronary heart disease; (iii) evidence of a decreased plaque

progression under statins, (iv) pooled analyses of primary and secondary

prevention trials showing that reduction of total serum cholesterol reduces the

incidence of stroke, especially with the highest rate of cholesterol reduction, and

in patients with the highest risk of stroke (i.e., with statins in secondary

prevention trials), and (v) prophylactic neuroprotection induced by

hypolipidemic agents in animal models of cerebral ischemia. Data provided by

trials conducted in subjects with coronary heart disease and in asymptomatic

individuals should now be confirmed in stroke patient



Keywords: animal/asymptomatic/atherosclerosis/AVERAGE CHOLESTEROL

LEVELS/BRAIN ISCHEMIC TOLERANCE/CAROTID

ATHEROSCLEROSIS/cerebral/cerebral hemorrhage/cerebral

ischemia/cholesterol/COA REDUCTASE INHIBITORS/COENZYME-A

REDUCTASE/coronary heart disease/CORONARY

HEART-DISEASE/dementia/DENSITY-LIPOPROTEIN

CHOLESTEROL/disease/fibrates/heart/heart disease/high density

lipoprotein/high-density lipoprotein

cholesterol/hypercholesterolemia/HYPERTENSION/incidence/ischemia/ischemi

c/ischemic stroke/low density lipoprotein/low-density lipoprotein

cholesterol/MYOCARDIAL-INFARCTION/neuroprotection/NEW-YORK/NIT

RIC-OXIDE SYNTHASE/plaque/prevention/primary/primary and secondary

prevention/randomized/randomized trials/risk/risk factors/secondary/secondary

prevention/serum/SERUM- CHOLESTEROL/statins/statistical/stroke/stroke

prevention/transient ischemic attacks

(TIA)/treatment/trials/triglycerides/vascular/vascular risk



Barnett, H.J.M. (2002), Stroke prevention in the elderly. Clinical and Experimental

Hypertension, 24 (7-8), 563-571.



Abstract: The incidence of stroke and risk factors peak in subjects greater than or equal

to75 years. Highest risk patients benefit most from effective therapy. For this

reason, all strategies of proven value in stroke prevention must be assiduously

applied. Control of hypertension, hyperlipidemia, diabetes mellitus and cessation

of cigarette smoking are obligatory at all ages but are of special importance in

the elderly. Antithrombotic drugs have been proven beneficial for patients at

high risk. Lower risk subjects, including those with asymptomatic carotid artery

disease, gain no proven benefit from anti-platelet drugs. Patients with

non-valvular atrial fibrillation (NVAF), a condition that increases with age,

require anticoagulant therapy. Strict regulation of the INR is required otherwise

aspirin is recommended. Without evidence of organ failure, elderly patients with

severely stenotic symptomatic carotid artery disease should receive

endarterectomy. They benefit most. The evidence for benefit from

endarterectomy in asymptomatic subjects at any age is weak and cannot be

recommended



Keywords: ACETYLSALICYLIC-ACID/age/anticoagulant/anticoagulant

therapy/antiplatelet/antiplatelet drugs/antiplatelet

therapy/ASPIRIN/asymptomatic/ASYMPTOMATIC CAROTID

STENOSIS/atrial fibrillation/carotid/carotid artery/carotid artery disease/carotid

endarterectomy/cigarette smoking/diabetes/diabetes

mellitus/disease/drugs/elderly/elderly

patients/ENDARTERECTOMY/fibrillation/high

risk/hyperlipidemia/HYPERTENSION/incidence/INR/NEW-YORK/non-valvula

r atrial fibrillation/nonvalvular atrial fibrillation/prevention/RISK/risk

factors/smoking/stroke/stroke prevention/therapy/TICLOPIDINE/TRIAL



McInnes, G.T. (2002), Clinical trials and tribulations. Clinical and Experimental

Pharmacology and Physiology, 29 (11), 951-955.



Abstract: 1. Pharmacologists should be involved in all stages of drug development.

Often neglected is the final step, the clinical trials and other studies that

determine clinical utility. The present article illustrates how

pharmacoepidemiology can facilitate evaluation of the clinical potential of

different drugs used to treat hypertension. 2. The evidence base for the drug

treatment of hypertension is very strong. Large-scale outcome trials, largely

based on diuretics, indicate that stroke events are prevented to the extent

expected from blood pressure reduction, but there appears to be a shortfall in the

prevention of coronary heart disease events. 3. On theoretical grounds, newer

agents may be expected to have benefits in coronary heart disease prevention

beyond blood pressure reduction. Recent trials with angiotensin-converting

enzyme inhibitors and calcium channel blockers suggest no advantage over

conventional drugs, but short-comings in these studies mean that each is

uninformative. 4. Observational studies based on pharmacoepidemiological

principles offer an alternative approach to evaluating outcomes in treated

hypertensives. 5. Evidence from the Glasgow Blood Pressure Clinic database

suggest that there are outcome differences between antihypertensive agents.

Angiotensin-converting enzyme inhibitor treatment is associated with a mortality

advantage, whereas calcium channel blocker therapy is associated with a poorer

prognosis. Preliminary findings from a primary care database support these

observations. 6. Long-term follow up of a well-documented high-risk clinical

population may allow detection of outcome differences not apparent in relatively

short-term clinical trials. 7. Appropriate interpretation of observational data

necessitates an understanding of the strengths and limitations of observational

data. Clinical pharmacologists have a critical role in design and evaluation of

pharmacoepidemiology studies



Keywords: angiotensin converting enzyme inhibitors/angiotensin-converting enzyme

inhibitors/antihypertensive agents/AUSTRALIA/blocker/BLOCKERS/blood

pressure/BLOOD-PRESSURE/calcium/calcium channel/calcium channel

blocker/calcium channel blockers/CALCIUM-CHANNEL

BLOCKADE/CANCER/CARDIOVASCULAR MORBIDITY/clinical

pharmacology/clinical trials/coronary heart

disease/design/detection/development/disease/diuretics/drugs/evaluation/experim

ental pharmacology/heart/heart disease/high

risk/HYPERTENSION/hypertension/interpretation/MORTALITY/MYOCARDI

AL-INFARCTION/observational

studies/outcome/pharmacoepidemiology/population/prevention/primary/primary

care/prognosis/RANDOMIZED TRIAL/RISK/stroke/therapy/treatment/trials



Bornstein, N., Corea, F., Gallai, V. and Parnetti, L. (2002), Heart-brain relationship:

Atrial fibrillation and stroke. Clinical and Experimental Hypertension, 24 (7-8),

493-499.



Abstract: In Western countries, stroke is the second cause of death and the first cause of

disability. Cardiogenic embolism is the most frequent cause of recurrent strokes.

Nonvalvular atrial fibrillation (NVAF) is the most common source of

cardiogenic embolism, with a stroke recurrence rate of about 10% per year.

Randomised trials have shown that anticoagulation and aspirin are safe in

patients with NVAF, leading to 70% and 22% risk reduction of strokes,

respectively. Many potential candidates to anticoagulation fail to receive the

appropriate treatment for primary and secondary prevention. More efforts should

be spent to increase the number of treated subjects, in order to achieve effective

prevention on stroke



Keywords: ACUTE

MYOCARDIAL-INFARCTION/ANTICOAGULATION/ASPIRIN/atrial

fibrillation/ATTITUDES/cause of

death/death/disability/EMBOLISM/fibrillation/FRAMINGHAM/HYPERTENSI

ON/MANAGEMENT/NEW-YORK/OUTCOMES/PREVENTION/primary/prim

ary and secondary prevention/recurrence/RISK/secondary/secondary

prevention/stroke/stroke prevention/stroke recurrence/treatment/trials



Regesta, G. (2002), Medical therapy for secondary prevention of stroke. Clinical and

Experimental Hypertension, 24 (7-8), 555-562.



Abstract: The identification and modification of risk factors for stroke and their

appropriate management can lead to reduction of stroke incidence. The real

impact on recurrences of risk factors associated with lifestyles has not been

thoroughly investigated, and the possible role of their modification in secondary

prevention is principally extrapolated from primary prevention studies. On the

other hand, several pathological conditions such as hypertension, atria]

fibrillation, carotid stenosis, and diabetes are known to favour the risk of

recurrence. Available antiplatelet regimens offer only partial protection against

stroke and more efficacious antithrombotic agents would be useful. There is no

doubt that warfarin is effective in preventing recurrence in stroke patients with

atrial fibrillation. However, a careful etiological subtyping of stroke is

recommended before starting treatment



Keywords: antiplatelet/antithrombotic/antithrombotic agents/ASPIRIN/atrial

fibrillation/ATRIAL-FIBRILLATION/carotid/carotid

stenosis/CEREBRAL-ISCHEMIA/CEREBROVASCULAR-DISEASE/COMM

UNITY-STROKE/diabetes/fibrillation/HYPERTENSION/incidence/ISCHEMIC

STROKE/management/NEW-YORK/prevention/primary/primary

prevention/PROJECT/protection/RANDOMIZED

TRIAL/recurrence/REDUCTASE INHIBITORS/risk/risk factors/risk factors for

stroke/RISK- FACTORS/secondary/secondary prevention/stenosis/stroke/stroke

incidence/therapy/treatment/warfarin



Wang, H., Delaney, K.H., Kwiecien, J.M., Smeda, J.S. and Lee, R.M.K.W. (1997),

Prevention of stroke with perindopril treatment in stroke-prone spontaneously

hypertensive rats. Clinical and Investigative Medicine-Medecine Clinique et

Experimentale, 20 (5), 327-338.



Abstract: Objective: To determine the protective effects of perindopril treatment in the

prevention of stroke and the relation between preventive effects and the

histopathology of the brain and kidneys in male stroke-prone spontaneously

hypertensive rats (SHRSP). Design: Prospective animal study. Interventions:

Beginning at 6 weeks of age, SHRSP were treated with either distilled water

(control) or perindopril for different periods (8, 12 or 24 weeks) and at different

dosages (1 or 4 mg/kg per day). Outcome measures: Regular determination of

systolic blood pressure, heart rate and body weight until death; at necropsy,

macroscopic and microscopic examinations of the brain and kidneys. Results:

Control SHRSP developed severe hypertension (up to 250 mm Hg) by 11 weeks

of age and died of stroke within 14 weeks of age. Treatment with perindopril (4

mg/kg per day for 8 or 12 weeks or either 1 or 4 mg/kg per day for 24 weeks)

attenuated the blood pressure rise and prevented stroke. In untreated SHRSP, the

last blood pressure measurement before the first stroke sign was significantly

higher than in SHRSP of the same age treated with perindopril. Withdrawal of

the treatment resulted in a rise in blood pressure in all the treatment groups, to

approximately 260 mm Hg within 4 weeks. Most of the rats treated for 8 or 12

weeks died within 10 weeks after withdrawal of treatment, whereas those treated

for 24 weeks survived up to 43 weeks of age. Treatment also prevented damage

to the brain and kidneys and reduced the severity of lesions in the brain and

kidneys after treatment withdrawal. Conclusion: Treatment of SHRSP with

perindopril prevents stroke through the suppression of blood pressure rise and

prevention of tissue damage in the brain and the kidneys. Longer treatment

decreased the rate of mortality due to stroke after the withdrawal of treatment as

well as the severity of lesions in the brain and kidneys



Keywords: age/animal/ASSOCIATION/blood pressure/control/heart/HEMORRHAGIC

STROKE/hypertension/mortality/perindopril/prevention/rats/severity/SHRSP/str

oke/stroke-prone spontaneously hypertensive rats/treatment

Wikstrand, J. (1991), Reducing the Risk for Coronary Events and Stroke in

Hypertensive Patients - Comments on Present Evidence. Clinical Cardiology, 14

(7), 25-35.



Abstract: Therapeutic options for initial antihypertensive treatment include the four most

popular classes of drugs: diuretics, beta blockers, angiotensin-converting enzyme

(ACE) inhibitors, and calcium antagonists. The practitioner must decide which

agent is appropriate for each patient, the main goal of treatment being to prevent

stroke and coronary events-sudden death and myocardial infarction. A 40%

reduction in stroke can probably be achieved with any antihypertensive treatment,

but data show that it is much more difficult to reduce the risk of coronary events.

Available evidence from studies in men indicates that certain beta blockers are

superior to thiazide diuretics for the prevention of coronary events. Results from

the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) Trial

showed that the risk for coronary events was 24% lower in patients receiving

metoprolol than in patients receiving diuretics (p 4.1), were 28.3, 14.1, and 15.6%. Patient

involvement in treatment positively influenced quality of control. By contrast,

age 70-80 years or absence of congestive heart failure negatively affected quality

of anticoagulation [p = 0.07, odds ratio (OR), 1.7 (95% confidence interval,

0.94-3.08), p = 0.014, OR, 2.06 (95% confidence interval, 1.15-3.7) respectively].

The percentage of patients admitted with stroke who had been adequately

anticoagulated was significantly lower than that of patients who had no stroke

(21 vs. 44.4%). Adequacy of anticoagulation in patients with cardiac prosthetic

valves was superior compared with the rest of the patient population (56.7 vs.

42% with optimal, and only 14.5 vs. 28.3% with poor anticoagulation,

respectively), indicating that under the same conditions a better quality of

treatment could be achieved



Keywords: age/anticoagulation/ANTITHROMBOTIC THERAPY/atrial

fibrillation/bleeding/cardiac/CARE/chronic atrial

fibrillation/community/congestive heart

failure/control/fibrillation/follow-up/heart/heart

failure/hospital/INR/International Normalized Ratio/International Normalized

Ratio control/Israel/MANAGEMENT/ORAL

ANTICOAGULATION/population/prevention/stroke/STROKE

PREVENTION/treatment/UNIVERSITY HOSPITALS/valves/WARFARIN



White, W.B. (2003), Clinical trial experience around the globe: Focus on calcium-

channel blockers. Clinical Cardiology, 26 (2), 7-11.



Abstract: Although certain classes of drugs appear to possess benefits apart from their

blood-pressure lowering capability, reduction of blood pressure remains the

single most important action of antihypertensive therapy. Calcium-channel

blockers (CCBs) have long been recognized as potent agents for hypertension

therapy. This is especially true for the prevention of stroke in hypertensive

patients as evidenced from the Systolic Hypertension in Europe (Syst-Eur) and

Systolic Hypertension in China (Syst-China) trials with a long acting

dihydropyridine CCB. The same can be said for beta blockers in patients post

myocardial infarction. However, most recent clinical trials have underscored the

necessity of multiple drug therapy to achieve the goals of blood pressure

reduction coupled with outcomes reduction. For example, the many recent

large-scale clinical trials have required an average of three or more agents to

achieve goal. Thus, the paradigm for hypertension management has been altered

to determine the best treatment regimen rather than the best initial agent. While

response rates to individual agents across a wide spectrum of patients vary little,

not all drugs are equally suited as companion products. In this article, we discuss

the most recent outcome trials with the long acting CCBs alone or in

combination with other drugs. The evidence shows that calcium antagonists

remain an important part of hypertension management, including in those

individuals at risk of cardiac and cerebrovascular events



Keywords: ACTIVE TREATMENT/ANTAGONISTS/ANTIHYPERTENSIVE

THERAPIES/antihypertensive therapy/benefits/beta-blockers/blood

pressure/blood pressure lowering/calcium/calcium antagonists/calcium

channel/calcium channel

blockers/calcium-antagonists/cardiac/CARDIOLOGY/cardiovascular

events/CARDIOVASCULAR MORBIDITY/cerebrovascular/China/CLINICAL

CARDIOLOGY/clinical trials/combination/CT/dihydropyridine/drug/drug

safety/drug therapy/drugs/Europe/hypertension/infarction/ISOLATED

SYSTOLIC HYPERTENSION/management/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/OLDER

PATIENTS/outcome/OUTCOMES/outcomes

research/prevention/RANDOMIZED

TRIAL/RISK/stroke/therapy/treatment/trial/trials/USA



Panagiotopoulos, K., Toumanidis, S., Vemmos, K., Saridakis, N. and Stamatelopoulos,

S.H. (2003), Secondary prognosis after cardioembolic stroke of atrial origin: The

role of left atrial and left atrial appendage dysfunction. Clinical Cardiology, 26

(6), 269-274.



Abstract: Background: Secondary prevention studies for cardioembolic strokes show a

remarkable variability in stroke recurrence rates. Various reports have raised

questions regarding differences in baseline clinical characteristics and in

methodology to explain this wide variability. Hypothesis: The purpose of the

present study is to examine the 2-year outcome after first cardioembolic stroke of

atrial origin and to correlate secondary prognosis with left atrial and left atrial

appendage dysfunction. Methods: Baseline evaluation included computed

tomographic and/or magnetic resonance scanning, Doppler scanning, digital

subtraction angiography, and transthoracic and transesophageal

echocardiography to establish the diagnosis of atrial source of emboli.

Twenty-six patients in nonrheumatic atrial fibrillation and 13 in sinus rhythm

were followed for recurrent stroke and vascular death as endpoints (event+/-).

Results: Patients in sinus rhythm had a total of 23% (standard deviation +/- 12%)

recurrence rate. All event (+) patients were on aspirin and died from this second

cardioembolic stroke. Of patients in nonrheumatic atrial fibrillation, 50% were

event (+) at the end of the first year (death rate 46%). Patients on warfarin

therapy had 20% recurrence rate versus 70% on aspirin (relative risk 0.18, 95%

confidence interval, 0.05-0.48, p 0.041). Inward peak velocity of left atrial

appendage was the only echocardiographic variable significantly reduced in

event (+) patients (21 +/- 7 vs. 31 +/- 17 cm/s, p 0.048). Conclusions: Patients

with nonrheumatic atrial fibrillation and first atrial origin cardioembolic stroke

are at increased risk for recurrence if severe dysfunction of the left atrial

appendage is present and if they do not receive warfarin treatment. Patients with

sinus rhythm and first atrial origin cardioembolic stroke form a small stroke

subgroup, in which recurrences are accompanied by a remarkably high death rate



Keywords: angiography/aspirin/atrial/atrial appendage/atrial

fibrillation/cardioembolic/cardioembolic stroke/CARDIOLOGY/CLINICAL

CARDIOLOGY/death/diagnosis/digital subtraction/digital subtraction

angiography/Doppler/echocardiography/emboli/evaluation/EVENTS/FIBRILLA

TION/FLOW/left atrial

appendage/methodology/nonrheumatic/outcome/PREVENTION/prognosis/recur

rence/recurrent stroke/relative risk/risk/secondary/sinus rhythm/stroke/stroke

recurrence/therapy/transesophageal

echocardiography/treatment/USA/vascular/warfarin



Gotto, A.M. (2003), Risks and benefits of continued aggressive statin therapy. Clinical

Cardiology, 26 (4), 3-12.



Abstract: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase

inhibitors, or statins, are a well-tolerated, effective class of medications for the

reduction of low-density lipoprotein cholesterol (LDL-C) and total cholesterol

levels. Extensive data from clinical trials demonstrate that these agents reduce

fatal and nonfatal cardiovascular risk in primary and secondary prevention

patients, including women and the elderly. A threshold value for LDL-C

reduction below which there is no further clinical benefit has not yet been

identified. In the Heart Protection Study (HPS), significant relative risk reduction

occurred even among patients with LDL-C levels 12 mu mol/l should increase and/or supplement their

dietary intake of vitamins



Keywords: adhesion molecules/age/atherosclerosis/cardiovascular/cardiovascular

disease/cardiovascular

diseases/CHRONIC-RENAL-FAILURE/coagulation/CORONARY-ARTERY

DISEASE/diabetes/diagnosis/diet/dietary

intake/disease/diseases/EARLY-PREGNANCY LOSS/elderly/elderly

subjects/ENDOTHELIAL-CELLS/FOLIC-ACID/formation/Germany/history/ho

mocysteine/hyperhomocysteinemia/hyperlipidemia/LDL/metabolism/METHYL

ENETETRAHYDROFOLATE REDUCTASE/METHYLMALONIC

ACID/methylmalonic acid/muscle/PERIPHERAL

VASCULAR-DISEASE/PLASMA HOMOCYSTEINE

LEVELS/postmenopausal women/prevalence/prevention/prospective

studies/renal/renal disease/risk/risk

factor/S-ADENOSYLMETHIONINE/serum/smooth/stroke/therapy/thrombosis/t

reatment/vegetarians/venous thrombosis/vitamin deficiency/vitamins/women

Goldenberg, G.M., Silverstone, F.A., Rangu, S. and Leventer, S.L. (1999), Outcomes of

long-term anticoagulation in frail elderly patients with atrial fibrillation. Clinical

Drug Investigation, 17 (6), 483-488.



Abstract: Objective: To assess the outcomes of long-term anticoagulation in elderly

nursing home patients with atrial fibrillation (AF) and investigate the influence

of age, gender and co-morbid conditions. Design: A retrospective chart review

was performed in five randomly selected nursing facilities. Patients: Thirteen

males and 74 females with nonrheumatic AF, and a mean age of 82.4 years (SD

7.7 years) were included; 74 patients (85%) were older than 75 years. 92% were

Caucasian, 74% had a prior cerebral event [61 disabling strokes and three

transient ischaemic attacks (TIA)]. All had one to five co-morbid conditions

known to be stroke risk factors (mean 2.7, SD 0.9). Two and more risk factors

were present in 91% of the patients, and three and more risk factors were present

in 63% of the patients. Interventions: Treatment with warfarin was given for 12

to 72 months, (mean 25.8 months, SD 4.3 months). The mean dose of warfarin

was 2.8mg (SD 1.1mg). Twelve monthly international normalised ratio (INR)

values were extracted for each patient. Outcome Measures: A stroke/TIA or a

major bleed was considered an adverse outcome. A multivariate logistic

regression model was used to analyse the data. Results: Sixteen patients (18.3%)

had adverse outcomes: four strokes, one TIA and 11 bleeds. Half of the events,

three strokes and five bleeds, were fatal. Gastro-intestinal bleeds had a 56%

mortality rate. Patients with and without adverse outcomes were similar in terms

of age and intensity of anticoagulation (mean INR 2.1, SD 0.5 and 0.4). Adverse

events were seen in 12% of females and in 54% of males. The influence of

gender was independent of age, number of co-morbid conditions and intensity of

anticoagulation entered in the multivariate model. Conclusions: The patients in

this study had a rate of bleeds higher than in reported clinical trials. Their older

age (85% older than 75 years) and greater co-morbidity (91% had more than two

stroke risk factors) were the likely causes of this difference. The outcomes of

anticoagulation were better in females than in males. Further studies are required

on outcomes of anticoagulation in elderly patients with AF



Keywords: AF/age/anticoagulation/atrial fibrillation/AUCKLAND/cerebral/clinical

trials/comorbidity/COMPLICATIONS/DRUG/elderly/fibrillation/INFARCTION

/INR/mortality/NEW-ZEALAND/nonrheumatic/PREVALENCE/PREVENTIO

N/PROTHROMBIN TIME/review/risk/risk

factors/STROKE/THERAPY/TIA/transient/transient ischaemic

attacks/trials/WARFARIN



Gallerani, M., Manfredini, R., Donega, P., Lanza, F., Da Busti, M., Vigna, G.B. and

Fellin, R. (2000), Adverse haematological effects of ticlopidine - A report of four

cases. Clinical Drug Investigation, 19 (3), 231-237



Keywords: ANTIPLATELET/ASPIRIN/AUCKLAND/CHINESE

PATIENTS/CHOLESTATIC

HEPATITIS/DRUG/NEUTROPENIA/NEW-ZEALAND/SECONDARY

PREVENTION/SEVERE

APLASTIC-ANEMIA/STROKE/THERAPY/THROMBOTIC

THROMBOCYTOPENIC PURPURA/ticlopidine



Wu, N., Zhu, J.R. and Chen, K.A. (2002), Tolerability of ramipril 10 mg/day in

high-risk cardiovascular Chinese patients. Clinical Drug Investigation, 22 (11),

771-781.



Abstract: Objective: The aim of this study was to investigate the tolerability of ramipril

10 mg/day in high-risk cardiovascular Chinese patients, following similar criteria

to those used for patient selection in the Heart Outcomes Prevention Evaluation

(HOPE) study and through the collection of adverse event data by Chinese

cardiologists. Design and subjects: This was a non- comparative study with

single-group non-blind assessment carried out in 76 nationwide investigational

sites. The target population was around 1000 patients. Men and women aged

greater than or equal to55 years were eligible for the study if they had one of the

following risk factors for developing major cardiovascular events: a history of

coronary artery disease, stroke, peripheral vascular disease or diabetes plus at

least one other cardiovascular risk factor. Patients initially received ramipril

2.5mg tablets orally once daily, and were then titrated up to 5 mg/day and 10

mg/day at 2-week intervals. The maintenance dosage was 10 mg/day for I month.

For patients with stable heart failure, the starting dosage was 1.25 mg/day,

titrating up to the same maintenance dosage (10 mg/day). Adverse events were

closely followed up and recorded. 981 patients were eligible for the

intention-to-treat (ITT) analysis. Twenty-three patients dropped out at their own

request or because of protocol violation. 958 patients (97.7%) completed the

study per protocol. Main results: 880 of 958 (91.8%) patients reached and

remained at the 10 mg/day dosage level; 78 of 958 (8.1%) stayed at 5mg/day or

2.5 mg/day. 168 patients (17.5%) had at least one adverse event. Fifty-eight

patients (6.0%) stopped the treatment because of an adverse event; 110 (11.5%)

completed the study in spite of adverse events. Altogether, 185 instances of

adverse events were observed, mainly consisting of cough, dizziness,

hypotension, rash and serum creatinine elevation. Most adverse events were

possibly or probably related to ramipril. Three patients experienced serious

adverse events, including one death, but investigation failed to show any

evidence of a relationship to ramipril treatment. Conclusion: Ramipril was well

tolerated in Chinese patients with high-risk cardiovascular diseases. Patients

were able to tolerate the full effective dosage level of 10 mg/day



Keywords: adverse events/aged/AUCKLAND/cardiovascular/cardiovascular

diseases/cardiovascular events/cardiovascular risk/China/Chinese/coronary artery

disease/death/diabetes/disease/diseases/DRUG/heart/heart failure/high

risk/history/hypotension/NEW-ZEALAND/peripheral vascular

disease/population/ramipril/risk/risk factor/risk

factors/serum/stroke/treatment/vascular/vascular disease/women

Lechner, H., Schmidt, R., Reinhart, B., Grieshofer, P., Koch, M., Fazekas, F.,

Niederkorn, K., Horner, S., Irmler, A. and Freidl, W. (1994), The Austrian

Stroke Prevention Study - Serum Fibrinogen Predicts Carotid Atherosclerosis

and White-Matter Disease in Neurologically Asymptomatic Individuals. Clinical

Hemorheology, 14 (6), 841-846.



Abstract: To determine the influence of various hemorheologic factors on carotid

atherosclerois and white matter abnormalities in normals we studied 112

neurologically asymptomatic individuals aged 50 to 70 years by Doppler

sonography and MRI. Atherosclerotic vessel wall changes and white matter foci

were noted in 66 (58.9%) and 62 (55.4%) individuals, respectively. After

correcting for group differences in age and mean arterial blood pressure by the

use of an analysis of covariat test, subjects with carotid disease had higher

plasma fibrinogen concentrations than those with a normal vessel wall status

(327.1+/-72.7 mg/dl vs 296.3+/-67.1 g/dl, p=0.03) A similar association was

found in the presence of MRI white matter abnormalities (330.1+/-76.7 mg/dl vs

295.1+/-60.4 mg/dl, p=0.04). Partial correlations revealed positive relationship

between fibrinogen level and the severity of both carotid (r=0.21, p=0.03) and

white matter damage (r-0.24, p-0.009). Other theologic variables including whole

blood and plasma viscosity, hematocrit as well as red cell transit time were not

related to evidence of abnormal imaging findings. Our data demonstrate a clear

association between plasma fibrinogen with large and small vessel

atherosclerosis. As to whether elevations of serum fibrinogen are only the

epiphenomenon of atherosclerotic damage or represent a vascular risk factor per

se can only be determined by prospective longitudinal studies



Keywords: aged/atherosclerosis/blood pressure/carotid/CAROTID

ATHEROSCLEROSIS/ENGLAND/fibrinogen/MRI WHITE MATTER

DISEASE/MYOCARDIAL-INFARCTION/NORMAL

VOLUNTEERS/PLASMA

FIBRINOGEN/PLASMA-FIBRINOGEN/risk/RISK-FACTORS/severity/SIGN

AL HYPERINTENSITIES/vascular



Le Devehat, C., Khodabandehlou, T. and Mosnier, M. (2000), Effect of naftidrofuryl on

platelet aggregation in plasma from aspirin treated patients: an in vitro study.

Clinical Hemorheology and Microcirculation, 22 (3), 197-204.



Abstract: This study concerns an in vitro evaluation of the effect of naftidrofuryl on

platelet aggregation in plasma of 15 diabetic patients, who were being treated

with aspirin, and who were suffering from chronic arterial disease of the lower

limbs. Platelet aggregation, induced either spontaneously or by aggregating

agents, was measured in platelet-rich plasma (PRP). The results show that

serotonin (5-HT)- and adenosine 5'- diphosphate (ADP)-induced platelet

aggregation significantly decreased after addition of naftidrofuryl. Decreases

were achieved with naftidrofuryl at a low dose (0.06 mu M) and became more

marked with naftidrofuryl at higher concentrations. In contrast, naftidrofuryl did

not appear to modify routinely spontaneous platelet aggregation. These results

show an in vitro antiaggregating effect of naftidrofuryl on platelets of aspirinized

patients. However, the clinical interest of a such coadministration of

naftidrofuryl and aspirin in patients, has still to be confirmed in a double blind

randomized trial



Keywords:

adenosine/aggregation/aspirin/BINDING/evaluation/FIBRINOGEN/naftidrofury

l/NETHERLANDS/platelet aggregation/platelets/randomized/randomized

trial/SECONDARY PREVENTION/STROKE



Gey, K.F., Stahelin, H.B. and Eichholzer, M. (1993), Poor Plasma Status of Carotene

and Vitamin-C Is Associated with Higher Mortality from

Ischemic-Heart-Disease and Stroke - Basel Prospective-Study. Clinical

Investigator, 71 (1), 3-6.



Abstract: Previous cross-cultural comparisons of the mortality from ischemic heart

disease. in European communities with associated plasma levels of essential

antioxidants have revealed strong inverse correlations for vitamin E and

relatively weak correlations for other antioxidants. Similarly, in a case- control

study in Edinburgh low plasma levels of vitamin E were significantly associated

with an increased risk of previously undiagnosed angina pectoris whereas low

levels of other essential antioxidants lacked statistical significance. The current

Basel Prospective Study is particularly well suited to elucidate the impact of

antioxidants other than vitamin E. In this population (which was recently

evaluated regarding cancer mortality) the plasma levels of vitamins E and A are

exceptionally high and above the presumed threshold level of risk for ischemic

heart disease. The present 12-year follow-up of cardiovascular mortality in this

study reveals a significantly increased relative risk of ischemic heart disease and

stroke at initially low plasma levels of carotene (5.5 mmol/l who have

coronary heart disease, other forms of atherosclerotic vascular disease, or Who

are free of vascular disease but have a risk of major coronary events greater than

or equal to 1.5% per year. Choice of an appropriate treatment policy will require

(i) knowledge of the proportion of the population who Will need treatment for

secondary prevention, and (ii) targeting of treatment for primary prevention at a

specified absolute risk of coronary heart disease events, Selection of an

appropriate coronary heart disease risk for primary prevention requires

consideration of the number needed to be treated to prevent one coronary heart

disease event, the proportion of the population requiring treatment, the

cost-effectiveness of treatment and the total cost of treatment. 2. In a random

stratified sample of subjects aged 35-69 years from the Health Survey for

England 1993 we first examined the prevalence of subjects with cardiovascular

disease and serum cholesterol >5.5 mmol/l who may be candidates for secondary

prevention, In those free of cardiovascular disease we then examined the

prevalence of subjects with serum cholesterol >5.5 mmol/l who had three

different levels of coronary heart disease risk: coronary heart disease event rates

of 4.5% per year, 3.0% per year and 1.5% per year, These subjects may be

candidates for primary prevention depending on the treatment policy selected. 3.

For secondary prevention, 4.8% (95% confidence interval 4.3-5.3) of the U.K.

population aged 35-69 years might be candidates for 3-

hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor treatment, comprising

2.4% (2.0 to 2.7) with a history of myocardial infarction, 1.9% (1.6 to 2.2) with

angina and 0.5% (0.3-0.7) with a history of stroke - all with total cholesterol >5.5

mmol/l. The prevalence of these diagnoses with total cholesterol >5.5 mmol/l

increased with age, from 1.5% at age 35-39 years to 16.2% at age 65-69 years in

men, and from 0.2% at age 35-39 years to 10.0% at age 65-69 years in women.

Approximately 13 people would need treatment for 5 years to prevent one

coronary event, at a cost of pound 36 000 per event prevented. The number

needing treatment for Secondary prevention would increase substantially if

treatment was extended to patients above 70 years of age or to those with serum

cholesterol less than or equal to 5.5 mmol/l. 4. Primary prevention aimed at a

coronary event risk of 4.5% per year would lead to treatment of only 0.3%

(0.2-0.4) of those aged 35-69 years, and those treated would be predominantly

older men with additional risk factors for coronary heart disease. The number

needed to be treated and cost per coronary event prevented would be similar to

those for secondary prevention. 5. Primary prevention targeted at subjects with a

coronary event rate of 3.0% per year would entail treating 3.4% (3.0- 3.9) of all

those aged 35-69 years. At this level of risk, 20 people would need treatment for

5 years to prevent one coronary event, at a cost of pound 55 000 per event

prevented. 6. Primary prevention aimed at a coronary event rate Of 1.5% per

year would entail (18.7-20.6) of all subjects aged 35-69 years, and about 80% of

men aged 60-69 years for primary or Secondary prevention. At this level of risk,

40 people would need treatment for 5 years to prevent one event, at a cost of

pound 111 000 per event saved. 7. Guidelines for 3-hydroxy-3-

methylglutaryl-coenzyme A reductase inhibitor treatment should take into

account the considerable workload and financial resources needed to implement

secondary prevention of coronary heart disease, the accepted first priority. For

primary prevention they need to consider the number needed to be treated to

prevent one event, the number of subjects needing treatment, the

cost-effectiveness of treatment and the total cost of treatment for the population.

Considering only the number needed to be treated we would propose treatment

for secondary prevention plus primary prevention at a coronary event rate of

3.0% per year. This would entail treating about 8.2% of the U.K. population aged

35-69 years, at an annual cost for drug therapy alone about pound 18 million per

million of the U.K. population



Keywords: angina/CARDIOVASCULAR

RISK/cholesterol/CLINICAL-TRIALS/coronary heart disease/coronary

risk/FOLLOW-UP/GUIDELINES/lipids/MANAGEMENT/MILD

HYPERTENSION/MORTALITY/myocardial infarction/primary

prevention/PRIMARY-CARE/REDUCTION/risk factors/secondary

prevention/SERUM-CHOLESTEROL

CONCENTRATION/stroke/treatment/trials



Giles, T.D. (1997), Hypertension and pathologic cardiovascular remodeling: A potential

therapeutic role for T-type calcium antagonists. Clinical Therapeutics, 19

27-38.



Abstract: Increased myocardial mass (cardiac hypertrophy, left ventricular hypertrophy

[LVH]) is an example of the widespread structural cardiovascular changes, often

referred to as remodeling, that may be present in association with sustained high

blood pressure. LVH strongly predicts myocardial infarction, stroke, and

cardiovascular death in patients with hypertension. As a result, prevention or

reversal of hypertensive LVH is widely accepted as a desirable therapeutic goal.

Although the molecular mechanisms responsible for remodeling are unclear, it is

believed that mechanical, endocrine, paracrine, and autocrine factors control the

remodeling process. Certain antihypertensive drugs may have particularly

favorable long-term effects in that they prevent and correct these structural

changes in addition to reducing arterial pressure. However, the mechanism by

which they achieve these effects is not well understood. It is theorized that

angiotensin-converting enzyme inhibitors do so by preventing the generation of

growth-promoting/mitogenic peptides and that beta-blockers interfere with the

growth-promoting effects of catecholamines. In experimental models, the

selective blockade of T-type calcium-ion (Ca2+) channels with mibefradil has

been demonstrated to have antiproliferative effects in both the renal and cardiac

vasculature; in patients with LVH, mibefradil reduced the left ventricular mass

index. Therefore, blockade of T-type Ca2+ channels may be useful in the

prevention or regression of cardiovascular remodeling. However, further

research will be required before the clinical implications of these findings can be

assessed



Keywords: angiotensin converting enzyme inhibitors/angiotensin-converting enzyme

inhibitors/ANGIOTENSIN-II/beta-blockers/blood pressure/CA2+

CHANNELS/calcium antagonists/cardiac

hypertrophy/CARDIAC-HYPERTROPHY/cardiovascular

remodeling/CELLS/CLINICAL IMPLICATIONS/control/drugs/high blood

pressure/hypertension/hypertrophy/infarction/left ventricular

hypertrophy/LEFT-VENTRICULAR HYPERTROPHY/mibefradil/myocardial

infarction/MYOCARDIAL-INFARCTION/NEW-YORK/prevention/RATS/SM

OOTH-MUSCLE/stroke/STRUCTURAL-CHANGES



Gonzalez, E.R. (1998), Antiplatelet therapy in atherosclerotic cardiovascular disease.

Clinical Therapeutics, 20 B18-B41.



Abstract: Arterial thrombosis frequently leads to death or disability from stroke,

peripheral arterial disease, or myocardial infarction (MI). Treating the underlying

causes of these diseases is the key to producing significant reduction in

morbidity, mortality, and health care costs. Prevention of arterial thrombosis is

the primary indication for antiplatelet therapy, and intense research has been

conducted in the past decade to develop novel antiplatelet agents with favorable

safety profiles. The results of the Antiplatelet Trialists' Collaboration, which

definitively established the rationale for antiplatelet agents in the prevention of

death, MI, and stroke, were an important stimulus for this research. This large

meta- analysis combined data from 145 randomized trials and showed that

antiplatelet therapy (most commonly aspirin, 75 to 325 mg/d) reduced the risk of

vascular events, including nonfatal MI, nonfatal stroke, and vascular death, by

25% in patients at high risk for occlusive vascular disease. The limitations and

adverse effects associated with traditional antiplatelet agents such as aspirin have

prompted the search for newer antiplatelet agents. Clinical trials such as the

Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE)

study, which was the first study to evaluate aspirin and clopidogrel in patients

with cerebrovascular, cardiac, and peripheral arterial disease, have established

the importance of newer antiplatelet effects in the management of patients with

diseases associated with atherosclerosis. The pathophysiology of atherosclerosis,

the mechanisms of action of antiplatelet agents, and the results of these and other

clinical trials that document the value of antiplatelet agents in atherosclerosis are

reviewed in this paper

Keywords: antiplatelet agents/antiplatelet therapy/ARTERIAL

THROMBOSIS/ASPIRIN/atherosclerosis/CAPRIE study/cardiovascular

disease/clinical trials/clopidogrel/costs/DIPYRIDAMOLE/diseases/health/health

care/health care costs/infarction/INTERMITTENT

CLAUDICATION/morbidity/mortality/myocardial

infarction/NEW-YORK/PHARMACOLOGY/PLATELET-FUNCTION/PREVE

NTION/randomized

trials/risk/safety/STROKE/SWEDISH-TICLOPIDINE-MULTICENTER/therapy

/thrombosis/TRIAL/trials/vascular/vascular disease



Shah, H. and Gondek, K. (2000), Aspirin plus extended-release dipyridamole or

clopidogrel compared with aspirin monotherapy for the prevention of recurrent

ischemic stroke: A cost-effectiveness analysis. Clinical Therapeutics, 22 (3),

362-370.



Abstract: Objective: The goal of this health economic analysis was to asses the

cost-effectiveness of a fixed combination of aspirin plus extended-release

dipyridamole (ASA/ER-DP) or clopidogrel compared with ASA monotherapy

for prevention of recurrent ischemic stroke. Background: The second European

Stroke Prevention Study (ASA/ESPS-2), a large scale clinical trial, demonstrated

that a new therapy-a fixed combination of ASA/ER- DP-is more effective than

ASA monotherapy for the prevention of recurrent ischemic stroke. Methods: We

used data from ESPS-2 to create a health economic model that estimates the

incremental cost and cost-effectiveness of ASA/ER-DP during the 2-year time

frame after an ischemic stroke. The modal was developed from a payor

perspective. The analysis used direct cost estimates for stroke from a Medicare

claims database analysis. Efficacy data were obtained From clinical trials to

determine the incremental cost per stroke averted for ASA/ER-DP or clopidogrel

versus ASA. Sensitivity analyses also were con ducted to test the reliability and

robustness of the model. Results: The results of the analysis demonstrated that

ASA/ER-DP was cost-effective compared with ASA monotherapy for the

secondary prevention of stroke, with a cost-effectiveness ratio of $28,472. The

model remained robust over a range of assumptions and cost estimates.

Clopidogrel, however, was not cost-effective compared with ASA (cost per

stroke averted, $161,316) in either the base-case analysis or any of the sensitivity

analyses. Conclusion: ASA/ER-DP thus Offers a cost-effective alternative to

ASA monotherapy for the prevention of recurrent ischemic stroke



Keywords: aspirin/cerebral infarction/cerebrovascular disease/clinical

trials/clopidogrel/cost/cost effectiveness/cost-effectiveness/cost-effectiveness

analysis/costs and cost

analysis/CT/dipyridamole/FIRST-EVER/health/ischemic/ischemic stroke/model

(economic)/NEW-YORK/prevention/RISK/secondary prevention/stroke/trials



Gross, C.P., Vogel, E.W., Dhond, A.J., Marple, C.B., Edwards, R.A., Hauch, O.,

Demers, E.A. and Ezekowitz, M. (2003), Factors influencing physicians'

reported use of anticoagulation therapy in nonvalvular atrial fibrillation: A

cross-sectional survey. Clinical Therapeutics, 25 (6), 1750-1764.



Abstract: Background: Some elderly patients with nonvalvular atrial fibrillation (NVAF)

who might benefit from warfarin therapy do not receive it. Objective: The goal

of this cross-sectional study was to identify physicians' attitudes and beliefs that

are associated with their reported use of warfarin in case scenarios. Methods: A

self-administered survey was mailed to a cross-section of general internists

randomly selected from a national pool of physicians in the American Medical

Association Masterfile. Fourteen clinical vignettes were used, incorporating

various comorbid conditions and risk factors for either major bleeding episode or

embolic cerebrovascular accident (CVA). The outcome measure was the number

of case vignettes for which warfarin was recommended. Results: A total of 142

completed surveys (33% of 426 eligible respondents; 109 men, 32 women [1

respondent did not provide gender]; mean [SD] age, 45 [10] years) were received.

The median number of case vignettes for which warfarin was recommended was

10 (interquartile range, 8-12). We found no relationship between the perceived

benefits of warfarin and its use in the case vignettes. However, the perceived risk

for warfarin-associated hemorrhage was strongly associated with reported

warfarin use (P 10-fold

higher than literature-based estimates, and physicians providing higher risk

estimates tended to use warfarin less often. On multivariate logistic regression,

physicians who recommended warfarin use in more vignettes were less likely to

report anticipated regret of committing an error of omission (ischemic CVA in an

untreated NVAF patient) (P 70% of patients aged greater

than or equal to65 years. When ACE-inhibitor treatment costs were included in

the calculation of treatment costs, the expense to avert I stroke was estimated at

$13,766 for years 1 to 2 after randomization and $12,281 for years 2 to 3. By

years 3 to 4, ramipril treatment resulted in 21 fewer strokes and produced an

estimated savings of $52,861. Conclusion: Ramipril 10 mg/d was a cost-effective

means of preventing first and recurrent ischemic strokes in the HOPE Study

patient population. Copyright (C) 2003 Excerpta Medica, Inc



Keywords: ACE

inhibitor/age/aged/ASPIRIN/benefits/cardiovascular/cost/costs/DIPYRIDAMOL

E/DISEASE/economics/evaluation/EVENTS/health/health care/health care

costs/heart/high risk/HOPE

Study/hospitalization/incidence/ischemic/NEW-YORK/outcomes/population/pre

vention/ramipril/relative risk/risk/SPONTANEOUSLY HYPERTENSIVE

RATS/stroke/therapy/treatment/US/USA/use



Michota, F.A. (2003), Venous thromboembolism prophylaxis in the medically ill patient.

Clinics in Chest Medicine, 24 (1), 93-+.



Abstract: General medical patients with clinical risk factors for venous

thromboembolism (VTE) have received either low-dose unfractionated heparin

(LDUH) twice or three times daily or once-daily low molecular weight heparin

(LMWH); however, current evidence suggests that the twice-daily LDUH may

not be efficacious in the acutely ill medical inpatient. LDUH three times daily

may be efficacious in most medical patients; however, it is associated with an

increased risk for bleeding. The preferred strategy for prevention in the

medically ill population at high to very high risk for VTE is LMWH. For patients

who have a high to very high risk for bleeding, nonpharmacologic strategies,

such as elastic stockings or intermittent pneumatic compression devices, are

recommended



Keywords: bleeding/DEEP-VEIN THROMBOSIS/DOUBLE-BLIND/heparin/high

risk/HOSPITAL PATIENTS/low molecular weight heparin/LOW-DOSE

HEPARIN/medical/medical patients/MOLECULAR-WEIGHT

HEPARIN/POPULATION/PREVENTION/prophylaxis/PULMONARY-EMBO

LISM/risk/risk factors/RISK-FACTORS/STROKE

PATIENTS/thromboembolism/unfractionated heparin/USA/venous

thromboembolism/weight



Leira, E.C. and Adams, H.P. (1999), Management of acute ischemic stroke. Clinics in

Geriatric Medicine, 15 (4), 701-+.



Abstract: Management of an acute ischemic stroke is multifaceted. Treatment in a

specialized stroke unit reduces mortality and morbidity. Components of care

include interventions to control or prevent medical or neurologic complications,

rehabilitation, and initiations of therapies to forestall recurrent stroke. The key to

modern treatment is the emergent administration of tissue plasminogen activator

(rtPA). Thrombocyte treatment improves outcome when it is given within 3

hours of onset of stroke to carefully selected patients



Keywords: acute/acute ischemic

stroke/administration/AMERICAN-HEART-ASSOCIATION/ASPIRIN/complic

ations/control/EMERGENCY/GUIDELINES/HEALTH-CARE-PROFESSIONA

LS/ischemic/ischemic stroke/morbidity/mortality/plasminogen

activator/PREVENTION/recurrent

stroke/rehabilitation/rtPA/STATEMENT/stroke/stroke unit/THROMBOLYTIC

THERAPY/TICLOPIDINE/treatment/TRIAL



Tong, D.C. and Albers, G.W. (1999), Antithrombotic management of atrial fibrillation

for stroke prevention in older people. Clinics in Geriatric Medicine, 15 (4),

645-+.



Abstract: Atrial fibrillation (AF) is a common cardiac condition in the elderly population.

The primary concern in individuals with AF is the risk of stroke. The

management of AF for stroke prevention requires an understanding of the

relative risks and benefits of antithrombotic therapy. Numerous randomized

clinical trials have improved tremendously our understanding of the relative

merits of anticoagulation and aspirin, and indicate that anticoagulation is the

appropriate treatment for the majority of individuals with AF. In patients who

have contraindications to anticoagulation, aspirin is recommended

Keywords: AF/anticoagulation/antithrombotic/antithrombotic therapy/ASPIRIN/atrial

fibrillation/clinical trials/COMBINED

WARFARIN/elderly/fibrillation/HEART-VALVE

REPLACEMENT/HEMORRHAGIC

COMPLICATIONS/MICROEMBOLI/ORAL

ANTICOAGULATION/PATIENT

SELF-MANAGEMENT/PREVALENCE/prevention/randomized/risk/RISK-

FACTORS/stroke/stroke prevention/THERAPY/treatment/trials



Laird, R.D. and Studenski, S.S. (1999), Management of hypertension for stroke

prevention in older people. Clinics in Geriatric Medicine, 15 (4), 663-+.



Abstract: It is no longer acceptable to attribute elevated blood pressure in elderly people

to the natural processes of aging and thereby withhold treatment. Sound evidence

demonstrates increased risk of cardiovascular disease with increasing levels of

blood pressure and decreased incidence of cardiovascular disease with blood

pressure control. Hypertension is known to be the most modifiable risk factor for

stroke. Given projected demographic shifts in the population, the number of

older Americans with hypertension and increased risk of morbidity and mortality

from stroke will grow during the first part of the next century. Health care

providers should familiarize themselves with the unique pathophysiology of

hypertension in elderly people, and integrate appropriate approaches to

comprehensive evaluation and management into practice



Keywords: aging/blood pressure/blood pressure

control/BLOOD-PRESSURE/cardiovascular/cardiovascular

disease/control/DISEASE/elderly/evaluation/HEALTH/hypertension/incidence/I

SOLATED SYSTOLIC

HYPERTENSION/MORBIDITY/MORTALITY/prevention/REDUCTION/RIS

K/risk factor/stroke/stroke prevention/THERAPY/treatment/TRIAL



Goldstein, L.B. (1999), Carotid endarterectomy for stroke prevention in older people.

Clinics in Geriatric Medicine, 15 (4), 685-+.



Abstract: The efficacy of endarterectomy for patients with symptomatic high-grade

stenosis of the extracranial carotid artery has been firmly established. Those with

asymptomatic carotid disease may also be candidates for the operation. A

thorough understanding of the benefits and risks of the operation for the

individual patient is necessary in determining whether to recommend the

operation



Keywords: 1001 ANGIOGRAMS/ARTERY

STENOSIS/asymptomatic/ASYMPTOMATIC PATIENTS/carotid/carotid

artery/CEREBRAL-ISCHEMIA/COMPLICATION

RATES/DECISION-ANALYSIS/endarterectomy/NATURAL-HISTORY/PREO

PERATIVE ASSESSMENT/prevention/RISK/stroke/stroke

prevention/TRANSIENT ISCHEMIC ATTACKS

Hylek, E.M. (2001), Oral anticoagulants - Pharmacologic issues for use in the elderly.

Clinics in Geriatric Medicine, 17 (1), 1-+.



Abstract: Clinical indications for oral anticoagulant therapy have greatly expanded,

particularly among the elderly. Optimal use of oral anticoagulants in the geriatric

population requires an understanding of the mechanism of action of warfarin and

the pharmacokinetic and pharmacodynamic differences in this age group. Many

factors affect the dose response of warfarin and the stability of anticoagulation

control, including age, medications, diet, and comorbid illness. Important

considerations in the initiation of warfarin dosing and the long-term management

of anticoagulation in the elderly are discussed



Keywords: age/anticoagulant/anticoagulant

therapy/anticoagulants/anticoagulation/ATRIAL-FIBRILLATION/BLEEDING

COMPLICATIONS/control/diet/dose

response/DRUG-METABOLISM/elderly/HUMAN-LIVER/management/mecha

nism of action/oral anticoagulant therapy/oral

anticoagulants/population/RACEMIC

WARFARIN/RISK-FACTORS/SEPARATED ENANTIOMORPHS/STROKE

PREVENTION/therapy/use/VITAMIN-K/warfarin/WARFARIN THERAPY



Savitz, S.I., Gupta, G., Singh, M. and Rosenbaum, D.M. (2001), Antithrombotic and

thrombolytic therapy for ischemic stroke. Clinics in Geriatric Medicine, 17 (1),

149-+.



Abstract: Antithrombotic and thrombolytic agents form the cornerstone of stroke

prevention and treatment. Large, randomized trials also have highlighted the

effectiveness and safety of early and continuous antiplatelet therapy in reducing

atherothrombotic stroke recurrence. Aspirin has become the antiplatelet

treatment standard against which several other antiplatelet agents (i.e.,

ticlopidine, clopidogrel, aspirin/dipyridamole) have been shown to be more

effective. The prevention of cardioembolic stroke, on the other hand, is best

accomplished with oral anticoagulation, barring any contraindications. The

thrombolytic agent rt-PA improves outcome in patients with ischemic stroke

treated within 3 hours of onset. The risk- benefit ratio is narrow due to an

increased risk for bleeding, but studies do not support a higher risk in the

geriatric population



Keywords: anticoagulation/antiplatelet/antiplatelet agents/antiplatelet

therapy/antiplatelet treatment/ASPIRIN

USE/bleeding/cardioembolic/cardioembolic

stroke/clopidogrel/DIPYRIDAMOLE/FIRST-EVER/INTRAVENOUS

HEPARIN/ischemic/ischemic stroke/oral

anticoagulation/outcome/PLASMINOGEN-ACTIVATOR/population/PREVEN

T STROKE/prevention/PROGRESSION/randomized/RANDOMIZED

CONTROLLED TRIAL/randomized

trials/recurrence/RISK/rtPA/safety/stroke/stroke prevention/stroke

recurrence/therapy/thrombolytic/thrombolytic agents/thrombolytic

therapy/TICLOPIDINE/treatment/trials



Singer, D.E. and Go, A.S. (2001), Antithrombotic therapy in atrial fibrillation. Clinics in

Geriatric Medicine, 17 (1), 131-+.



Abstract: Atrial fibrillation is a hallmark of aging, affecting 6% of individuals aged 65

years or older. Atrial fibrillation also increases the risk for ischemic stroke by

fivefold. A consistent series of randomized, controlled trials have demonstrated

that long-term anticoagulation largely reverses the risk for stroke posed by atrial

fibrillation. This article reviews these trials and other studies bearing on the

optimal intensity of anticoagulation for atrial fibrillation, the selection of patients

with atrial fibrillation for long-term anticoagulation, and the efficacy of aspirin

as an alternative stroke-preventive agent



Keywords: aged/aging/ANTICOAGULATION/ASPIRIN/atrial

fibrillation/CONTROLLED TRIAL/fibrillation/intensity/ischemic/ischemic

stroke/NATIONAL

PATTERNS/randomized/risk/RISK-FACTORS/SELF-MANAGEMENT/stroke/

STROKE

PREVENTION/therapy/THROMBOEMBOLISM/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/trials/WARFARIN USE



Beyth, R.J. (2001), Hemorrhagic complications of oral anticoagulant therapy. Clinics in

Geriatric Medicine, 17 (1), 49-+.



Abstract: Although the efficacy of anticoagulant therapy has been established for many

conditions that are prevalent among the elderly population, the decision to

initiate anticoagulant therapy in the elderly population is not straightforward

because elderly patients with multiple comorbidities and varying levels of

functional status are not routinely included in clinical trials of efficacy. The true

benefits of anticoagulant therapy will be realized when health care providers and

elderly patients can accurately assess the absolute risk versus the benefit

associated with anticoagulant therapy



Keywords: absolute risk/anticoagulant/anticoagulant therapy/BLEEDING

COMPLICATIONS/CASE-FATALITY RATES/CEREBRAL AMYLOID

ANGIOPATHY/clinical trials/complications/DEEP-VEIN

THROMBOSIS/elderly/ELDERLY PATIENTS/functional status/health/health

care/NONRHEUMATIC ATRIAL-FIBRILLATION/NONSTEROIDAL

ANTIINFLAMMATORY DRUGS/oral anticoagulant therapy/PEPTIC-ULCER

DISEASE/population/PULMONARY-EMBOLISM/risk/status/STROKE

PREVENTION/therapy/trials



Maurer, M.S. and Bloomfield, D.M. (2002), Atrial fibrillation and falls in the elderly.

Clinics in Geriatric Medicine, 18 (2), 323-+.

Abstract: Atrial fibrillation is an extremely rare cause of falls and syncope in the elderly.

The routine use of ambulatory ECG monitoring to search for atrial fibrillation in

elderly patients who fall is not recommended. Among elderly patients with atrial

fibrillation who fall, short pauses of less than 3 seconds are nonspecific and are

as common in patients who fall as they are in those who do not. Furthermore,

most pauses are not associated with symptoms. Although the decision to implant

a pacemaker for extremely long pauses is often straightforward, the decision to

implant a pacemaker in patients who fall and who have short pauses ideally

should be made after symptoms clearly have been associated with the

dysrhythmia. This type of symptom-rhythm correlation is extremely valuable and

often requires long-term ambulatory monitoring with external or internal

(implanted) event or loop recorders. Among the growing population of elderly

persons with chronic atrial fibrillation, oral anticoagulant therapy has been

shown to have significant benefit and is under-used, particularly in frail residents

of long-term care facilities



Keywords: 3 SECONDS/anticoagulant/anticoagulant therapy/atrial/atrial

fibrillation/chronic/chronic atrial fibrillation/DIZZINESS/DROP

ATTACKS/elderly/elderly patients/falls/fibrillation/monitoring/oral

anticoagulant therapy/pacemaker/population/PREVALENCE/RECURRENT

FALLS/RISK-FACTORS/SICK-SINUS SYNDROME/STROKE

PREVENTION/symptoms/SYNCOPE/therapy/use/VENTRICULAR PAUSES



Kohn, H.S. (1996), Prevention and treatment of elbow injuries in golf. Clinics in Sports

Medicine, 15 (1), 65-&.



Abstract: Golf interest is on the increase, resulting in a corresponding increase in

golf-related tendon injuries. Injuries are best avoided by a good strength and

flexibility program, proper warm-up exercises, and good stroke mechanics.

Treatment is directed toward restoring the integrity of the muscle/tendon unit at

the elbow and preventing recurrences



Keywords: SPORTS/stroke/treatment



Chimowitz, M.I. (1994), Warfarin Or Aspirin As Secondary Prevention of Ischemic

Stroke. Cns Drugs, 2 (5), 341-346.



Abstract: Until recently, the choice between aspirin (acetylsalicylic acid) or warfarin for

the secondary prevention of stroke was largely based on empirical evidence.

However, as stroke prevention trials have focused on patients with specific

vascular pathologies, clearcut guidelines for the use of aspirin or warfarin are

beginning to emerge. Warfarin is generally considered first-line therapy in

patients presenting with minor stroke or transient ischaemic attack related to

mitral stenosis, valvular atrial fibrillation, a mechanical prosthetic heart valve,

acute myocardial infarction or cardiomyopathy. Several recent multicentre

studies suggest that warfarin is also the most effective drug far stroke prevention

in patients with nonvalvular atrial fibrillation, unless the patient is less than 65

years old and has lone atrial fibrillation, is older than 75 years, or is at high risk

of haemorrhagic complications. Aspirin is a safe and effective alternative choice

in these settings. There are no prospective studies comparing aspirin with

warfarin in patients with symptomatic high grade stenosis of a major intracranial

artery. However, a recent retrospective multicentre study suggests that warfarin

may reduce the risk of stroke, myocardial infarction or vascular death by almost

50% compared with aspirin in these patients. Ongoing studies will help to clarify

whether warfarin or aspirin is superior for preventing stroke in patients with

intracranial penetrating artery disease, craniocervical arterial dissection,

antiphospholipid antibodies or right-to- left interatrial shunts, and in patients with

stroke of undetermined cause



Keywords: acute myocardial infarction/ANTICOAGULATION/aspirin/atrial

fibrillation/CHRONIC

ATRIAL-FIBRILLATION/complications/DRUG/DRUGS/fibrillation/heart/myo

cardial infarction/NEW-ZEALAND/prevention/prospective

studies/RANDOMIZED TRIAL/RISK/secondary prevention/stroke/stroke

prevention/TICLOPIDINE/transient/trials/vascular/Warfarin



Dafer, R., Tietjen, G.E. and Asherson, R.A. (1997), Drug treatment of stroke in patients

with antiphospholipid antibodies. Cns Drugs, 8 (3), 219-226.



Abstract: There are a number of therapeutic options for the prevention of stroke (primary

or recurrent) or other thrombotic events in antiphospholipid antibody-positive

individuals, although none is of proven benefit, Control of modifiable vascular

risk factors and avoidance of thrombogenic drugs should be recommended for all

persons with antiphospholipid antibodies, whether symptomatic or not, Therapies

to prevent thrombosis include antiplatelet agents and anticoagulants, with

warfarin the preferred choice in high risk patients who have recurrent events.

Immune-based therapies, including plasma exchange, immunoglobulins,

corticosteroids and immunosuppressants, are alternative treatment modalities for

patients who have recurrent events despite receiving high-dosage anticoagulants



Keywords: ANTICARDIOLIPIN

ANTIBODIES/ANTICOAGULANT/anticoagulants/antiplatelet

agents/AUTOIMMUNE THROMBOCYTOPENIA/CEREBRAL

INFARCTIONS/CEREBROVASCULAR-DISEASE/DOSE INTRAVENOUS

IMMUNOGLOBULIN/DRUG/DRUGS/FETAL

LOSS/INTERNAL/NEW-ZEALAND/PLASMA-EXCHANGE/prevention/risk/r

isk factors/stroke/SYSTEMIC

LUPUS-ERYTHEMATOSUS/thrombosis/treatment/vascular/VENOUS

THROMBOSIS/warfarin



Mousa, S.A. (2000), Potential role of platelet glycoprotein IIb/IIIa antagonists in

cerebrovascular disorders. Cns Drugs, 13 (3), 155-160.

Abstract: Studies have confirmed the benefit of established antiplatelet therapies [aspirin

(acetylsalicylic acid), clopidogrel, or a combination of aspirin and dipyridamole]

in cerebrovascular disorders such as stroke. Recent data indicate that

glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist antiplatelet agents (which

are currently marketed or are being investigated for their efficacy in

cardiovascular indications) may also be beneficial in patients who have had a

stroke. These agents may have potential value as monotherapy or as adjuncts to

thrombolytics or interventional procedures. However, GPIIb/IIIa antagonists

carry a risk of cerebral haemorrhage, which may be higher in patients with acute

stroke than in patients with transient ischaemic attack or partial occlusion



Keywords: acetylsalicylic acid/acute/ACUTE MYOCARDIAL-INFARCTION/acute

stroke/antiplatelet/antiplatelet

agents/aspirin/AUCKLAND/cardiovascular/cerebral/cerebrovascular/cerebrovas

cular

disorders/clopidogrel/DRUG/DRUGS/GPIIB-IIIA/haemorrhage/MONOCLONA

L-ANTIBODY/NEW-ZEALAND/NONRHEUMATIC

ATRIAL-FIBRILLATION/PLASMINOGEN-ACTIVATOR/PREVENTION/R

ANDOMIZED TRIAL/RECEPTOR

ANTAGONIST/risk/STROKE/thrombolytics/transient/transient ischaemic

attack/UNSTABLE ANGINA



Yasaka, M. and Yamaguchi, T. (2001), Secondary prevention of stroke in patients with

nonvalvular atrial fibrillation - Optimal intensity of anticoagulation. Cns Drugs,

15 (8), 623-631.



Abstract: Nonvalvular atrial fibrillation (NVAF) is frequently seen in elderly people and

has become a main cause of cardioembolic stroke. The efficacy of

anticoagulation for primary prevention of stroke or transient ischaemic attacks

(TIAs) in patients with NVAF has been established by prospective, randomised

and controlled trials. Warfarin decreased the frequency of all strokes by 68% and

the rate of the combined outcome of stroke, systemic embolism or death by 48%.

Anticoagulation with warfarin using international normalised ratios (INRs)

ranging from 2.0 to 3.0 is recommended for patients with NVAF, who have any

of the risk factors identified by the Atrial Fibrillation Investigators (AFI)

[previous stroke or TIA, history of hypertension, diabetes mellitus, advanced age

( greater than or equal to 65 years old), congestive heart failure and coronary

artery disease], the American College of Chest Physicians (ACCP) [increased

age (>75 years old), prior stroke, hypertension and heart failure], or the Stroke

Prevention in Atrial Fibrillation (SPAF) investigators [women >75 years old,

prior stroke, systolic blood pressure >160mm Hg, recent heart failure, and

fractional shortening 38.5 degrees C within the first 24 hrs of

admission) occurred in 29.9% of patients admitted to the PICU with traumatic

brain injury. Risk factors predicting early hyperthermia included Glasgow Coma

Scale score in the emergency department less than or equal to 8, pediatric trauma

score less than or equal to 8, cerebral edema or diffuse axonal injury on initial

head computed tomography scan, admission blood glucose >150 mg/dL (8.2

mmol/L), admission white cell count >14,300 cells/mm3 (14.3 x 10(9) cells/L),

and systolic hypotension. The presence of early hyperthermia significantly

increased the risk for Glasgow Coma Scale score 20 IU/hr). Between day 7 and 12, insulin requirements

decreased by 40% on stable caloric intake. Brief, clinically harmless

hypoglycemia occurred in 5.2% of intensive insulin-treated patients on median

day 6 (2-14) vs. 0.8% of conventionally treated patients on day 11 (2-10). The

outcome benefits of intensive insulin therapy were equally present regardless of

whether patients received enteral feeding. Multivariate logistic regression

analysis indicated that the lowered blood glucose level rather than the insulin

dose was related to reduced mortality (p 75 years. The answer is probably to use low intensity

anticoagulant therapy (international normalised ratio 2.0 to 3.0), which is safer

but no less effective than higher intensity regimens. Few data are available in the

literature on physicians' attitudes to anticoagulation in elderly patients with AF.

Although the results of randomised clinical trials in AF seem to suggest that

anticoagulants and/or aspirin (acetylsalicylic acid) are underused in the elderly,

over 90% of the patients initially screened were excluded from randomisation,

making the sample highly selected. Compared with randomised controlled trials,

some observational studies seem to indicate a higher likelihood of using

anticoagulation and have targeted the intensity of anticoagulation according to

age and clinical scenario



Keywords: acetylsalicylic

acid/AF/age/aged/AGING/anticoagulant/anticoagulants/anticoagulation/aspirin/a

trial fibrillation/ATTITUDES/clinical trials/complications/CORONARY

HEART-DISEASE/DRUG/elderly/EMBOLISM/FEATURES/fibrillation/FRAM

INGHAM/NEW-ZEALAND/observational

studies/POPULATION/PREVENTION/PROGNOSIS/risk/STROKE/therapy/tre

atment/trials/WARFARIN



Bhana, N. and McClellan, K.J. (2001), Indobufen - An updated review of its use in the

management of atherothrombosis. Drugs & Aging, 18 (5), 369-388.



Abstract: Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet

cyclooxygenase enzyme thereby suppressing thromboxane synthesis, Clinical

trials have evaluated the efficacy of oral indobufen in the secondary prevention

of thromboembolic complications in patients with or without atrial fibrillation, in

the prevention of graft occlusion after coronary artery bypass graft (CABG)

surgery and in the treatment of intermittent claudication. In the secondary

prevention of thromboembolic events indobufen 200mg once or twice daily was

significantly more effective than no treatment although not as effective as

ticlopidine 250mg once or twice daily, during 1-year nonblind clinical trials.

Compared with placebo, indobufen 100mg twice daily significantly reduced the

risk of stroke in a small 28-month trial of patients at increased risk of systemic

embolism (50% had atrial fibrillation). Furthermore, in patients with

nonrheumatic atrial fibrillation and a recent cerebrovascular event enrolled in the

1-year Studio Italiano Fibrillazione Atriale (SIFA) trial. indobufen 100 or 200mg

twice daily was as effective as warfarin (titrated to produce an international

normalised ratio of 2.0 to 3.5) in the secondary prevention of thromboembolic

events; the incidences of the composite end-point of major vascular events (10.6

vs 9.0%) and recurrent stroke (5 vs 4%) were similar between treatments. In 2

large 12-month trials, the Studio Indobufene nel Bypass Aortocoronarico

(SINBA) and the UK study, indobufen 200mg twice daily was as effective as

aspirin (acetylsalicylic acid) 300 or 325mg plus dipyridamole 75mg 3 times daily

in the prevention of early and late occlusion of saphenous grafts in patients after

CABG surgery. Indobufen 200mg twice daily for 6 months significantly

improved walking capacity compared with placebo, and caused a more

pronounced improvement in both pain-free and total walking distance than either

pentoxifylline 300mg or aspirin 500mg twice daily in separate 6- and 12-month

studies of patients with intermittent claudication. Oral indobufen up to 200mg

twice daily was generally well tolerated in > 5000 patients with atherosclerotic

disease. Adverse events (predominantly gastrointestinal), reported by 3.9% of

patients, rarely required withdrawal from treatment. in the SINBA and UK

studies, fewer adverse events and less gastrointestinal bleeding were seen with

indobufen than with aspirin plus dipyridamole treatment, while in the SIFA trial,

noncerebral bleeding events occurred significantly less frequently in indobufen

than warfarin recipients (0.6 vs 5.1 %) and major bleeding events occurred only

in the warfarin group. Conclusion: Indobufen is as effective as warfarin in the

prophylaxis of thromhoembolic events in at risk patients with nonrheumatic

atrial fibrillation, as aspirin plus dipyridamole in the prevention of CABG

occlusion and may be more effective than aspirin or pentoxifylline in improving

walking capacity in patients with intermittent claudication. The improved

tolerability profile of indobufen (favourable gastric tolerance and reduced

haemorrhagic complications) compared with aspirin 300 to 325mg 3 times daily

or warfarin, in addition to a similar antiplatelet effect, suggests indobufen can be

considered a drug with a definite role in the management of atherothrombotic

events. In particular, indobufen may be an effective alternative for at risk patients

with nonrheumatic atrial fibrillation in whom anticoagulant therapy is

contraindicated or who are at higher risk of bleeding



Keywords: acetylsalicylic acid/adverse

events/aggregation/AGING/anticoagulant/anticoagulant

therapy/antiplatelet/aspirin/atherothrombosis/atrial

fibrillation/ATRIAL-FIBRILLATION/AUCKLAND/bleeding/BLEEDING-

TIME/CABG/cerebrovascular/cerebrovascular event/clinical

trials/complications/dipyridamole/disease/DRUG/embolism/fibrillation/HEART-

DISEASE/incidences/indobufen/INTERMITTENT

CLAUDICATION/ISCHEMIC

ATTACK/management/NEW-ZEALAND/nonrheumatic/platelet/platelet

aggregation/PLATELET-AGGREGATION/prevention/prophylaxis/recurrent

stroke/review/risk/secondary/SECONDARY

PREVENTION/stroke/surgery/therapy/thromboembolic

complications/thromboembolic events/THROMBOXANE-B2

PRODUCTION/ticlopidine/treatment/trial/trials/use/vascular/VASCULAR-DIS

EASE/VENOUS DISEASE/warfarin

Mungall, M.M.B., Gaw, A. and Shepherd, J. (2003), Statin therapy in the elderly - Does

it make good clinical and economic sense? Drugs & Aging, 20 (4), 263-275.



Abstract: HMG-CoA reductase inhibitors (statins) have been established as the dominant

treatment for coronary heart disease (CHD). This dominance is based on an

impressive body of clinical trial evidence showing significant benefits in primary

prevention of cardiovascular events in individuals at risk for CHD and in

secondary prevention of such events in patients with CHD and high or normal

plasma cholesterol levels. There is, however, significant room for improvement

in the treatment of CHD with respect both to drug efficacy and to the disparity

between evidence-based medicine and actual clinical practice particularly in

relation to treatment strategies for the elderly. Current statins fall short of

requirements for 'ideal' lipid-lowering treatment in several respects; 'super' statins

and other agents currently in development may satisfy more of these

requirements. Moreover, available therapies are not applied optimally, because

of physician nonacceptance and/or patient noncompliance; thus, the majority of

patients with CHD or its risk factors still have cholesterol levels that exceed

guideline targets. There is also evidence that older patients with CHD, or at high

risk of CHD, are undertreated-possibly because of concerns regarding the

increased likelihood of adverse events or drug interactions or doubts regarding

the cost effectiveness of statin therapy in this population. This group is of

particular clinical relevance, since it is showing a proportionate rapid expansion

in most national populations. To address their potential healthcare needs, the

ongoing Pravastatin in the Elderly at Risk (PROSPER) study is assessing the

effects of pravastatin in elderly patients (5804 men and women aged 70-82 years)

who either have preexisting vascular disease or are at significant risk for

developing it, with the central hypothesis that statin therapy (pravastatin 40

mg/day) will diminish the risk of subsequent major vascular events compared

with placebo. After a 3.2-year treatment period, a primary assessment will be

made of the influence of statin treatment on major cardiovascular events (a

combination of CHD death, nonfatal myocardial infarction, and fatal or nonfatal

stroke). Optimal deployment of the currently available agents and of newer

agents (no matter how well they satisfy requirements for ideal treatment)

ultimately depends on the establishment of an evidence base and may require

far-reaching educational programmes that change the way risk factor

management is viewed by caregivers and patients alike



Keywords: adverse events/aged/AGING/ALL-CAUSE

MORTALITY/AUCKLAND/benefits/C-REACTIVE

PROTEIN/cardiovascular/cardiovascular events/CARDIOVASCULAR-

DISEASE/CHD/cholesterol/clinical practice/clinical trial/COENZYME-A

REDUCTASE/combination/coronary heart disease/CORONARY

HEART-DISEASE/cost/cost

effectiveness/cost-effectiveness/death/DENSITY-LIPOPROTEIN

CHOLESTEROL/development/disease/DRUG/drug interactions/elderly/elderly

patients/guideline/heart/heart disease/high risk/HMG-CoA reductase

inhibitors/infarction/lipid

lowering/lipid-lowering/management/men/MIDDLE-AGED

MEN/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/NEW-ZEALAND/population/pravas

tatin/prevention/primary/primary

prevention/PRIMARY-PREVENTION/risk/risk factor/risk

factors/SCANDINAVIAN- SIMVASTATIN-SURVIVAL/secondary/secondary

prevention/statin/statin

therapy/statins/stroke/therapy/treatment/trial/vascular/vascular disease/vascular

events/women



Ratnasabapathy, Y., Lawes, C.M.M. and Anderson, C.S. (2003), The perindopril

protection against recurrent stroke study (PROGRESS) - Clinical implications

for older patients with cerebrovascular disease. Drugs & Aging, 20 (4), 241-251.



Abstract: Blood pressure levels are strongly predictive of the risks of first-ever and

recurrent stroke. The benefits of blood pressure-lowering therapy for the

prevention of fatal and non- fatal stroke in middle-aged individuals are well

established. However, until recently, there has been uncertainty about the

consistency of such benefits across different patient groups and in particular, for

older people and in those with a history of stroke. This paper discusses the

evidence surrounding the effectiveness of blood pressure-lowering therapy,

specifically in older patients with a history of stroke, with particular attention

paid to the results from the Perindopril Protection Against Recurrent Stroke

Study (PROGRESS). PROGRESS was a randomised, double-blind,

placebo-controlled trial of 6105 individuals with a history of cerebrovascular

disease recruited from 172 hospital outpatient clinics in ten countries.

Participants (mean age 64 years; range 26-91 years) were randomly assigned to

receive active treatment with an ACE inhibitor-based blood pressure-lowering

regimen (perindopril) with or without addition of the diuretic indapamide, or

matched placebo. At the end of follow up (mean of 4 years), active treatment

reduced the incidence of total stroke by 28% (95% CI 17-38%) and the rate of

major vascular events by 26% (95% CI 16-34%). Importantly, benefits of

treatment were consistent across key patient subgroups, including those with and

without hypertension, patients who were Asian and non-Asian, and for both

ischaemic and haemorrhagic strokes subtypes. Current evidence is now strong

for clinicians to consider blood pressure-lowering therapy as pivotal in the

prevention of stroke, especially in patients with a known history of

cerebrovascular disease (and vascular disease, in general), irrespective of blood

pressure levels, as soon as patients are clinically stable after an acute stroke or

other vascular event. Additional age-specific analyses of the PROGRESS data,

together with those from other completed trials, will provide more reliable

information about the size of the benefits of blood pressure-lowering therapy,

specifically for different age groups, and particularly in the oldest old (those aged

>80 years). In the meantime though, an ACE inhibitor plus diuretic treatment

regimen that maximises the degree of blood pressure reduction has a good safety

profile and is an effective treatment that should be considered in all patients with

stroke, including the elderly

Keywords: ACE inhibitor/acute/acute stroke/age/aged/AGING/ANTIHYPERTENSIVE

TREATMENT/AUCKLAND/benefits/blood pressure/blood pressure

lowering/BLOOD-PRESSURE/CALCIUM-ANTAGONISTS/CARDIOVASCU

LAR MORTALITY/cerebrovascular/cerebrovascular disease/CORONARY

HEART-DISEASE/disease/DOUBLE-BLIND/DRUG/elderly/history/hospital/hy

pertension/incidence/indapamide/ischaemic/ISOLATED SYSTOLIC

HYPERTENSION/J-CURVE/MYOCARDIAL-INFARCTION/NEW-ZEALAN

D/old/older

people/perindopril/prevention/PROGRESS/protection/RANDOMIZED

CONTROLLED TRIALS/recurrent

stroke/results/risks/safety/stroke/therapy/treatment/trial/trials/vascular/vascular

disease/vascular event/vascular events



Hu, F.B. (2001), The role of n-3 polyunsaturated fatty acids in the prevention and

treatment of cardiovascular disease. Drugs of Today, 37 (1), 49-56.



Abstract: Growing evidence has suggested an important role of n-3 polyunsaturated fatty

acids in reducing risk of cardiovascular disease in the general population and

patients with preexisting heart disease. In particular, several long-term

epidemiologic studies have found an inverse association between fish

consumption and risk of coronary heart disease or stroke. Two secondary

prevention trials have found that increasing fish consumption or fish oil

supplementation significantly reduced coronary death among patients with

existing myocardial infarction. In addition, epidemiologic and clinical studies

have suggested that a-linolenic acid (ALA), a short-chain n3-3 fatty acid from

plant sources, may have similar cardiac benefits as long-chain n-3 fatty acids

from fish. Potential mechanisms through which n-3 polyunsaturated fatty acids

protect against CVD include their antiarrhythmic and antithrombotic effects, and

improving insulin sensitivity and endothelial function. (C) 2001 Prous Science.

All rights reserved



Keywords: ALPHA-LINOLENIC

ACID/antithrombotic/cardiac/CARDIAC-ARRHYTHMIAS/cardiovascular/cardi

ovascular disease/coronary heart disease/CORONARY

HEART-DISEASE/death/DIETARY-FAT/disease/DRUG/DRUGS/EICOSAPE

NTAENOIC ACID/endothelial function/fatty acid/FISH CONSUMPTION/fish

oil/heart/heart disease/infarction/mechanisms/MEN/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/OIL/population/prevention/RISK/sec

ondary/secondary prevention/SPAIN/stroke/treatment/trials



Bagchi, D., Das, D.K., Tosaki, A., Bagchi, M. and Kothari, S.C. (2001), Benefits of

resveratrol in women's health. Drugs Under Experimental and Clinical Research,

27 (5-6), 233-248.



Abstract: Resveratrol and trans-resveratrol are powerful phytoestrogens, present in the

skins of grapes and other plant foods and wine, which demonstrate a broad

spectrum of pharmacological and therapeutic health benefits. Phytoestrogens are

naturally occurring plant-derived nonsteroidal compounds that are functionally

and structurally similar to steroidal estrogens, such as estradiol, produced by the

body, Various studies, reviewed herein, have demonstrated the health benefits of

phytoestrogens in addressing climacteric syndrome including vasomotor

symptoms and postmenopausal health risks, as well as their anticarcinogenic,

neuroprotective and cardioprotective activities and prostate health and bone

formation promoting properties. Conventional HRT drugs have been

demonstrated to cause serious adverse effects including stroke and gallbladder

disease, as well as endometrial, uterine and breast cancers. Recent research

demonstrates that trans-resveratrol binds to human estrogen receptors and

increases estrogenic activity in the body. We investigated the effects of protykin,

a standardized extract of trans-resveratrol from Polygonum cuspidatum, on

cardioprotective function, the incidence of reperfusion-induced arrhythmias and

free radical production in isolated ischemic/reperfused rat hearts. The rats were

orally treated with two different daily doses of protykin for 3 weeks. Coronary

effluents were measured for oxygen free radical production by electron spin

resonance (ESR) spectroscopy in treated and drug-free control groups. In rats

treated with 50 and 100 mg/kg of protykin, the incidence of reperfusion-induced

ventricular fibrillation was reduced from its control value of 83% to 75% (p

2 days of AF and

embolizes by being dislodged from increases in. shear forces. This widely

accepted concept further holds that newly formed atrial thrombus, in the setting

of AF, organizes over a span of 14 days. The results of studies based on,

observations from transesophageal echocardiography examinations have

provided provocative insight into the temporal sequence of atrial thrombus

formation, embolization, and resolution in AF or atrial flutter and have expanded

the traditional concept of thromboembolism in these atrial dysrhythmias. Namely,

left atrial thrombus may form before the onset of AF in the face of sinus rhythm.

Conversion to sinus rhythm may increase the thrombogenic milieu of the Left

atrium. Importantly, atrial thrombus may form in the acute phase of AF. Last,

thrombi may require > 14 days to become immobile or to resolve. Findings

similar to those of acute AF have been reported in patients with atrial flutter and

coexisting cardiac pathology. On the basis of these emerging insights fostered by

the use of transesophageal echocardiography, it appears appropriate to consider

anticoagulation in patients presenting with acute AF or atrial flutter with

coexisting cardiac pathology predisposing to left atrial thrombus



Keywords: acute/AF/anticoagulation/ANTITHROMBOTIC THERAPY/APPENDAGE

FUNCTION/arrhythmia/arrhythmias/atrial arrhythmias/atrial fibrillation/atrial

flutter/cardiac/DIRECT-CURRENT

CARDIOVERSION/echocardiography/elderly/ELECTRICAL

CARDIOVERSION/EMBOLIC

COMPLICATIONS/embolism/fibrillation/FLOW

VELOCITY/formation/MITRAL-VALVE DISEASE/pathology/risk/sinus

rhythm/SPONTANEOUS ECHO

CONTRAST/stroke/thromboembolism/thrombus/THROMBUS

FORMATION/transesophageal echocardiography/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/use



Fagan, S.M. and Chan, K.L. (2000), Transesophageal echocardiography risk factors for

stroke in nonvalvular atrial fibrillation. Echocardiography-A Journal of

Cardiovascular Ultrasound and Allied Techniques, 17 (4), 365-372.



Abstract: Atrial fibrillation is a common. arrhythmia, particularly in the older age groups.

It confers an. increased risk of thromboembolism to these patients, and multiple

clinical risk factors have been identified to be useful in predicting the risks of

thromboembolic events. Recent studies ha ve evaluated the role of

transesophageal echocardiography (TEE) in the evaluation, of patients with atrial

fibrillation. The purpose of this review is to evaluate the significance of

transesophageal echocardiographic findings in the prediction of thromboembolic

events, particularly stroke, in, patients with nonvalvular atrial fibrillation, with an

emphasis on recently reported prospective studies. Aortic plaque and Left atrial

appendage abnormalities are identified as independent predictors of

thromboembolic events. Although they are associated with clinical events, they

also have independent incremental prognostic values. Other transesophageal

echocardiographic findings, such as patent foramen ovale and atrial septal

aneurysm, have not been found to be predictors of thromboembolic events in this

patient group. Thus, TEE is a useful tool in stratifying patients with nonvalvular

atrial fibrillation into different risk groups in terms of thromboembolic events,

and it will Likely play an important role in future studies to assess new treatment

strategies in high-risk patients with atrial fibrillation



Keywords: age/aneurysm/ANTICOAGULATION/AORTIC-ARCH/arrhythmia/atrial

appendage/atrial fibrillation/atrial septal

aneurysm/echocardiography/evaluation/fibrillation/foramen ovale/high

risk/MITRAL-VALVE DISEASE/nonvalvular atrial fibrillation/patent/PATENT

FORAMEN

OVALE/plaque/predictors/PREVALENCE/PREVENTION/prospective

studies/review/risk/risk factors/risk factors for stroke/SEPTAL

ANEURYSM/SPONTANEOUS ECHO

CONTRAST/stroke/THROMBOEMBOLIC

COMPLICATIONS/thromboembolic

events/thromboembolism/THROMBUS/transesophageal

echocardiography/treatment



Asinger, R.W. (2000), Role of transthoracic echocardiography in atrial fibrillation.

Echocardiography-A Journal of Cardiovascular Ultrasound and Allied

Techniques, 17 (4), 357-364.

Abstract: Atrial fibrillation is a major clinical problem that is predicted to be

encountered more frequently as the population ages. The clinical management of

atrial fibrillation has become increasingly complex as new therapies and

strategies have become available for ventricular rate control, conversion to sinus

rhythm, maintenance of sinus rhythm, and prevention, of thromboembolism.

Clinical and transthoracic echocardiographic features are important in,

determining etiology and directing therapy for atrial fibrillation. Left atrial size,

left ventricular wall thickness, and left ventricular function have independent

predictive value for determining the risk of developing atrial fibrillation. Left

atrial size may have predictive value in, determining the success of cardioversion

and maintaining sinus rhythm in selected clinical settings but has Less value in

the most frequently encountered group, patients with nonvalvular atrial

fibrillation, in whom the duration of atrial fibrillation is the most important

feature. When selecting pharmacological agents to control ventricular rate,

convert to sinus rhythm, and maintain normal sinus rhythm, transthoracic

echocardiography (TTE) allows noninvasive evaluation of left ventricular

function and hence guides management. The combination. of clinical and

transthoracic echocardiographic features also allows risk stratification for

thromboembolism and hemorrhagic complications in atrial fibrillation. High-risk

clinical features for thromboembolism supported by epidemiological

observations, results of randomized clinical trials, and meta-analyses include

rheumatic valvular heart disease, prior thromboembolism, congestive heart

failure, hypertension, older (> 75 years old) women, and diabetes. Small series of

cases also suggest those with hyperthyroidism and hypertrophic cardiomyopathy

are at high risk. TTE plays a unique role in. confirming or discovering high-risk

features such as rheumatic valvular disease, hypertrophic cardiomyopathy, and

decreased left ventricular function. Validation. of the risk stratification scheme

used in the Stroke Prevention in Atrial Fibrillation-IV trial is welcomed by

clinicians who are faced daily with balancing the benefit and risks of

anticoagulation to prevent thromboembolism in patients with atrial fibrillation



Keywords: anticoagulation/atrial fibrillation/cardiomyopathy/cardioversion/clinical

trials/complications/congestive heart

failure/control/diabetes/disease/echocardiography/ELECTRICAL

CARDIOVERSION/etiology/evaluation/fibrillation/FOLLOW-UP/FRAMINGH

AM/heart/heart disease/heart failure/high risk/hypertension/left atrial

function/left atrial size/MECHANICAL

FUNCTION/NATURAL-HISTORY/nonvalvular atrial

fibrillation/population/PREDICTORS/prevention/randomized/risk/risk

stratification/RISK-FACTORS/sinus rhythm/SIZE/SYSTEMIC

EMBOLIZATION/therapy/THROMBOEMBOLIC

STROKE/thromboembolism/transthoracic echocardiography/trials/women



Fava, E., Bortolani, E., Ducati, A. and Schieppati, M. (1992), Role of Sep in Identifying

Patients Requiring Temporary Shunt During Carotid Endarterectomy.

Electroencephalography and Clinical Neurophysiology, 84 (5), 426-432.

Abstract: EEGs and short-latency somatosensory evoked potentials (SEPs) to median

nerve stimulation were recorded during 151 carotid endarterectomies, performed

under general anaesthesia. Carotid occlusion did not affect either EEG or SEP in

120 cases (group A). In 31 cases the EEG showed "ischaemic" abnormalities

(group B). A temporary shunt was inserted only in 16 B patients showing also

severely depressed cortical SEPs within 2 min after carotid occlusion (group B

shunt). In 15 B patients in whom SEPs were less affected, the operation was

completed without shunt (group B no shunt). One intraoperative stroke occurred

in group A and two in group B shunt. No neurological complications occurred in

group B no shunt. Overall stroke rate was 2%. On retrospective analysis, latency

and amplitude of N20 and P25 waves proved to be uninfluenced by carotid

occlusion in group A, but were significantly affected in group B shunt. P25

amplitude alone was reduced in B no shunt. An arbitrary index (need-for-shunt

index, NSI) was made in order to rate changes of P25 latency and amplitude. Its

mean values were significantly different in the 3 groups. A threshold value is

suggested above which shunt is required, as a useful adjunct to EEG, in order to

balance prevention of brain ischaemia against the risks of shunt



Keywords: ARTERY OCCLUSION/CAROTID ENDARTERECTOMY/CEREBRAL

BLOOD-FLOW/COMPLICATIONS/EEG/INTRAOPERATIVE

MONITORING/ISCHEMIA/RESPONSES/SELECTIVE

SHUNT/SOMATOSENSORY EVOKED POTENTIALS/SOMATOSENSORY

EVOKED-POTENTIALS/STUMP PRESSURE



Sites, C.K. (2000), Hormones, women, and cardiovascular disease: Primary vs.

secondary prevention after menopause. Endocrinologist, 10 (2), 113-117.



Abstract: Hormone replacement therapy (HRT) may provide greater benefits or risks to

women after menopause depending on the patient's clinical history. This review

focuses on the effects of HRT on primary vs. secondary prevention of

cardiovascular disease. For women without known cardiovascular disease, HRT

may reduce risk through improvement in lipids, cardiac contractility, and body

composition. The improvement in vasodilatation with estrogen may be diluted by

the addition of a progestin, The effects of HRT on coagulation and vascular

inflammation are more difficult to interpret. For women with known disease,

HRT may reduce subclinical atherosclerosis and increase long-term survival after

coronary artery bypass grafting, However, it may not prevent subsequent cardiac

events and may increase the short- term risk of thrombosis for these patients.

Understanding the risks and benefits of HRT relative to cardiovascular history

should allow physicians to provide useful information to patients



Keywords: ANGIOPLASTY/atherosclerosis/bypass

grafting/cardiac/cardiovascular/cardiovascular

disease/coagulation/COHORT/contractility/disease/estrogen/ESTROGEN

REPLACEMENT THERAPY/history/HRT/inflammation/INSULIN

SENSITIVITY/lipids/menopause/POSTMENOPAUSAL

WOMEN/prevention/primary/PROGESTIN/review/RISK/secondary

prevention/STROKE/therapy/THICKNESS/thrombosis/USERS/vascular/women



Rifkind, B.M. (1998), Clinical trials of reducing low-density lipoprotein concentrations.

Endocrinology and Metabolism Clinics of North America, 27 (3), 585-+.



Abstract: Much diverse evidence suggests that the plasma levels of low- density

lipoprotein (LDL) cholesterol play a causal role in the pathogenesis of

atherosclerotic coronary heart disease. Until recently, clinical trials of LDL

lowering, while showing significant reductions in coronary heart disease (CHD)

rates, were not entirely convincing and left some questions of long- term toxicity

unresolved. The results of a series of new trials using members of the powerful

statin class of drugs are now being reported. Whether they are primary or

secondary prevention studies, they have been uniformly successful in reducing

mortality and morbidity from CHD and even total mortality, and have decreased

the need for revascularization procedures. Their effectiveness is apparent in

many different subgroups such as women, diabetics, hypertensives, and in stroke

prevention. Statin drugs also have proven to be remarkably safe over the duration

of the studies. Angiographic studies show an impact on coronary or carotid

lesions



Keywords: ATHEROSCLEROSIS/carotid/cholesterol/CHOLESTEROL

LEVELS/clinical trials/coronary heart disease/CORONARY

HEART-DISEASE/drugs/heart/LDL/morbidity/MORTALITY/MYOCARDIAL-

INFARCTION/POPULATION/PRAVASTATIN/PREVENTION/PROGRESSI

ON/secondary prevention/SERUM-CHOLESTEROL/stroke/stroke

prevention/toxicity/trials/women



Kuller, L.H. (2000), Epidemiology and prevention of stroke, now and in the future.

Epidemiologic Reviews, 22 (1), 14-17



Keywords: ASSOCIATION/CARDIOVASCULAR-DISEASE/FACTOR

INTERVENTION TRIAL/HYPERTENSION/ISCHEMIC

STROKE/MORTALITY/MYOCARDIAL-INFARCTION/OLDER

ADULTS/prevention/RISK-FACTORS/stroke/WHITE-MATTER LESIONS



Rafflenbeul, W. (2000), Fish for a healthy heart. Ernahrungs-Umschau, 47 (11), 432-+.



Abstract: omega -3 fatty acids have been shown to possess hypolipemic,

antihypertensive, antiinflammatory, antithrombotic and antiarrhythmic properties

making them of interest in the prevention of coronary artery disease and stroke,

mild hypertension, type 2 diabetes, autoimmune nephropathy, rheumatoid

arthritis, Crohn's disease or chronic obstructive pulmonary disease. For

prevention of coronary heart disease complications a stabilization of membrane

eletrophysiologic function in a manner that makes it less vulnerable to fatal

arrhythmias is most important. Besides all the attention to common risk factors in

trying to keep the heart healthy, a Little fish two times per week is a prudent

advice, particularly if it substitutes other sources of protein, like fatty meats, and

is served with a green salad and legumes



Keywords:

antithrombotic/arrhythmias/CHD/complications/CONSUMPTION/CONTROLL

ED TRIAL/coronary artery disease/CORONARY

ATHEROSCLEROSIS/coronary heart

disease/diabetes/DIETARY-INTAKE/DISEASE/fish/Germany/heart/heart

disease/hypertension/MORTALITY/MYOCARDIAL-INFARCTION/N-3

FATTY-ACIDS/omega-3 fatty acids/PREVENT

RESTENOSIS/prevention/pulmonary/RISK/risk factors/stroke/type 2 diabetes



Dundas, R., Morgan, M., Redfern, J., Lemic-Stojcevic, N. and Wolfe, C. (2001), Ethnic

differences in behavioural risk factors for stroke: Implications for health

promotion. Ethnicity & Health, 6 (2), 95-103.



Abstract: Objectives. Ethnic minority groups are at a higher risk of stroke and heart

disease. However, designing effective prevention strategies requires responding

to the needs of different ethnic groups. The aims of this study were to estimate

the prevalence of four behavioural risk factors (smoking, drinking, exercise and

weight) for stroke among Black Caribbeans, Black Africans and Whites, and also

to examined reported willingness to change these behaviours. Design. A random

sample of 311 Black Caribbean, 300 White, and 105 Black Africans aged 45-74

registered with 16 practices in south London were surveyed in 1995. Information

was obtained on smoking, drinking and exercise patterns, body mass index and

perceptions of being at risk of stroke, and willingness to change risk behaviour.

Results. White respondents (31% age and sex standardised prevalence) were

more likely to smoke than Black Caribbeans (23%) and Black Africans (10%) (p

27) than Black Caribbeans (60%) and Black Africans (68%) (p = 0.001).

A high proportion of smokers wished to give up (89% Black African: 83% Black

Caribbean; 74% White). A higher proportion of Black Caribbeans (35%)

reported a willingness to reduce their alcohol intake compared to only 15% of

Whites (p = 0.040). There was a difference between groups in attitudes to weight

reduction with 69% Black Caribbean women expressing a desire to be thinner

compared to 86% Whites and 82% Black Africans (p = 0.051). Conclusion.

Strategies to reduce behavioural risk factors for heart attack and stroke need to

emphasise different risk factors among ethnic groups, especially in relation to

alcohol use in the White population and weight in the Black Caribbean

population. Influencing the change of these behaviours requires working in

partnership with local community groups



Keywords: age/aged/alcohol/attitudes/body mass

index/community/disease/England/ethnic groups/ethnicity/exercise/health/health

promotion/heart/heart disease/population/prevalence/prevention/risk/risk

factors/risk factors for stroke/sex/smoking/stroke/use/weight/women



Carlsson, J., Miketic, S., Dees, G., Haun, S., Cuneo, A. and Tebbe, U. (2000), Stroke

prevention practices in patients with atrial fibrillation and pacemaker therapy -

Evidence for under-use of anticoagulation. Europace, 2 (2), 115-118.



Abstract: This study presents a survey of pacemaker patients followed in a pacemaker

clinic. Three hundred and twenty-six patients of mean age 77.7 +/- 9.6 years,

52% female, 75% VVI, 25% dual chamber were analysed. One hundred and

forty (43%) were in atrial fibrillation and were older, 80.5 +/- 7.1 years,

compared with 75.5 +/- 11.4 years (P=0.014) for those in sinus rhythm.

Temporary pacemaker reprogramming was necessary in 86% in order to

determine the abnormal rhythm. Thirty-nine (28%) of those in atrial fibrillation

were anticoagulated; 37% were on aspirin; only 10.8% of those in atrial

fibrillation who were not anticoagulated had contraindications to this therapy.

Prevalence of atrial fibrillation increased with age, whereas that of

anticoagulation decreased with age. In conclusion, the majority of pacemaker

patients with atrial fibrillation, for whom anticoagulation is indicated, fails to

receive it: those caring for these patients are urged to ensure its much wider use.

(Europace 2000; 2: 115-118) (C) 2000 The European Society of Cardiology



Keywords: age/anticoagulation/ANTITHROMBOTIC THERAPY/aspirin/atrial

fibrillation/COMMUNITY/ENGLAND/fibrillation/Germany/HOSPITALS/LON

DON/NATIONAL PATTERNS/oral

anticoagulation/pacemaker/prevention/PRIMARY-CARE/SICK SINUS

SYNDROME/sinus

rhythm/survey/therapy/THROMBOEMBOLISM/use/VVI/WARFARIN USE



Freidl, W., Schmidt, R., Stronegger, W.J., Fazekas, F. and Reinhart, B. (1996),

Sociodemographic predictors and concurrent validity of The Mini Mental State

Examination and The Mattis Dementia Rating Scale. European Archives of

Psychiatry and Clinical Neuroscience, 246 (6), 317-319.



Abstract: The Mini Mental State Examination (MMSE) and the Mattis Dementia Rating

Scale (MDRS) are among the most commonly used screening tests for dementia.

The goals of our study were, firstly, to identify sociodemographic factors which

may explain the variance of test results in a community sample and, secondly, to

investigate the interrelationship of these two dementia screening tests in order to

evaluate the concurrent validity. A total of 1947 subjects were investigated in the

setting of the Austrian Stroke Prevention Study (ASPS). Our study confirms

most previous results demonstrating a relationship of higher dementia test scores

with both younger age and higher educational level. Interestingly, the results we

obtained suggest only a weak relationship and poor concurrent validity of the

two tests. The total scores of the two tests show poor joint variance. This could

lead to the conclusion that these tests evaluate different cognitive domains

Keywords: AGE/concurrent validity/dementia/dementia

screening/EDUCATION/POPULATION/predictors



Lindblad, U., Rastam, L. and Ranstam, J. (1993), Acute Myocardial-Infarction in

Patients Treated for Hypertension in the Skaraborg-Hypertension-Project.

European Heart Journal, 14 (3), 291-296



Keywords: ACUTE MYOCARDIAL

INFARCTION/BLOOD-PRESSURE/CARDIOVASCULAR

MORBIDITY/COHORT STUDY/COMMUNITY/CORONARY

HEART-DISEASE/FEMALE/HEART/HYPERTENSION/MALE/MEDICAL-C

ARE PROGRAM/MORTALITY/PRIMARY HEALTH CARE/PRIMARY

PREVENTION/PRIMARY PREVENTIVE TRIAL/STROKE



Debelder, M.A., Lovat, L.B., Tourikis, L., Leech, G. and Camm, A. (1993), Left Atrial

Spontaneous Contrast Echoes - Markers of Thromboembolic Risk in Patients

with Atrial-Fibrillation. European Heart Journal, 14 (3), 326-335



Keywords:

COMPLICATIONS/ECHOCARDIOGRAPHY/EMBOLISM/FRAMINGHAM/

HEART/MITRAL-VALVE

DISEASE/PREVALENCE/PREVENTION/SPONTANEOUS CONTRAST

ECHOES/STASIS/STROKE/SYSTEMIC

EMBOLIZATION/THROMBOEMBOLISM/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY



Gosse, P. and Clementy, J. (1995), Coronary Reserve in Experimental Myocardial

Hypertrophy. European Heart Journal, 16 22-25.



Abstract: Three types of dysfunction of the coronary circulation have been described in

experimental models of hypertension associated with left ventricular hypertrophy:

(1) reduced coronary reserve, (2) a relative decrease in perfusion of

subendocardial layers, (3) a shift to the right, i.e. to higher pressures, of the

circulation pressure autoregulation range. These abnormalities are also observed

in hypertensive patients although it is significant that they do not appear to be

related to the extent of left ventricular hypertrophy. The exact causes of these

abnormalities have yet to be elucidated. Left ventricular hypertrophy does nor

seem to be an essential factor although in certain experimental models of

hypertension, there does appear to be a mismatch between the development of

the coronary vasculature and hypertrophy of the myocytes. The stresses in

vessels due to the increase in systolic, and especially intraventricular diastolic

pressure can be viewed as additional aggravating factors The essential

abnormalities are structural and/or functional alterations in arterial walls. The

structural alterations are reflected by a narrowed lumen due to parietal thickening.

This may result from growth of muscle fibres (hypertrophy or hyperplasia) or

collagen tissue and/or remodelling of tissues with no overall change in mass.

Functionally, the reduced ability of the arteries to stretch, resulting from

endothelial alterations may also play a role in the abnormalities observed in

hypertensive patients. In our studies, we examined the effect of the

antihypertensive drug perindopril on the coronary circulation in the renovascular

hypertensive rat (two kidneys-1 clip). We found that this inhibitor of angiotensin

converting enzyme (ACE) led to a regression of left ventricular hypertrophy with

a return to normal of the coronary reserve Other studies using either this model

or the spontaneously hypertensive rat have also pointed to a beneficial action of

ACE inhibitors and other antihypertensive agents on the coronary circulation

with reversal of the structural alterations in arterioles. Coronary disease is the

main cause of mortality in hypertensive patients. Ironically, antihypertensive

therapy has yet to live up to its promise of reducing significantly either the

incidence or severity of coronary disease in such patients. Specific alterations of

the coronary circulation may account for the relative failure of-antihypertensive

drugs, despite their proven efficacy in other systems (e.g. stroke prevention). The

coronary circulation is unique in certain important respects. It is tightly regulated,

maintaining an almost constant flow rate over a wide range of aortic arterial

pressures (40-160 mmHg). Extraction of oxygen by the myocardium is almost

maximal under resting conditions, and so the circulatory reserve depends almost

entirely on the capacity to increase blood flow. This reserve is quite large since

there may be a 4 to 5-fold increase in coronary flow rate in response to effort

Another significant detail is that myocardial contraction may lead to an

interruption of coronary flow, especially in the deep subendocardial layers,

which thus tend to be perfused solely during diastole. This East factor can be

seen as the Achilles heel of the coronary circulation, which may be severely

limited by myocardial hypertrophy, especially in patients with hypertension



Keywords:

angiotensin/ARRHYTHMIAS/BLOOD-FLOW/CARDIAC-HYPERTROPHY/C

IRCULATION/CORONARY BLOOD FLOW/coronary disease/CORONARY

RESERVE/development/DYSFUNCTION/ENGLAND/EXERCISE/HEART/HE

ART-DISEASE/hypertension/HYPERTENSIVE

HEART/hypertrophy/incidence/LEFT VENTRICULAR

HYPERTROPHY/LEFT-VENTRICULAR

HYPERTROPHY/mortality/muscle/PRESSURE-FLOW

RELATIONSHIPS/prevention/rat/severity/SPONTANEOUSLY

HYPERTENSIVE RATS/stroke/stroke prevention



Koenig, W. (1995), Recent Progress in the Clinical Aspects of Fibrinogen. European

Heart Journal, 16 54-59.



Abstract: This article provides an overview of recently accumulated evidence on the

pathogenetic role of fibrinogen in various vascular beds; and tries to elucidate

determinants for patients' susceptibility so that subgroups at particular risk of

severe clinical complications can be characterized more accurately. Based on the

considerably elevated risk of cardiovascular complications associated with

increased levels of plasma fibrinogen, the potential value of lowering fibrinogen

in the primary or secondary prevention of atherosclerotic disease is now

recognized as an important topic for consideration. Recent progress in this field

will also be reviewed



Keywords: ACTIVATION/ANGIOTENSIN-CONVERTING ENZYME

INHIBITORS/ANTIPLATELET

DRUGS/APHERESIS/ARTERY/ATHEROSCLEROSIS/complications/CORON

ARY

HEART-DISEASE/CYTOKINES/DIABETES/ENGLAND/FIBRATES/FIBRIN

OGEN/HEART/HEMOSTASIS/ISCHEMIC HEART

DISEASE/MYOCARDIAL-INFARCTION/PERIPHERAL ARTERIAL

DISEASE/PLASMA- FIBRINOGEN/PLATELET

AGGREGATION/prevention/RISK/secondary

prevention/STATINS/STROKE/THROMBOLYTIC

AGENTS/TICLOPIDINE/vascular



Qizilbash, N. (1995), Fibrinogen and Cerebrovascular-Disease. European Heart Journal,

16 42-46.



Abstract: The importance of fibrinogen has been identified in two prospective

observational studies. Reactive elevations in fibrinogen levels that occur within

hours of a major stroke invalidate most cross-sectional case-control studies

evaluating fibrinogen as a risk factor. However, as no elevation is seen following

fresh episodes of transient ischaemic attacks, reliable conclusions drawn from a

case-control study using such patients support the findings of the prospective

studies. The association is related to occlusive stroke, but the relationship with

intracerebral haemorrhage is unclear. The relationship has been found to be

independent of other haemostatic and haemorheological factors (e.g. von

Willebrand factor, tissue plasminogen activator and packed cell volume).

Adjustment for regression dilution bias would further strengthen the observed

relationship. Therefore, after blood pressure, fibrinogen is the most important

potentially treatable risk factor for ischaemic stroke. There are several

mechanisms whereby fibrinogen could promote atherothromboembolism:

thrombosis through a hypercoagulable state; the acceleration of atherosclerosis;

or the reduction of blood flow due to high blood or plasma viscosity. The

mechanism, however, is unlikely to be mediated through high blood viscosity per

se as secondary erythrocytosis (another major determinant of blood viscosity)

has not consistently been found to be a risk factor for stroke. Studies relating

fibrinogen levels to the degree of carotid artery stenosis support the accelerating

influence of fibrinogen on atherosclerosis. Fibrinogen should be considered a

risk factor for ischaemic stroke and included in the assessment of individual risk

factors. For stroke prevention, individuals with high fibrinogen values but no

other risk factors should be considered for therapies to reduce the overall risk of

future stroke, i.e. blood pressure reduction and antiplatelet therapy, as well as

regular exercise, weight loss and possibly the adoption of a vegetarian diet



Keywords: antiplatelet therapy/atherosclerosis/BEZAFIBRATE/blood pressure/BLOOD

RHEOLOGY/CARDIOVASCULAR RISK FACTOR/carotid/case-control

studies/cell volume/CORONARY

HEART-DISEASE/diet/DRUGS/ENGLAND/exercise/FIBRATE/FIBRINOGE

N/GERIATRIC/HEART/LIPIDS/observational

studies/PLASMA-FIBRINOGEN/PRECIPITATION/prevention/prospective

studies/risk/risk factors/STROKE/stroke

prevention/thrombosis/transient/TRANSIENT ISCHEMIC

ATTACK/TRANSIENT ISCHEMIC ATTACKS/TREATMENT



Fuster, V. and Chesebro, J.H. (1995), Aspirin for Primary Prevention of

Coronary-Disease. European Heart Journal, 16 16-20



Keywords: ATHEROSCLEROSIS/CARDIOVASCULAR-

DISEASE/ENGLAND/HEART/ISCHEMIC-HEART-DISEASE/LOW-DOSE

WARFARIN/MEN/MYOCARDIAL INFARCTION/PLATELET

INHIBITOR/RISK/STROKE/THROMBOSIS/TRIAL



Nighoghossian, N., Perinetti, M., Barthelet, M., Adeleine, P. and Trouillas, P. (1996),

Potential cardioembolic sources of stroke in patients less than 60 years of age.

European Heart Journal, 17 (4), 590-594.



Abstract: Minor potential cardioembolic sources of stroke such as atrial septal aneurysm

or patent foramen ovale are important risk factors for cryptogenic stroke. We

aimed to determine the prevalence of these abnormalities through an exhaustive

aetiological work-up. One hundred and eighteen stroke patients under 60 years of

age, who had no evidence of a significant cardiac source of embolism, were

classified into four groups following transoesophageal echocardiography and

assessment of cervical arteries. Group A comprised 30 patients (25.4%) who had

an arteriopathy, probably related to stroke without ally cardiac abnormality;

group B, had only a potential cardiac source; group C, nine (7.6%) had an

obvious arterial source of stroke and incidental cardiac abnormalities; group D,

30 (25.4%) had neither cardiac or arterial source. Data were analysed with the

Chi-square test to compare risk factors between groups, and variance analysis

was used to compare age between groups. Significance was assessed as P50 ml.m(-2) (odds ratio=7.1, 95%

confidence interval=[1.5; 25.8]), anterior infarct location (odds ratio=4.1, 95%

confidence interval= [1.4; 11.5]) and reocclusion of the infarct-related artery

(odds ratio=7.3, 95% confidence interval=[1.3; 27.3]). Angioplasty of a patent

but significantly narrowed infarct-related artery was not found predictive.

Conclusions This study demonstrates that reocclusion of a previously open

infarct-related artery, as well as the initial low stroke volume index, enlarged

end- systolic volume index and anterior infarct location are independent

predictors of long-term left ventricular enlargement. These results emphasize the

impact of long-term sustained patency of the infarct-related artery on the

prevention of left ventricular dysfunction. The need for a larger randomized trial

is recognised



Keywords: 12- MONTH FOLLOW-UP/ANGIOPLASTY/coronary

angioplasty/coronary patency/coronary

reopening/ENGLAND/HEART/infarction/LATE CORONARY

REPERFUSION/left ventricular remodelling/myocardial

infarction/PATENCY/patent/PHASE-I/predictors/prevention/randomized/RAND

OMIZED TRIAL/stroke/SURVIVAL/THROMBOLYTIC THERAPY/TIMI

TRIAL/TISSUE PLASMINOGEN-ACTIVATOR



Ericsson, C.G. (1998), Results of the Bezafibrate Coronary Atherosclerosis Intervention

Trial (BECAIT) and an update on trials now in progress. European Heart

Journal, 19 H37-H41.



Abstract: Bezafibrate is a latest generation fibrate derivative that substantially reduces

total plasma cholesterol and triglyceride concentrations and increases high

density lipoprotein (HDL) cholesterol. The Bezafibrate Coronary Atherosclerosis

Intervention Trial (BECAIT) was a double-blind, placebo- controlled trial over 5

years to assess the angiographic benefits of bezafibrate retard (400 mg.day(-1))

in young, male, post-myocardial infarction (post-MI) patients. The trial

demonstrated that without lowering serum low density lipoprotein cholesterol,

progression of coronary atherosclerosis was prevented and the coronary event

rate reduced. In subgroup analyses, bezafibrate decreased the rate of progression

of coronary atherosclerosis and coronary event rate in young post-MI patients,

primarily by slowing the progression of mild-to-moderate lesions. Additional

studies are underway to explore further the benefits of this fibrate in coronary

heart disease. The Bezafibrate Infarction Prevention study is the first trial to

investigate the effects of raising HDL cholesterol and lowering triglycerides in

patients with established coronary disease. The Lower Extremity Arterial

Disease Event Reduction study is assessing the benefit of lowering fibrinogen in

the prevention of major ischaemic heart disease and stroke in patients with

peripheral vascular disease



Keywords: ARTERY

DISEASE/atherosclerosis/BECAIT/bezafibrate/CHOLESTEROL/coronary

disease/coronary heart disease/DESIGN/ENGLAND/fibrinogen/HEART/high

density lipoprotein/hyperlipidaemia/INFARCTION

PREVENTION/prevention/REGRESSION/stroke/trials/TRIGLYCERIDE-RICH

LIPOPROTEINS/triglycerides/vascular/vascular disease



Yusuf, S. and Lonn, E. (1998), Anti-ischaemic effects of ACE inhibitors: review of

current clinical evidence and ongoing clinical trials. European Heart Journal, 19

J36-J44.



Abstract: Important ongoing experimental and clinical research is evaluating the

potential use of ACE inhibitors in a wider range of patients, in addition to their

well accepted use in heart failure, left ventricular dysfunction and hypertension.

We review briefly the clinical data supporting a potential role for ACE inhibitors

in the prevention of myocardial infarction and stroke and the wider use of these

agents in hypertension, renal disease and diabetes. We also briefly review the

major ongoing trials evaluating these hypotheses



Keywords: angiotensin-converting enzyme

inhibitors/ANGIOTENSIN-CONVERTING-ENZYME/CAPTOPRIL/CHRONI

C STABLE ANGINA/clinical trials/CORONARY-ARTERY

DISEASE/diabetes/ENGLAND/GENE POLYMORPHISM/HEART/heart

failure/hypertension/ISCHEMIC-HEART-DISEASE/myocardial

infarction/MYOCARDIAL-

INFARCTION/PECTORIS/PLASMA-RENIN/prevention/RISK/stroke/trials



Muiesan, M.L. and Agabiti-Rosei, E. (1999), Hypertension, quantitative benefits of

treatment: optimal intervention points and management in aircrew. European

Heart Journal Supplements, 1 (D), D32-D36.



Abstract: The risks associated with arterial hypertension, and particularly increased

cardiovascular, cerebral fatal and non- fatal events are well established, as are

those with end-stage renal disease. The incidence of stroke and, to a lesser extent,

of fatal and non-fatal coronary events, is significantly reduced by lowering high

blood pressure, as demonstrated in previous studies. The relative benefit of

therapy is fairly uniform in most intervention trials, independent of severity of

hypertension and of patient age. However, the absolute benefit varies between

the different trials and is much greater in severe hypertensive and/or elderly

patients, in whom the absolute risk of cardiovascular events is also higher.

Antihypertensive treatment is more cost-effective in high-risk patients than in

those without complications in the short term. In young and middle-aged patients

with mild hypertension, earlier treatment, though less cost-effective, is likely to

be more effective in the prevention of end organ damage development, and the

reduction of subsequent morbid events in the long term. This should help

subjects achieve their full life-span. Possible strategies to improve the benefit of

antihypertensive treatment have been recently investigated by appropriate trials

and it has been suggested that the use of cardiovascular drugs which have

tissue-protective properties may have an additional benefit similar to that

achieved by lowering the blood pressure



Keywords: absolute risk/age/aircrew licensing/antihypertensive treatment/arterial

hypertension/ARTERIAL-HYPERTENSION/aviation/blood

pressure/BLOOD-PRESSURE/cardiovascular/cardiovascular

events/CARDIOVASCULAR RISK/cerebral/complications/coronary artery

disease/CORONARY HEART-DISEASE/development/drugs/elderly/end-stage

renal disease/ENGLAND/HEART/high blood

pressure/hypertension/HYPERTROPHY/incidence/LEFT-VENTRICULAR

MASS/MEN/MORBID EVENTS/POPULATION/prevention/renal/renal

disease/risk/severity/stroke/therapy/treatment/TRIALS



Haberl, R.L. and Dembowski, K. (1999), Atherothrombosis: common factor in stroke,

myocardial infarction and peripheral vascular disease. European Heart Journal,

20 A41-A44.



Abstract: Thrombosis superimposed on atherosclerosis causes approximately 60% of all

brain infarctions. Patients with atherothrombotic occlusion of the cerebral

vasculature are also at increased risk for occlusion within other vascular beds, as

is suggested by the presence of similar risk factors for occlusive disease in the

cerebral, cardiac and peripheral circulation. Because of this, there is a need for

treatments that address a single occurrence of atherothrombosis, such as

occlusion of the cerebral vessels, but which also provide effective protection

against other potential occurrences of ischaemia throughout the body.

Antithrombotic therapy is a key aspect of secondary treatment for patients who

have experienced brain infarctions. Secondary prevention of a recurrent cerebral

infarct may thus constitute primary prevention for both heart disease and

peripheral arterial disease



Keywords: antithrombotic therapy/atherosclerosis/BLOOD-PRESSURE/brain/BRAIN

INFARCTION/CAROTID STENOSIS/cerebral/cerebral

vessels/CHLAMYDIA-PNEUMONIAE/CHOLESTEROL

LEVELS/CORONARY-ARTERY

DISEASE/ENGLAND/HEART/HEART-DISEASE/infarction/INFECTION/isch

aemia/MEN/myocardial/myocardial infarction/peripheral arterial

disease/peripheral vascular disease/prevention/primary/primary

prevention/RISK/risk factors/stroke/therapy/treatment/vascular/vascular

disease/vasculature



Packard, C.J. (1999), Major statin trials: relationship between lipid changes and

cardiovascular events. European Heart Journal Supplements, 1 (T), T2-T6.



Abstract: The lipid hypothesis, that lowering plasma cholesterol leads to a reduction in

coronary heart disease risk, is now regarded as proven. Five large-scale, clinical

outcome trials have shown that pravastatin, simvastatin and lovastatin are able to

reduce the incidence of myocardial infarction and, in the case of pravastatin and

simvastatin, decrease the risk of cardiovascular death and improve survival.

Subgroup analyses show that the benefits are independent of gender and other

treatment modalities such as antihypertensive agents and aspirin. An unexpected

further benefit was the reduction in the risk of stroke



Keywords: antihypertensive agents/aspirin/atherosclerosis/AVERAGE

CHOLESTEROL LEVELS/cardiovascular events/cholesterol/coronary heart

disease/CORONARY HEART-DISEASE/disease

risk/ENGLAND/HEART/incidence/infarction/low density

lipoprotein/MEN/myocardial/myocardial

infarction/PRAVASTATIN/PRIMARY-

PREVENTION/REDUCTION/risk/SERUM-CHOLESTEROL/stroke/therapy

goals/treatment/trials



Haberl, R.L. and Dembowski, K. (1999), Atherothrombosis: common factor in stroke,

myocardial infarction and peripheral vascular disease. European Heart Journal

Supplements, 1 (A), A41-A44.



Abstract: Thrombosis superimposed on atherosclerosis causes approximately 60% of all

brain infarctions. Patients with atherothrombotic occlusion of the cerebral

vasculature are also at increased risk for occlusion within other vascular beds, as

is suggested by the presence of similar risk factors for occlusive disease in the

cerebral, cardiac and peripheral circulation. Because of this, there is a need for

treatments that address a single occurrence of atherothrombosis, such as

occlusion of the cerebral vessels, but which also provide effective protection

against other potential occurrences of ischaemia throughout the body.

Antithrombotic therapy is a key aspect of secondary treatment for patients who

have experienced brain infarctions. Secondary prevention of a recurrent cerebral

infarct may thus constitute primary prevention for both heart disease and

peripheral arterial disease



Keywords: antithrombotic therapy/atherosclerosis/BLOOD-PRESSURE/brain/BRAIN

INFARCTION/CAROTID STENOSIS/cerebral/cerebral

vessels/CHLAMYDIA-PNEUMONIAE/CHOLESTEROL

LEVELS/CORONARY-ARTERY

DISEASE/ENGLAND/HEART/HEART-DISEASE/infarction/INFECTION/isch

aemia/MEN/myocardial/myocardial infarction/peripheral arterial

disease/peripheral vascular disease/prevention/primary/primary

prevention/RISK/risk factors/stroke/therapy/treatment/vascular/vascular

disease/vasculature



Frost, L., Engholm, G., Moller, H. and Husted, S. (1999), Decrease in mortality in

patients with a hospital diagnosis of atrial fibrillation in Denmark during the

period 1980-1993. European Heart Journal, 20 (21), 1592-1599.



Abstract: Background Atrial fibrillation is associated with increased mortality. We

hypothesized that the death rate in atrial fibrillation patients in Denmark has

diminished during the period 1980-1993. Methods In a random sample of half of

the Danish population, 30 330 patients were found to have a diagnosis of

incident atrial fibrillation in the Danish National Hospital Discharge Register

1980-1993. Information on previous and concomitant cardiovascular and

metabolic diseases during the period 1977-1993 was sought in the register. The

temporal trend in total and cardiovascular mortality in the cohort of atrial

fibrillation patients was analysed. Results A significant decrease in total and

cardiovascular mortality was seen, 12-13% for total mortality and 17-18% for

cardiovascular mortality. By adjusting for the decreasing cardiovascular

mortality rate in the general population, a decrease in the relative risk of total

mortality of 8-13% with time was seen for the atrial fibrillation cohort, compared

with the population risk, while no reduction in the relative risk of cardiovascular

death was seen. Conclusion A significant decrease in mortality with calendar

period occurred in the cohort of atrial fibrillation patients. (C) 1999 The

European Society of Cardiology



Keywords: atrial fibrillation/cardiovascular/cardiovascular

mortality/diagnosis/diseases/ENGLAND/epidemiology/fibrillation/HEART/hosp

ital/IMPACT/mortality/POPULATION/PREVENTION/prognosis/relative

risk/risk/RISK-FACTORS/STROKE/TRENDS/WARFARIN



Verheugt, F.W.A. (1999), Anticoagulation and certification to fly: risks and benefits of

different strategies. European Heart Journal Supplements, 1 (D), D114-D117.



Abstract: Atrial fibrillation is a common arrhythmia, especially in the elderly. The

presence of atrial fibrillation increases the risk of stroke three- to fivefold. This

risk largely relates to dilatation of the left side of the heart and a history of

previous stroke. Both anticoagulant and antiplatelet therapy have been shown to

reduce the stroke risk with acceptable safety. High-risk patients should receive

full dose oral anticoagulation (INR 2.0-3.0) and the low-risk patient, antiplatelet

therapy. Oral anticoagulation carries a significant risk of bleeding complications,

especially when the full dose regime is applied. Only low-risk individuals with

lone atrial fibrillation are likely to be eligible for certification to fly and should

be limited to multi-crew operation



Keywords: aircrew licensing/anticoagulant/anticoagulation/antiplatelet/antiplatelet

therapy/arrhythmia/atrial

fibrillation/ATRIAL-FIBRILLATION/aviation/complications/echocardiography/

elderly/ENGLAND/fibrillation/HEART/history/INR/Netherlands/oral

anticoagulation/PREVENTION/risk/safety/STROKE/stroke/therapy/WARFARI

N



Meade, T., Sleight, P., Collins, R., Armitage, J., Parish, S., Peto, R., Youngman, L.,

Buxton, M., de Bono, D., Fuller, J., Keech, A., Mansfield, A., Pentecost, B.,

Simpson, D., Warlow, C., O'Toole, L., Doll, R., Wilhelmsen, L., Fox, K., Hill, C.,

Sandercock, P., Barton, J., Bray, C., Jayne, K., Lawson, A., Harding, P., Lay, M.,

Wallendszus, K., Benjamin, N., Webster, J., Jamieson, J., Donald, L., Blandford,

R., Carrington, L., McMahon, H., Cheetham, D., Reckless, J., Brice, L.,

Carpenter, R., Christmas, J., Flower, C., Cooper, I., Frampton, S., Pickerell, E.,

Wells, J., Scott, M., Crowe, V., Shaw, A., Shannon, L., Jones, S., Faulkner, G.,

Lavery, A., O'Leary, H., Watson, R., Capewell, C., Hughes, S., Bain, S., Jones,

A., Holmes, G., Jewkes, C., Bellamy, T., Harrison, P., Buller, N., Nield, H.,

Smith, E., Vint, P., Crook, P., Williams, J., Bateson, M., Cawley, P., Gill, P.,

Simpson, K., Armitage, M., Cope, C., Tricksey, J., Wilson, M., Cottrell, S.,

Jones, C., Llewellyn, M., Smith, P., Woodsford, T., Vincent, R., Joyce, E.,

Skipper, N., Peters, P., Lemon, M., Stansbie, D., Kidan, A.H., Halestrap, M.,

Gibbons, A., Meredith, J., Dawkins, C., Papouchado, M., Baker, L., Boulton, K.,

Dawe, C., Lewis, A., Wisby, J., Brown, M., Emeny, J., Smith, W., Trutwein, D.,

Cornwell, M., Lloyd, D., White, C., Khalifa, M., MacKereth, N., Martin, G.,

Baxter, M., Chambers, R., Glenn, S., Kerr, J., Golesworthy, G., Watts, A.,

Baines, G., Groom, J., Price, L., Barlow, I., Mallya, S., Lewis, S., Maiden, J.,

Nash, M., Lowe, V., Scott, A., Cozens, S., Hannah, J., Hinwood, M., Millward,

J., Murphy, J., Charters, M., Graham, B., Banks, M., Nobbs, R., Kemp, T.,

Turner, P., Sheldrake, S., Labib, M., Pearson, R., Sidaway, J., Davies, P.,

Hodgkiss, M., MacLeod, D., Stuart, R., Albrock, J., Fisher, J., Stuart, F.,

Swainson, C., Glenn, S., Johnston, J., Sadler, S., Curren, M., Feirnie, S.,

Stenhouse, L., Lindley, R., Warlow, C., Kenny, A., Waddell, F., Brownlie, M.,

Guilar, I., Marshall, A., Went, J., Clarke, S., Inman, A., Simmonds, J., Duook, B.,

Mortimore, G., Pascoe, A., Cobbe, S., Campbell, C., Young, H., Keeble, M.,

Absalom, S., Bracey, N., Falco, L., Stone, D., Tildesley, G., Carr, B., Longstaff,

G., Turner, A., Wilkinson, H., Wilkinson, S., Hillson, R., Brookes, D., Capper,

B., Price, K., Badrick, V., Griffiths, H., Fitzgerald, J., Lewis, S., Campbell, P.,

Baines, G., Claypole, G., Lomas, J., Rogers, A., Brown, A., Cheshire, J., Rowley,

J., Ball, S., Prentice, C., Hall, A., Atha, P., Caffrey, K., Currie, W., Hague, C.,

Hall, S., Maguire, P., Rose, C., Watson, R., Buxton, A., Wedgwood, A., Gilbey,

S., Currie, W., Drury, K., Hall, S., Rose, C., Wilson, J., Vaughn, M., Humphrey,

P., Blocksage, J., McSloy, R., Ost, K., Owen, L., Saminaden, S., Watling, D.,

Wiseman, J., Davies, J., Kehely, A., Kooner, J., Capper, B., Corbett, I., Peters, J.,

Price, K., Van Goethem, M., Chambers, J., Crawshaw, M., O'Sullivan, J., Powell,

S., Reoch, M., Sanders, J., Beament, M.F., Fangrad, B., Williams, Y., Banim, S.,

Crake, T., Ford, B., Glynn, V., Ismail, S., Buller, N., Coats, A., Aitken, L.,

Cruddas, E., Serup-Hansen, K., Nosworthy, D., Reilly, N. and Coppack, S.

(1999), MRC BHFHeart Protection Study of cholesterol-lowering therapy and of

antioxidant vitamin supplementation in a wide range of patients at increased risk

of coronary heart disease death: early safety and efficacy experience. European

Heart Journal, 20 (10), 725-741.



Abstract: Aims In observational studies, prolonged lower blood total cholesterol levels -

down at least to 3 mmol . l(-1) - are associated with lower risks of coronary heart

disease. Cholesterol-lowering therapy may, therefore, be worthwhile for

individuals at high risk of coronary heart disease events irrespective of their

presenting cholesterol levels. Observational studies also suggest that increased

dietary intake of antioxidant vitamins may be associated with lower risks of

coronary heart disease. The present randomized trial aims to assess reliably the

effects on mortality and major morbidity of cholesterol-lowering therapy and of

antioxidant vitamin supplementation in a wide range of different categories of

high-risk patients. Methods and Results Men and women aged 40 to 80 years

were eligible provided they were considered to be at elevated risk of coronary

heart disease death because of past history of myocardial infarction or other

coronary heart disease, occlusive disease of non-coronary arteries, diabetes

mellitus or treated hypertension; had baseline blood total cholesterol of 3.5 nmol .

l(-1) or greater and no clear indications for, or contraindications to, either of the

study treatments. Eligible patients who completed a pre-randomization run-in

phase on active treatment were randomly allocated to receive simvastatin (40 mg

daily) or matching placebo tablets and, in a '2 x 2 factorial' design: antioxidant

vitamins (600 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene daily)

or matching placebo capsules. Follow-up visits after randomization are

scheduled at 4, 8 and 12 months, and then 6- monthly, for at least 5 years.

Between July 1994 and May 1997, 15 454 men and 5082 women were

randomized, with 9515 aged over 65 years at entry. Diagnostic criteria

overlapped, with 8510 (41%) having had myocardial infarction (most of whom

were either female, or elderly or with low blood cholesterol), 4869 (24%) some

other history of coronary heart disease, 3288 (16%) cerebrovascular disease,

6748 (33%) peripheral vascular disease? 5963 (29%) diabetes mellitus (of whom

3985 had no history of coronary heart disease) and 8455 (41%) treated

hypertension. Baseline non-fasting total cholesterol levels were less than 5.5

mmol . l(-1) in 7882 (38%) participants. and LDL (low density lipoprotein)

cholesterol less than 3.0 mmol . l(-1) in 6888 (34%). During a mean follow-up of

25 months (range: 13 to 47 months), no significant differences had been

observed between the treatment groups in the numbers of patients with muscle

symptoms, other possible side-effects leading to termination of study treatment,

or elevated liver and muscle enzymes. After 30 months of follow-up, 81% of

randomized patients remained compliant with taking their study simvastatin or

placebo tablets, and allocation to simvastatin produced average reductions in

non-fasting blood total and LDL cholesterol of about 1.5-1.6 mmol . l(-1) and

1.1-1.2 mmol . l(-1) respectively. Eighty-seven per cent of patients remained

compliant with taking their vitamin or placebo capsules, and allocation to the

vitamin supplement produced an average increase in plasma vitamin E levels of

about 24 mu mol . l(-1). Based on this initial follow-up period, the estimated

annual rate of non-fatal myocardial infarction or fatal coronary heart disease is

2.4%, annual stroke rate is 1.3%. and annual all- cause mortality rate is 2.2%.

Conclusion The Heart Protection Study is large, it has included a wide range of

patients at high risk of vascular events, and the treatment regimens being studied

are well-tolerated and produce substantial effects on blood lipid and vitamin

levels. The study should, therefore, provide reliable evidence about the effects of

cholesterol- lowering therapy and of antioxidant vitamin supplements on all-

cause or cause-specific mortality and major morbidity in a range of different

categories of individuals for whom uncertainty remains about the balance of

benefits and risks of these treatments



Keywords:

aged/ALPHA-TOCOPHEROL/ANGINA-PECTORIS/antioxidant/antioxidant

vitamins/arteries/beta carotene/BETA-

CAROTENE/CARDIOVASCULAR-DISEASE/cerebrovascular/cerebrovascular

disease/cholesterol/cholesterol-lowering/coronary heart

disease/design/diabetes/diabetes

mellitus/elderly/England/heart/history/hypertension/infarction/LDL/LDL

cholesterol/LDL-cholesterol/low density

lipoprotein/LOW-DENSITY-LIPOPROTEIN/men/morbidity/mortality/muscle/

myocardial/myocardial infarction/MYOCARDIAL-INFARCTION/observational

studies/ORAL SUPPLEMENTATION/peripheral vascular disease/PRIMARY

PREVENTION/randomized/randomized trial/REQUIRING PROLONGED

OBSERVATION/risk/safety/SERUM-

CHOLESTEROL/simvastatin/stroke/therapy/treatment/vascular/vascular

disease/vitamin C/vitamin E/vitamins/women



Grover, S.A. (2000), Lipid management: what are the predictors of benefit? European

Heart Journal Supplements, 2 (L), L2-L6.



Abstract: Clinicians, patients, and healthcare payers are now faced with the reality of the

enormous burden of treating hyperlipidaemia and hypertension for primary or

secondary prevention. On the basis of results of short-term clinical trials these

risk factors will require lifelong therapy. A need therefore exists for disease

simulation models that can estimate the long-term benefits of therapy for specific

groups of patients. To evaluate fully the benefits of possible treatments, both

cerebrovascular events and coronary events must be considered. Recent clinical

trial results suggest that, for lipid modification, previous models focusing only on

coronary disease may underestimate the impact on stroke. The Cardiovascular

Disease Life Expectancy Model was developed to estimate the benefits of risk

factor modification in the primary and secondary prevention of cardiovascular

disease, including coronary disease and stroke. It is shown that epidemiological

data can be used to forecast the benefits of therapy demonstrated in randomized

clinical trials



Keywords: cardiovascular/cardiovascular disease/Cardiovascular Disease Life

Expectancy Model/cerebrovascular/CHOLESTEROL/clinical trials/coronary

disease/CORONARY-HEART-DISEASE/COST-EFFECTIVENESS/ENGLAN

D/HEART/HYPERCHOLESTEROLEMIA/hyperlipidaemia/hypertension/MOR

TALITY/PRAVASTATIN/predictors/prevention/primary/primary

prevention/PROGRAM/randomized/REDUCTION/RISK/risk factor/risk

factors/SECONDARY PREVENTION/secondary

prevention/simulation/stroke/therapy/trials



Lauterbach, K.W., Binnen, T., Evers, T., Harnischmacher, U., Ludwig, D., Hanrath, P.,

Krone, W., Lehmacher, W., Leys, D., Neuhaus, K.L. and Windler, E. (2000),

Primary prevention of stroke: RESPECT. European Heart Journal Supplements,

2 (D), D51-D53



Keywords:

CHOLESTEROL/ENGLAND/Germany/HEART/METAANALYSIS/PRAVAS

TATIN/prevention/REDUCTASE INHIBITORS/stroke/TRIALS



van Hout, B.A. and Simoons, M.L. (2001), Cost-effectiveness of HMG coenzyme

reductase inhibitors - Whom to treat? European Heart Journal, 22 (9), 751-761.



Abstract: Aims Treatment guidelines have been developed for both 'primary' and

'secondary' prevention of coronary heart disease. These should consider both the

efficacy as well as the costs of such treatment, particularly the costs of treatment

with HMG co-enzyme A reductase inhibitors (statins). In the context of guideline

development in The Netherlands, the cost effectiveness of treatment with statins

was analysed. Methods Following a modelling approach, cost effectiveness was

analysed as a function of a patient's initial risk for new coronary heart disease

events, combining results from 4S, CARE, LIPID, WOSCOPS and AFCAPS

with Dutch cost data. For each sex and age group, an estimate was made of the

level of cardiovascular risks that might correspond to a cost-effectiveness ratio

under NLG 40 000 (Euro 18 151) per life year gained. Results If the 10-year risk

of myocardial infarction, stroke or cardiovascular death was estimated at 9%

(AFCAPS/ TexCAPS), 20% (WOSCOPS), 36%, (CARE) 36% (LIPID) and 47%

(4S), cost effectiveness was estimated at Euro 51 400, Euro 26 013, Euro 9970,

Euro 8028 and Euro 6695. The arbitrary threshold of NLG 40 000

(approximately Euro 18 000) was achieved at a 10 year coronary heart disease

event risk ranging from 19% to 26% for different age groups. Assuming the

effectiveness of statin treatment decreased with age, a 10-year risk,

corresponding to Euro 18 000, varied from 11% (under age 30) to 41% (over age

80). Patients at higher risk levels should be considered for statin therapy.

Conclusions Treatment costs for primary or secondary prevention are determined

predominantly by the costs of statin drugs. The developed model allows

comparison of cost effectiveness of statin therapy across a wide range of subjects

with or without coronary heart disease. The consensus committee in the

Netherlands postulated that drug therapy should be considered in subjects with or

without coronary heart disease in which cost-effectivenesss is similar. Such

groups can be identified using the presented model. When cost effectiveness

ratios up to Euro 18 000 per life year gained are deemed acceptable, statin

treatment should be considered in most patients with known cardiovascular

disease (secondary prevention), and in a limited group of subjects who are at

high risk of developing coronary heart disease (primary prevention). (Eur Heart J

2001; 22: 751- 761, doi:10.1053/euhj.2000.2308) (C) 2001 The European

Society of Cardiology



Keywords: 4S/age/AVERAGE CHOLESTEROL

LEVELS/cardiovascular/cardiovascular disease/CARE/consensus/coronary heart

disease/CORONARY-ARTERY DISEASE/cost/cost

effectiveness/cost-effectiveness/costs/death/development/disease/drug

therapy/drugs/ECONOMIC-EVALUATION/ENGLAND/EVENTS/guideline/gu

idelines/HEART/heart disease/HEART- DISEASE/high risk/HMG coenzyme

reductase inhibitors/infarction/LIPID/MORTALITY/myocardial/myocardial

infarction/Netherlands/PRAVASTATIN/prevention/primary/primary

prevention/PROGRESSION/RISK/secondary/SECONDARY

PREVENTION/sex/statin/statins/stroke/therapy/treatment/treatment

guidelines/WOSCOPS



Marchioli, R. (2001), Treatment with n-3 polyunsaturated fatty acids after myocardial

infarction: results of GISSI-Prevenzione Trial. European Heart Journal

Supplements, 3 (D), D85-D97.



Abstract: GISSI-Prevenzione was conceived as a population, pragmatic trial on patients

with recent myocardial infarction conducted in the framework of the Italian

public health sysem. In GISSI- Prevenzione, patients were invited to follow

Mediterranean dietary habits, and were treated with up-to-date preventive.

pharmacological interventions. Long-term n-3 PUFA 1 g daily, but not vitamin E

300 mg daily, was beneficial for death and for combined death, non-fatal

myocardial infarction, and stroke. All the benefit, however, was attributable to

the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden

death. At variance from the orientation of a scientific scenario largely dominated

by the 'cholesterol- heart hypothesis', GISSI-Prevenzione results indicate n-3

PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant

pharmacological treatment for secondary prevention after myocardial infarction.

As to the relevance and comparability of GISSI-Prevenzione results, up to 5-7

lives could be saved per 1000 patients with previous myocardial infarction

treated with n-3 PUFA (1 g daily) per year. Such a result is comparable to that

observed in the LIPID trial, where 5.2 lives could be saved per 1000

hypercholaesterolemic, CHD patients treated with pravastatin for 1 year. The

choice in favour of a relatively low-dose regimen (1 g capsule daily) more

acceptable for long-term treatment in a population of patients following

Mediterranean dietary habits, the pattern of effects seen in GISSI-Prevenzione

(namely, reduction of overall mortality with no decrease in the rate of non-fatal

myocardial infarction), all suggest that it can confidently be said that n-3 PUFA

treatment should be considered a recommended new component of secondary

prevention. The importance of this combined/additive effect is further suggested

by the preliminary analyses (to be submitted in the final form for publication) of

the interplay between diet and n-3 PUFA: there is an interesting direct

correlation between size of the effect and 'correctness' of background diets. It can

be anticipated that a conceptual barrier must be overcome: a 'dietary drug' should

be added to 'dietary advice', which remains fundamental to allow this statement

to become true in clinical practice. (C) 2001 The European Society of Cardiology



Keywords:

ALPHA-TOCOPHEROL/cardiac/cardiovascular/CARDIOVASCULAR-DISEA

SE/CHD/cholesterol/cholesterol-lowering/clinical practice/clinical

trial/CORONARY

HEART-DISEASE/death/diet/ENGLAND/FISH-OIL/health/HEART/infarction/

LONG-CHAIN/LOW-DENSITY-LIPOPROTEIN/mortality/myocardial/myocar

dial infarction/n-3 PUFA/pharmacological

treatment/PLACEBO-CONTROLLED

TRIAL/population/pravastatin/prevention/public health/RANDOMIZED

CONTROLLED TRIAL/RAT CARDIAC

MYOCYTES/risk/secondary/secondary

prevention/stroke/sudden/treatment/trial/vitamin E/VITAMIN-E

CONSUMPTION



Marchioli, R., Avanzini, F., Barzi, F., Chieffo, C., Di Castelnuovo, A., Franzosi, M.G.,

Geraci, E., Maggioni, A.P., Marfisi, R.M., Mininni, N., Nicolosi, G.L., Santini,

M., Schweiger, C., Tavazzi, L., Tognoni, G. and Valagussa, F. (2001),

Assessment of absolute risk of death after myocardial infarction by use of

multiple-risk-factor assessment equations - GISSI-Prevenzione mortality risk

chart. European Heart Journal, 22 (22), 2085-2103.



Abstract: Aims To present and discuss a comprehensive and ready to use prediction

model of risk of death after myocardial infarction based on the very recently

concluded follow-up of the large GISSI-Prevenzione cohort and on the integrated

evaluation of different categories of risk factors: those that are non- modifiable.

and those related to lifestyles, co-morbidity, background. and other conventional

clinical complications produced by the index myocardial infarction. Methods

The 11 324 men and women recruited in the study within 3 months from their

index myocardial infarction have been followed-up to 4 years. The following risk

factors have been used in a Cox proportional hazards model: non-modifiable risk

factors: age and sex, complications after myocardial infarction: indicators of left

ventricular dysfunction (signs or symptoms of acute left ventricular failure

during hospitalization. ejection fraction, NYHA class and extent or ventricular

asynergy at echocardiography), indicators of electrical instability (number of

premature ventricular beats per hour, sustained or repetitive arrhythmias during

24-h Holler monitoring), indicators of residual ischaemia (spontaneous angina

pectoris after myocardial infarction, Canadian Angina Classification class, and

exercise testing results); cardiovascular risk factors: smoking habits, history of

diabetes mellitus and arterial hypertension, systolic and diastolic blood pressure.

blood total and HDL cholesterol, triglycerides, fibrinogen, leukocytes count,

intermittent claudication. and heart rate. Multiple regression modelling was

assessed by receiver operating characteristic (ROC) analysis. Generalizability of

the models was assessed through cross validation and bootstrapping techniques.

Population and Results During the 4 years of follow-up, a total of 1071 patients

died. Age and left ventricular dysfunction were the most relevant predictors of

death. Because of pharmacological treatments, total blood cholesterol,

triglycerides, and blood pressure values were not significantly associated with

prognosis. Sex-specific prediction equations were formulated to predict risk of

death according to age, simple indicators of left ventricular dysfunction.,

electrical instability, and residual ischaemia along with the following

cardiovascular risk factors: smoking habits, history of diabetes mellitus and

arterial hypertension, blood HDL cholesterol, fibrinogen, leukocyte count,

intermittent claudication, and heart rate. The predictive models produced on the

basis of information available in the routine conditions of clinical care after

myocardial infarction provide ready to use and highly discriminant criteria to

guide secondary prevention strategies. Conclusions and Implications Besides

documenting what should be the preferred and practicable focus of clinical

attention for today's patients, the experience of GISSI-Prevenzione suggests that

periodically and prospectively collected databases on 'naturalistic' cohorts could

be an important option for updating and verifying the impact of guidelines,

which should incorporate the different components of the complex profile of

cardiovascular risk. The GISSI Prevenzione risk function is a simple tool to

predict risk of death and to improve clinical management of subjects with recent

myocardial infarction. The use of predictive risk algorithms can favour the shift

from medical logic, based on the treatment of single risk factors, to one (C) 2001

The European Society of Cardiology



Keywords: absolute risk/acute/age/angina/angina pectoris/arrhythmias/arterial

hypertension/ASPIRIN/blood

pressure/BLOOD-PRESSURE/cardiovascular/cardiovascular risk/cardiovascular

risk factors/CARDIOVASCULAR-DISEASE/cholesterol/CLINICAL-

PRACTICE/comorbidity/complications/congestive heart

failure/CORONARY-HEART-DISEASE/death/diabetes/diabetes

mellitus/diastolic blood

pressure/echocardiography/ENGLAND/evaluation/exercise/fibrinogen/guideline

s/HDL/HDL

cholesterol/HEART/history/hospitalization/hypertension/infarction/ischaemia/isc

haemia./left ventricular/left ventricular

dysfunction/medical/men/monitoring/mortality/myocardial/myocardial

infarction/PLASMA-FIBRINOGEN/prediction/predictors/prevention/prognosis/

PROGNOSTIC-SIGNIFICANCE/residual/risk/risk

factors/secondary/SECONDARY

PREVENTION/sex/smoking/STROKE/symptoms/treatment/triglycerides/UNIT

ED-STATES/use/validation/women



Anand, I.S. and Florea, V.G. (2001), Diuretics in chronic heart failure - benefits and

hazards. European Heart Journal Supplements, 3 (G), G8-G18.



Abstract: Diuretics are indispensable in the management of oedema of chronic heart

failure (CHF). When given to patients with congestion, diuretics relieve

symptoms and improve cardiac performance. However, the use of diuretics in

patients without fluid retention may have deleterious effects because they may

decrease stroke volume and blood pressure, resulting in neurohormonal

activation. Moreover, the effects of diuretics on electrolyte and metabolic

imbalance may trigger ventricular arrhythmias with adverse consequences on

survival. Whereas treatment of hyper-tension with diuretics prevents the

development of CHF, no randomized trial has assessed the effects of diuretics on

mortality in patients with CHF. Reduced mortality using spironolactone in

patients with CHF in the RALES trial may not be related to its diuretic effects.

Baseline use of a non-potassium-sparing diuretic in the SOLVD prevention and

treatment trials was associated with an increased risk of arrhythmic death. As

only limited data are available on improved prognosis with diuretics, long-term

randomized mortality trials should be conducted. The recent TORIC study may

be the first step in this direction. (Eur Heart J Supplements 2001; 3 (Suppl G):

G8-G18) (C) 2001 The European Society of Cardiology



Keywords: activation/ANGIOTENSIN-ALDOSTERONE

SYSTEM/arrhythmia/arrhythmias/ATRIAL NATRIURETIC PEPTIDE/blood

pressure/BODY-WATER/cardiac/CONGESTIVE

CARDIAC-FAILURE/CONVERTING-ENZYME

INHIBITION/death/development/DISTAL CONVOLUTED

TUBULE/diuretics/electrolyte disturbances/ENGLAND/heart/heart

failure/hypertension/LEFT-VENTRICULAR

DYSFUNCTION/management/mortality/PLASMA

HORMONES/prevention/prognosis/randomized/randomized

trial/RENAL-FUNCTION/risk/SKELETAL-MUSCLE/stroke/survival/symptom

s/torasemide/treatment/trial/trials/use



Frykman, V., Beerman, B., Ryden, L. and Rosenqvist, M. (2001), Management of atrial

fibrillation: discrepancy between guideline recommendations and actual practice

exposes patients to risk for complications. European Heart Journal, 22 (20),

1954-1959.



Abstract: Aims To assess compliance to guidelines in the management of patients with

atrial fibrillation. Methods and Results A total of 728 questionnaires were mailed

to physicians with the intention of studying 'theoretical' compliance to practice

guidelines. A retrospective evaluation of 200 records from consecutive patients

hospitalized with atrial fibrillation was performed in order to verify 'actual'

compliance to guidelines. The response rate to the questionnaires was 68%, More

than 94% of the physicians stated that patients with risk factors for

thromboembolic complications and chronic atrial fibrillation should receive

long-term warfarin treatment. Of evaluated records. 108 patients were in chronic

atrial fibrillation with at least one risk factor for stroke. and with no known

contraindication to warfarin. In this group, only 40% received warfarin.

Moreover. several other discrepancies were detected as regards the use of

antiarrhythmic therapy. Conclusion This study reveals a clear discrepancy

between recommendations in guidelines and actual practice in patients with atrial

fibrillation. The most important finding was a significant under use of

thromboembolic prophylaxis in patients at high risk for such events.

Implementation and the study of adherence to management guidelines on atrial

fibrillation need to be carefully reviewed by surveys of actual clinical practice in

order to establish reasonable therapeutic quality. (C) 2001 The European Society

of Cardiology



Keywords: adherence/antiarrhythmic

treatment/anticoagulation/ANTICOAGULATION/atrial fibrillation/chronic atrial

fibrillation/clinical

practice/COMMUNITY/complications/ENGLAND/evaluation/fibrillation/guidel

ine/guidelines/HEART/high risk/LEFT-VENTRICULAR

DYSFUNCTION/management guidelines/PHYSICIAN VARIATION/practice

guidelines/PREVENTION/PROPHYLAXIS/risk/risk factor/risk

factors/stroke/TACHYCARDIA/therapy/THROMBOEMBOLIC

COMPLICATIONS/treatment/TRIAL/use/WARFARIN



Eikelboom, J.W., Weitz, J.I., Budaj, A., Zhao, F., Copland, I., Maciejewski, P., Johnston,

M. and Yusuf, S. (2002), Clopidogrel does not suppress blood markers of

coagulation activation in aspirin-treated patients with non-ST-elevation acute

coronary syndromes. European Heart Journal , 23 (22), 1771-1779.



Abstract: Aims The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE)

Study demonstrated that clopidogrel plus aspirin was superior to aspirin alone for

prevention of recurrent vascular events in patients with acute coronary

syndromes. The aim of this study was to compare the effect of these two

regimens on biochemical markers of platelet and coagulation activation. Methods

and Results We studied 485 patients with non-ST-elevation acute coronary

syndrome who were randomized to clopidogrel (300 mg loading dose followed

by 75 mg daily) or placebo for a period of 3-12 months. All patients also

received aspirin (recommended dose 75325 mg daily). Blood levels of P- selectin,

prothrombin fragment F1.2, D-dimer, and von Willebrand factor were measured

at baseline, day 7 (or hospital discharge), and at day 30 after randomization.

Patients receiving clopidogrel Plus aspirin compared with aspirin alone had

similar baseline geometric mean plasma levels of P-selectin (50-2 vs 51.7

ng.ml(-1), P=0.45), prothrombin fragment F1.2 (1.13 vs 1.12 nmol.l(-1), P=0.94),

D-dimer (467 vs 460 ng. ml(- 1), P=0.85), and von Willebrand factor levels (1.89

vs 1.85 U. ml(-1), P=0.59) and there also were no significant differences at day 7,

or day 30. However, compared with baseline, there was a significant rise in

prothrombin fragment F1.2 at day 7 (from 1.12 to 1-39 nmol.l(-1), P1 mm (RR = 1.90; 95% Cl:

1.18-3.05), and left ventricular (LV) dysfunction (watt motion index 25

emboli detected in any 10 min period or those with emboli that distorted the

arterial waveform were commenced on an incremental infusion of dextran 40.

Results: the majority of patients destined to embolise will do so within the first 2

postoperative hours. Dextran therapy was instituted in nine patients (5%) and

rapidly controlled this phase of embolisation although the dose had to be

increased in three (33%). No patient suffered a postoperative carotid thrombosis

but one suffered a minor stroke on day 5 and was found to have profuse

embolisation on TCD; high dose dextran therapy was again instituted, the

embolus count rate fell rapidly and he made a good recovery thereafter. Overall,

the death and disabling stroke rate was 1.2% and the death/any stroke rate was

2.4%. Conclusion: three hours of postoperative TCD monitoring is as effective as

6 h in the prevention of postoperative carotid thrombosis



Keywords: ARTERY THROMBOSIS/carotid/carotid

endarterectomy/Dextran/DIAGNOSIS/Doppler/emboli/embolus/ENDARTEREC

TOMY/England/monitoring/perioperative

stroke/prevention/risk/stroke/TCD/therapy/thrombosis/transcranial

Doppler/ULTRASOUND



Leppala, J.M., Virtamo, J. and Heinonen, O.P. (1999), Validation of stroke diagnosis in

the National Hospital Discharge Register and the Register of Causes of Death in

Finland. European Journal of Epidemiology, 15 (2), 155-160.



Abstract: The validity of stroke diagnosis in the National Hospital Discharge Register

and the Register of Causes of Death was examined among 546 middle-aged men

in Finland. The subjects were cases of cerebrovascular diseases of the

Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and identified by

record linkage to the registers. In all, 375 events with cerebrovascular disease as

hospital discharge diagnosis and 218 events with cerebrovascular disease as the

underlying cause of death were reviewed using specific criteria modified from

the classifications of the National Survey of Stroke and the WHO MONICA

Study. For hospital stroke diagnoses, there was agreement on diagnosis for all

strokes in 90%, for subarachnoid hemorrhage in 79%, intracerebral hemorrhage

in 82%, and cerebral infarction in 90%. The respective agreement rates for stroke

as the underlying cause of death were 97%, 95%, 91%, and 92%. The data were

insufficient for review in 1% and 3% of the stroke events, respectively. Age,

observation year and trial supplementation with alpha -tocopherol or

beta-carotene had no effect on validity. In conclusion, the validity of stroke

diagnosis was good in registers of hospital diagnoses and causes of death

justifying their use for endpoint assessment in epidemiological studies



Keywords: ACCURACY/beta carotene/cerebral/cerebral

infarction/cerebrovascular/cerebrovascular disease/cerebrovascular

diseases/diagnosis/diseases/Finland/hemorrhage/hospital/hospital discharge

register/infarction/intracerebral

hemorrhage/linkage/men/NETHERLANDS/register of causes of

death/review/stroke/subarachnoid hemorrhage/validation/validity



Wandell, P.E. (1999), Drug use in patients with atrial fibrillation in Swedish primary

health care: a comparison 5 years apart. European Journal of Clinical

Pharmacology, 55 (4), 333-337.



Abstract: Objective: A study of the utilization of drugs, particularly antithrombotic

agents and anti-arrhythmic agents, in patients with atrial fibrillation (AF) with

changes over time in primary health care. Methods: Surveys were done of

patients with AF over 1-year periods, 1992-1993 (n = 135) and 1997-1998 (n =

144), respectively, at a community health centre in Stockholm County.

Information on the prescription of drugs was obtained from the computerized

medical records. Results: The rate of antithrombotic treatment increased from

62.2% to 79.2% (P = 0.001), owing to an in creased use of antiplatelet agents

from 36.3% to 47.9% (P = 0.037), while the use of anticoagulant agents was on

an equal level (25.9% vs 31.3%). The use of any antithrombotic agent in the

primary prevention of thromboembolic events in AF increased from 20.0% to

41.0% (P = 0.000). The mean doses of aspirin, when used, increased from 123 to

142 mg (P = 0.036, one-tailed student's t-test). The use of sotalol also increased,

from 14.2% to 25.2% (P = 0.024). Conclusions: Despite the increased use of

antithrombotic agents, there is still an under-prescription of anticoagulant agents

and of doses of aspirin



Keywords:

AF/anticoagulant/anticoagulants/ANTICOAGULATION/antiplatelet/antiplatelet

agents/antithrombotic/aspirin/atrial

fibrillation/COST-EFFECTIVENESS/drugs/fibrillation/health/health

care/MANAGEMENT/NEW-YORK/prevention/primary/primary health

care/primary prevention/STROKE PREVENTION/THERAPY/thromboembolic

events/treatment/WARFARIN

Akyuz, A., Bolayir, E., Dener, S., Topalkara, K. and Topaktas, S. (1999), The effect of

aspirin, ticlopidine and their low-dose combination on platelet aggregability in

acute ischemic stroke: a short duration follow-up study. European Journal of

Neurology, 6 (1), 57-61.



Abstract: We investigated the effects of aspirin (300 mg/d), ticlopidine (500 mg/d) and

their low-dose combination (aspirin 100 mg/d plus ticlopidine 250 mg/d) on the

platelet aggregability using the Wu and Hoak method. Each treatment group

consisted of 25 patients with acute ischemic stroke. Platelet aggregation ratios

(PAR) were measured on the 1St (before treatment), 10th and 90th days in the

treatment groups and compared with those of 25 control cases. On the first day,

comparison of PAR in each treatment group with the control was significant,

while the differences between treatment groups were not significant. On the 90th

day, differences of PAR between aspirin and control were significant, but

differences between the other treatment groups and the control group were not

significant, indicating a lower anti-aggregant efficacy of aspirin. Our study

suggests that PAR determination can be used to assess the efficacy of

anti-aggregant drugs. Our crude observation also suggests a higher

anti-aggregant efficacy of ticlopidine, and aspirin plus ticlopidine, than aspirin.

In addition, proper doses of aspirin plus ticlopidine may be a good choice for the

prevention of ischemic stroke. Further studies are required to assess whether

PAR determination could be useful for assessing patients at risk of stroke, and

for drug selection for the prevention of stroke. fur J Neurol 6:57-61 (C) 1999

Lippincott Williams & Wilkins



Keywords: ACETYLSALICYLIC-ACID/acute/acute ischemic

stroke/AGGREGATION/aspirin/aspirin plus

ticlopidine/CEREBRAL-ISCHEMIA/control/drugs/ischemic/ischemic

stroke/platelet

aggregation/prevention/risk/stroke/THERAPY/ticlopidine/treatment



Hoffmann, M. and Robbs, J. (1999), Carotid endarterectomy after recent cerebral

infarction. European Journal of Vascular and Endovascular Surgery, 18 (1),

6-10.



Abstract: Objectives: whether timing of carotid endarterectomy (CEA) was significant in

terms of morbidity and mortality for significant carotid stenosis.

Design/materials: comparison was made of patients requiring CEA performed in

less than 6 weeks or more than 6 weeks after their stroke. To enable

quantification in terms of clinical presentation, aetiology and handicap,

standardised scales were incorporated into the registry protocol. A postoperative

event was considered to have occurred if a stroke or death from any cause took

place within one month of surgery. Results: patients with CEA (n = 1005) and

stroke numbered 232. Comparison was made of the early (n = 86) and late

surgery groups (n = 121) in terms of demography risk factors, clinical findings,

quantitative neurological deficit, handicap and degree of carotid stenosis with no

significant differences found except for race. There was no difference in

morbidity ansi mortality (M+M) between the early and late surgery group. The

relative risk (RR) of >6 week group was 1.90 (CI: 0.52-6.94) with an odds ratio

of 1.96 (CI: 0.45-9.63). There is, therefore, a trend of a two-fold risk of MM in

the >6 week group. Conclusion: we propose that the historical 6-week wait

period for CEA post stroke is outdated



Keywords: ATHEROSCLEROSIS/carotid/carotid endarterectomy/carotid

stenosis/cerebral/cerebral

infarction/CLASSIFICATION/endarterectomy/ENGLAND/infarction/ISCHEMI

C STROKE/morbidity/mortality/PREVENTION/race/relative risk/risk/risk

factors/STENOSIS/stroke/SURGERY/timing/TRIAL



Amaro, P., Nunes, A., Macoas, F., Ministro, P., Baranda, J., Cipriano, A., Martins, I.,

Rosa, A., Pimenta, I., Donato, A. and Freitas, D. (1999), Ticlopidine-induced

prolonged cholestasis: a case report. European Journal of Gastroenterology &

Hepatology, 11 (6), 673-676.



Abstract: We report a case of ticlopidine-induced prolonged cholestasis in a 60-year-old

man with no previous hepatobiliary disease who presented with sudden right

upper abdominal pain, jaundice and pruritus three months after starting

ticlopidine therapy. Other drugs taken by the patient were not considered

probable causes, The diagnostic evaluation showed no biliary obstruction and

other possible causes of intra-hepatic cholestasis were excluded, The liver biopsy

showed a cholestatic hepatitis with bile duct damage. The disease ran a severe

and protracted course, but symptoms and jaundice eventually subsided five

months after drug withdrawal, More than a year later, relevant abnormalities of

liver function tests consistent with anicteric cholestasis still persist, fulfilling

criteria for a minor form of drug-induced prolonged cholestasis. This syndrome

has been reported infrequently in relation to several drugs, mainly

chlorpromazine, and only once with ticlopidine. Eur J Gastroenterol Hepatol

11:673-676. (C) 1999 Lippincott Williams & Wilkins



Keywords: BLOOD/cholestasis/DISORDERS/drug-induced prolonged

cholestasis/drugs/evaluation/HEPATITIS/JAUNDICE/pain/PREVENTION/STR

OKE/therapy/ticlopidine



Boysen, G. and Porsdal, V. (1999), The value of stroke prophylaxis. European Journal

of Neurology, 6 S25-S29.



Abstract: Primary prevention of stroke goes along two lines. By mass strategy society

promotes healthier life styles and by high risk strategy individuals with certain

risk factors are indentified and specific prophylactic measures instituted.

Treatment of arterial hypertension reduces stroke risk. Antihypertensive

treatment by diuretics is more cost effective than other antihypertensive drugs,

and more so in the elderly than in the middle aged. In patients with non-vascular

atrial fibrillation (NVAF) and a high risk of ischaemic stroke anticoagulation is

cast saving provided the frequency of intracerebral haemorrhage is low. In low

risk NVAF patients aspirin is to be preferred, both clinically and economically.

In secondary stroke prevention in patients without a cardioembolic source aspirin

as well as the combination of aspirin and dipyridamole are cost saving. Eur J

Neurol 6 (suppl 2):S25-S29 (C) 1999 Lippincott Williams & Wilkins



Keywords: aged/anticoagulation/antihypertensive drugs/arterial

hypertension/ASPIRIN/atrial fibrillation/ATRIAL-FIBRILLATION/carotid

endarterectomy/cerebrovascular

disease/cost/COST-EFFECTIVENESS/dipyridamole/drugs/elderly/ENGLAND/f

ibrillation/hypertension/intracerebral haemorrhage/ischaemic

stroke/prevention/PREVENTION/prophylaxis/risk/risk factors/stroke/stroke

prevention/treatment



Simons, P.C.G., Algra, A., van de Laak, M.F., Grobbee, D.E. and van der Graaf, Y.

(1999), Second Manifestations of ARTerial disease (SMART) study: Rationale

and design. European Journal of Epidemiology, 15 (9), 773-781.



Abstract: The Second Manifestations of ARTerial disease (SMART) study is a

single-centre prospective cohort study among patients, newly referred to the

hospital with (1) clinically manifest atherosclerotic vessel disease, or (2) marked

risk factors for atherosclerosis. The first objectives of the SMART study are to

determine the prevalence of concomitant arterial disease at other sites, and risk

factors in patients presenting with a manifestation of arterial disease or vascular

risk factor and to study the incidence of future cardiovascular events and its

predictors in these high-risk patients. At least 1000 patients, aged 18 to 80 years,

will undergo baseline examinations, including a questionnaire on cardiovascular

disease, height, weight and blood pressure measurements, blood tests for glucose,

lipids, creatinine and homocysteine, urinary tests for microproteinuria, resting

twelve-lead electrocardiogram, ultrasound scanning of the abdominal aorta,

kidneys and the carotid arteries, measurements of common carotid intima-media

thickness and arterial stiffness, and a treadmill test to assess atherosclerosis of

the leg arteries. Abnormal findings are reported to the treating specialist and

general practitioner with a treatment suggestion according to current practice

guidelines. Recruitment and baseline examinations began in September 1996. All

cohort members will be followed for clinical cardiovascular events for a

minimum of three years. In the scope of secondary prevention, the study is

expected to support the design of solid based screening and treatment

programmes and evidence-based cardiovascular medicine to reduce morbidity

and mortality, and improve quality of life, in high-risk patients



Keywords: aged/ASYMPTOMATIC CAROTID DISEASE/atherosclerosis/blood

pressure/cardiovascular/cardiovascular disease/cardiovascular

events/CARDIOVASCULAR-DISEASE/carotid/carotid arteries/cohort

study/design/glucose/guidelines/hospital/incidence/INTEROBSERVER

AGREEMENT/INTIMA-MEDIA

THICKNESS/lipids/morbidity/MORTALITY/MYOCARDIAL-

INFARCTION/Netherlands/predictors/prevention/quality of life/risk/RISK

FACTOR/risk factors/secondary prevention/STROKE

PATIENTS/SURGICAL-TREATMENT/treatment/vascular/VASCULAR-DISE

ASE



Culebras, A. (1999), Stroke: the saving grace of neurology. European Journal of

Neurology, 6 S31-S35.



Abstract: Stroke is the third leading cause of morbidity and mortality. Prevention and

acute stroke intervention have improved the functional, neurologic and quality of

life outcomes of stroke victims while reducing mortality. The gold standard

establishes the neurologist as the leading physician of the infrastructure required

for best care management in stroke. The future calls for a shift of neurologic

workforces towards stroke care. This may require retraining of current

neurologists and a structured expansion of the subspecialty of stroke neurology.

Eur J Neurol 6 (suppl 2):S31-S35 (C) 1999 Lippincott Williams & Wilkins



Keywords: acute/clinical

pathway/DIAGNOSIS/ENGLAND/HEALTH/ICD10-NA/LENGTH/morbidity/

MORTALITY/neurologist/neurology/outcome research/quality of

life/RANDOMIZED CONTROLLED TRIAL/STAY/stroke/stroke team/stroke

unit/thrombolysis/UNIT



Woo, J. (2000), Relationships among diet, physical activity and other lifestyle factors

and debilitating diseases in the elderly. European Journal of Clinical Nutrition,

54 S143-S146.



Abstract: Diet and physical activity are two major lifestyle factors that play a role in the

prevention or management of debilitating conditions affecting older people. Both

under- and overnutrition predispose to diseases. Low sodium and high potassium

intakes, as well as the consumption of fruits and vegetables are associated with a

reduction of hypertension and diseases arising from hypertension such as stroke

and dementia. Dietary patterns (consumption of quantity and types of fats,

cholesterol, vegetable oils, fish) are important in the prevention of coronary heart

disease. Calcium and vitamin D intakes are important factors in the development

of osteoporosis, while various dietary factors have been linked to the

development of cancer. Physical activity is important in the prevention of

functional decline and increased survival, reduced incidence of falls and fractures,

and has various cardiovascular health benefits. Apart from prevention of diseases,

exercise also has an important role in improving function in some chronic

diseases such as heart failure or chronic obstructive pulmonary disease. Both diet

and exercise interact, so that public health recommendations often take the form

of lifestyle modification advice in the prevention of disease and disability



Keywords: aging/BLOOD-PRESSURE/BODY-MASS INDEX/BONE

LOSS/CALCIUM/cancer/cardiovascular/China/Chinese/cholesterol/coronary

heart disease/CORONARY

HEART-DISEASE/dementia/development/diet/dietary

intake/disability/disease/diseases/elderly/ENGLAND/exercise/fats/fractures/GE

NERAL MEDICAL PATIENTS/health/heart/heart disease/heart failure/Hong

Kong/hypertension/incidence/lifestyle/lifestyle

modification/osteoporosis/physical activity/POSTMENOPAUSAL

WOMEN/potassium/prevention/public health/RANDOMIZED CONTROLLED

TRIAL/RISK/sodium/stroke/TAI-CHI/vegetable/vitamin D



Gao, M.Y., Sillesen, H.H., Lorentzen, J.E. and Schroeder, T.V. (2000), Eversion carotid

endarterectomy generates fewer microemboli than standard carotid

endarterectomy. European Journal of Vascular and Endovascular Surgery, 20

(2), 153-157.



Abstract: Objectives: to test whether the occurrence of microembolism differed between

eversion and standard carotid endarterectomy (CEA). Design: prospective,

non-randomised transcranial Doppler(TCD) monitoring study of 61 patients.

Materials and methods: eversion CEA was performed in 27 and standard CEA in

34 patients. Surgery was performed under general anaesthesia. Three (5%)

patients had a shunt inserted based on continuous EEG monitoring. Continuous

middle cerebral artery TCD monitoring (EME, TC-4040) was performed

intraoperatively and for 45 min postoperatively on day 1, day 2-3, day 4-5 and

after 3 months. Unidirectional signals lasting >25 ms, having intensities of >9 dB

were considered to represent embolic events. Results: intraoperative embolic

events were detected in 50 (93%) of 54 patients in whom successful

intraoperative TCD monitoring was achieved. Events occurred most frequently

immediately following clamp release (85%), without difference between the two

techniques. Embolic events were encountered postoperatively in four (15%) and

16 (48%) patients having eversion and standard CEA, respectively (p 90%. These effects were partially, to

nearly completely, attenuated by the addition of MgCl2 to the infusate containing

added ethanol. Of special interest was the observation that attenuation of the

vasoconstrictive effect of ethanol by Mg2+ persisted despite a subsequent

ethanol challenge without added Mg2+. The results obtained demonstrate that,

depending on dose, ethanol can produce prompt and severe vasoconstriction of

the intact cerebral microcirculation and that infusion of moderate doses of Mg2+

can largely attenuate and prevent this response. We conclude that appreciable,

graded changes in cerebral cytochrome oxidase aa(3), blood volume and the state

of hemoglobin occur at minimal tissue levels of ethanol which can be modulated

by Mg2+. (C) 2002 Elsevier Science B.V. All rights reserved



Keywords:

acute/administration/ALCOHOL/alcohol/BLOOD-FLOW/brain/cerebral/cerebra

l blood flow/cerebral microcirculation/cytochrorne

oxidase/DAMAGE/fiber/HEAD TRAUMA/hemoglobin/HEMORRHAGIC

STROKE/hernoglobin/IN-VIVO P-

31-NMR/magnesium/MG2+/microcirculation/NEAR-INFRARED

SPECTROSCOPY/NETHERLANDS/optical spectroscopy/prevention/rat/RAT

HIPPOCAMPUS/rats/stroke/TRAUMATIC BRAIN INJURY/vascular



Ness, A.R., Hughes, J., Elwood, P.C., Whitley, E., Smith, G.D. and Burr, M.L. (2002),

The long-term effect of dietary advice in men with coronary disease: follow-up

of the Diet and Reinfarction trial (DART). European Journal of Clinical

Nutrition, 56 (6), 512-518.



Abstract: Objective: To assess the long-term effect of dietary advice on diet and

mortality after a randomised trial of men with a recent history of myocardial

infarction. Design: Questionnaire survey and mortality follow-up after a trial of

dietary advice. Setting: Twenty-one hospitals in south Wales and south-west

England. Subjects: Former participants in the Diet and Reinfarction Trial. Main

outcome measures: Current fish intake and cereal fibre intake. All-cause

mortality, stroke mortality and coronary mortality. Results: By February 2000,

after 21 147 person years of follow-up, 1083 (53%) of the men had died.

Completed questionnaires were obtained from 879 (85%) of the 1030 men alive

at the beginning of 1999. Relative increases in fish and fibre intake were still

present at 10 y but were much smaller. The early reduction in all-cause mortality

observed in those given fish advice (unadjusted hazard 0.70 (95% Cl 0.54, 0.92))

was followed by an increased risk over the next 3 y (unadjusted hazard 1.31

(95% Cl 1.01, 1.70). Fat and fibre advice had no clear effect on coronary or

all-cause mortality. The risk of stroke death was increased in the fat advice

group- the overall unadjusted hazard was 2.03 (95% Cl 1.14, 3.63). Conclusions:

In this follow-up of a trial of intensive dietary advice following myocardial

infarction we did not observe any substantial long-term survival benefit. Further

trials of fish and fibre advice are feasible and necessary to clarify the role of

these foods in coronary disease



Keywords: all-cause mortality/CARDIOVASCULAR-DISEASE/cereal/coronary

disease/coronary heart disease/DEATH/diet/dietary

advice/disease/England/fat/fibre/fish/HEART-

DISEASE/history/hospitals/infarction/LONDON/MECHANISMS/men/mortality

/myocardial/myocardial infarction/outcome/POLYUNSATURATED

FATTY-ACIDS/PREVENTION/randomised controlled

trial/RECURRENCE/risk/STROKE/stroke/stroke

mortality/survey/survival/trial/trials



Munts, A.G., Mess, W.H., Bruggemans, E.F., Walda, L. and Ackerstaff, R.G.A. (2003),

Feasibility and reliability of on-line automated microemboli detection after

carotid endarterectomy. A transcranial Doppler study. European Journal of

Vascular and Endovascular Surgery, 25 (3), 262-266.



Abstract: Objectives: recently, a new algorithm for transcranial Doppler (TCD)

ultrasound detection of microembolic signals (MES) was developed. In the

present study, we investigated its on-line performance in TCD monitoring after

carotid endarterectomy (CEA) and assessed off-line its accuracy in detecting

MES. Materials and Methods: first, the feasibility of MES detection in TCD

monitoring after CEA in a routine clinical setting was evaluated in 50 patients.

Second, to test the reliability of the software a 2-h digital audio study tape was

made and analysed by the algorithm and five human experts, The "gold standard"

was defined as the agreement between human experts: a MES was considered to

be present if at least three human observers agreed. Results: TCD monitoring for

emboli detection after CEA was well tolerated by the patients and could be

performed reliably. In the study tape, the human gold standard detected 107 MES,

with 93 MES having an intensity of greater than or equal to7 dB. The software

detected 81 and 77 MES, respectively. Using the 7 dB intensity threshold, the

software had no false positives and 16 false negatives. The kappa value between

the human gold standard and the software was 0.91, the proportion of specific

agreement was 0.83. Conclusions: the tested algorithm provides a reliable

method for automated on- line microemboli detection after CEA. This Makes

monitoring of the effectiveness of antiplatelet agents in the prevention of stroke

after CEA more practicable



Keywords: antiplatelet/antiplatelet agents/automated emboli detection/carotid/carotid

endarterectomy/cerebral embolism/CEREBRAL

MICROEMBOLISM/detection/Doppler/emboli/emboli detection/EMBOLIC

SIGNALS/endarterectomy/ENGLAND/human/intensity/interobserver

agreement/LONDON/microemboli/monitoring/Netherlands/prevention/STROKE

/TCD/transcranial/transcranial Doppler/ultrasonography/ultrasound



Bendixen, B.H. and Adams, H.P. (1996), Ticlopidine or clopidogrel as alternatives to

aspirin in prevention of ischemic stroke. European Neurology, 36 (5), 256-257



Keywords: aspirin/ischemic stroke/MULTICENTER/prevention/stroke



Sivenius, J., Diener, H.C., Bendixen, B.H., Adams, H.P., Barnett, H.J.M. and Meldrum,

H.E. (1996), Upcoming alternatives to aspirin for antiaggregant therapy in stroke

prevention. European Neurology, 36 (5), 253-256



Keywords: aspirin/CEREBRAL-ISCHEMIA/CONTROLLED

TRIAL/DIPYRIDAMOLE/DIVERSITY/HETEROGENEITY/prevention/SECO

NDARY PREVENTION/stroke/stroke prevention



Barnett, H.J.M. and Meldrum, H.E. (1996), Critique of two putative therapies in stroke

prevention using platelet inhibitors. European Neurology, 36 (5), 258-259



Keywords: ASPIRIN/DRUGS/prevention/SECONDARY PREVENTION/stroke/stroke

prevention/TICLOPIDINE/TRIAL



Zhen, Q. (1998), A review of therapeutic potentials in ischemic stroke. European

Neurology, 39 21-25.



Abstract: Stroke is one of the leading causes of death in the world. There are as yet no

effective treatments for the ischemic cerebral lesion itself. Nevertheless, five

potential therapeutic objectives can be identified. For cerebral infarction, the best

treatment is prevention, including targeted preventive treatments for specific

subsets of patients or individuals with different risk factors. Incidence rates and

mortality rates of stroke have been successfully reduced in certain developed

countries by adoption of a public health approach to the prevention and control

of risk factors. To rescue the still viable but injured nerve cells, within the

ischemic penumbra, effective therapy should be begun at the earliest possible

time. Measures to halt or reverse programmed cell death, to enhance the intrinsic

autoprotective and repair mechanisms, are under active study. The existence of

down- regulated brain regions, where normal nerve cells have far less activities

to perform due to interruption of information exchange with the infarct area, and

the possibility to reactivate them are worthy of attention



Keywords: apoptosis/autoprotective mechanisms/cerebral/cerebral infarction/cerebral

ischemia/control/down-regulated brain

regions/EXPRESSION/health/infarction/ischemic penumbra/ischemic

stroke/mortality/NERVE GROWTH-FACTOR/penumbra/prevention/prevention

and control/RAT/risk/risk factors/stroke/therapy/TRANSIENT FOREBRAIN

ISCHEMIA/treatment



Marti-Fabregas, J., Valencia, C., Pujol, J., Garcia-Sanchez, C. and Marti-Vilalta, J.L.

(2002), Fibrinogen and the amount of leukoaraiosis in patients with symptomatic

small-vessel disease. European Neurology, 48 (4), 185-190.



Abstract: We investigated whether there is a direct correlation between plasma

fibrinogen levels and the amount of leukoaraiosis (LA) in patients with

symptomatic small-vessel disease. The study included 28 patients: 12 with a

first-ever lacunar infarction (U) and 16 with Binswanger's disease (BD). The

mean age was 71 years (SD 8.6), and 21 were men. For each patient, we recorded

demographic data, vascular risk factors and the results of blood chemistry

analysis including fibrinogen (g/l), hematocrit (decimal fraction) and total serum

proteins (g/l). A cerebral MR scan was performed in each patient and an LA

score was obtained by an investigator blind to clinical data, using a

serniquantified scale in six areas of each cerebral hemisphere (0-4 points in each

area, total scoring range 0-48 points). Results: The mean (SD) for the LA score

was 18.9 (10.7) and for plasma fibrinogen 3.97 (1.1). Pearson's and Spearman's

correlation coefficients between fibrinogen and LA score were 0.43 (p = 0.02)

and 0.49 (p = 0.007), respectively. Multiple- regression analysis between groups

(LI or BD) and fibrinogen versus LA score showed the strongest association for

the BD group (p = 0.014) and a direct relation with fibrinogen (p = 0.018). No

statistically significant association was found between LA score and age, sex,

any vascular risk factor, hematocrit or total serum protein. Conclusion: There is a

significant correlation between plasma fibrinogen levels and the amount of LA in

patients with symptomatic cerebral small- vessel disease. This result suggests

that fibrinogen may be involved in the pathophysiology of LA in these patients.

Copyright (C) 2002 S. Karger AG, Basel



Keywords: age/AUSTRIAN STROKE PREVENTION/Binswanger's

disease/BINSWANGERS-DISEASE/CARDIOVASCULAR

EVENTS/cerebral/DEMENTIA/disease/fibrinogen/hematocrit/HYPERVISCOSI

TY/infarction/lacunar

infarction/leukoaraiosis/men/MR/pathophysiology/PLASMA-FIBRINOGEN/ris

k/risk factor/risk factors/RISK-FACTORS/serum/sex/Spain/SUBCORTICAL

ARTERIOSCLEROTIC ENCEPHALOPATHY/TRANSIENT ISCHEMIC

ATTACKS/vascular/vascular risk/vascular risk factors/WHOLE-BLOOD

VISCOSITY



Ruff, L.K., Volmer, T., Nowak, D. and Meyer, A. (2000), The economic impact of

smoking in Germany. European Respiratory Journal, 16 (3), 385-390.



Abstract: Smoking is a high-risk behaviour affecting health and economic welfare of

society. Thus it is important to quantify the economic burden smoking places on

social institutions in Germany. Approximately 33.4% of the male and 20.4% of

the female population are current smokers. This study investigates the health care

costs of smoking based on 1996 figures, focusing on the seven most frequent

diseases associated with the inhalation of tobacco smoke: chronic obstructive

pulmonary disease (COPD, international classification of diseases (ICD)

490-491); lung cancer (ICD 162); stroke (ICD 434-438); coronary artery disease

(ICD 410-414); cancer of the mouth and larynx (ICD 140-149, 161) and

artherosclerotic occlusive disease (ICD 440). A data search was carried out on

MEDLINE, the German Institute for Medical Documentation and Information,

and the Internet as well as in databases of health insurance companies and the

German Federal institute of statistics. Direct and indirect casts mere calculated

separately. The results estimate the total smoking related health care costs

(attributable fraction due to smoking) for COPD to be 5.471 billion EURO (73%),

for lung cancer 2.593 billion EURO (89%), for cancer of the mouth and larynx

0.996 billion EURO (65%), for stroke 1.774 billion EURO (28%), for coronary

artery disease 4.963 billion EURO (35%) and for artherosclerotic occlusive

disease 0.761 billion EURO (28%). The economic burden of smoking related

health care costs for Germany is 16.6 billion EURO. Smoking is therefore

responsible for 47% of the overall costs of these diseases (35.2 billion EURO). In

the view of the high costs for smoking, of which almost 50% are due to

respiratory disease, pneumologists should enhance their effort in primary,

secondary and tertiary prevention



Keywords:

CANADA/cancer/CIGARETTE-SMOKING/CONSEQUENCES/COPENHAGE

N/coronary artery

disease/COSTS/DEATH/DENMARK/diseases/Germany/HEALTH/health

care/health care costs/high risk/lung

cancer/NEW-YORK-STATE/population/prevention/primary/smoking/stroke/tob

acco



Weisburger, J.H. (1996), Human protection against non-genotoxic carcinogens in the US

without the Delaney clause. Experimental and Toxicologic Pathology, 48 (2-3),

201-208.



Abstract: Cancers of many types are major chronic diseases with a high fatality rate and

a high cost to society. In the USA, the Delaney Clause was implemented in 1958

because the public believed that many cancers stem from food additives and food

contaminants. In the intervening years, research has provided key information

about the mechanisms of carcinogenesis and demonstrated that there are two

major classes of carcinogens, genotoxic and non-genotoxic. Two case reports are

presented, of sodium saccharin and ethylenebisdithio-carbamates that were

banned based on the Delaney Clause in an unjustified manner, based on the

underlying mechanisms not relevant for non- genotoxic carcinogens. Also, the

causes of major cancers have been discovered. Most cancers are associated with

lifestyle, specifically tobacco and excessive alcohol use, inappropriate nutritional

traditions, and lack of exercise. These lifestyle components involve now known

genotoxic carcinogens and importantly, nongenotoxic carcinogens. The effect of

non- genotoxic carcinogens is highly dose dependent and also reversible upon

lowering the dose below a threshold. Thus, it is quite possible to lower human

cancer risk, and also the risk of related chronic diseases such as coronary heart

disease, hypertension and stroke, adult on-set diabetes, by proper lifestyle

adjustments. Clearly, the Delaney Clause plays no role in disease prevention



Keywords: CANCER/cancer etiology/cancer

prevention/carcinogenesis/carcinogens/CELL-CULTURES/CHEMICALS/coron

ary heart disease/Delaney Clause/diseases/exercise/genotoxic

carcinogens/heart/hypertension/INDUCTION/lifestyle/LIVER/MICE/non-genot

oxic carcinogens/nutrition/prevention/RATS/risk/stroke/tobacco



Rissanen, T., Voutilainen, S., Nyyssonen, K. and Salonen, J.T. (2002), Lycopene,

atherosclerosis, and coronary heart disease. Experimental Biology and Medicine,

227 (10), 900-907.



Abstract: Diets rich in fruits and vegetables containing carotenoids have been of interest

because of their potential health benefit against chronic diseases such as

cardiovascular diseases (CVD) and cancer. Interest particularly in lycopene is

growing rapidly following the recent publication of epidemiological studies that

have associated high lycopene levels with reductions in CVD incidence. Two

studies were conducted. In the first one, we examined the role of lycopene as a

risk-lowering factor with regard to acute coronary events and stroke in the

prospective Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study. The

subjects were 725 middle-aged men free of coronary heart disease and stroke at

the study baseline. In a Cox's proportional hazards' model adjusting for

covariates, men in the lowest quartile of serum levels of lycopene had a 3.3-fold

(P 70% symptomatic extracranial carotid stenosis



Keywords: ASPIRIN/RANDOMIZED TRIAL/TICLOPIDINE



Dalen, J.E. (1994), Atrial-Fibrillation - Reducing Stroke Risk with Low-Dose

Anticoagulation. Geriatrics, 49 (5), 24-&.



Abstract: Atrial fibrillation (AF) is the primary disorder predisposing patients to

systemic embolism. Its incidence increases with age, rising from 2 to 4% of

Americans aged 60 to 12% of women and 16% of men over age 75. AF is

commonly associated with hypertension and coronary heart disease-particularly

congestive heart failure. Five trials published since 1989 showed that giving oral

anticoagulants to patients with AF can safely and effectively reduce the risk of

embolic stroke. Long-term warfarin therapy is recommended by the American

College of Chest Physicians for patients with AF who have associated

cardiovascular disease, thyrotoxicosis, or are age 60 or older. The ACCP

recommends an INR range of 2.0 to 3.0, which is as effective as high-intensity

treatment but less likely to cause bleeding



Keywords: AF/aged/anticoagulants/cardiovascular

disease/fibrillation/GERIATRIC/heart/hypertension/incidence/PREVENTION/ri

sk/stroke/THERAPY/treatment/trials/WARFARIN/women



Fiore, L.D. (1996), Anticoagulation: Risks and benefits in atrial fibrillation. Geriatrics,

51 (6), 22-&.



Abstract: Anticoagulation with warfarin has been shown to be effective in preventing

ischemic stroke in patients with atrial fibrillation. However, physicians have

been reluctant to prescribe this therapy for patients age 60 and older because of

the associated risk of bleeding during antithrombotic therapy. Four clinical

features independently increase the risk of stroke in individuals with atrial

fibrillation: previous stroke or transient ischemic attach, diabetes, history of

hypertension, and advancing age. In individual patients, bleeding complications

can be reduced by eliminating loading doses, monitoring therapy frequently

during the initiation phase, targeting lower INRs, recognizing the potential for

drug interactions, and identifying clinical risk factors



Keywords: atrial fibrillation/BLEEDING

COMPLICATIONS/fibrillation/history/hypertension/ischemic stroke/ORAL

ANTICOAGULANTS/OUTPATIENTS/PREDICTION/PREVENTION/PROTH

ROMBIN TIME/risk factors/STROKE/THERAPY/THROMBOEMBOLIC

COMPLICATIONS/WARFARIN



Reddy, M.P. and Reddy, V. (1997), After a stroke: Strategies to restore function and

prevent complications. Geriatrics, 52 (9), 59-&.



Abstract: Mortality and morbidity are high in elderly stroke patients. Early mobilization

and prevention of stroke-related complications improve their ability to participate

in a more intense and comprehensive rehabilitation program. An interdisciplinary

approach to stroke rehabilitation restores functional loss, improves quality of life,

and decreases long- term economic costs. Important parts of stroke rehabilitation

include patient and family education, treatment of stroke- related complications,

and prevention of recurrent stroke. A healthy and caring spouse, continence of

bladder and bowel, and ability to feed oneself are the most positive predictors of

stroke outcome



Keywords:

complications/costs/education/elderly/GERIATRIC/LENGTH/morbidity/predict

ors/prevention/quality of life/REHABILITATION/STAY/stroke/stroke

outcome/treatment



Dwolatzky, T., Sonnenblick, M. and Nesher, G. (1997), Giant cell arteritis and

polymyalgia rheumatica: Clues to early diagnosis. Geriatrics, 52 (6), 38-&.

Abstract: Giant cells arteritis (GCA) and polymyalgia rheumatica (PMR) are closely

related disorders found predominantly in older patients. These disorders, which

are being recognized more frequently, are more common in women, in

Caucasians, and in various geographic locations. Early recognition and treatment

may prevent possible catastrophic consequences of GCA, such as blindness,

stroke, or dissection of the aorta. Although diagnosis is fairly easy with the

classic presentation, it may be missed when the patient presents with nonspecific

constitutional symptoms. An increased awareness among primary care

physicians will aid in the prevention of much of the morbidity and mortality

related to these diseases



Keywords:

awareness/COUNTY/diagnosis/diseases/dissection/GERIATRIC/INVOLVEME

NT/morbidity/mortality/prevention/primary care/stroke/TEMPORAL

ARTERITIS/treatment/women



Chandramouli, B.V. and Kotler, M.N. (1998), Atrial fibrillation: Preventing

thromboembolism and choosing nondrug therapies. Geriatrics, 53 (7), 53-60.



Abstract: A major consequence of atrial fibrillation (AF) is stroke. For stroke prevention

in AF, the American Heart Association recommends aspirin, 325 mg/d, for

low-risk patients. For all others, anticoagulation with warfarin to a target INR of

2 to 3 is recommended if warfarin is not contraindicated. Approximately 0.3% of

patients receiving warfarin suffer intracranial hemorrhage. For restoration of

sinus rhythm in recent AF, direct current cardioversion is the treatment of choice

if a trial of antiarrhythmic drug therapy has failed or is contraindicated. Potential

complications include thromboembolism, ventricular arrhythmia, and pulmonary

edema. Permanent pacemakers can be used to control conduction disturbances

such as sick sinus syndrome and to prevent paroxysmal AF. Radiofrequency AV

nodal ablation provides symptomatic relief for some patients with chronic or

paroxysmal AF. Surgical techniques are also being developed for AF. These

include left atrial isolation and the corridor and maze procedures



Keywords: AF/ANTICOAGULATION/aspirin/atrial

fibrillation/CARDIOVERSION/COMPLICATIONS/direct current/drug

therapy/fibrillation/GERIATRIC/hemorrhage/INR/MANAGEMENT/prevention/

stroke/stroke

prevention/therapy/thromboembolism/THROMBUS/treatment/warfarin



Ramirez-Lassepas, M. (1998), Stroke and the aging of the brain and the arteries.

Geriatrics, 53 S44-S48.



Abstract: Stroke continues to be the third most common cause of death and a major

cause of disability among those aged 70 years and older. The risk of stroke

doubles for every decade after age 55. Tt is 25% higher in men. Age,

cardiovascular disease, and hypertension, are major determinants of cerebral

blood flow; all have a negative impact on cerebral reperfusion. The risk of stroke

can be reduced at any age by treating and correcting concomitant risk factors:

hypertension; heart disease and cardiac arrhythmias (treatment with

anticoagulants); transient ischemic attacks (treatment by platelet inhibitors or

anticoagulants); and carotid stenosis (by endarterectomy). Cessation of smoking,

control of diabetes, reduction of serum lipids, and control of obesity can reduce

the risk of stroke. When stroke occurs, early treatment with rt-PA and aggressive

patient care results in reduced mortality and morbidity and makes for better

neurologic outcomes. Finally, prevention, of stroke reduces risk of vascular

dementia and makes a better functioning advanced age



Keywords: age/aged/anticoagulants/cardiovascular disease/carotid/carotid

stenosis/cerebral blood

flow/dementia/diabetes/DISEASE/ENDARTERECTOMY/GERIATRIC/heart/h

ypertension/lipids/morbidity/mortality/obesity/PREVENTION/reperfusion/RISK

/risk factors/smoking/stroke/TICLOPIDINE/transient/treatment/TRIAL/vascular



Eugene, J.R., Abdallah, M., Miglietta, M., Vernenkar, V.V., Pascual, R., Briones, R.,

Barnes, T. and Hager, J. (1999), Carotid occlusive disease: Primary care of

patients with or without symptoms. Geriatrics, 54 (5), 24-+.



Abstract: Of the half-million strokes that occur each year in the United States, 20 to 30%

can be directly linked to carotid occlusive disease. The degree of stenosis

involving the carotid bifurcation is an important predictor of stroke risk.

Asymptomatic disease may be diagnosed on routine physical exam or screening

of the carotid bifurcation in patients with risk factors for ischemic strokes.

Symptomatic disease includes transient ischemic attacks, stroke in evolution, and

complete stroke. Duplex ultrasound scanning is the standard test for the initial

evaluation of carotid artery disease. Patients undergoing surgery should also have

magnetic resonance angiography or an angiogram of the carotid vessels. Stroke

prevention includes lifestyle modification such as cessation of smoking, strict

dietary and medical management of hyperlipidemia, diabetes, and hypertension.

Antiplatelet, anticoagulant, and thrombolytic therapy can be used where

indicated



Keywords: anticoagulant/ARTERY STENOSIS/BIFURCATION/carotid/carotid

artery/carotid occlusive

disease/diabetes/DUPLEX/ENDARTERECTOMY/evaluation/GERIATRIC/hyp

erlipidemia/hypertension/ischemic/lifestyle/lifestyle modification/magnetic

resonance angiography/MAGNETIC-RESONANCE ANGIOGRAPHY/medical

management/NATURAL-HISTORY/PLAQUE

MORPHOLOGY/prevention/RISK/risk

factors/smoking/STROKE/surgery/therapy/thrombolytic

therapy/transient/transient ischemic attacks/ULTRASONOGRAPHY/United

States



Hemphill, J.C. (2000), Ischemic stroke - Clinical strategies based on mechanisms and

risk factors. Geriatrics, 55 (3), 42-+.

Abstract: Ischemic stroke is a common disorder associated with significant morbidity

and mortality. Results of several pivotal clinical trials completed within the last

decade have helped refine stroke prevention and treatment strategies.

Endarterectomy for symptomatic carotid artery stenosis, anticoagulation in atrial

fibrillation, and IV t-PA treatment of hyperacute ischemic stroke may reduce the

burden of stroke. Ongoing studies are addressing newly recognized risk factors,

such as aortic arch and intracranial atherosclerosis, as well as neuroprotective

agents and locally delivered thrombolytics. Successful patient management

requires a targeted clinical approach based on vascular localization and risk

factor assessment



Keywords: AMERICAN-HEART-ASSOCIATION/anticoagulation/atherosclerosis/atrial

fibrillation/ATRIAL- FIBRILLATION/carotid/carotid artery/carotid artery

stenosis/clinical

trials/COUNCIL/fibrillation/GERIATRIC/GUIDELINES/ischemic/ischemic

stroke/MANAGEMENT/morbidity/mortality/PREVENTION/risk/risk factor/risk

factors/stenosis/stroke/stroke prevention/symptomatic carotid artery

stenosis/t-PA/THROMBOLYTIC

THERAPY/thrombolytics/treatment/trials/vascular



Aronow, W.S. (2001), Cholesterol 2001 - Rationale for lipid-lowering in older patients

with or without CAD. Geriatrics, 56 (9), 22-+.



Abstract: Statin treatment of men and women age greater than or equal to 50 with

coronary artery disease (CAD) and hypercholesterolemia reduces the risk of

all-cause mortality, cardiovascular mortality, coronary events, coronary

revascularization, stroke, and intermittent claudication. The target serum

ow-density lipoprotein (LDL) cholesterol level Is 125 mg/dL despite diet therapy. Statins are

also effective in seducing cardiovascular events in older persons with

hypercholesterolemia but without cardiovascular disease. Consider using statins

in patients age 50 to 80 without cardiovascular disease, serum LDL cholesterol >

130 mg/dL, and serum high-density lipoprotein (HDL) cholesterol 70%

can be managed surgically, whereas those with less stenosis can be treated with

platelet antiaggregant therapy. Acute stroke is a medical emergency.

Thrombolytic therapy with tissue plasminogen activator within 3 hours of event

onset can significantly Improve outcomes in selected ischemic stroke patients.

Patients with Intracerebral hemorrhage usually present with acute onset of

Identifiable neurologic deficits



Keywords: acute/ASPIRIN/atrial/carotid/carotid stenosis/cause of

death/cerebrovascular/death/diabetes/disability/GERIATRIC/hemorrhage/hypert

ension/ischemic/ischemic

stroke/lipids/management/medical/outcomes/plasminogen

activator/platelet/prevention/primary/primary care/RISK/secondary/secondary

stroke prevention/serum/stenosis/stroke/stroke patients/stroke

prevention/therapy/TIA/transient/transient ischemic attacks/TRIAL/United

States/USA



Gupta, G. and Aronow, W.S. (2002), Hormone replacement therapy - An analysis of

efficacy based on evidence. Geriatrics, 57 (8), 18-+.

Abstract: Hormone replacement therapy (HRT) has been a staple of management of the

postmenopausal life phase. Over time, and after estrogen therapy was modified

to induce progestin, an increasing number of observational reports suggested that

HRT conferred benefits well beyond those of managing or minimizing hot

flushes, mood swings and vaginal dryness. In short, HRT was believed to

improve women's health and even extend life. One of the most significant

theorized benefits was protection against cardio- and cerebrovascular events.

Other benefits-protection against osteoporosis, reduction in incontinence

symptoms, and improved cognition-have also been linked with HRT. The

validity of these theories depended largely on observational studies and

anecdotal reports, and only lilghtly (or not at all) on randomized clinical trial

data. Nevertheless, significant clinical data refuting HRT's proposed benefits has

been available for several years. Findings from these investigations, including

new results from two very large trials, show that beyond managing traditional

menopause symptoms, HRT has little or no role in protection against certain

diseases or conditions associated with aging. Indeed, long-term use of HRT may

be contraindicated in most older women with intact uteruses



Keywords: aging/cerebrovascular/clinical

trial/COHORT/DISEASE/diseases/estrogen/ESTROGEN-REPLACEMENT/GE

RIATRIC/health/HEART/HRT/incontinence/management/menopause/observatio

nal studies/OSTEOPOROSIS/POSTMENOPAUSAL

WOMEN/PREVENTION/protection/randomized/randomized clinical

trial/RANDOMIZED CONTROLLED

TRIAL/STROKE/symptoms/therapy/trial/trials/use/USERS/validity/women



Messinger-Rapport, B.J. and Thacker, H.L. (2002), Prevention for the older woman - A

practical guide to managing cardiovascular disease. Geriatrics, 57 (7), 22-+.



Abstract: American women are more likely to die from cardiovascular disease than from

any other cause. Although hypertension is most prevalent, most deaths are

attributed to coronary heart disease. Heart disease in women manifests

approximately 12 to 15 years later than in men, up until menopause. Then the

severity of coronary artery lesions in women accelerates until it equals. or

surpasses that of men by the late 70s or early 80s. Physicians can help Ider,

women reduce their risk for heart disease and stroke by managing hypertension

and hypercholesterolemia and providing beta-blocker treatment when indicated

after MI. Nonpharmacologic interventions may be effective as well. New

guidelines,for aspirin help identify women, under age 80 who would benefit most

from antiplatelet therapy



Keywords: age/ANTIHYPERTENSIVE DRUG- TREATMENT/antiplatelet/antiplatelet

therapy/aspirin/beta-blocker/cardiovascular/cardiovascular

disease/CONTROLLED TRIALS/coronary heart disease/CORONARY

HEART-DISEASE/DENSITY-LIPOPROTEIN

CHOLESTEROL/disease/ELDERLY MEN/GERIATRIC/heart/heart

disease/hypercholesterolemia/hypertension/ISOLATED SYSTOLIC

HYPERTENSION/men/menopause/MORTALITY/MYOCARDIAL-INFARCTI

ON/RANDOMIZED TRIAL/risk/RISK

PATIENTS/severity/stroke/therapy/treatment/women



Aronow, W.S. (2003), C-reactive protein - Should it be considered a coronary risk factor?

Geriatrics, 58 (5), 19-+.



Abstract: C-reactive protein (CRP) is an acute phase reactant which is not associated.

With coronary atheroscierosis in many studies. However, it has been

demonstrated in many, but not all, studies to predict cardiovascular events.

Increased CRP levels may reflect tissue damage and inflammation not only in the

arteries, but anywhere in the body. Elevated CRP levels may be induced by

metabolic, infective, immunologic, or other processes. Increased CRP levels are

probably an indirect marker of any increased cytokine response to inflammatory

stimuli that are critical for atherosclerotic plaque progression and rupture. A

large-scale prospective trial is needed to investigate whether reduction of

elevated CRP will reduce cardiovascular events



Keywords: acute/arteries/AVERAGE CHOLESTEROL LEVELS/C-reactive

protein/cardiovascular/cardiovascular events/cardiovascular

risk/CARDIOVASCULAR-DISEASE/coronary atherosclerosis/coronary

risk/GERIATRIC/HEART- DISEASE/inflammation/inflammatory

response/ISCHEMIC

STROKE/MYOCARDIAL-INFARCTION/plaque/PRIMARY

PREVENTION/progression/risk/risk factor/STABLE

ANGINA-PECTORIS/STATIN THERAPY/SUBCLINICAL

ATHEROSCLEROSIS/trial/UNSTABLE ANGINA/USA



Dillavou, E. and Kahn, M.B. (2003), Peripheral vascular disease - Diagnosing and

treating the 3 most common peripheral vasculopathies. Geriatrics, 58 (2), 37-42.



Abstract: a common sign of generalized atherosclerosis, peripheral vascular disease

(PVD) occurs as a results of arterial narrowing or obstruction that restricts blood

flow to distal tissues. Prevalence of PVD ranges from 3% in patients age >55, to

11% in patients age >65, to 20% in those age 75 and older.

Cerebrovascular/carotid disease, abdominal aortic aneurysm, and peripheral

arterial occlusive disease are the most common peripheral vasculopathies seem

by primary care physicians. All require aggressive medical management to

prevent potentially serious complications and may require referral to vascular

surgeons for evaluation. Prevention remains the best therapy



Keywords: abdominal aortic

aneurysm/age/aneurysm/AORTIC-ANEURYSMS/arterial/atherosclerosis/blood

flow/cerebrovascular/cartoid

disease/complications/disease/evaluation/GERIATRIC/INTERMITTENT

CLAUDICATION/management/medical/medical management/peripheral

occlusive arterial disease/peripheral vascular disease/primary/primary

care/results/RISK-FACTORS/STROKE/therapy/USA/vascular/vascular disease



Mehta, N.N. and Greenspon, A.J. (2003), Atrial fibrillation - Rhythm versus rate control.

Geriatrics, 58 (4), 39-44.



Abstract: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered

in primary care practice. Because the prevalence increases with age and the

overall population is steadily aging, physicians of all specialties will be faced

with managing more AF patients. AF independently increases mortality as well

as the risk of stroke, subsequent coronary events, and congestive heart failure.

Stroke prevention is particularly important in older patients, since they are at

highest risk for these events. In addition, because of an increased risk of

proarrhythmia, older adults should be managed cautiously with antiarrhythmic

drugs. Data are now emerging on the optimal management of older patients with

persistent AF. For each patient, physicians will have to answer the question: is

rhythm control better than rate control?



Keywords: adults/AF/age/aging/antiarrhythmic

drugs/ANTICOAGULATION/arrhythmia/atrial fibrillation/cardiovesrsion

anticoagulation therapy/congestive heart

failure/control/drugs/DYSFUNCTION/fibrillation/GERIATRIC/heart/heart

failure/MANAGEMENT/mortality/NODE/older

adults/population/prevalence/prevention/primary/primary care/risk/RISK

FACTOR/STROKE/stroke/TACHYCARDIA/THERAPY/USA



Reed, P.S., Foley, K.L., Hatch, J. and Mutran, E.J. (2003), Recruitment of older African

Americans for survey research: A process evaluation of the community and

church-based strategy in the Durham Elders Project. Gerontologist, 43 (1),

52-61.



Abstract: Purpose: The disproportionately high burden of morbidity and mortality

among older African Americans is due, in part, to a lack of understanding of the

factors contributing to these outcomes. In order to more fully understand the

factors that contribute to African American morbidity and mortality, researchers

must identify strategies for increasing the inclusion of older African Americans

in research on social and health phenomena. Design and Methods: This article is

a process evaluation describing the successes and challenges associated with

recruitment of older African Americans into research. It considers an effort to

nurture collaboration between university and community institutions to both

facilitate research endeavors and offer meaningful and culturally-appropriate

contributions to the community. Results: The primary challenges discovered in

this observational process evaluation of a church-based recruitment strategy

include the effective coordination of a community research advisory board,

ensuring participant autonomy, and reducing concerns of exploitation among

potential participants. Implications: A strategy of coordinating a community

research advisory board to incorporate the views of community members and to

drive a church-based recruitment procedure provides a starting point for tapping

into an immensely important segment of society historically ignored by the

research community



Keywords: African American/African Americans/ANTIPLATELET STROKE

PREVENTION/CLINICAL

RESEARCH/community/evaluation/HEALTH/minority

elders/morbidity/morbidity and

mortality/mortality/outcomes/PARTICIPATION/PARTNERSHIP/partnerships/P

OPULATIONS/primary/recruitment/research/research

participants/RETENTION/SOCIETY/survey/TRIALS/TUSKEGEE/USA/WOM

EN



Gaddi, A., Cicero, A.F.G., Nascetti, S., Poli, A. and Inzitari, D. (2003), Cerebrovascular

disease in Italy and Europe: It is necessary to prevent a 'pandemia". Gerontology,

49 (2), 69-79.



Abstract: In Italy and Europe, strokes are the third most common cause of death and

resulting invalidity. In the ever-increasing 80- years-old-and-over population,

strokes become more serious due to the clinical presentation during the acute

phase and the ten times higher mortality, but also in relation to the twice as high

resulting disability as for younger subjects. With the growing number of ailing

and not-self-sufficient elderly, other resources will have to be relocated to this

field of public health. Then, the dependence index and the ensuing equivalence

based on estimates for the first decades of 2000 will create more difficulties in

retrieving the funds for social policies. However, stroke prevention is possible

both through correct behavioural habits and pharmacological means. Besides the

well- known preventive effects of an adequate antihypertensive, antidiabetic

and/or antiaggregant/anticoagulant therapy, there is increasing evidence of the

effectiveness of statin therapy in stroke prevention. Subjects with a personal

history of cerebrovascular events have an increased coronary risk and vice versa.

The greatest part of the risk factors for the cerebrovascular disease coincides

with those for cardiovascular disease, for which the correction of the former

automatically involves a reduction in incidence of both pathologies. In this

context, a statin's rational use can therefore represent an important tool for the

combined prevention of the two pathologies. Finally, different hypotheses link

the origin of Alzheimer's disease to that of progressive cerebrovascular dementia

caused by cerebral microcirculation damage. The aim of this review is to resume

the actual knowledge about the epidemiology of cerebrovascular disease in Italy

and Europe, and about the means available to prevent this phenomenon.

Copyright (C) 2003 S. Karger AG, Basel



Keywords: acute/aging/Alzheimer's disease/ALZHEIMERS-

DISEASE/BLOOD-PRESSURE/BRAIN

INFARCTION/cardiovascular/cardiovascular disease/CAROTID-ARTERY

STENOSIS/cause of death/cerebral/CEREBRAL INFARCTION/cerebral

microcirculation/cerebrovascular/cerebrovascular disease/CORONARY

HEART-DISEASE/coronary risk/death/DELAYING HOSPITAL

ADMISSION/dementia/disability/disease/elderly/epidemiology/Europe/health/hi

story/incidence/ISCHEMIC STROKE

SUBTYPES/Italy/knowledge/microcirculation/mortality/NONRHEUMATIC

ATRIAL-FIBRILLATION/population/prevention/public health/review/risk/risk

factors/RISK-FACTORS/statin/statin therapy/statins/stroke/stroke

prevention/therapy/use



Bruning, J., Faust, M. and Krone, W. (2003), Hormone replacement therapy. Effect on

lipid metabolism and coronary heart disease. Gynakologe, 36 (3), 210-215.



Abstract: Hormone replacement therapy (HRT) for postmenopausal women has been

initiated on the basis of observational studies indicating that a reduction in

cardiovascular complications results. This assumption was supported by the fact

that estrogen, either alone or in combination with progestin, exhibits a positive

effect on the lipid profile and endothelial function. Recently, randomised studies

have examined the effect of HRT both in the primary and secondary prevention

of coronary heart disease. These indicate that HRT probably increases the risk of

myocardial infarction. Moreover, there is evidence for an increased risk of stroke

and embolism. These data indicate that HRT is not a currently valid therapeutic

concept for the reduction of cardiovascular morbidity and mortality. It should,

therefore, only be considered for severe postmenopausal symptoms and should

only be used short-term



Keywords: cardiovascular/cardiovascular

morbidity/combination/complications/coronary heart

disease/disease/embolism/endothelial

function/ESTRADIOL/ESTROGEN/Germany/HEALTH/heart/heart

disease/HERS/hormone replacement therapy (HRT)/HRT/infarction/lipid

profile/LIPOPROTEINS/metabolism/morbidity/morbidity and

mortality/mortality/myocardial/myocardial

infarction/NEW-YORK/observational studies/POSTMENOPAUSAL

WOMEN/prevention/primary/primary and secondary

prevention/PROGESTIN/results/RISK/secondary/SECONDARY

PREVENTION/stroke/symptoms/therapy/USA/WHI/women



Fahlman, M.M., Boardley, D., Flynn, M.G., Bouillon, L.E., Lambert, C.P. and Braun,

W.A. (2000), Effects of hormone replacement therapy on selected indices of

immune function in postmenopausal women. Gynecologic and Obstetric

Investigation, 50 (3), 189-193.



Abstract: The purpose of this study was to examine the effects of long- term hormone

replacement therapy (HRT) on selected indices of resting immune function in

postmenopausal women. Postmenopausal women aged 54-66 were divided into

two groups, those taking HRT (n = 17) and controls (n = 19). Blood samples

were obtained and analyzed for mononuclear cell numbers, lymphocyte

proliferation (LP) and natural cell-mediated cytotoxicity (NCMC), There were

no significant differences between groups for mononuclear cell numbers. LP was

significantly higher for HRT, while NCMC was significantly lower for HRT,

HRT is currently being prescribed to postmenopausal women for prevention of a

variety of medical conditions including osteoporosis, cardiovascular disease,

stroke, and Alzheimer's disease yet HRT is often associated with altered immune

parameters. In this study, women taking HRT had increased lymphocyte

blastogenesis and decreased NCMC compared to controls, Copyright (C) 2000 S.

Karger AG, Basel



Keywords: aged/Alzheimer's disease/BREAST-CANCER/cardiovascular/cardiovascular

disease/CELL/CORONARY

HEART-DISEASE/ESTRADIOL/estrogen/ESTROGEN

THERAPY/FOLLOW-UP/hormone replacement therapy/HRT/immune

function/lymphocyte proliferation/MORTALITY/natural cell-mediated

cytotoxicity/ORAL-CONTRACEPTIVES/osteoporosis/postmenopausal

hormone replacement/postmenopausal

women/prevention/RISK/stroke/SYSTEM/therapy/women



Pengo, V., Zasso, A., Barbero, F., Garelli, E. and Biasiolo, A. (1997), Low intensity

warfarin therapy. Haematologica, 82 (6), 710-712.



Abstract: Background and Objective. Several studies comparing different intensities of

oral anticoagulant treatment have clearly shown a relationship between bleeding

complications and prolongation of prothrombin time. In the early '50s, de Takats

suggested that low-dose oral anticoagulants might be as effective as higher doses

in preventing thrombosis, at a lower risk of bleeding. This review article

examines the potential of low dose warfarin therapy. information sources. The

authors have been working in this field, contributing original papers. In addition,

the material examined in this article includes articles published in the journals

covered by the Science Citation Index(R) and Medline(R). State of art and

Perspectives. The hypothesis that low-dose oral anticoagulants can be effective

in preventing thrombosis was first proven by experiments in animal models, and

showed that a prothrombin time ratio as low as 1.14 using rabbit brain

thromboplastin was still able to confer some inhibition of experimental

thrombosis. Low-dose or very low-dose warfarin were subsequently

demonstrated to be effective in patients with morbid obesity and decreased

antithrombin III functional and antigenic levels, in patients with indwelling

catheters, in patients undergoing gynecological surgery, as well as in patients

with stage IV breast cancer. Low-dose warfarin is also effective in the prevention

of embolic strokes in patients with non-rheumatic atrial fibrillation. However,

older patients (>75 years), who have a very high risk of bleeding, might be safer

taking a very low dose of warfarin (i.e., a daily dose of 1- 1.25 mg). Moreover,

after a period of run-in, a fixed, very low-dose warfarin schedule does not need

further laboratory control, which is a factor that could contribute to the full

acceptance of treatment by patients and could stimulate a broader prescription of

warfarin for the primary prevention of stroke in older patients with nonrheumatic

atrial fibrillation. Therefore, we have organized a multicenter clinical trial in

which 1000 patients with non-rheumatic atrial fibrillation will be randomized to

receive either a fixed mini-dose of warfarin or a standard dose. Positive results

might permit the treatment of most older patients with non-rheumatic atrial

fibrillation, creating a benefit for the community as a consequence of its effective

prevention of disabling strokes. (C) 1997, Ferrata Storti Foundation



Keywords: animal/anticoagulant/anticoagulant treatment/anticoagulants/atrial

fibrillation/ATRIAL-FIBRILLATION/complications/control/fibrillation/HEART

-VALVES/LOW-DOSE WARFARIN/obesity/ORAL

ANTICOAGULANT-THERAPY/oral anticoagulants/prevention/primary

prevention/prothrombin

time/RABBITS/RISK/stroke/surgery/therapy/THROMBOPLASTIN/THROMB

OSIS/treatment/TRIAL/warfarin



Carolei, A., Sacco, S. and Marini, C. (2001), Antiaggregant therapy and/or anticoagulant

therapy in the cerebrovascular patient. Haematologica, 86 (11), 36-39



Keywords: ACETYLSALICYLIC-ACID/anticoagulant/anticoagulant

therapy/ASPIRIN/ATRIAL-FIBRILLATION/CEREBRAL-ISCHEMIA/cerebro

vascular/RANDOMIZED TRIAL/SECONDARY/STROKE

PREVENTION/therapy/TICLOPIDINE/WARFARIN



Nicolini, A., Ghirarduzzi, A., Iorio, A., Silingardi, M., Malferrari, G. and Baldi, G.

(2002), Intracranial bleeding: epidemiology and relationships with

antithrombotic treatment in 241 cerebral hemorrhages in Reggio Emilia.

Haematologica, 87 (9), 948-956.



Abstract: Background and Objectives. Anticoagulant (AC) and antiplatelet (AP) drugs

are effectively used in the prevention of thromboembolic events, with the

trade-off of bleeding side effects, particularly intracranial. The aim of this study

was to determine the incidence of intracranial bleeding in the population of

Reggio Emilia and to investigate the potential effect of AC and AP drugs. Design

and Methods. We reviewed all the patients admitted for cerebral hemorrhages to

our hospital between April 1998 and September 2000. Data were collected with a

standardized form. All the patients were followed-up to estimate long-term

mortality. chi(2) and t-tests were used as appropriate. Logistic regression

analysis was performed to test predictors of mortality. Pharmaceutical

department data were employed to estimate the total number of patients receiving

AC and AP drugs. Results. We found 241 cases (107/134 female/male, mean age

61 years, 133/107 spontaneous/traumatic events, 0.32/1000/year overall).

Twenty-nine and 47 of these patients were being given AC or AP drugs,

respectively (4.9/1000/year and 3.7/1000/year). The relative risk of intracranial

bleeding was 11.5 in AP and 15.3 in AC treated patients. Two patients (one

underwent neurosurgery and one thrombolytic treatment) were excluded from

mortality and risk factors analysis. Six patients were lost from follow-up and

excluded from mortality analysis. Overall mortality was 100/233 (42.9%);

mortality in traumatic events was 25/103 (24.2%) versus 75/130 (57.7%) in

spontaneous events. Mortality was 19/29 (65.5%), 26/47 (55.3%) and 55/157

(35%) in AC recipients, AP recipients, and untreated patients, respectively. This

increased risk was mainly confined to traumatic events (p = 0.06), without

difference between AC and AP recipients, At the time of the event, the mean

duration of oral AC treatment was 26.3 months (range 1120). Mean INR was =

3.1 (range 1.6-8.8). Mortality was significantly predicted by the Glasgow Coma

Scale Score (GCS) at admission (p 0.1). The results of these studies

demonstrate that Orgaran is effective in deep vein thrombosis prophylaxis in

patients with acute ischaemic stroke. Orgaran is more effective than standard

low-dose heparin, and is recommended for the prevention of deep vein

thrombosis in patients with acute ischamic stroke



Keywords: DEEP VEIN THROMBOSIS/HEMORRHAGE/HEPARIN/ISCHEMIC

STROKE/LOW-MOLECULAR-WEIGHT

HEPARINOID/ORG-10172/ORGARAN/PROPHYLAXIS/VENOUS

THROMBOSIS



Coccheri, S., Palareti, G. and Fortunato, G. (1994), Antithrombotic Drugs in Peripheral

Obliterative Arterial Diseases. Haemostasis, 24 (2), 118-127.



Abstract: In the natural history of patients with peripheral obliterative arterial disease

(ROAD) the prognosis of the complaint ''intermittent claudication'' is relatively

good and the amputation rate is presently only about 3%. However, ROAD

patients carry a high risk of cardiovascular events and their cumultative mortality

rate within 10 years is as high as 40- 50%. Atherothrombotic events in the

coronary and, less frequently, cerebral arteries are by far the first cause of death

and disability in these patients. The rationale for antithrombotic drugs in the

treatment of POAD lies in the pivotal role of platelet activation and thrombin

formation in the evolution of the atherothrombotic lesions, but also in the effect

of some of these drugs on the regulation of microcirculatory responses. In acute

thrombotic arterial occlusion, Heparin is the ''first application'' drug, especially in

support of interventional revascularisation procedures. Regional thrombolysis

often coupled with angioplasty (PTA), or systemic thrombolysis, are effective in

revascularisation of especially infrainguinal-supra popliteal occlusions. However,

controlled clinical trials are needed. In chronic ROAD, intermittent claudication

can be improved with a rational walking exercise programme, but, besides

pentoxyphilline, especially ticlopidine significantly adds to the benefits of

exercise. Regarding districtual progression of atherothrombosis and especially

cardiovascular events, both aspirin and ticlopidine have been shown effective in

single studies or meta-analyses. In a recent observational study of pooled data the

cumulative endpoint including myocardial infarction, stroke and vascular death

was reduced by 25 +/- 10% in the generality of patients treated with antiplatelet

drugs. Finally, in critical limbs ischemia (CLI), some prostanoid compounds as

Iloprost and Prostaglandin F1 favourably influence rest pain and ulcer healing,

but less evidence is available on their effects on hard events as amputation and

death. In conclusion, following the general indication to ''be conservative'' in the

treatment of these patients, it seems clear that antithrombotic drugs have become

by far a key medication in all different phases of POAD



Keywords: angioplasty/ANTITHROMBOTIC

DRUGS/ASPIRIN/BLOOD/BYPASS-SURGERY/cardiovascular events/clinical

trials/CRITICAL LEG

ISCHEMIA/DOUBLE-BLIND/exercise/formation/history/INTERMITTENT

CLAUDICATION/ischemia/mortality/MULTICENTER/myocardial

infarction/POAD/PREVENTION/PROGRESSION/risk/stroke/thrombolysis/TIC

LOPIDINE/treatment/TRIAL/trials/vascular/VASCULAR-DISEASE



Sasaki, Y., Ishii, I., Giddings, J.C. and Yamamoto, J. (1996), Protective effects of

ticlopidine and aspirin, administered alone and in combination, on thrombus

formation in rat cerebral vessels. Haemostasis, 26 (3), 150-156.

Abstract: The protective effects of ticlopidine and d,l-lysine acetylsalicylate (L-ASA),

used alone and in combination, on the pathogenesis of thrombosis in cerebral

blood vessels were investigated in a rat animal model using a Ile-Ne laser

method, Ticlopidine and L-ASA, given orally at a concentration from 100 mg/kg,

inhibited thrombus formation in a dose-dependent manner. Ticlopidine (300

mg/kg p.o) inhibited thrombosis in arterioles and venules for 3 days after

administration, The inhibitory activity of L-ASA (300 mg/kg p.o.) was less

prolonged than that of ticlopidine and was observed fur only approximately 24 h.

Combined administration of ticlopidine and L-ASA significantly enhanced and

prolonged the antithrombotic effects of either drug given alone, The results

demonstrate that ticlopidine and L-ASA have potent antithrombotic properties in

rat cerebral blood vessels in vivo



Keywords: ADENOSINE/animal/ANTIPLATELET AGENTS/aspirin/cerebral

vessels/d/l-lysine acetylsalicylate/helium-neon

laser/PHARMACOLOGY/PREVENTION/rat/STROKE/THERAPY/THROMB

OMODULIN/thrombosis/thrombus/ticlopidine



Lechler, E., Schramm, W., Flosbach, C.W., Bergemann, W., Brockhaus, W., Egbring, R.,

Garbor, M., Geidel, H., Hengstmann, J.H., Jager, K., Keller, F., Lenz, K.,

Ludwig, M., Maurin, N.J.A., Niessner, H., PicklPfeffer, S., Platt, D., Schauer, J.,

Schentke, K.U., Schulz, J., Slany, J., Teufel, J., Halbritter, R., Thiele, G., Thier,

W.H., Treese, N. and Wagner, T. (1996), The venous thrombotic risk in

non-surgical patients: Epidemiological data and efficacy safety profile of a low-

molecular-weight heparin (enoxaparin). Haemostasis, 26 49-56.



Abstract: In a multicentre, randomized, double-blind controlled trial comparing the

low-molecular-weight heparin enoxaparin (40 mg) with a standard

unfractionated heparin (Ca-heparin, 3 x 5,000 U) in deep-vein thrombosis

prophylaxis in a highrisk group of 959 hospitalized medical patients, enoxaparin

was at least as efficacious as standard heparin, with fewer adverse events



Keywords: adverse events/DEEP-VEIN-THROMBOSIS/DOUBLE-BLIND

TRIAL/epidemiology/heparin/INTERNAL/LOW-DOSE

HEPARIN/low-molecular-weight heparin/MEDICAL INPATIENTS/medical

patients/MYOCARDIAL-INFARCTION/PREVENTION/PROPHYLAXIS/risk/

safety/STROKE/SUBCUTANEOUS

HEPARIN/THROMBOEMBOLISM/thrombosis/thrombosis

prophylaxis/unfractionated heparin/venous thrombosis



Harenberg, J., Roebruck, P. and Heene, D.L. (1996), Subcutaneous low-molecular

weight heparin versus standard heparin and the prevention of thromboembolism

in medical inpatients. Haemostasis, 26 (3), 127-139.



Abstract: In a multicenter, double-blind clinical trial in 1,968 inpatients 1 daily

subcutaneous administration of LMW heparin plus 2 placebo injections or 3 x

5,000 IU unfractionated (UF) heparin was given for 10 (8-11) days. The primary

end point was the incidence of proximal deep-vein thrombosis or pulmonary

embolism. Patients were assessed during the study period for development of

proximal deep-vein thrombosis by compression sonography at days I and 10 and

for pulmonary embolism by scintigraphy in symptomatic patients. Aim of the

study was to demonstrate the equivalence of both treatment regimens. A total cf

1,968 patients were randomized to receive UF or LMW heparin. Of these, 378

patients were excluded during the study period, so that 780 patients on UF and

810 on LMW heparin were included in the efficacy analysis. Four primary end

points were observed with UF and 6 with LMW heparin, demonstrating the

equivalence of treatments (p = 0.012). Additionally, pulmonary embolism was

suspected as the cause of death in 6 patients who died during the study (3 per

treatment group). A higher frequency of death (n = 32) was observed in the

LMW-heparin group (p = 0.02) particularly documented in a part of the centers.

Safety analysis showed a higher frequency of local pruritus, local erythema and

subcutaneous hematoma, a higher increase in plasma levels of triglycerides, total

cholesterol, alanine aminotransferase and aspartate aminotransferase, and a

decrease of antithrombin III in patients receiving UF heparin. A decrease in

platelet count (values ranging between 40,000 and 80,000 mu l) was observed in

4 patients with UF and in none with LMW heparin. No severe thrombocytopenia

was observed. Subcutaneous LMW heparin is as effective as UF heparin for

prophylaxis of thromboembolism in bedridden, hospitalized medical patients



Keywords: ACUTE ISCHEMIC STROKE/cholesterol/DEEP-VEIN

THROMBOSIS/development/DOUBLE-BLIND TRIAL/heparin/low-

molecular-weight

heparin/MYOCARDIAL-INFARCTION/prevention/PROPHYLAXIS/prophylax

is/pulmonary

embolism/RABBITS/RISK/SURGERY/thromboembolism/thrombosis/treatment/

triglycerides/VENOUS THROMBOSIS



Harker, L.A., Hanson, S.R., Wilcox, J.N. and Kelly, A.B. (1996), Antithrombotic and

antilesion benefits without hemorrhagic risks by inhibiting tissue factor pathway.

Haemostasis, 26 76-82.



Abstract: The effects of inhibiting tissue factor-dependent thrombus formation on

vascular neointimal lesion formation have been evaluated by inhibiting tissue

factor activity using intravenous injections of active-site inactivated recombinant

factor VIIa (FVIIai) administered to baboons immediately prior to initiating

bilateral femoral balloon artery angioplasty and surgical carotid endarterectomy.

FVIIai abolished thrombus formation at sites of vascular injury and decreased

vascular lesion formation by approximately 50 percent at 30 days. We conclude

that thrombus formation at sites of vascular injury is predominately tissue

factor-dependent and that transient inhibition of tissue factor activity prevents

both vascular thrombosis and vascular lesion formation, which implies that

transiently inhibiting tissue factor at the time of elective mechanical vascular

procedures may be useful in reducing clinical restenosis

Keywords: angioplasty/carotid/carotid

endarterectomy/COAGULATION/endarterectomy/formation/HIRUDIN/IIIA/IN

TERRUPTION/PREVENTION/STROKE/THROMBOSIS/thrombus/TICLOPID

INE/tissue factor/TRIAL/vascular neointimal lesion/vascular thrombosis



Ridker, P.M. (1997), Intrinsic fibrinolytic capacity and systemic inflammation: Novel

risk factors for arterial thrombotic disease. Haemostasis, 27 2-11.



Abstract: Traditional risk factors, e.g. hyperlipidemia, cigarette consumption, blood

pressure, family history, and diabetes, predict 65 years, and chronic heart failure were considered to be

clinical risk factors for thromboembolism. Setting: Tertiary cardiac care centre.

Patients: 301 consecutive patients with non- rheumatic atrial fibrillation

scheduled for TOE. Results: 255 patients presented with clinical risk factors. 158

patients had reduced left atrial blood flow velocities, dense spontaneous echo

contrast, or both. Logistic regression analysis showed that a reduced left

ventricular ejection fraction and age > 65 years were the only independent

predictors of a thrombogenic milieu (both p 75 years of age, or patients with ''lone'' or paroxysmal atrial fibrillation.

It is well established that patients with chronic atrial fibrillation undergoing

medical or DC-cardioversion are at risk for thromboembolic complications. In

previous studies, this risk appears to be in the range of 2% without concomitant

anticoagulation, but only 0.33% in those patients with concomitant

anticoagulation. Thus, it is widely accepted that patients should be

anticoagulated for at least 2 weeks prior and after planned cardioversion.

Recently, an alternative concept has been proposed omitting anticoagulation

before cardioversion; instead, transesophageal echocardiography is used to

exclude intracardiac thrombi. Because, it is known that mechanical function of

the left atrium and appendage is still impaired after cardioversion, this concept of

echocardiographic-guided cardioversion does not a sign the necessity of

anticoagulation at the day of cardioversion, and 2 weeks afterwards. The safety

aspects of this concept of echocardiographic-guided cardioversion is under

current investigation



Keywords: anticoagulation/ARTERIAL EMBOLISM/atrial

fibrillation/CARDIOVERSION/CEREBRAL INFARCTION/clinical

trials/echocardiography/elderly/EMBOLIC

COMPLICATIONS/fibrillation/FRAMINGHAM/HEART-DISEASE/oral

anticoagulation/prevention/primary

prevention/risk/RISK-FACTORS/safety/secondary

prevention/STROKE/THROMBOEMBOLIC

COMPLICATIONS/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/trials/URBAN/warfarin



Horstkotte, D., Piper, C., Wiemer, M. and Schultheiss, H.P. (1998), Diagnostic approach

and optimal treatment of aortic valve stenosis. Herz, 23 (7), 434-440.



Abstract: The slow progression of valvular aortic stenosis enables the left ventricular

myocardium to adapt itself to the increasing afterload. When myocardial

adaption is exhausted, surgical intervention is urgent, the prognosis, however, is

already limited. To quantify the hemodynamic severity of aortic stenosis,

transaortic pressure gradients (dp) measured by Doppler echocardiography or

hemodynamically are inappropriate, because dp is significantly dependent on the

transaortic flow volume. In severe aortic stenosis, despite constant narrowing of

the aortic valve aerea, the reduced stroke volume results in decreasing transaortic

pressure gradients. With aortic valve resistance or transaortic pressure loss (PL) -

the quotient of pressure gradient and stroke volume - the hemodynamic severity

of aortic stenosis can be described accurately. If PL is known, a decompensated

aortic stenosis (PL > 1 mm Hg/ml) may be differentiated from myocardial failure

of another etiology and a concomitant left ventricular outflow tract obstruction.

With respect to medical therapy, the prevention of bacterial endocarditis and

thromboembolic complications is important. Knowing the potential danger of

syncopies and ventricular arrhythmias during exercise with increasing severity of

aortic stenosis, patients have to be informed about their limited functional

capacity. The occurrence of typical symptoms during the natural history of

chronic aortic stenosis (e, g, dizziness, syncopes, angina pectoris, arrhythmias)

manifestation of ST-T-alterations or silent myocardial ischemias and

demonstration of an inadequat myocardial adaption to the chronic pressure

overload in asymptomatic patients are accepted indications for a surgical

intervention. If the indication for surgery remains uncertain, stress tests (e, g,

radionuclidventriculography) may be performed to demonstrate an exhausted

myocardial adaption. If the PL and the severity of aortic valve/anulus

calcification is known, the progression of a chronic aortic stenosis can be

estimated. This might be important. if a cardiosurgical intervention has to be

performed for other indications and aortic stenosis is co-existent but does not

require an intervention at that time. For prognostic reasons myocardial

decompensation due to aortic stenosis is an indication for an urgent surgical

intervention. Attempts for medical recompensation or bridging strategies (e. g.

ballon valvotomie) worsens the prognosis significantly



Keywords: angina/aortic stenosis/aortic stenosis and intervention strategies/aortic

stenosis and medical therapy/aortic stenosis and myocardial failure/aortic

stenosis and stress tests/complications/diagnostic standards in suspected

stenosis/echocardiography/etiology/exercise/history/prevention/prognosis/progre

ssion of aortic stenosis/severity/stress/stroke/surgery/treatment/URBAN



Jung, W. and Luderitz, B. (1998), Implantable atrial defibrillator. Herz, 23 (4), 251-259.



Abstract: Atrial fibrillation (AF) is a frequent and costly health care problem

representing the most common arrhythmia resulting in hospital admission. Total

mortality and cardiovascular mortality are significantly increased in patients with

AF compared to controls. In addition to symptoms of palpitations, patients with

AF have an increased risk of stroke and may also develop decreased exercise

tolerance and left ventricular dysfunction. All of these problems may be reversed

with restoration and maintenance of sinus rhythm. External electrical

cardioversion has been a remarkably effective and safe method for termination of

this arrhythmia. Originally described by Lown et al. in 1963, it has been a well

accepted mode of acute therapy. However, this technique requires general

anesthesia or heavy sedation. Internal atrial defibrillation has been evaluated as

an alternative approach to the external technique for over 2 decades. Recent

studies have shown that low-energy internal atrial defibrillation using biphasic

shocks is an effective and safe means in restoring sinus rhythm in patients with

AF and should be considered especially in patients in whom external

cardioversion attempts have failed. Implantable Atrial Defibrillator: Recently, a

stand alone IAD, the Metrix(TM) System (model 3000 and 3020),has entered

clinical investigation. Atrial defibrillation is accomplished by a shock delivered

between electrodes in the right atrium and the coronary sinus. The right atrium

lead has an active fixation in the right atrium. The coronary sinus lead has a

natural spiral configuration for retention in the coronary sinus, and can be

straightened with a stylet. Both leads are 7 French in diameter and the

defibrillation coils are each 6 cm in length. The electrodes may be placed using

separate leads, or very soon by using a single bipolar lead. A separate bipolar

right ventricular lead is used for R wave synchronization and post shock pacing.

The Metrix(TM) defibrillator can be used to induce AF by using R wave

synchronous shocks and can store intracardiac electrograms (EGMs) for up to 2

minutes from the most recent 6 AF episodes. The device can be programmed into

one of the following operating modes: fully automatic, patient activated, monitor

mode, bradycardia pacing only, and off. As AF is not life-threatening, in the

automatic mode the device is only intermittently active in detecting and treating

AF, and this "sleep wake-up" cycle interval is programmable. The device

employs extensive processing both for detection and R wave synchronization. In

April 1996, the phase I Metrix(TM) multicenter clinical trial was started. As of

May 1997, a total of 51 Metrix(TM) systems had been implanted as part of the

phase I multicenter clinical trial. Preliminary data suggest that both defibrillation

thresholds and electrograms are stable over time (implant to 3 months).

Detection accuracy has been excellent (100% specificity, 92.3% sensitivity) and

there have been no errors of R wave selection for synchronization. No

proarrhythmias have resulted from over 3700 shocks delivered. The device is

effective in electrically converting 96 % of the spontaneous episodes of AF. In

27% of episodes several shocks were required because of early recurrence of AF.

In 5 patients. the atrial defibrillator was removed: 2 infections, 1 cardiac

tamponade, 1 permanent loss of telemetry, 1 patient required His-Bundle

ablation because of frequent episodes of drug refractory AF with rapid

ventricular response. Initial clinical experience under controlled conditions with

the Metrix(TM) system suggests that the implantable atrial defibrillator may

offer a therapeutic alternative for a subgroup of patients with drug refractory,

symptomatic, long lasting, and infrequent episodes of AF. Further efforts must

be undertaken to reduce the patient discomfort associated with internal atrial

defibrillation in an attempt to make this new therapy acceptable to a larger

patient population with AE Combined Atrioventricular Defibrillator Recently, a

new dual-chamber defibrillator, the 7250 Jewel(R) AF AMD, has entered clinical

evaluation. Concern has been raised whether or not a stand alone implantable

atrial defibrillator is safe enough or should provide ventricular backup

defibrillation in the rare case of shock induced ventricular proarrhythmia. The

availability of a dual-chamber defibrillator has reactivated the discussion about

the safety of a stand alone implantable atrial defibrillator. The most important

new features of the 7250 Jewel(R) AF AMD system include: dual-chamber

pacing, a new dual-chamber detection criterion for rejection of supraventricular

tachycardias, detection and treatment modalities of atrial arrhythmias. prevention

strategies for atrial arrhythmias. Initial clinical experience with the 7250 Jewel(R)

AF AMD device that combines both detection and treatment in the atrium as well

as in the ventricle indicates a significant improvement in the management of

patients with both suproventricular and ventricular tachyarrhythmias

Keywords: AF/atrial arrhythmias/atrial fibrillation/CARDIOVERSION/combined

atrioventricular defibrillator/evaluation/exercise/FIBRILLATION/health/health

care/hospital/implantable atrial defibrillator/internal

cardioversion/mortality/prevention/recurrence/risk/safety/stroke/therapy/treatme

nt/URBAN



Weizel, A. (1999), Treatment with HMG-CoA reductase inhibitors - More than lipid

lowering? Herz, 24 (1), 42-50.



Abstract: An elevated plasma cholesterol concentration is an established risk factor for

coronary heart disease. Dietary and drug interventions with fibrate. nicotinic acid

and colestyramine have resulted in a decreased rate of major coronary events but

failed to decrease mortality. Studies using the: more potent lipid lowering statins

have shown remarkable results in primary (WOSCOPS, AFCAPS, TexCAPS)

and secondary prevention (4S, CARE, LIPID). The use of these drugs reduced

the risk for coronary events as well as the need for interventions. Furthermore,

improvement of angina has been shown in several studies, in high-risk patients

coronary heart disease associated mortality and overall mortality was reduced.

Lowering of cholesterol was shown to be effective in women, older people and

diabetics. Lipid lowering improves prognosis after heart transplant and could be

an alternative to PTCA. Furthermore it was also shown that cholesterol lowering

reduces the incidence of stroke. New mechanisms are discussed to explain the

rapid onset of clinical improvement. Among these are: influences on

inflammatory processes in the plaque, on vascular smooth muscle activity, on

coagulation and on endothelial dysfunction



Keywords: angina/angina

pectoris/ANGINA-PECTORIS/CARE/cholesterol/CHOLESTEROL

LEVELS/cholesterol-lowering/coagulation/coronary heart

disease/CORONARY-ARTERY DISEASE/drugs/heart/HEART- DISEASE/high

risk/HMG-CoA reductase inhibitors/incidence/lipid lowering/MIDDLE-AGED

MEN/mortality/muscle/myocardial

infarction/MYOCARDIAL-INFARCTION/plaque/PRAVASTATIN/prevention/

primary/prognosis/risk/risk factor/SCANDINAVIAN SIMVASTATIN

SURVIVAL/secondary

prevention/SERUM-CHOLESTEROL/smooth/statins/stroke/TOTAL

MORTALITY/URBAN/vascular/women



Szucs, T.D., Berger, K., Marz, W. and Schafer, J. (2000), Cost-effectiveness of

pravastatin in secondary prevention in patients with myocardial infarction or

instable angina in germany. An analysis on the basis of the LIPID trial. Herz, 25

(5), 487-494.



Abstract: Secondary coronary prevention with lipid lowering drugs has become a major

issue in health policy formulation due to the large upfront investment in drug

therapy. The recently completed LIPID trial with pravastatin in secondary

prevention immediately raise the question whether pravastatin might be

cost-effective in Germany. We conducted a cost-effectiveness analysis from the

perspective of third party payers. The following costs were included in the

analysis: daily treatment costs of pravastatin, non-fatal myocardial infarction,

coronary bypass operations and stroke. Life years gained were obtained by

applying the declining exponential approximation of life expectancy. All

calculations were standardized to 1,000 treated patients. The net costs of treating

1,000 patients (i.e, drug costs minus the costs of sequelae and interventions) are

DM 8.4 Mio. In addition, a total of 405 life years may be saved through

treatment. The corresponding cost-effectiveness of pravastatin treatment is DM

20 674-,(DM 17314,-, discounted by 3% p.a.). The results suggest that the

cost-effectiveness of pravastatin in secondary prevention lies well within the

threshold of other commonly accepted medical interventions and ma!: be

considered an economically viable approach for secondary coronary prevention



Keywords: angina/ATHEROSCLEROSIS/AVERAGE CHOLESTEROL

LEVELS/CONVENIENT APPROXIMATION/coronary heart

disease/CORONARY HEART-DISEASE/cost analysis/cost

effectiveness/cost-effectiveness/cost-effectiveness analysis/costs/DEALE/drug

therapy/drugs/EVENTS/Germany/health/infarction/LIFE EXPECTANCY/lipid

lowering/lipids/myocardial/myocardial

infarction/pravastatin/prevention/secondary

prevention/status/stroke/THERAPY/treatment/unstable angina pectoris/URBAN



Schreiber, C., Augustin, N., Holper, K. and Lange, R. (2001), Thrombosis of a

mechanical prosthetic heart valve after inadequate anticoagulation with

low-molecular-weight heparin. Herz, 26 (7), 482-484.



Abstract: Case Report: A 55-year-old woman with a mechanical aortic prosthesis was

admitted with pulmonary edema and suspect of valvular malfunction. The patient

had a anticoagulation therapy at the time with low-molecular-weight heparin

only. Echocardiography confirmed a failing mobility of a prosthetic valve leaflet.

Emergency aortic valve replacement was performed. Conclusion: According to

international approved guidelines an adequate anticoagulation after mechanical

prosthetic heart valve replacement is provided either by oral anticoagulants, or,

in the case of pregnancy or surgical procedures, by unfractioned heparins. The

use of low-molecular- weight heparin as sole anticoagulant remains a matter of

controversy in the literature. In recent years low-molecular- weight heparins

were mainly administered for prevention and treatment of deep vein thrombosis,

pulmonary embolism, stroke, and instable angina



Keywords:

angina/anticoagulant/anticoagulants/anticoagulation/COMPLICATIONS/deep

vein thrombosis/embolism/Germany/guidelines/heart/heparin/heparins/low

molecular weight heparin/low-molecular-weight heparin/mechanical heart

valves/oral anticoagulants/prevention/prosthesis/prosthetic valve

thrombosis/pulmonary

embolism/stroke/therapy/thrombosis/treatment/URBAN/use

Funck, R.C., Pomsel, K., Grimm, W., Hufnagel, G. and Maisch, B. (2001), Prevention

of atrial arrhythmias by pacing. Herz, 26 (1), 18-29.



Abstract: Background: Atrial fibrillation is the most frequent arrhythmia. it can impair

quality of life considerably. Due to thromboembolic complications it contributes

to the patients' morbidity and mortality and to the costs for their medical

treatment. Prevention: In chronic atrial fibrillation there is a need for adequate

anticoagulation and heart rate control. In paroxysmal and intermittent atrial

fibrillation it should be sought to prevent its progression to chronic atrial

fibrillation. Since atrial fibrillation initiates negative processes of remodeling

within the atrial myocardium, it has the tendency to perpetuate itself. From a

theoretical point of view, it can be expected that all means which prevent

episodes of atrial fibrillation or which terminate it immediately after its onset, are

able to prevent or at least to delay the progression to chronic atrial fibrillation.

Pharmacologic treatment is usually used to prevent recurrences of atrial

fibrillation. Based on the actual data it can also be expected that pacemakers with

special preventive pacing algorithms are able to reduce the atrial arrhythmic

burden. Besides consequent overdrive pacing, more sophisticated algorithms like

"suppression of premature atrial contractions", "post exercise response",

"automatic rest rate" or "post mode-switch pacing" have been developed. They

can be applied either alone or in combination with special lead positions

(interatrial septal pacing or pacing of the triangle of Koch) or special stimulation

configurations like dual site right atrial pacing or biatrial pacing. These pacing

strategies cover the most relevant onset mechanisms of atrial fibrillation.

Furthermore, there are algorithms to treat atrial tachyarrhythmias actively by

antitachycardia pacing (ATP). First clinical results have shown that a bout 2/3 of

the diagnosed atrial tachyarrhythmias could be terminated by these means

immediately after their onset. Ongoing Trials: This article gives an overview

over the principles of pacing in the management of atrial arrhythmias and

ongoing clinical trials in this field. Before a definite judgement on the clinical

relevance of these new preventive and therapeutic pacing strategies can be given,

the results of these ongoing controlled clinical studies have to be analyzed



Keywords: anticoagulation/antitachycardia pacing/arrhythmia/arrhythmias/atrial

arrhythmias/atrial fibrillation/atrial flutter/atrial pacing/chronic atrial

fibrillation/clinical

trials/combination/complications/control/costs/exercise/FIBRILLATION/Germa

ny/heart/heart rate/management/mechanisms/medical/medical

treatment/morbidity/MORTALITY/myocardium/pacemaker/pacemakers/pacing/

PREVALENCE/prevention/preventive pacing/PROGNOSIS/quality of

life/REFRACTORINESS/RISK/SICK-SINUS

SYNDROME/stimulation/STROKE/TERM FOLLOW-UP/thromboembolic

complications/treatment/TRIAL/trials/URBAN



Schuchert, A. and Meinertz, T. (2002), Prevention of arterial thromboembolism in

patients with atrial fibrillation. Herz, 27 (4), 322-328.

Abstract: Background: Patients with atrial fibrillation have a 5% risk per year for

ischemic stroke. The aim of antithrombotic therapy is to prevent arterial

thromboembolic events. As anticoagulation increases the frequency of bleeding,

the risk and benefits of this therapy have to be assessed for each patient. Patients

at Risk: The patients can be classified as low risk ( 6% stroke/year). Parameters for

the risk stratification are the patient age and cardiac as well as non-cardiac

diseases. Prevention: Patients with a low risk need no anticoagulation or can take

aspirin. Patients with a high risk should receive oral anticoagulation with an INR

range from 2.0 to 3.0. Newer guidelines recommend also for patients with

intermediate level of stroke risk instead of aspirin the prescription of oral

anticoagulation. Patients with a medium risk can interrupt the oral

anticoagulation before surgery or invasive diagnostic procedures for 1 week,

patients with a high risk should receive heparin. 3-4 weeks before and after

cardioversion the standard therapy is oral anticoagulation



Keywords: age/ANTICOAGULATION/antithrombotic/ANTITHROMBOTIC

THERAPY/arterial/aspirin/ASPIRIN THERAPY/atrial/atrial

fibrillation/bleeding/cardiac/cardioversion/diagnostic/diseases/ELDERLY

PATIENTS/EMBOLISM/fibrillation/FIXED MINIDOSE

WARFARIN/Germany/guidelines/heparin/high risk/INR/ischemic/ISCHEMIC

STROKE/oral anticoagulation/RISK/risk

stratification/stroke/surgery/therapy/thromboembolic

events/thromboembolism/THYROTOXICOSIS/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/URBAN



Hambrecht, R. (2002), Exercise in moderate heart failure - a critical reappraisal. Herz,

27 (2), 179-186.



Abstract: Background: Exercise intolerance in patients with chronic heart failure (CHF)

shows no correlation to the degree of left ventricular dysfunction. This surprising

finding has directed attention to peripheral changes in CHF. During the last years

several different peripheral factors as determinants of exercise intolerance have

been defined, i.e. abnormalities in ventilation, reduced endothelium-dependent

vasodilatation of peripheral conduit and resistance vessels, and altered skeletal

muscle metabolism. Skeletal muscle alterations are characterized by a reduced

oxidative capacity, a catabolic state with reduced local IGF-I expression and

muscle atrophy, chronic inflammation with local expression of the inducible

isoform of nitric oxide synthase (iNOS) and an accelerated rate of programmed

cell death (apoptosis). Effects of Physical Exercise: Physical exercise training

has evolved as an important therapeutic approach to influence these non-cardiac

causes of exercise intolerance. After the first studies documenting the effect of

aerobic training on the peripheral causes of exercise intolerance in CHF the

question was asked: Should we treat the heart or the periphery to improve

exercise intolerance in CHF? Today, we have come closer to the answer: It is

now clear that these two systems are not mutually exclusive. Exercise training in

CHF has been shown to improve skeletal muscle metabolism and function, to

avert muscle catabolism, to reduce neurohumoral overactivation, to reverse

endothelial dysfunction and to contribute to the prevention of pathologic left

ventricular remodeling. After 6 months of regular exercise training oxidative

capacity of the working skeletal muscle increases by approximately 40%.

Regular exercise training leads to a significant improvement of

endothelium-dependent vasodilatory capacity of peripheral resistance vessels,

thereby reducing peripheral resistance in particular during exercise. These

beneficial training effects result in a small, but significant improvement of stroke

volume and reduction in cardiomegaly, Conclusion: Although several questions

regarding patient selection, optimal training protocol and training intensity

remain unanswered, exercise training can been seen as an established adjunct to

pharmacotherapy in CHF. We may soon reach the conclusion that by treating the

periphery with exercise programs we are in fact treating the heart, as well. All

exercise-induced adaptations converge to increase peak oxygen uptake by up to 2

ml/kg.min. For patients in stable CHF on optimal cardiac medication a

combination of in-hospital and home-based aerobic endurance training in

combination with local muscle strength training seems most promising. Although

exercise training offers no causal treatment of CHF, it has great potentials as an

adjunct therapy directed at improving exercise tolerance and expanding the

physical limits of CHF patients



Keywords: apoptosis/cardiac/causes/chronic/chronic heart

failure/combination/CONTROLLED TRIAL/CORONARY-ARTERY

DISEASE/cytokines/death/ENDOTHELIAL DYSFUNCTION/exercise/exercise

training/FACTOR-ALPHA/Germany/heart/heart

failure/inflammation/intensity/left ventricular/left ventricular

dysfunction/LEFT-VENTRICULAR FUNCTION/metabolism/muscle/nitric

oxide/NITRIC-OXIDE/ORAL L-ARGININE/oxygen uptake/physical

capacity/prevention/REGULAR PHYSICAL

EXERCISE/SKELETAL-MUSCLE/stroke/therapy/treatment/TUMOR-NECRO

SIS-FACTOR/URBAN/vascular resistance/vessels



Burkhard-Meier, C., Deutsch, H.J., LaRosee, K., Hopp, H.W. and Erdmann, E. (1998),

Transcatheter closure of patent foramen ovale in 43 year old patient with stroke

by ASD Occlusion System (ASDOS (R)). Herz Kreislauf, 30 (3), 84-89.



Abstract: Patent foramen ovale (PFO) is a common finding in patients with cryptogenic

stroke. We report the transcatheter closure of patent foramen ovale in a 43 year

old patient with stroke by ASD Occlusion System (ASDOS(R)). A PFO may be

detected by both invasive and noninvasive techniques. Transoesophageal contrast

echocardiography has a greater sensitivity compared to transthoracal echo in

detecting a PFO. Predictive risk factors for further neurologic events in patients

with PFO are a large degree of shunt by contrast echocardiography and atrial

septal aneurysm. Possibly patients with PFO and risk factors for stroke

recurrence will take advantage from transcatheter closure

Keywords: ASD Occlusion System (ASDOS (R))/ATRIAL SEPTAL

ANEURYSM/BUTTONED DEVICE/CONTRAST TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/CRYPTOGENIC

STROKE/echocardiography/EVENTS/foramen ovale/PARADOXICAL

EMBOLISM/paradoxical embolism/patent/patent foramen

ovale/PREVENTION/RECURRENCE/RISK/risk

factors/shunt/stroke/transcatheter closure/TRANSCRANIAL DOPPLER

ULTRASOUND



Gramzow, K., Kohler, A. and Podhaisky, H. (1999), Metabolic and haemostatic risk

factors in patients with extracranial atherosclerotic carotid disease. Herz

Kreislauf, 31 (1), 7-10.



Abstract: In 32 patients with TIA or minor stroke due to symptomatic exctracranial

carotid disease the atherogenic risk factors were analysed in comparison to a

healthy control group. The pathogenetic role of arterial hypertension and

smoking could be confirmed. Elevated levels of cholesterol, LDL-cholesterol,

Lp(a), apolipoprotein B in connection with reduced HDL- cholesterol

concentrations were found I;With regard to haemostatic variables the levels of

hematocrit fil,rinogen and PAI-I were increased. Concerning the stroke

prevention the modification of metabolic and haemostatic factors is of essential

importance



Keywords: arterial hypertension/ARTERY/carotid/carotid atherosclerotic

disease/cholesterol/control/HDL/HDL cholesterol/hemostatic

parameters/hypertension/LDL cholesterol/LDL-cholesterol/lipid

parameters/LIPOPROTEIN(A)/MR/PLAQUE/prevention/risk/risk

factors/smoking/STROKE/stroke prevention/TIA/ultrasonography



Barker, D.J.P. (2003), Coronary heart disease: A disorder of growth. Hormone Research,

59 35-41.



Abstract: A new 'developmental' model for the origins of coronary heart disease and the

related disorders of type 2 diabetes, hypertension and stroke is emerging. The

finding that people who develop these disorders have altered growth in utero,

during infancy and childhood provides a new starting point for research. The

immediate prospect for prevention is through protecting infant growth and

preventing accelerated weight gain in children made vulnerable to later disease

by small size at birth and during infancy. Ultimately we need to optimize

maternal diet and composition before and during pregnancy. Despite current

levels of nutrition in Western countries the nutrition of many fetuses and infants

remains suboptimal because the nutrients available are unbalanced or because

their delivery is constrained by the long and vulnerable fetal supply line.

Copyright (C) 2003 S. Karger AG, Basel



Keywords: ADULT LIFE/BIRTH-WEIGHT/BLOOD- PRESSURE/BODY-MASS

INDEX/CATCH-UP GROWTH/CHILDHOOD GROWTH/children/coronary

heart disease/developmental plasticity/diabetes/diet/disease/England/fetal and

childhood growth/heart/heart

disease/HORMONE/hypertension/IN-UTERO/infant/INFANT

GROWTH/INSULIN-RESISTANCE

SYNDROME/nutrients/nutrition/prevention/REDUCED FETAL

GROWTH/research/stroke/type 2 diabetes/weight



Love, B.B. and Biller, J. (1992), Therapeutic Options in Stroke Prevention. Hospital

Formulary, 27 (11), 1106-&.



Abstract: Recently, there have been several important advances in the area of stroke

prevention. Platelet antiaggregants are first- line agents for preventing stroke in

patients without evidence of cardiac embolization. Antiplatelet agents that are

beneficial include aspirin and ticlopidine. No benefit has been demonstrated with

dipyridamole, sulfinpyrazone, and pentoxifylline. Anticoagulants have been

proven to be effective in prevention of stroke in patients with non-valvular atrial

fibrillation. Guidelines for the surgical management of symptomatic carotid

stenosis have come from the results of the North American Symptomatic Carotid

Endarterectomy Trial, the European Carotid Surgery Trial, and the Veterans

Administration Cooperative Study. Patients with angiographically defined

symptomatic ipsilateral carotid stenosis greater-than-or-equal- to 70% have been

shown to benefit from carotid endarterectomy. Patients with 50%. This article reviews

these important advances in stroke prevention



Harbison, J.W. (1993), Ticlopidine and Stroke Prevention. Hospital Practice, 28 (9A),

20-22



McCrory, D.C. and Matchar, D.B. (1996), Stroke prevention: The emerging strategies.

Hospital Practice, 31 (3), 123-&.



Abstract: Warfarin prophylaxis in patients with non-valvular atrial fibrillation may be

one of the most valuable public-health interventions. Barriers to its optimal

utilization include wariness about bleeding complications and concern about age-

related sensitivity to the drug. The risks, however, may be minimized by creation

of anticoagulation clinics to ensure optimal dosing and follow-up



Keywords: anticoagulation/atrial

fibrillation/COMPLICATIONS/fibrillation/POLICY/prevention/prophylaxis/RIS

K-FACTORS/Warfarin



Benfante, R. (1992), Studies of Cardiovascular-Disease and Cause-Specific Mortality

Trends in Japanese-American Men Living in Hawaii and Risk Factor

Comparisons with Other Japanese Populations in the Pacific Region - A Review.

Human Biology, 64 (6), 791-805.

Abstract: The Honolulu Heart Program (HHP) is a long-term prospective epidemiologic

study of cardiovascular disease (CVD) in male descendants of Japanese migrants

to Hawaii. The article is a review of data from recent and past HHP studies

relevant to the Seventeenth Pacific Science Congress symposium "Changes in

Disease Patterns in the Western Pacific and Southeast Asia." The Ni-Hon-San

Study, which compared CVD rates and risk factors in Japanese men living in

Japan, Hawaii (HHP), and California, showed that coronary heart disease (CHD)

and stroke mortality rates in Hawaii were intermediate between rates in Japan

and California. Gradients in CVD risk factors were similar to the gradients in

disease rates. From 1966 to 1984 trends in incidence rates for CHD, stroke, and

cause-specific mortality were compared for the 8006 participants and 3130

nonparticipants in the HHP. CHD and stroke rates declined by about 40% for the

total HHP cohort. There was a larger decline for CHD mortality (over 60%) in

the nonparticipants. There was also a much greater decline in total mortality and

cancer mortality rates in the nonparticipants. The results of the reviewed studies

show that the subjects, although sharing a common ethnic background,

experience different rates of disease when living in diverse geographic and

cultural locales. This finding supports evidence that environmental and

behavioral factors influence chronic disease rates and provides a basis for

intervention and prevention. The finding that nonparticipants in epidemiologic

studies can show different incidence trends suggests that caution should be used

in interpreting trends limited only to participants



Keywords: ACCULTURATION/CALIFORNIA/CARDIOVASCULAR

DISEASE/CORONARY

HEART-DISEASE/DIET/HEALTH/HEART/JAPANESE

ANCESTRY/MORTALITY RATES/PREVALENCE/RISK

FACTORS/STROKE/TRENDS



Stamler, J. (1991), Blood-Pressure and High Blood-Pressure - Aspects of Risk.

Hypertension, 18 (3), 95-107.



Abstract: This report deals with three aspects of risk related to blood pressure and high

blood pressure. The first aspect of risk concerns distributions of systolic blood

pressure (SBP) and diastolic blood pressure (DBP) in the adult population and

their relation to long-term risk of morbidity and mortality. By middle age, only a

minority (about 20%) of Americans have optimal SBP and DBP levels, 20 cigarettes/day vs. never-smokers was found for total stroke (relative risk

(RR)=1.6 (95% confidence interval (CI), 1.1- 2.4)). The excess risk of total

stroke was particularly evident among hypertensives (RR=2.3 (1.2-4.4)). The

multivariate RR of ischemic stroke was 1.6 (1.0-2.5) for total subjects, and 2.2

(1.0-5.0) among hypertensives. Significant excess risks among current smokers

of >20 cigarettes/day vs. never-smokers were also found for coronary heart

disease (RR=4.6 (1.6-12.9)) and total cardiovascular disease (1.9 (1.3-2.7)). The

estimated proportion of the events attributable to current smoking was 30 (95%

Cl, 11-44)% for total stroke and 34 (5-54)% for coronary heart disease. In

conclusion, current smoking of >20 cigarettes per day increased the risk of both

total stroke and ischemic stroke among Japanese middle-aged men, and

particularly among middle-aged hypertensive men



Keywords: age/aged/cardiovascular/cardiovascular disease/cardiovascular

risk/cardiovascular risk factors/CEREBRAL-

HEMORRHAGE/CEREBROVASCULAR-DISEASE/cigarette

smoking/CIGARETTE-SMOKING/coronary heart disease/CORONARY

HEART-DISEASE/disease/FOLLOW-UP/follow-up

studies/HAWAII/heart/heart

disease/hemorrhagic/history/HYPERTENSION/ischemic/ischemic

stroke/Japan/JAPANESE/JAPANESE MEN/LIFE/men/middle-aged

men/MYOCARDIAL-INFARCTION/POPULATION/PREVENTION/prospecti

ve study/relative risk/risk/risk factors/risks/smoking/stroke



Floyd, R.A., Hensley, K., Forster, M.J., Kelleher-Anderson, J.A. and Wood, P.L. (2002),

Nitrones as neuroprotectants and antiaging drugs. Increasing Healthy Life Span:

Conventional Measures and Slowing the Innate Aging Process, 959 321-329.



Abstract: Specific nitrones have been used for more than 30 years in analytical

chemistry and biochemistry to trap and stabilize free radicals for the purpose of

their identification and characterization. PBN (alpha-phenyl-tert-butyl nitrone),

one of the more widely used nitrones for this purpose, has been shown to have

potent pharmacologic activities in models of a number of aging-related diseases,

most notably the neurodegenerative diseases of stroke and Alzheimer's disease.

Studies in cell and animal models strongly suggest that PBN has potent antiaging

activity. A novel nitrone, CPI-1429, has been shown to extend the life span of

mice when administration was started in older animals. It has also shown

efficacy in the prevention of memory dysfunction associated with normal aging

in a mouse model. Mechanistic studies have shown that the neuroprotective

activity of nitrones is not due to mass-action free radical- trapping activity, but

due to cessation of enhanced signal transduction processes associated with

neuroinflammatory processes known to be enhanced in several

neurodegenerative conditions. Enhanced neuroinflammatory processes produce

higher levels of neurotoxins, which cause death or dysfunction of neurons.

Therefore, quelling of these processes is considered to have a beneficial effect

allowing proper neuronal functioning. The possible antiaging activity of nitrones

may reside in their ability to quell enhanced production of reactive oxygen

species associated with age-related conditions. On the basis of novel ideas about

the action of secretory products formed by senescent cells on bystander cells, it is

postulated that nitrones will mitigate these processes and that this may be the

mechanism of their antiaging activity



Keywords: administration/aging/Alzheimer's

disease/animal/BRAIN/BUTYL-ALPHA-PHENYLNITRONE/CEREBRAL

ISCHEMIC-INJURY/death/disease/diseases/DMPO/drugs/free radical/free

radicals/learning/LIFE-SPAN/memory/neurons/NEW-YORK/nitrones/normal

aging/OXIDATIVE DAMAGE/OXIDE SYNTHASE

GENE/PBN/prevention/RADICAL- TRAPPING AGENT/SENESCENCE/signal

transduction/SPIN-TRAP/stroke



Dalal, P.M. (1997), Strokes in the elderly: prevalence, risk factors & the strategies for

prevention. Indian Journal of Medical Research, 106 325-332.



Abstract: Current demographic trends suggest that the Indian population will survive

through the peak years of occurrence of stroke (age 55-65 yr) and

stroke-survivors in the elderly with varying degree of residual disability, will be

a major medical problem, The available data from community surveys from

different regions of India for 'hemiplegia' presumed to be of vascular origin

indicate a crude prevalence rate in the range of 200 per 100,000 persons. Thus,

the anticipated costs of rehabilitation of stroke-victims will pose enormous

socio-economic burden an our meagre health-care resources, similar to what is

now faced by industrialised nations in the West. Therefore, prevention of strokes

at any age should be our main strategy in national health planning. Among all

risk factors for strokes, hypertension is one of the most important and treatable

factor. Community screening surveys, by well defined WHO protocol, have

shown that nearly 15 per cent of the urban population is 'hypertensive' (160/95

mm Hg or more). Though high blood pressure has the highest attributable risk

for stroke, there are many reasons such as patient's compliance in taking

medicines and poor follow up in clinical practice that may lead to failure in

reducing stroke mortality. In subjects who have transient ischaemic attacks

(TIAs), regular use of antiplatelet agents like aspirin in prevention of stroke is

well established. It is also mandatory to prohibit tobacco use and adjust dietary

habits to control body weight, and associated conditions like diabetes mellitus

etc., should be treated. It is advisable to initiate community screening surveys on

well defined populations for early detection of hypertension and TIAs. Primary

health care centres should be the base-stations for these surveys because data

gathered from urban hospitals will not truly reflect the crude prevalence rates for

the community to design practical prevention programmes



Keywords: age/ANTIOXIDANT/antiplatelet agents/aspirin/blood pressure/CEREBRAL

INFARCTION/cerebrovascular

disease/CEREBROVASCULAR-DISEASE/COMMUNITY/control/costs/detecti

on/diabetes/diabetes mellitus/elderly/FIBRINOLYTIC-ACTIVITY/health/health

care/HEMATOCRIT/high blood pressure/hypertension/hypertension

epidemiology/INDIA/INTERSALT/MORTALITY/POPULATION/prevention/r

ehabilitation/risk/risk factors/risk factors in stroke/stroke/stroke

prevention/strokes in elderly/tobacco/transient/vascular/YOUNG



Mayer, S.A. (2002), Intracerebral hemorrhage: natural history and rationale of

ultra-early hemostatic therapy. Intensive Care Medicine, 28 S235-S240.



Abstract: Stroke is a major health problem worldwide, causing high morbidity and

mortality. Intracerebral hemorrhage (ICH) accounts for 15% of stroke cases in

the US and Europe and up to 30% in Asian populations. It is less treatable than

other forms of stroke and causes higher morbidity and disability. Data suggest

that early hematoma growth is the principal cause of early neurological

deterioration after ICH. Prospective and retrospective studies indicate that early

hematoma growth occurs in 18-38% of patients scanned within 3 h of ICH onset,

and that hematoma volume is an important predictor of 30-day mortality. As

hematoma growth in acute ICH is a dynamic process, intervention with

ultra-early hemostatic therapy could lead to minimization and even prevention of

early hematoma growth. Recombinant activated factor VII (rFVIIa, 'NovoSeven'),

a powerful initiator of hemostasis, is approved for the treatment of bleeding in

patients with hemophilia and inhibitors and may also promote hemostasis in

patients with normal coagulation. rFVIIa acts locally at the bleeding site without

activating systemic coagulation and may be a valuable therapy during the

hyperacute stage of ICH. A randomized, double-blind, placebo-controlled,

dose-ranging trial is currently in progress to investigate the potential of rFVIIa as

an ultra-early hemostatic therapy to prevent or minimize hematoma growth in

ICH patients without coagulopathy



Keywords: acute/bleeding/BLOOD-FLOW/CARE/causes/CEREBRAL-

HEMORRHAGE/CHRISTMAS DISEASE/coagulation/CONTROLLED

TRIAL/disability/DOUBLE-BLIND/early hematoma

growth/Europe/health/hematoma/HEMATOMA

ENLARGEMENT/hemorrhage/hemostasis/history/intracerebral

hemorrhage/morbidity/morbidity and mortality/mortality/natural

history/NEW-YORK/NovoSeven/prevention/randomized/RECOMBINANT

FACTOR VIIA/rFVIIa/STROKE/therapy/TIME-COURSE/TRANEXAMIC

ACID/treatment/trial/US/USA



Okada, M., Miida, T., Hama, H., Yata, S., Sunaga, T., Tsuda, A. and Saito, H. (2000),

Possible risk factors of carotid artery atherosclerosis in the Japanese population:

A primary prevention study in non-diabetic subjects. Internal Medicine, 39 (5),

362-368.



Abstract: Objective Hyperinsulinemia has been associated with the risk of coronary

heart disease, stroke, and renal disease in nondiabetic subjects. However, direct

evidence that hyperinsulinemia per se is directly associated with atherosclerosis

has been conflicting. The present study was designed to investigate the

cross-sectional association of carotid artery atherosclerosis with insulin,

independent of well-known cardiovascular risk factors, in nondiabetic subjects.

Methods and Subjects Between 1996 and 1997, 1,335 subjects (620 men and 715

women) were recruited from one Japanese community, interviewed, and

examined. Clinical measurements in the study included intimal-medial thickness

(IMT) of the carotid artery, fasting plasma insulin, serum total cholesterol (TC),

triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density

lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), hemoglobin type

HbA(1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), and

body mass index (BMI). We divided the subjects of both genders into three

subgroups according to age (40-49 years of age; 50-59; and 60-69). Results

Using simple regression analysis, we found that IMT was significantly correlated

with at least one of TC, LDL-C, HbA(1c), SBP, DBP, and BMI in each subgroup.

The results of multivariate analysis showed that IMT was independently

correlated with TC, HDL-C, LDL-C, SEP and BMI in males and with TC, TG,

HDL-C, LDL-C, HbA(1c), SEP, DBP, and BMI in females. Insulin levels

showed no correlation with IMT in either males or females. Conclusion Fasting

hyperinsulinemia does not appear to be correlated with carotid artery

atherosclerosis based on the present cross- sectional results



Keywords: age/atherosclerosis/blood pressure/body mass index/body mass index

(BMI)/cardiovascular/cardiovascular risk/cardiovascular risk

factors/CARDIOVASCULAR-DISEASE/carotid/carotid

artery/cholesterol/community/coronary heart disease/CORONARY

HEART-DISEASE/cross-sectional study/diastolic blood

pressure/disease/GLUCOSE/heart/heart disease/HELSINKI

POLICEMEN/hemoglobin/high density lipoprotein/high-density lipoprotein

cholesterol

(HDL-C)/hyperinsulinemia/HYPERINSULINEMIA/INSULIN-RESISTANCE

SYNDROME/INTERNAL/intimal-medial thickness (IMT)/JAPAN/low density

lipoprotein/low-density lipoprotein cholesterol

(LDL-C)/MEDICINE/MELLITUS/men/MIDDLE- AGED MEN/multivariate

analysis/population/prevention/primary/primary prevention/renal/renal

disease/risk/risk factors/SENSITIVITY/serum/stroke/systolic blood

pressure/WALL THICKNESS/women



Yasaka, M., Minematsu, K. and Yamaguchi, T. (2001), Optimal intensity of

international normalized ratio in warfarin therapy for secondary prevention of

stroke in patients with non-valvular atrial fibrillation. Internal Medicine, 40 (12),

1183-1188.



Abstract: Objective To determine optimal intensity of international normalized ratio

(INR) of warfarin therapy for the prevention of ischemic events in patients with

non-valvular atrial fibrillation (NVAF), we evaluated the risk of severe recurrent

stroke, systemic embolism and major hemorrhagic complications according to

INR and age. Methods We carried out the National Cardiovascular Center

(NCVC) NVAF Secondary Prevention Study and analyzed data with those of

Japanese Nonvaluvular Atrial Fibrillation-embolism Secondary Prevention

Cooperative Study to elucidate relationships of major stroke and hemorrhage

with INR and age. In both studies, all patients with cardioembolic stroke were

given warfarin, monitored with INR every month, and followed up for primary

endpoints of stroke and embolism to other parts of the body, and for secondary

endpoints of major hemorrhagic complications requiring blood transfusion or

hospitalization. We regarded ischemic stroke with NIH stroke scale (NIHSS)

score greater than or equal to10 or systemic embolism as a major ischemic event

and ischemic stroke with NIHSS score 41 different criteria reported. These specific

laboratory variations can affect those patients considered appropriate for CEA.

Conclusions. This study highlights the most significant areas for future

standardisation to be Doppler angle and interpretation criteria, if CDUS is to be a

primary tool in recommending patients for CEA, when indicated by clinical trial

results



Keywords: carotid/carotid artery disease/carotid stenosis/carotid stenosis

ultrasonography/Doppler/duplex/endarterectomy/England/evaluation/interpretati

on/prevention/primary/protocols/stroke/stroke

prevention/surgery/ultrasonography/ultrasound/vascular



Migdalis, I.N., Varvarigos, N., Charalabides, J., Leontiades, E., Gerolimou, B.,

Mantzara, F. and Karmaniolas, K. (2001), Effect of buflomedil on early carotid

atherosclerosis in type 2 diabetic patients. International Angiology, 20 (2),

126-130.



Abstract: Background. An increased thickness of the carotid artery wall is thought to be

a sign of early atherosclerosis. We have investigated the effect of early treatment

with buflomedil on the prevention of the arterial wall thickening. Methods.

Eighty patients with Type 2 diabetes were studied. Oral buflomedil (600 mg once

daily) was administered for 12 months in 42 patients randomly selected, while 38

received no treatment. The two groups were matched for age, sex, body mass

index (BMI), duration of diabetes and glycaemic control. Arterial wall thickness

was measured as the mean of the maximum intima media thickness (IMT) in 8

carotid segments measured by B-mode ultrasound. Results. Blood pressure and

lipid levels remained unchanged in the two studied groups while no difference

was found in metabolic control between them. The IMT increase over 12 months

was 0.04 mm in the buflomedil group whereas in that without buflomedil it was

0. 10 mm. Conclusions. We conclude that buflomedil treatment may be useful in

decreasing the progression rate of arterial wall thickness



Keywords: administration and dosage/age/arterial wall/ARTERIAL-

WALL/ASYMPTOMATIC HYPERGLYCEMIA/atherosclerosis/body mass

index/carotid/carotid artery/carotid artery

diseases/CHOLESTEROL/control/diabetes/diabetes

mellitus/HYPERLIPIDEMIA/MYOCARDIAL-INFARCTION/non insulin

dependent/pathology/PLUS MEDIAL

THICKNESS/POPULATION/prevention/RISK-FACTORS/sex/STROKE/treatm

ent/ultrasound/vasodilator agents/WALL THICKNESS



Pflieger, K.L., Treiber, F.A., Davis, H., Mccaffrey, F.M., Raunikar, R.A. and Strong,

W.B. (1994), The Effect of Adiposity on Childrens Left-Ventricular Mass and

Geometry and Hemodynamic-Responses to Stress. International Journal of

Obesity, 18 (2), 117-122.



Abstract: This study evaluated the relationship between adiposity, left ventricular mass

and geometry, and haemodynamic parameters at rest and during laboratory

stressors in a sample of 69 normotensive children with positive family histories

of essential hypertension. Children were classified as overweight if they were

above the 85th percentile of weight-for-height for their age and gender compared

to national normative data. Nineteen children (7 whites, 12 blacks) were

classified as overweight and the remaining 50 (26 whites, 24 blacks) were not

overweight. Overweight children were found to have higher resting systolic and

diastolic blood pressures, heart rates (HR), cardiac output (CO) and stroke

volumes (SV), and lower resting total peripheral resistance than the

non-overweight children. No differences were noted in haemodynamic reactivity

to the stressors. Echocardiographic findings indicated that the overweight

children had greater left ventricular mass indexed by height(2.7), interventricular

septal thickness and left ventricular end diastolic diameter (LVEDD) compared

to non- overweight children. These findings are the first to indicate that the

higher resting pressures of overweight normotensive children are a reflection of

increased preload (i.e. greater HR, SV, CO, LVEDD). These findings point out

the early deleterious effects of obesity on the cardiovascular system in the young

and highlight the need for effective obesity prevention and intervention

programmes



Keywords: ADIPOSITY/ADOLESCENTS/ADULTS/BLOOD-PRESSURE

RESPONSE/CARDIAC-OUTPUT/CARDIOVASCULAR

REACTIVITY/CARDIOVASCULAR

RESPONSE/CHILDHOOD/ENGLAND/ESSENTIAL-

HYPERTENSION/HEALTHY-CHILDREN/heart/hypertension/HYPERTROPH

Y/LEFT VENTRICULAR MASS/M-MODE

ECHOCARDIOGRAPHY/OBESITY/prevention/RISK-FACTORS/STRESS/str

oke/SYSTOLIC FUNCTION



Khaspekov, L.G., Lyzhin, A.A., Victorov, I.V., Dupin, A.M. and Erin, A.N. (1995),

Hypoxic and Posthypoxic Neuronal Injury in Hippocampal Cell- Culture -

Attenuation by Lipophylic Antioxidant U-18 and Superoxide-Dismutase.

International Journal of Neuroscience, 82 (1-2), 33-45.



Abstract: The neuroprotective effects of synthesized lipophylic antioxidant from

hindered phenol class (U-18) and hydrophylic antioxidative enzyme superoxide

dismutase (SOD) were tested on long-term mouse hippocampal cell cultures

exposed to hypoxia/reoxygenation. The application of U-18 to the cultures

during 6-8 hr hypoxia followed by 16-18 hr reoxygenation in the absence of

antioxidant significantly reduced neuronal death. Thus, lipophylic free radical

scavenger may exert a delayed neuroprotective effect, probably owing to

persistent incorporation into phospholipid membranes and prevention of their

lipid peroxidation by means of prolonged intramembranous free radical

quenching. On the other hand, the exposure of the cultures to U-18 during 15 hr

hypoxia without subsequent reoxygenation also led to significant reduction of

neuronal death compared with that observed without antioxidant. These findings

suggest that free radical neuronal damage may occur under conditions of

prolonged restricted oxygen access to the neurons. The hypoxic/posthypoxic

neuronal injury significantly decreased in the cultures exposed to hydrophylic

cytoplasmic enzyme SOD (300 U/ml). The neuroprotective effects of both

lipophylic U-18 and hydrophylic SOD on the cultures exposed to

hypoxia/reoxygenation might reflect the damaging free radical overproduction in

different morphofunctional compartments of the nerve cell



Keywords:

ACID/ANTIOXIDANTS/DEATH/ENGLAND/GLUCOSE/HIPPOCAMPAL

CELL CULTURE/HYPOXIA

REOXYGENATION/LIPID-PEROXIDATION/MECHANISMS/NERVOUS-S

YSTEM

TRAUMA/neurons/NEUROTOXICITY/OXYGEN/prevention/RADICAL

FORMATION/STROKE

Gulliford, M.C. (1995), Controlling Non-Insulin-Dependent Diabetes-Mellitus in

Developing-Countries. International Journal of Epidemiology, 24 S53-S59.



Abstract: The epidemiological transition has brought an increasing burden of chronic

non-communicable disorders to middle- and even low- income countries. This

paper reviews the problem with particular reference to non-insulin-dependent

diabetes mellitus (NIDDM) in the English-speaking Caribbean region. Surveys

conducted over the last three decades have documented a high prevalence of

NIDDM in a number of communities and evidence has accumulated to support

the control of obesity and physical inactivity in the primary prevention of

non-insulin-dependent diabetes. The problem of introducing and monitoring

suitable interventions on a long-term basis in high-risk populations in different

cultures has yet to be addressed. The impact of diabetes on health status in

developing countries has not been well documented but it is clear that there are

high levels of acute illness from disorders of glycaemic control, long-term

disability from blindness and limb amputation and premature mortality from

stroke, coronary heart disease and renal disease. Present evidence suggests that

improving the quality of preventive clinical management can be the most

immediately productive approach to controlling health problems from diabetes.

Achieving this objective within the social, organizational and resource

constraints of the Caribbean presents a range of problems. identifying the most

cost- effective means of improving existing services is therefore the most

immediate research priority for NIDDM in the English- speaking countries of the

Caribbean



Keywords: BLOOD-PRESSURE/coronary heart disease/CORONARY

HEART-DISEASE/COSTS/diabetes

mellitus/ENGLAND/HEALTH/heart/IMPAIRED

GLUCOSE-TOLERANCE/mortality/NIDDM/prevention/primary

prevention/RESISTANCE

SYNDROME/RETINOPATHY/STRATEGIES/stroke/TRINIDAD



Chao, C.K.S., Grigsby, P.W., Perez, C.A., Camel, H.M., Kao, M.S., Galakatos, A.E. and

Boyle, W.A. (1995), Brachytherapy-Related Complications for Medically

Inoperable Stage-I Endometrial Carcinoma. International Journal of Radiation

Oncology Biology Physics, 31 (1), 37-42.



Abstract: Purpose: The current study was conducted to investigate the incidence and risk

factors for medical complications associated with low dose rate brachytherapy in

patients with medically inoperable Stage I endometrial cancer treated with

irradiation alone. Methods and Materials: From 1965 through 1991 at

Mallinckrodt Institute of Radiology, 150 implants were performed on 96 patients

who were deemed medically unfit for hysterectomy because of advanced age,

obesity, and various medical problems. The records of these patients were

examined retrospectively to determine the incidence of medical complications

that occurred in the first 30 days following the initiation of brachytherapy. The

association of risk factors that precluded major surgery and the occurrence of

brachytherapy-related complications was examined by logistic regression.

Results: Of these 96 patients, 40 patients were older than 75 years, and 31

patients were deemed morbidly obese. Medical problems included hypertension

in 45 patients, and diabetes in 37; there was a history of congestive heart failure

in 23, stroke in 11, myocardial infarction in 10, and thromboembolism in 8.

There were concurrent malignancies in five patients. Implants were performed

using intrauterine Simon-Heyman capsules, tandems, and vaginal ovoids in all

patients. General anesthesia was used for 98 implants, spinal anesthesia for 26,

local anesthesia for 25, and epidural anesthesia for 1. The duration of anesthesia

ranged from 30 to 120 min (median, 60 min). The duration of radioisotope

application ranged from 11 to 96 h (median, 46 h). Preventive measures included

low dose subcutaneous heparin in 55 patients (since 1978), and intermittent

pneumatic compression boots in 29 (since 1985). Four patients developed

life-threatening complications including myocardial infarction (two patients),

congestive heart failure (one patient), and pulmonary embolism (one patient).

Two of these four patients died; one with a myocardial infarction and the other

with pulmonary embolism. The morbidity rate was thus 4.2% (4 out of 96), and

the mortality was 2.1% (2 out of 96). Although the four serious complications

occurred within 30 days of the procedure, only one complication and one death

occurred during treatment. There was no correlation between occurrence of

complications and medical risk factors, type and duration of anesthesia, or type

and duration of implant. Conclusions: There is a low incidence of complications

associated with conventional low dose rate brachytherapy. The procedure is well

tolerated in patients with medically inoperable Stage I endometrial cancer. In

comparison to the predicted serious complication rate of surgery in these patients,

the number of life-threatening complications from brachytherapy appears to be

quite acceptable



Keywords:

ADENOCARCINOMA/ANESTHESIA/BRACHYTHERAPY/COMPLICATIO

NS/COMPRESSION/DEEP-VEIN THROMBOSIS/ENDOMETRIAL

CARCINOMA/ENGLAND/heart/heparin/history/hypertension/incidence/morbid

ity/MORTALITY/myocardial infarction/MYOCARDIAL-

INFARCTION/OBESITY/PREVENTION/pulmonary embolism/RADIATION

THERAPY/risk/risk

factors/stroke/SURGERY/thromboembolism/treatment/VENOUS

THROMBOEMBOLISM



Yoshida, M., Nakamura, Y., Higashikawa, M. and Kinoshita, M. (1996), Predictors of

ischemic stroke in non-rheumatic atrial fibrillation. International Journal of

Cardiology, 56 (1), 61-70.



Abstract: We retrospectively analyzed the clinical features of patients with

non-rheumatic atrial fibrillation to identify risk factors of ischemic stroke.

Non-rheumatic atrial fibrillation is associated with an increased risk of ischemic

stroke. However, the predictors of ischemic stroke in non-rheumatic atrial

fibrillation are unclear. The study population consisted of 122 patients with

non-rheumatic atrial fibrillation who had no previous clinical cerebral strokes at

the start of the follow- up. Patients with cardiomyopathy and paroxysmal or

intermittent atrial fibrillation were excluded from the study. The mean age was

61.7+/-12.8 years. We defined two endpoints; namely, occurrence of ischemic

stroke (endpoint 1), and ischemic stroke or cardiac death (endpoint 2). During

the follow-up, 18 patients had ischemic stroke and 6 patients experienced cardiac

death. The 5-year event-free rates for endpoints 1 and 2 were 87.4% and 85.0%,

respectively. A Cox analysis revealed that endpoint 1 was significantly

associated with age (risk ratio (RR)=1.106, P=0.0052), end-diastolic left

ventricular dimension (RR=0.882, P=0.0393), end-systolic left ventricular

dimension (RR=1.149, P=0.0323) and the thickness of the interventricular

septum (RR=1.493, P=0.0111). Endpoint 2 was associated with age (RR=1.122,

P=0.0004), left atrial dimension (RR=1.057, P=0.0666), end-diastolic left

ventricular dimension (RR=0.935, P=0.0426), fractional shortening (RR=0.880,

P=0.0001) and the thickness of the left ventricular posterior wall (RR=1.644,

P=0.0004). The present results suggest that, in addition to left ventricular

dimensions and left atrial dimension, left ventricular hypertrophy may be

associated with ischemic stroke



Keywords: FRAMINGHAM/INTERNAL/ischemic stroke/non-rheumatic atrial

fibrillation/predictors/PREVENTION/RISK/risk factors/stroke/SYSTEMIC

EMBOLIZATION/THROMBOEMBOLIC COMPLICATIONS/WARFARIN



Schulzer, M. and Mancini, G.B.J. (1996), 'Unqualified success' and 'unmitigated failure':

Number-needed- to-treat-related concepts for assessing treatment efficacy in the

presence of treatment-induced adverse events. International Journal of

Epidemiology, 25 (4), 704-712.



Abstract: Background. Common indices for the quantal assessment of treatment efficacy

are reviewed, The absolute risk reduction is a practical index for public health

considerations. Its reciprocal has been termed the 'Number Needed to Treat'

(NNT), representing the health effort that must on average be expended to

accomplish one tangible treatment target. We extend the NNT to evaluate

outcome combinations of treatment benefits versus treatment harms. Methods.

We describe the mathematical context of the NNT, and extend it to evaluate

outcome combinations (treatment success/failure with/without treatment-induced

adverse effects) in a treated population. These extensions are carried out

assuming either independence or positive association between treatment benefit

and treatment harm. A method is provided for calculating the standard errors of

these extended NNT values. Applications to cost-effectiveness analysis are

discussed. Results. We calculate NNT in three recent therapeutic studies. The

results of a trial of the prevention of strokes with warfarin in patients with non-

valvular atrial fibrillation are analysed to evaluate treatment success (stroke

prevention) against treatment-induced bleeds. An NNT-related cost-benefit

analysis is also carried out. We also analyse the results of a study of two

modalities of chemotherapeutic treatment in small-cell lung cancer, and of two

modalities of surgical intervention in the treatment of cholelithiasis. Conclusions.

The NNT are useful in direct evaluation of outcome-specific treatment benefits

versus treatment-induced harms. They may also be used in cost- effectiveness

analyses and are helpful in guiding public health programmes towards the

identification of optimal treatment strategies



Keywords: adverse events/atrial

fibrillation/ATRIAL-FIBRILLATION/BRITISH/CHOLECYSTECTOMY/GOL

D STANDARD/health/NNT/PERSPECTIVE/stroke/STROKE

PREVENTION/treatment/treatment efficacy/warfarin



Kuzniar, J., Splawinska, B., Malinga, K., Mazurek, A.P. and Splawinski, J. (1996),

Pharmacodynamics of ticlopidine: Relation between dose and time of

administration to platelet inhibition. International Journal of Clinical

Pharmacology and Therapeutics, 34 (8), 357-361.



Abstract: In spite of long clinical experience with ticlopidine (T) knowledge of its

pharmacodynamics is limited. In this study relation between dose and time of

administration of T to platelet inhibition was investigated in 62 healthy

volunteers ex vivo in whole blood and platelet rich plasma. Gender-related

sensitivity of platelets to ticlopidine was also evaluated. Inhibition of

ADP-induced platelet aggregation by T, 500 mg, daily, was almost identical in

both sexes. 100 mg daily did not inhibit ADP-induced platelet aggregation even

after 14 days of administration. 250 mg daily induced strong inhibition on day 5

of administration comparable to the inhibition obtained with 500 mg daily dose.

The antiplatelet (ADP) effect of T (500 mg, daily) was present on day 2-3 and

full inhibitory effect on day 4 of administration. T-1/2 of antiplatelet (ADP)

activity of T was 5.3 days and full recovery of platelets activity 11-13 days. No

rebound phenomenon was present. T (regardless the dose) inhibited platelet

aggregation induced by small but not high concentrations of collagen and was

without effect on arachidonic acid-induced platelet aggregation. Therefore, T is

not suitable for treatment of acute event, 250 mg daily dose should be used

especially for combination with other drugs and 11 days washout interval seems

necessary to change the treatment or to perform surgery



Keywords: ADP/aggregation/ASPIRIN/pharmacodynamics/platelet

aggregation/platelets/PREVENTION/STROKE/ticlopidine/treatment



Muller, T. (1997), Pharmacological rationale for stroke prevention with acetylsalicylic

acid (ASA) and dipyridamole combined. International Journal of Clinical

Practice, 6-13.



Abstract: The Second European Stroke Prevention Study (ESPS-2) has demonstrated

equivalent efficacy in secondary stroke prevention for acetylsalicylic acid (ASA,

25 mg bid) and dipyridamole (modified-release preparation, 200 mg bid).

Combining both agents is twice as effective and sets a new standard in this

therapeutic area. The pharmacological effects of these treatments were

investigated in a randomised, double-blind, clinical pharmacology trial before

ESPS-2. The inhibition of mural platelet thrombus formation by treatment with

ASA, modified-release dipyridamole (DP), their combination, and placebo (using

doses and preparations identical to ESPS-2) was investigated ex vivo using blood

samples collected both before and 2 hours after a 3.5-day treatment in 96 healthy

subjects. Significant inhibition of platelet thrombus formation was observed for

both ASA and DP The size of all thrombi was reduced by similar to 45% with

ASA (p 0.98 for men and > 0.91 for women). The estimated percentage rate of

coronary heart disease (CHD, P 140/90 mm Hg; manage elevated lipids by diet,

exercise, and cholesterol-lowering medications (if necessary); treat diabetes; lose

weight so that BMI is 25

(RR = 0.71, 95% CI : 0.51-0.99) or current smokers (RR = 0.40, 95% CI :

0.18-0.86) comparing highest to the lowest categories of intake. Conclusions Our

results suggest an inverse association between vegetable intake and risk of CHD.

These prospective data support current dietary guidelines to increase vegetable

intake for the prevention of CHD



Keywords: age/aged/alcohol/angioplasty/antioxidants/aspirin/beta

carotene/beta-carotene/body mass index/bypass

grafting/cancer/carotenoids/carotenoids

antioxidants/CHD/cholesterol/CONSUMPTION/coronary angioplasty/coronary

heart disease/diabetes/diet/dietary

guidelines/disease/ENGLAND/FIBER/FRUIT/guidelines/heart/heart

disease/history/hypertension/infarction/men/MORTALITY/myocardial/myocardi

al infarction/physical activity/POPULATION/prevention/prospective

study/QUESTIONNAIRE/randomized/randomized trial/relative

risk/risk/smoking/stroke/treatment/trial/US/US MEN/use/vegetable/vegetables



Paffenbarger, R.S., Blair, S.N. and Lee, I.M. (2001), A history of physical activity,

cardiovascular health and longevity: the scientific contributions of Jeremy N

Morris, DSc, DPH, FRCP. International Journal of Epidemiology, 30 (5),

1184-1192.



Abstract: Since Hippocrates first advised us more than 2000 years ago that

exercise-though not too much of it-was good for health, the epidemiology of

physical activity has developed apace with the epidemiological method itself. It

was only in the mid-20th century that Professor Jeremy N Morris and his

associates used quantitative analyses, which dealt with possible selection and

confounding biases, to show that vigorous exercise protects against coronary

heart disease (CHD). They began by demonstrating an apparent protection

against CHD enjoyed by active conductors compared with sedentary drivers of

London double-decker buses. In addition, postmen seemed to be protected

against CHD like conductors, as opposed to less active government workers. The

Morris group pursued the matter further, adapting classical infectious disease

epidemiology to the new problems of chronic, non-communicable diseases.

Realizing that if physical exercise were to be shown to contribute to the

prevention of CHD, it would have to be accomplished through study of

leisure-time activities, presumably because of a lack of variability in intensities

of physical work. Accordingly, they chose typical sedentary middle-management

grade men for study, obtained 5-minute logs of their activities over a 2-day

period, and followed them for non-fatal and fatal diseases. In a subsequent study,

Morris et al. queried such executive-grade civil servants by detailed mail-back

questionnaires on their health habits and health status. They then followed these

men for chronic disease occurrence, as in the earlier survey. By 1973 they had

distinguished between 'moderately vigorous' and 'vigorous' exercise. In both of

these civil service surveys, they demonstrated strong associations between

moderately vigorous or vigorous exercise and CHD occurrence, independent of

other associations, in age classes 35-64 years. In the last 30 years, with

modern-day computers, a large number of epidemiological studies have been

conducted in both sexes, in different ethnic groups, in broad age classes, in a

variety of social groups, and on most continents of the world. These studies have

extended and amplified those of the Morris group, thereby helping to solidify the

cause-and-effect evidence that exercise protects against heart disease and averts

premature mortality



Keywords: ACUTE MYOCARDIAL-INFARCTION/age/all-cause

mortality/ALUMNI/cardiovascular/cardiovascular health/chronic

disease/coronary heart disease/CORONARY HEART-DISEASE/DEPENDENT

DIABETES-MELLITUS/disease/diseases/ENGLAND/epidemiology/ethnic

groups/exercise/exercise science/EXERTION/health/heart/heart

disease/history/incidence rates/LEISURE-TIME/longevity/medical

history/men/mortality/non-communicable diseases/physical

activity/PREVENTION/prospective cohort studies/PROTECTION/social

medicine/status/STROKE/survey/VIGOROUS EXERCISE



Sleight, P. (2001), Future perspectives and implications. International Journal of

Clinical Practice, 22-23.



Abstract: Over a 4.5 year follow-up period, the HOPE (Heart Outcomes Prevention

Evaluation) trial, and the MICRO-HOPE (Microalbuminuria, Cardiovascular,

and Renal Outcomes) and SECURE (Study to Evaluate Carotid Ultrasound

changes in patients treated with Ramipril and vitamin E) substudies have all

demonstrated a large benefit of ramipril versus placebo in patients over 55 years

at high risk (by reason of a prior vascular event), or by being diabetic subjects

with one additional risk factor. The baseline blood pressure on average was

normal, at 139/79 mmHg, and was modestly reduced by 3.3/1.4 mmHg. Patients

with known left ventricular dysfunction were excluded, as were those with

uncontrolled hypertension. The incidence of stroke was reduced by 32%,

myocardial infarction by 20% and cardiovascular death by 25%. The benefits

conferred were in addition to, and largely independent of, other conventional

treatments such as aspirin, lipid-lowering agents, beta -blockers, diuretics and

calcium channel blockers. The relative risk reduction was very similar whether

or not the patient was a known hypertensive at baseline. High dose ACE

inhibition with ramipril is applicable to a far wider population of patients at high

risk of cardiovascular events than the current indications of hypertension and left

ventricular dysfunction



Keywords: aspirin/blood pressure/calcium/calcium channel/calcium channel

blockers/cardiovascular/cardiovascular events/death/diuretics/England/high

risk/hypertension/incidence/infarction/left ventricular/left ventricular

dysfunction/lipid lowering/lipid-lowering/myocardial/myocardial

infarction/population/Ramipril/relative risk/risk/risk

factor/stroke/trial/vascular/vascular event/vitamin E



Diener, H.C., Darius, H., Bertrand-Hardy, J.M. and Humphreys, M. (2001), Cardiac

safety in the European Stroke Prevention Study 2 (ESPS2). International Journal

of Clinical Practice, 55 (3), 162-163.



Abstract: The second European Stroke Prevention Study investigated the prevention of

stroke and/or death in 6602 patients with transient ischaemic attack or stroke

with aspirin (25 mg b.d.), dipyridamole (400 mg b.d,), the combination of aspirin

and dipyridamole or placebo. This post hoc analysis investigated cardiac events

in patients with coronary heart disease or myocardial infarction (MI) at entry.

Dipyridamole did not result in a higher number of cardiac events, e,g, angina

pectoris, MI, or death from all causes. The combination of aspirin plus

dipyridamole was superior to either drug alone in the prevention of stroke



Keywords: angina/angina pectoris/aspirin/cardiac/causes/combination/coronary heart

disease/death/DIPYRIDAMOLE/disease/ENGLAND/Germany/heart/heart

disease/infarction/ischaemic/myocardial/myocardial

infarction/prevention/safety/stroke/transient/transient ischaemic attack



Gupta, A. and Thomas, P. (2002), Stroke prevention: Missed opportunities?

International Journal of Clinical Practice, 56 (5), 338-341.



Abstract: Identification and modification of risk factors can prevent strokes. Certain

previously unidentified risk factors for stroke can become apparent following

admission with acute stroke. The aim of the study was to investigate the prior

capture, identification and management of modifiable risk factors for stroke in

patients admitted to a hospital following acute stroke. One hundred consecutive

stroke patients admitted to a UK hospital were prospectively assessed for

modifiable risk factors. The extent of pre-admission risk factor management was

also determined. Pre-admission risk factors identified and effectively managed

were hypertension in non- diabetics (28%), hypertension in diabetics (7%),

previous cerebrovascular event (100%), diabetes (29%), smoking (50%

counselled), atrial fibrillation (81%), hypercholesterolaemia (100%), excess

alcohol (22% counselled) and obesity (52% counselled). Twenty-five new

modifiable risk factors were identified following incident stroke. In conclusion, a

significant number of patients admitted with acute stroke have their risk factors

poorly identified and controlled in the community. Despite the trial evidence

available, an evidence- practice gap exists and many stroke prevention

opportunities are being missed



Keywords: acute/acute stroke/alcohol/atrial/atrial

fibrillation/ATTITUDES/cerebrovascular/cerebrovascular event/CLINICAL

GUIDELINES/community/diabetes/ENGLAND/fibrillation/hospital/hypercholes

terolaemia/HYPERTENSION/MANAGEMENT/obesity/prevention/RISK/risk

factor/risk factors/risk factors for stroke/smoking/stroke/stroke patients/stroke

prevention/trial



Jabbour, S., Reddy, K.S., Muna, W.F.T. and Achutti, A. (2002), Cardiovascular disease

and the global tobacco epidemic: a wake- up call for cardiologists. International

Journal of Cardiology, 86 (2-3), 185-192.



Abstract: The global tobacco epidemic continues unabated with the recruitment of young

people, including women, to join the ranks of smokers. Even though

cardiovascular diseases account for some of the major tobacco-related morbidity

and mortality, cardiologists and their professional societies have lagged behind in

the crusade against tobacco. A great opportunity exists for more involvement and

leadership role by cardiologists, especially in countries where tobacco control

efforts are not well established. For this to happen, there is a need to identify

barriers to cardiologists' involvement in tobacco prevention and cessation efforts

and to devise locally- relevant strategies to address them. Also, the areas where

the contribution of cardiologists can be most fruitful must be identified.

Considering that a substantial portion of the future burden of cardiovascular

disease will occur among current tobacco users, treating tobacco dependence and

supporting tobacco quitters are the most urgent tasks for cardiologists interested

in reducing the human toll of tobacco. The cardiovascular community must

consider the variety of needs and available resources to fight tobacco in different

regions. Recommendations to involve more cardiologists in tobacco control, at

the clinical, public health and policy levels, are presented. (C) 2002 Elsevier

Science Ireland Ltd. All rights reserved



Keywords: cardiologist(s)/cardiovascular/cardiovascular disease/cardiovascular

diseases/community/control/disease/diseases/epidemic/health/human/morbidity/

mortality/PHYSICIANS/POPULATION/prevention/prevention/treatment/public

health/recruitment/SMOKERS/smoking/SMOKING CESSATION

INTERVENTIONS/STROKE/tobacco/women



Gupta, A. and Thomas, P. (2002), Knowledge of stroke symptoms and risk factors

among at-risk elderly patients in the UK. International Journal of Clinical

Practice, 56 (9), 634-637.



Abstract: Assessing patient knowledge can help healthcare providers in planning

measures directed at prevention, early identification and referral of patients. An

incorrect understanding of stroke symptoms may delay patients seeking

emergency help, thus missing the benefits of acute stroke treatments. Insufficient

knowledge about stroke risk factors may affect risk factor control. We conducted

a questionnaire-based interview among elderly patients at risk of stroke and

assessed their baseline knowledge of stroke symptoms and risk factors. A large

proportion were found to have an improper understanding of stroke symptoms

and risk factors. Stress was considered the commonest risk factor for stroke.

Most patients did not consider themselves to be at further risk of stroke. Further

education is needed as part of stroke prevention strategies to remove

misconceptions. Improved recognition of stroke symptoms when they occur will

help when seeking emergency medical help



Keywords: acute/acute stroke/control/education/elderly/elderly

patients/ENGLAND/knowledge/medical/PERCEPTIONS/PREVENTION/risk/ri

sk factor/risk factors/SIGNS/stroke/stroke prevention/symptoms



Liao, J.K. (2003), Role of statin pleiotropism in acute coronary syndromes and stroke.

International Journal of Clinical Practice, 51-57.



Abstract: Several landmark clinical trials have demonstrated the benefit of

lipid-lowering with statins for the primary and secondary prevention of coronary

heart disease. The clinical data in support of lowering cholesterol by statins are

unequivocal. The established mechanism of action is via sterol regulatory

element binding protein (SREBP) activation due to reduced hepatic cholesterol

synthesis and secondary upregulation of the low-density lipoprotein

(LDL)-receptor, leading to enhanced clearance of circulating cholesterol and

lipids. Although it is widely accepted that most clinical benefit obtained with

statins is a direct result of their lipid-lowering properties, there is still some

debate as to whether the so-called pleiotropic effects' of statins contribute to the

clinical outcome in vascular disease, or whether all the beneficial effects of

statins are simply due to lipid-lowering. For example, these agents appear to

display additional cholesterol- independent effects on various aspects of

cardiovascular disease, including improving endothelial function, decreasing

vascular inflammation and enhancing plaque stability. Thus, further studies are

needed to understand the full impact of statin therapy on each of these processes

and whether these effects contribute to the clinical benefits of statins in acute

coronary syndromes and stroke



Keywords: activation/acute/acute coronary syndromes/ARTERY

DISEASE/benefits/C-REACTIVE PROTEIN/cardiovascular/cardiovascular

disease/cholesterol/clinical trials/coronary heart disease/disease/endothelial

function/ENDOTHELIAL PROGENITOR CELLS/ENGLAND/heart/heart

disease/HEART-DISEASE/HMG-COA REDUCTASE/inflammation/lipid

lowering/lipid-lowering/lipids/low density lipoprotein/mechanism of

action/MYOCARDIAL-INFARCTION/NITRIC-OXIDE

SYNTHASE/outcome/plaque/prevention/primary/primary and secondary

prevention/PRIMARY HYPERCHOLESTEROLEMIA/RHO-

GTPASE/secondary/secondary prevention/statin/statin

therapy/statins/stroke/therapy/trials/USA/vascular/vascular disease/VASCULAR

SMOOTH-MUSCLE



Vazquez, E., Sanchez-Perales, C., Garcia-Cortes, M.J., Borrego, F., Lozano, C., Guzman,

M., Gil, J.M., Liebana, A., Perez, P., Borrego, M.J. and Perez, V. (2003), Ought

dialysis patients with atrial fibrillation be treated with oral anticoagulants?

International Journal of Cardiology , 87 (2-3), 135-139.



Abstract: Background: Dialysis patients with atrial fibrillation have an increased

thrombolic risk. Dicoumarin anticoagulant therapy is often considered

contra-indicated in chronic renal insufficiency in which the risk of haemorrhage,

though not defined, is perceived to be high. We assessed haemorrhage

complications in dialysis patients receiving dicoumarin anticoagulant therapy to

establish whether the haemorrhage risk justifies the contra-indication of

anticoagulant therapy in patients with atrial fibrillation. Patients and methods:,

Over a period of a decade in our dialysis centre, 29 patients receiving

anticoagulant therapy over a protracted period presented haemorrhage

complications. These were classified with respect to severity and location and

compared with 211 patients not receiving anticoagulant therapy. The relative risk

of haemorrhage was calculated and was compared to risk of thrombo- embolism

in dialysis patients with atrial fibrillation. Results: Of the 29 patients, nine had 13

episodes of haemorrhage complications (26 episodes/100 patient-years). None

was fatal, nor intra-cranial nor with serious clinical sequelae. In the group

without anticoagulants, 29 patients had 39 haemorrhage complications (11

episodes/100 patient-years); four (10.2%) intra-cranial and all fatal. The relative

risk of bleeding with anticoagulant therapy was 2.36 (95% confidence

interval=1.19-4.27). Conclusions: (1) Dialysis patients with anticoagulant

therapy presented with a higher risk of haemorrhage; (2) the relative risk of

bleeding was double that of the dialysis population without anticoagulant therapy;

(3) despite the high risk of haemorrhage that we observed, the high risk of

thrombo-embolism and the attendant serious sequelae to which dialysis patients

with atrial fibrillation are predisposed indicates that oral anticoagulation therapy

ought not to be considered automatically contra-indicated in this patient group

but that an exhaustive evaluation of the risk- benefit needs to be conducted on an

individual patient basis. (C) 2002 Elsevier Science Ireland Ltd. All rights

reserved



Keywords: anticoagulant/anticoagulant

therapy/anticoagulants/anticoagulation/ANTITHROMBOTIC

THERAPY/atrial/atrial

fibrillation/bleeding/chronic/COMPLICATIONS/dialysis/embolism/evaluation/fi

brillation/haemorrhage/haemorrhage complications/HEMODIALYSIS/high

risk/intracranial/oral anticoagulants/oral

anticoagulation/population/PREVENTION/relative risk/renal/renal

insufficiency/risk/RISK-FACTORS/severity/Spain/STROKE/therapy/thromboe

mbolism/WARFARIN

Dimakakos, P.B., Antoniou, A., Mourikis, D. and Katsaros, G. (1998), Surgical outcome

of carotid artery disease: Analysis of 367 carotid endarterectomies. International

Surgery, 83 (4), 350-354.



Abstract: Carotid endarterectomy is a method of prophylaxis. A total of 367 carotid

endarterectomies in 335 patients were performed during the period of 1989-1997:

222 (66.3%) were symptomatic and 113 (33.7%) asymptomatic patients. In all,

262 (78.2%) had unilateral, 41 (12.2%) contralateral occlusion and 32 (9.6%)

bilateral artery disease, All were operated on under general anesthesia without

using shunt or patch. Of the patients with bilateral occlusive disease, 17

underwent simultaneous and 15 staged endarterectomy; The mortality rate of the

first 30 postoperative days was 1.19% and the mortality/stroke rate 2.38%.

Transient neurogenic dysfunction occurred in 3.68%, myocardial ischemia in

0.89%, and postoperative hypertension in 16.7%. Endarterectomy of

symptomatic and asymptomatic patients with unilateral localisation, contralateral

occlusion or bilateral occlusive disease remains a highly acceptable prophylactic

method. The future will show whether other endovascular procedures affect the

broad application of carotid endarterectomy



Keywords:

AD-HOC-COMMITTEE/AMERICAN-HEART-ASSOCIATION/ANESTHESI

A/asymptomatic/CARDIAC EVENTS/carotid/carotid artery/carotid

endarterectomy/CEREBRAL-ISCHEMIA/complications following carotid

endarterectomy/endarterectomy/HYPERTENSION/ischemia/mortality/myocardi

al/MYOCARDIAL-

ISCHEMIA/OPERATIONS/PREVENTION/prophylaxis/results after carotid

endarterectomy/shunt/VASCULAR-SURGERY



Diener, H.C. and Weiller, C. (1993), Ticlopidine - Secondary Prevention of Ischemic

Myocardial- Infarction. Internist, 34 (12), 1150-1155



Keywords: ASPIRIN/NEW-YORK/STROKE



Diener, H.C. (1995), Risk-Factors and Prevention of Cerebral Arterial Vascular- Disease.

Internist, 36 (9), 868-874



Keywords:

ANTICOAGULATION/ASPIRIN/ATRIAL-FIBRILLATION/BLOOD-PRESS

URE/CORONARY HEART-DISEASE/RANDOMIZED

TRIAL/STROKE/TICLOPIDINE/WARFARIN



Windler, E. (2000), Another assessment of the CARE Study - Incidence of insult in

post-infarction patients during pravastatin therapy. Internist, 41 (10), 1120-1123



Keywords: AVERAGE CHOLESTEROL LEVELS/CARE/CORONARY

EVENTS/MEN/METAANALYSIS/MORTALITY/NEW-YORK/pravastatin/PR

EVENTION/REDUCTASE

INHIBITORS/RISK-FACTORS/STROKE/therapy/TRIALS

Nelles, G. and Diener, H.C. (2002), Prevention and rehabilitation of stroke in the elderly.

Internist, 43 (8), 941-948



Keywords: ASPIRIN/COPENHAGEN

STROKE/DOUBLE-BLIND/elderly/ELECTRICAL-STIMULATION/Germany/

METAANALYSIS/MOTOR

RECOVERY/NEW-YORK/PLASTICITY/rehabilitation/stroke/THERAPY/TRI

ALS/WRIST



Diener, H.C., Philipp, T. and Schrader, J. (2003), Hypertension and stroke. Internist, 44

(7), 786-+.



Abstract: Hypertension is the most important risk factor for stroke and vascular

dementia. Antihypertensive treatment reduces stroke risk by 40%. Most probably

all antihypertensive drugs are equally effective with the exception of

alpha-blockers. Blood pressure is increased in many patients with acute stroke. In

this phase sudden drops in blood pressure should be avoided. The combination of

an ACE-inhibitor and a diuretic reduced strokes by 28% after TIA or a first

stroke. Whether this is a drug specific effect or due to lowering blood pressure

per se is investigated at the moment



Keywords: ACE inhibitor/acute/acute stroke/ANTIHYPERTENSIVE DRUGS/blood

pressure/BLOOD- PRESSURE/CALCIUM-CHANNEL

BLOCKER/CARDIOVASCULAR

MORBIDITY/combination/dementia/drug/drugs/Germany/hypertension/ISOLA

TED SYSTOLIC HYPERTENSION/LIPID-LOWERING

TREATMENT/MORTALITY/NEW-YORK/OLDER PATIENTS/primary

prevention/RANDOMIZED-TRIAL/risk/risk factor/secondary

prevention/stroke/sudden/TIA/TRANSIENT ISCHEMIC

ATTACK/treatment/USA/vascular/vascular dementia



Faust, M. and Krone, W. (2003), End-organ damage in hyperlipidemias. Internist, 44 (7),

831-+.



Abstract: Epidemiological and experimental data have clearly demonstrated a strong

association between elevated LDL-cholesterol levels and coronary heart disease.

In concordance lipid-lowering trials with statins have shown a significant

reduction of cardiovascular events. Although stroke is mainly caused by

atherosclerotic vascular events, epidemiolgical data have so far failed to show a

significant relationship between elevated lipid levels and stroke incidence.

However, recent lipid intervention trials with statins have clearly demonstrated a

significant reduction in stroke incidence. Moreover, elevated cholesterol levels

are thought to contribute to progression of chronic renal insufficiency. In

addition, cholesterol crystal emboli are a rare but frequently serious complication

of vascular catheter interventions. Significant hypertriglyceridemia carries a

significant risk of acute pancreatitis and is thought to contribute to the

development of fatty liver disease

Keywords: acute/atherosclerosis/AVERAGE CHOLESTEROL

LEVELS/BLOOD-PRESSURE/cardiovascular/CARDIOVASCULAR

EVENTS/cholesterol/chronic/complication/coronary heart

disease/CORONARY-HEART-DISEASE/development/disease/emboli/experime

ntal/Germany/heart/heart

disease/hypercholesterolemia/hypertriglyceridemia/incidence/LDL

cholesterol/LDL-cholesterol/lipid

lowering/lipid-lowering/MEN/NEW-YORK/NONALCOHOLIC

STEATOHEPATITIS/PREVENTION/progression/renal/renal

insufficiency/risk/RISK-FACTORS/statins/STROKE/stroke/stroke

incidence/trials/TYPE-2 DIABETES-MELLITUS/USA/vascular/vascular events



Nistri, M., Mangiafico, S., Cellerini, M., Villa, G., Mennonna, P., Ammannati, E. and

Giordano, G.P. (2002), Percutaneous transluminal cerebral angioplasty and

stenting in acute vertebrobasilar ischemic stroke - Report of two cases.

Interventional Neuroradiology, 8 (2), 135-141.



Abstract: Reports of cerebral transluminal angioplasty and stenting in patients with

vertebrobasilar ischemic stroke are scanty. Herein we report on the use of

"monorail" coronary balloon angioplasty and stent balloon mounted catheters in

two patients with acute vertebrobasilar ischemic stroke, focussing on the

differences and possible advantages of the "monorail" technique in comparison

with the "over-the-wire" technique. In both patients, the clinical picture was

characterized by progressive brainstem symptoms followed by acute loss of

consciousness related to an atherothrombotic occlusion and subocclusion of the

dominant intracranial vertebral artery, respectively. In one patient, superselective

thrombolytic therapy and balloon angioplasty resulted in a dissection flap at the

vertebrobasilar junction. The latter was treated by successful deployment of a

coronary stent. In the other patient, the subocclusive lesion was directly treated

by angioplasty and stenting without thrombolytic therapy. The clinical outcome

was poor for one patient ("locked in" syndrome) while the other had a complete

clinical recovery. In acute atherothrombotic vertebrobasilar stroke transluminal

cerebral angioplasty and stenting may be successfully performed allowing vessel

recanalization



Keywords: acute/angioplasty/BALLOON ANGIOPLASTY/basilar artery/BASILAR

ARTERY-STENOSIS/cerebral/coronary stent/dissection/ENDOVASCULAR

PROCEDURES/EXPERIENCE/ischemic/ischemic

stroke/OCCLUSION/outcome/PREVENTION/recanalization/stent/stent

placement/stenting/stroke/symptoms/TECHNICAL

CASE-REPORT/therapy/thrombolytic/thrombolytic therapy/use/vertebral artery



Zhongrong, M., Feng, L., Shengmao, L., Fengshui, Z., Hongqi, Z., Moli, W. and Yang,

H. (2003), Natural history and treatment modalities of symptomatic bilateral

middle cerebral artery stenosis. Interventional Neuroradiology, 9 (1), 31-38.

Abstract: To assess the natural history, pathogenesis, and treatment modalities of

symptomatic bilateral middle cerebral artery stenosis, we retrospectively

evaluated a consecutive series of patients for their medical history, anamnesis,

and our treatment protocol. Treatment included transluminal angioplasty, bypass

surgery and/or conservative antiplatelet therapy for prevention of the stroke

attack and vessel reconstruction. Indications, feasibility, effectiveness, and

complications of treatment are also discussed. A series of 19 patients with

symptomatic bilateral middle cerebral artery (MCA) stenosis were treated

consecutively from 1998 to 2002. Medical history, anamnesis, and treatment

protocol were reviewed and evaluated retrospectively, Of these 19 patients, six

(six vessels, 31.57%) were treated by balloon (two vessels) or stent-assistant

angioplasty (four vessels), four (four vessels, 21.05%) were treated by bypass

surgery, 18 vessels plus ten vessels occluded before treatment (47.37%) were

conservatively treated by antiplatelet agents. 24 vessels (12 patients) were

followed from three months to four years by angiography (nine cases), TCD (12

cases), or MRA (five cases). A total of 38 vessels were involved (19 vessels), of

which ten vessels (10/38, 26.31%) had occluded before coming to our hospital.

Three patients (3/19, 15.78%) had a history of hypertension, five had a history of

smoking. The mean age of these 19 patients was 33 yrs (24 similar to 42 yrs),

with a slight male preponderance (males/females = 13/6). Initial clinical

presentations were TIAs (14/19, 73.68%) and minor stroke (5/19, 26.32%),

symptoms attacked alternatively for five patients (5/38, 13.16%). Seven vessels

(7/28, 25%) occluded within one to three years, of which three occluded

asymptomatically, four acutely occluded vessels accompanied acute stroke. Nine

vessels (9/28, 32.14%) were treated by conservative antiplatelet agents and one

treated by bypass surgery had related recurrent TIAs. Vessels treated by

angioplasty (balloon or stent) remained patent and free of symptoms. The

stenosed bilateral MCA may occlude within one to three years without

intervention. The pathogenesis of this special disease is unclear; it may be

genetic or due to asymptomatic infection. The results showed that earlier

appropriate treatment can resolve the clinical symptoms and somehow change

the natural history of this disease. Conservative medical therapy cannot prevent

further stroke attack. Collaterals are very important for these special patients



Keywords: acute/acute stroke/age/angiography/angioplasty/antiplatelet/antiplatelet

agents/antiplatelet therapy/asymptomatic/balloon/bypass/bypass

surgery/cerebral/cerebral

artery/China/complications/disease/genetic/history/hospital/hypertension/infectio

n/ISCHEMIC STROKE/medical/medical history/middle cerebral artery/middle

cerebral artery stenosis/MRA/natural history/OCCLUSIVE

CEREBROVASCULAR-DISEASE/patent/pathogenesis/PERCUTANEOUS

TRANSLUMINAL

ANGIOPLASTY/prevention/results/smoking/stenosis/stent/stroke/surgery/sympt

oms/TCD/therapy/treatment/vessels



Shelley, E., Daly, L., Graham, I., Beirne, A., Conroy, R., Gibney, M., Hickey, N.,

Kilcoyne, D., Lee, B., Odwyer, T., Radic, A. and Mulcahy, R. (1991), The

Kilkenny Health Project - A Community Research and Demonstration

Cardiovascular Health-Program. Irish Journal of Medical Science , 160 10-16.



Abstract: Ireland has one of the highest death rates in the world from coronary heart

disease (CHD) and has not shared in the rapid decline in mortality which has

occurred in other countries. The Kilkenny Health Project was established as a

community- based research and demonstration programme for cardiovascular

disease prevention in County Kilkenny and as a pilot project for future national

initiatives. The first phase of the health promotion programme in Kilkenny is

being carried out between 1985 and 1990. Changes in behaviour and in factors

associated with CHD will be estimated by the difference in changes over time

between Kilkenny and the reference area, as measured by independent random

sample surveys of men and women aged 35 to 64 years. CHD and stroke events,

fatal and non-fatal, will be registered in both areas from 1987-1992. The Project

has studied attitudes to CHD and its prevention. Health behaviours have been

studied in adults and in post-primary school pupils. Risk factors for CHD have

been measured in adults in accordance with the methods of the international

MONICA Project. It has been demonstrated that health and education

professionals can incorporate preventive activities and health education into

everyday practice



McDonnell, R., Fan, C.W., Johnson, Z. and Crowe, M. (2000), Prevalence of risk factors

for ischaemic stroke and their treatment among a cohort of stroke patients in

Dublin. Irish Journal of Medical Science, 169 (4), 253-257.



Abstract: Background The majority of strokes are due to ischaemia. Risk factors include

atrial fibrillation, hypertension and smoking. The incidence can be reduced by

addressing these risk factors. This study examines the prevalence of risk factors

and their treatment in a cohort of patients with ischaemic stroke registered on a

Dublin stroke database. Methods Patients admitted to any of three acute hospitals

with a diagnosis of stroke during a one-year period in 1997/98 were registered on

a database using the European Stroke Database format. Data relating to common

risk factors were analysed. Results There were 238 ischaemic stroke cases

registered. The most frequent medical risk factors were: hypertension (45%),

atrial fibrillation (27.3%), and previous disabling or non-disabling stroke

(33.2%). There was an increasing trend with advancing age for atrial fibrillation

(p 50%) ipsilateral internal carotid artery stenosis.

Design. - Prospective, randomized, multicenter trial. Setting. - Sixteen

university-affiliated Veterans Affairs medical centers. Patients. - Men who

presented within 120 days of onset of symptoms that were consistent with

transient ischemic attacks, transient monocular blindness, or recent small

completed strokes between July 1988 and February 1991. Among 5000 patients

screened, 189 individuals were randomized with angiographic internal carotid

artery stenosis greater than 50% ipsilateral to the presenting symptoms.

Forty-eight eligible patients who refused entry were followed up outside of the

trial. Outcome Measures. - Cerebral infarction or crescendo transient ischemic

attacks in the vascular distribution of the original symptoms or death within 30

days of randomization. Intervention. - Carotid endarterectomy plus the best

medical care (n = 91) vs the best medical care alone (n = 98). Results. - At a

mean follow-up of 11.9 months, there was a significant reduction in stroke or

crescendo transient ischemic attacks in patients who received carotid

endarterectomy (7.7%) compared with nonsurgical patients (19.4%), or an

absolute risk reduction of 11.70% (P = .011). The benefit of surgery was more

profound in patients with internal carotid artery stenosis greater than 70%

(absolute risk reduction, 17.7%; P =.004). The benefit of surgery was apparent

within 2 months after randomization, and only one stroke was noted in the

surgical group beyond the 30-day perioperative period. Conclusions. - For a

selected cohort of men with symptoms of cerebral or retinal ischemia in the

distribution of a high-grade internal carotid artery stenosis, carotid

endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral

ischemia. The risk of cerebral ischemia in this subgroup of patients is

considerably higher than previously estimated



Keywords: ASPIRIN/ATTACKS/CONTROLLED

TRIAL/DISEASE/EXTRACRANIAL

ARTERIES/HEAD/PERFORMANCE/RISK/STROKE



Probstfield, J.L. (1991), Prevention of Stroke by Antihypertensive Drug-Treatment in

Older Persons with Isolated Systolic Hypertension - Final Results of the Systolic

Hypertension in the Elderly Program (Shep). Jama-Journal of the American

Medical Association, 265 (24), 3255-3264.



Abstract: Objective. - To assess the ability of antihypertensive drug treatment to reduce

the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension.

Design. - Multicenter, randomized, double-blind, placebo-controlled. . Setting. -

Community-based ambulatory population in tertiary care centers. Participants. -

4736 persons (1.06%) from 447 921 screenees aged 60 years and above were

randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure

ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90

mm Hg. Of the participants, 3161 were not receiving antihypertensive

medication at initial contact, and 1575 were. The average systolic blood pressure

was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age

was 72 years, 57% were women, and 14% were black. Interventions. -

Participants were stratified by clinical center and by antihypertensive medication

status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5

mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol,

25 mg/d, or matching placebo; dose 2 was 50 mg/d. Main Outcome Measures. -

Primary. - Nonfatal and fatal (total) stroke. Secondary. - Cardiovascular and

coronary morbidity and mortality, all-cause mortality, and quality of life

measures. Results. - Average follow-up was 4.5 years. The 5-year average

systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg

for the active treatment group, and the 5-year average diastolic blood pressure

was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2

per 100 participants for active treatment and 8.2 per 100 for placebo. The relative

risk by proportional hazards regression analysis was 0.64 (P = .0003). For the

secondary end point of clinical nonfatal myocardial infarction plus coronary

death, the relative risk was 0.73. Major cardiovascular events were reduced

(relative risk, 0.68). For deaths from all causes, the relative risk was 0.87.

Conclusion. - In persons aged 60 years and over with isolated systolic

hypertension, antihypertensive stepped-care drug treatment with low-dose

chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%,

with 5-year absolute benefit of 30 events per 1 000 participants. Major

cardiovascular events were reduced, with 5- year absolute benefit of 55 events

per 1000



Keywords: CARE/MORTALITY/OSLO/POPULATION/RISK/TRIAL/TRIALS



Strandberg, T.E., Salomaa, V.V., Naukkarinen, V.A., Vanhanen, H.T., Sarna, S.J. and

Miettinen, T.A. (1991), Long-Term Mortality After 5-Year Multifactorial

Primary Prevention of Cardiovascular-Diseases in Middle-Aged Men.

Jama-Journal of the American Medical Association, 266 (9), 1225-1229.



Abstract: Objective. - To investigate the long-term effects of multifactorial primary

prevention of cardiovascular diseases (CVD). Design. - The 5-year randomized,

controlled trial was performed between 1974 and 1980. The subjects and their

risk factors were reevaluated in 1985. Posttrial mortality follow-up was

continued up to December 31, 1989. Setting. - Institute of Occupational Health,

Helsinki, Finland, and Second Department of Medicine, University of Helsinki.

Participants. - In all, 3490 business executives born during 1919 through 1934

participated in health checkups in the late 1960s. In 1974, 1222 of these men

who were clinically healthy, but with CVD risk factors, were entered into the

primary prevention trial; 612 were randomized to an intervention and 610 to a

control group. Interventions. - During the 5-year trial, the subjects of the

intervention group visited the investigators every fourth month. They were

treated with intensive dietetic- hygienic measures and frequently with

hypolipidemic (mainly clofibrate and/or probucol) and antihypertensive (mainly

beta- blockers and/or diuretics) drugs. The control group was not treated by the

investigators. Main Outcome Measures. - Total mortality, cardiac mortality,

mortality due to other causes. Results. - Total coronary heart disease risk was

reduced by 46% in the intervention group as compared with the control group at

end-trial. During 5 posttrial years, the risk factor and medication differences

were largely leveled off between the groups. Between 1974 and 1989 the total

number of deaths was 67 in the intervention group and 46 in the control group

(relative risk [RR], 1.45; 95% confidence interval [Cl], 1.01 to 2.08; P=.048);

there were 34 and 14 cardiac deaths (RR. 2.42; 95% Cl. 1.31 to 4.46. P =.001).

two and four deaths due to other CVD (not significant), 13 and 21 deaths due to

cancer (RR, 0.62; 95% Cl, 0.31 to 1.22; P = .15), and 13 and one deaths due to

violence (RR, 13.0;95% Cl, 1.70 to 98.7; P = .002), respectively. Multiple

logistic regression analysis of treatments in the intervention group did not

explain the 15- year excess cardiac mortality. Conclusion. - These unexpected

results may not question multifactorial prevention as such but do support the

need for research on the selection and interaction(s) of methods used in the

primary prevention of cardiovascular diseases



Keywords: BLOOD-PRESSURE/CHOLESTEROL/CORONARY

HEART-DISEASE/METABOLISM/OSLO/PROJECT/STROKE/THERAPY/T

RIAL



Manson, J.E., Stampfer, M.J., Colditz, G.A., Willett, W.C., Rosner, B., Speizer, F.E. and

Hennekens, C.H. (1991), A Prospective-Study of Aspirin Use and Primary

Prevention of Cardiovascular-Disease in Women. Jama-Journal of the American

Medical Association, 266 (4), 521-527.



Abstract: Objective.-The aim of the study was to examine prospectively the association

between regular aspirin use and the risk of a first myocardial infarction and other

cardiovascular events in women. Design. - Prospective cohort study including 6

years of follow-up. Setting. -Registered nurses residing in 11 US states.

Participants. - US registered nurses (n = 87 678) aged 34 to 65 years and free of

diagnosed coronary heart disease, stroke, and cancer at baseline. Follow-up was

96.7% of total potential person-years of follow-up. Main Outcome Measures.-

Incidence of myocardial infarction, stroke, cardiovascular death, and all

important vascular events. Results. - During 475 265 person-years of follow-up,

we documented 240 nonfatal myocardial infarctions, 146 nonfatal strokes, and

130 deaths due to cardiovascular disease (total, 516 important vascular events).

Among women who reported taking one through six aspirin per week, the

age-adjusted relative risk (RR) of a first myocardial infarction was 0.68 (95%

confidence interval [Cl], 0.52 to 0.89; P = .005), as compared with those women

who took no aspirin. After simultaneous adjustment for risk factors for coronary

disease, the RR was 0.75 (95% Cl, 0.58 to 0.99; P = .04). For women aged 50

years and older, the age-adjusted RR was 0.61 (95% Cl, 0.45 to 0.84; P = .002)

and the multivariate RR was 0.68 (95% Cl, 0.50 to 0.93; P = .02). We observed

no alteration in the risk of stroke (multivariate RR = 0.99; P = .94). The

multivariate RR of cardiovascular death was 0.89 (P = .56) and of important

vascular events was 0.85 (P = .12). When examined separately, the results were

nearly identical for the subgroups who took one through three and four though

six aspirin per week. Among women who took seven or more aspirin per week,

there were no apparent reductions in risk. Conclusions.-The use of one through

six aspirin per week appears to be associated with a reduced risk of a first

myocardial infarction among women. A randomized trial in women is necessary,

however, to provide conclusive data on the role of aspirin in the primary

prevention of cardiovascular disease in women



Keywords: ACETYLSALICYLIC-ACID/BLEEDING-TIME/CORONARY

HEART-DISEASE/HEALTHY- SUBJECTS/INHIBITION/LOW-DOSE

ASPIRIN/METABOLITES/PHYSICAL-ACTIVITY/PROSTACYCLIN

PRODUCTION/SEX



Mcgovern, P.G., Burke, G.L., Sprafka, J.M., Xue, S.L., Folsom, A.R. and Blackburn, H.

(1992), Trends in Mortality, Morbidity, and Risk Factor Levels for Stroke from

1960 Through 1990 - the Minnesota Heart Survey. Jama-Journal of the

American Medical Association, 268 (6), 753-759.



Abstract: Objective.-The Minnesota Heart Survey is a population-based study designed

to monitor and explain trends in cardiovascular mortality, morbidity, and risk

factors. Design.-Surveillance time-trends study. Methods.-The following trends

were examined among men and women aged 25 to 74 years living in

Minneapolis- St Paul, Minn: (1) stroke mortality from 1960 through 1990; (2)

risk factors in population-based surveys conducted in 1973 through 1974, 1980

through 1982, and 1985 through 1987; and (3) morbidity in a 50% sample of

hospitalized discharges for acute- stroke in 1970, 1980, and 1985.

Results.-Stroke mortality in Minneapolis-St Paul declined slowly from 1960

through 1972 (average fall, 2.4% per year), dropped sharply from 1972 through

1984 (average fall, 6.5% per year), but exhibited little change thereafter (average

fall, 1.5% per year). The average level of cardiovascular disease risk factors fell

from 1973-1974 to 1985-1987, with the exception of body mass index. In

particular, hypertension diagnosis, treatment, and control levels improved

substantially between 1973-1974 and 1980-1982, although there was little

improvement after 1980-1982. While discharge rates for hospital-coded acute

stroke declined substantially between 1970 and 1985 in both sexes, no clear trend

was observed in definite stroke rates as validated using standard clinical criteria.

Twenty-eight-day case fatality rates of definite stroke improved significantly

from 1970 to 1985. Conclusions.-The substantial decline in stroke mortality of

more than 50% from 1960 through 1990 appears to have been attributable to both

primary and secondary prevention. These data suggest that the long decline in

stroke mortality and morbidity in Minneapolis-St Paul has plateaued, although

improved detection of stroke with computed tomography prevents an

unequivocal conclusion



Keywords: CEREBROVASCULAR-DISEASE/DECLINE/POPULATION/SURVEY

EXPERIENCE/SURVIVAL



Benjamin, E.J., Levy, D., Vaziri, S.M., Dagostino, R.B., Belanger, A.J. and Wolf, P.A.

(1994), Independent Risk-Factors for Atrial-Fibrillation in A Population-Based

Cohort - the Framingham Heart-Study. Jama-Journal of the American Medical

Association, 271 (11), 840-844.



Abstract: Objective.-To determine the independent risk factors for atrial fibrillation.

Design.-Cohort study. Setting.-The Framingham Heart Study. Subjects.-A total

of 2090 men and 2641 women members of the original cohort, free of a history

of atrial fibrilltation, between the ages of 55 and 94 years. Main Outcome

Measures.-Sex-specific multiple logistic regression models to identify

independent risk factors for atrial fibrillation, including age, smoking, diabetes,

electrocardiographic left ventricular hypertrophy, hypertension, myocardial

infarction, congestive heart failure, and valve disease. Results.-During up to 38

years of follow-up, 264 men and 298 women developed atrial fibrillation, After

adjusting for age and other risk factors for atrial fibrillation, men had a 1.5 times

greater risk of developing atrial fibrillation than women. In the full multivariable

model, the odds ratio (OR) of atrial fibrillation for each decade of advancing age

was 2.1 for men and 2.2 for women (P1.62 mg/mmol) (P for trend 50% according to duplex

scanning developed in 13%, most (67%) within 2 years after CEA. Most of these

(77%) were asymptomatic, and only 0.3% (1 patient) presented with a permanent

neurologic deficit. The results of carotid endarterectomy are superior to those of

optimal medical management in symptomatic and asymptomatic patients in

terms of long-term stroke prevention. When low perioperative stroke

mortality/morbidity rates are achieved, carotid endarterectomy is justified for

treatment of patients with carotid bifurcation disease



Keywords: CAROTID ENDARTERECTOMY/CVA/STROKE



Strandgaard, S. and Paulson, O.B. (1992), Regulation of Cerebral Blood-Flow in Health

and Disease. Journal of Cardiovascular Pharmacology, 19 S89-S93.

Abstract: A review is given of the normal regulation of cerebral blood flow (CBF) and

its pathophysiology in hypertension and stroke. In otherwise healthy

hypertensive patients, the absolute level of CBF is the same as in normal subjects.

CBF autoregulation, however, is shifted towards higher pressure, thus impairing

the tolerance to hypotension. In most patients, this does not interfere with the

beneficial effect of treatment, i.e., stroke prevention. Cerebral ischemia, however,

may be provoked by over-zealous pressure lowering in selected clinical settings:

initial or intensified treatment of very severe hypertension, treatment of

hypertension in the elderly, and treatment of hypertension in acute stroke. In the

latter, a complicated sequence of brain ischemia and hyperemia makes

antihypertensive intervention difficult in the early phase, when blood pressure is

probably best allowed to decrease spontaneously



Keywords: ACUTE ISCHEMIC STROKES/ANTIHYPERTENSIVE

TREATMENT/AUTO- REGULATION/AUTOREGULATION/CEREBRAL

BLOOD FLOW/CONVERTING

ENZYME-INHIBITION/DIHYDRALAZINE/HYPERTENSION/HYPERTENS

IVE RATS/INDUCED HYPOTENSION/INFARCTION/STROKE/UPPER

LIMIT



Cruickshank, J.M. (1992), Beta-Blockers - Primary and Secondary Prevention. Journal

of Cardiovascular Pharmacology, 20 S55-S69.



Abstract: Coronary heart disease is the most frequent cause of death in Western,

industralized countries. Coronary risk factors are prevalent in such countries and

sometimes combine to constitute the so-called syndrome X-hypertension, central

obesity, serum lipid and clotting disturbances, and insulin resistance. Beta-

blockers, unlike calcium antagonists, have proved highly effective in secondary

prevention of myocardial infarction. If present at the time of the myocardial

infarction, beta-blockers (unlike calcium antagonists and diuretics) probably

decrease mortality 1 month later. Early intervention (within 12 h) of chest pain

with intravenous beta-blockers results in a 15% reduction in cardiovascular

mortality at 1 week. Later intervention (3-28 days) with oral non-ISA

beta-blockers results in a 30% reduction in mortality after 1 year; ISA-

containing beta-blockers are probably less effective (less decrease in heart rate).

Hydrophilicity/lipophilicity of beta- blockers is unimportant in terms of

decreased mortality. Primary prevention of myocardial infarction, unlike stroke,

in hypertensive patients has been disappointing, possibly due to

treatment-induced biochemical/lipid changes or inappropriate lowering of

diastolic blood pressure in high-risk subjects (J- curve effect). Beta-blockers

should be first-line therapy for hypertensive patients up to the age of 65 years,

particularly men (and nonsmokers) as Q-wave myocardial infarction is

significantly decreased by beta-blockers and significantly increased by diuretics.

However, in elderly hypertensive subjects, beta-blockers have not significantly

decreased myocardial infarction (unlike stroke), whereas diuretics have. The

effects of beta-blockers and diuretics on heart size (and thus coronary flow

reserve) in the elderly may be important. Thus, beta-blockers should be

second-line therapy for the elderly hypertensive individual but first-line if overt

ischemia (e.g., angina or recent myocardial infarction) also is present. In patients

with angina but normal blood pressure, beta-blockers tend to decrease and

calcium antagonists increase cardiovascular events. Thus, beta-blockers are

highly effective agents in the secondary prevention of myocardial infarction and

are moderately effective in primary prevention of myocardial infarction in

hypertensive patients (particularly men) under the age of 65 years



Keywords: ACUTE

MYOCARDIAL-INFARCTION/BETA-BLOCKERS/CORONARY

HEART-DISEASE/DRUG TRIALS/EARLY INTERVENTION/HEART/HIGH

BLOOD-PRESSURE/HYPERTENSIVE PATIENTS/INTRAVENOUS

ATENOLOL/LATE INTERVENTION/METOPROLOL

TRIAL/MORBIDITY/MORTALITY/PRIMARY PREVENTION/Q-WAVE

INFARCTION/SECONDARY PREVENTION/SUDDEN DEATH/UNSTABLE

ANGINA



Fuller, J.H. (1993), Hypertension and Diabetes - Epidemiologic Aspects As A Guide to

Management. Journal of Cardiovascular Pharmacology, 21 S63-S66.



Abstract: Elevated blood pressure (BP) is an important risk factor for both the large- and

small-vessel complications of diabetes. The following pathogenetic mechanisms

have been proposed to explain the association between hypertension and diabetes:

increases in total body exchangeable sodium associated with hyperglycemia,

alterations in the function of the renin-angiotensin- aldosterone system, and the

possible role of insulin resistance. Several prospective studies have shown that

both systolic and diastolic BP are important predictors of ischemic heart disease,

stroke, and renal disease mortality in diabetic patients. In spite of this strong

association, there is little evidence from randomized controlled trials on the

efficacy of BP lowering in the prevention of cardiovascular mortality in diabetic

patients. Prospective data from the WHO Multinational Study do not provide

clear evidence of benefit from treating diastolic BP 65 years of age and have other clinical or echocardiographic risk factors. In

these patients, adjusted-dose warfarin with target international normalized ratios

(INRs) 2.0 to 3.0 is effective and safe. The risk of stroke rises with INR values

3.0 result in an increase in intracerebral hemorrhages,

especially in the very elderly. In contrast, no anticoagulation seems warranted in

younger atrial fibrillation patients 7.4%) which compares

favourably with an estimated upper limit of 5.5% based on recent trial reports.

The present study highlights the difficulty in modelling local clinical practice on

results of major trials when standards of patient evaluation and surgical skill may

differ from those of the large studies. To justify generalization of indications for

intervention based on the multicentre trials, there must be continual monitoring

of local surgical results, and standardized use of diagnostic investigations



Keywords: 1001 ANGIOGRAMS/audit/carotid/carotid endarterectomy/carotid

stenosis/cerebral

infarction/endarterectomy/evaluation/morbidity/mortality/STENOSIS/STROKE/

stroke prevention/SURGERY/trials/ULTRASONOGRAPHY/vascular



Singer, S.T., Quirolo, K., Nishi, K., Hackney-Stephens, E., Evans, C. and Vichinsky,

E.P. (1999), Erythrocytapheresis for chronically transfused children with sickle

cell disease: An effective method for maintaining a low hemoglobin S level and

reducing iron overload. Journal of Clinical Apheresis, 14 (3), 122-125.

Abstract: Cerebrovascular accident (CVA) is a major complication of sickle cell disease

during childhood. Long-term transfusion reduces the hemoglobin S level and

generally prevents recurrent stroke, but it also results in progressive iron

overload that requires regular chelation therapy. Erythrocytapheresis offers an

alternative approach aimed at reducing the iron accumulation. We reviewed the

results of erythrocytapheresis in eight sickle cell patients (mean age of 12.1 years)

at high risk for a first or recurrent stroke. They were maintained at the standard

pre-transfusion hemoglobin S (Hb S) level of 30%. Over an average of 9 months

of erythrocytapheresis, none of the patients developed complications related to

the procedure or to the increased blood use. Ferritin levels decreased by a mean

of 26.5% in all patients. When evaluating the ferritin level in five patients, who

remained on chelation therapy with deferoxamine (DFO), the level dropped by a

mean of 32%. The levels remained stable in the three patients who were not on

DFO. The procedure is safe and effective in reducing iron overload and can

obviate the need for chelation therapy, even when the target Hb S is maintained

at the standard 30% range. (C) 1999 Wiley-Liss,Inc



Keywords:

age/ANEMIA/APHERESIS/CHELATION-THERAPY/complications/CVA/eryt

hrocytapheresis/hemoglobin/iron

overload/NEW-YORK/PREVENTION/recurrent stroke/risk/STROKE/stroke in

sickle cell disease/therapy/transfusion



Fried, L.P., Bandeen-Roche, K., Kaser, J.D. and Guralnik, J.M. (1999), Association of

comorbidity with disability in older women: The Women's Health and Aging

Study. Journal of Clinical Epidemiology, 52 (1), 27-37.



Abstract: There is substantial evidence that physical disability results from chronic

diseases and that the number of chronic diseases is associated with the presence

and severity of disability. There is some evidence that interactions between

specific diseases are of import in causing disability. Beyond arthritis, however,

little is known of the disease pairs that may be important to focus on in future

research. This study explores the associations between multiple disease pairs and

different types of physical disability, with the objective of

hypothesis;development regarding the importance of disease interactions. The

study population comprised a representative sample of 3841 women 65 years and

older living in Baltimore, screened for participation in the Women's Health and

Aging Study. The study design was cross-sectional. An interviewer-

administered screening questionnaire was administered regarding self-reported

physical disability in 15 tasks of daily life, history of physician diagnosis of 14

chronic diseases, and MiniMental State examination. Task difficulty was

empirically grouped into six subsets of minimally overlapping disabilities, with a

comparison group consisting of those with no difficulty in any task subset.

Multiple logistic regression models were fit assessing the relationship of major

chronic diseases and of interactions of disease pairs with each disability subtype

and with any disability, adjusting for confounders. Fourteen percent of the

population reported mobility difficulty only; 5%, upper extremity difficulty only;

9%, both of these difficulties but no others; 7%, difficulty in higher function but

not self-care tasks; 7%, self-care task difficulty but not higher function tasks; and

15%, difficulty in both higher function and self-care (weighted data). Almost all

in the latter three groups had difficulty, as well, in mobility or upper extremity

tasks. In regression models, specific disease pairs were synergistically associated

with different types of disability. For example, important disease pairs that

recurred in their associations with different disability types were the presence of

arthritis and visual impairments, arthritis and high blood pressure, heart disease

and cancer, lung disease and cancer, and stroke and high blood pressure. In

addition, the type of disability that a disease was associated with varied,

depending on the other disease that was present. Finally, when interactions were

accounted for, many diseases were no longer, in themselves, independently

associated with a given type of disability. Partitioning disability into six subtypes

was more informative in terms of associations than was evaluating a summary

category of "any disability." These findings provide a basis for further hypothesis

development and testing of synergistic relationships of specific diseases with

disabilities. If testing confirms these observations, these findings could provide a

basis for new strategies for prevention of disability by minimizing comorbid

interactions. J CLIN EPIDEMIOL 52;1:27-37, 1999. (C) 1999 Elsevier Science

Inc



Keywords: ADULTS/aging/ARTHRITIS/blood pressure/chronic

disease/comorbidity/design/development/diagnosis/disability/diseases/ELDERS/

ENGLAND/geriatrics/heart/high blood pressure/history/physical

disability/physical

function/PHYSICAL-DISABILITY/population/prevention/RISK/severity/stroke/

women



Kannel, W.B. (2000), Vital epidemiologic clues in heart failure. Journal of Clinical

Epidemiology, 53 (3), 229-235.



Abstract: The epidemiologic investigation of heart failure evolution by the Framingham

Heart Study has provided vital clues concerning the pathogenesis, predisposing

conditions, other predictive risk factors, and indicators of deteriorating

ventricular function related to the disease. This information is important in the

early detection of those susceptible to heart failure who are candidates for

preventive measures-of importance because the prevalence of the disease has not

declined despite the recent therapeutic advances. Epidemiologic investigation has

identified useful indicators for the disease including a low or falling vital

capacity suggesting diastolic dysfunction, a rapid resting heart rate in

compensation for a decreased stroke volume, and cardiomegaly indicating

myocardial hypertrophy or dilatation. Hypertension and coronary disease remain

the leading causes of the disease, and heart failure due to myocardial infarction

has increased in prevalence. Hypertension and coronary disease often coexist in

individuals who develop heart failure so that correction and prevention of these

conditions deserve a high priority. Early detection and correction of insulin

resistance is important because a threefold increase in the prevalence of diabetes

in the general population has serious implications for the incidence of heart

failure. In patients with hypertension, the occurrence of a myocardial infarction

increases the risk of developing heart failure five to sixfold, whereas angina

increases it less than twofold. In these patients, the presence of left ventricular

hypertrophy increases the risk of developing heart failure two- to three-fold.

Heart failure-related mortality remains unacceptably high, despite improvements

in treatment, indicating a need for early detection and treatment of predisposing

conditions. (C) 2000 Elsevier Science Inc. All rights reserved



Keywords: angina/coronary disease/detection/diabetes/DILATED

CARDIOMYOPATHY/DISEASE/ENGLAND/epidemiology/heart/heart

failure/HOSPITALIZATION/hypertension/HYPERTENSION/hypertrophy/incid

ence/infarction/insulin resistance/left ventricular

hypertrophy/MORTALITY/myocardial/myocardial

infarction/population/predisposing

conditions/prevalence/PREVENTION/PROGRESSION/risk/risk

factors/stroke/treatment/TRIALS



Ma, E., Gu, X.Q., Wu, X.H., Xu, T. and Haddad, G.G. (2001), Mutation in pre-mRNA

adenosine deaminase markedly attenuates neuronal tolerance to O-2 deprivation

in Drosophila melanogaster. Journal of Clinical Investigation, 107 (6), 685-693.



Abstract: O-2 deprivation can produce many devastating clinical conditions such as

myocardial infarct and stroke. The molecular mechanisms underlying the

inherent tissue susceptibility or tolerance to O-2 lack are, however, not well

defined. Since the fruit fly, Drosophila melanogaster, is extraordinarily tolerant

to O-2 deprivation, we have performed a genetic screen in the Drosophila to

search for loss-of-function mutants that are sensitive to low O-2. Here we report

on the genetic and molecular characterization of one of the genes identified from

this screen, named hypnos-2. This gene encodes a Drosophila pre-mRNA

adenosine deaminase (dADAR) and is expressed almost exclusively in the adult

central nervous system. Disruption of the dADAR gene results in totally unedited

sodium (Para), calcium (Dmca1A), and chloride (DrosGluCl-alpha) channels, a

very prolonged recovery from anoxic stupor, a vulnerability to heat shock and

increased O-2 demands, and neuronal degeneration in aged flies. These data

clearly demonstrate that, through the editing of ion channels as targets, dADAR,

for which there are mammalian homologues, is essential for adaptation to altered

environmental stresses such as O-2 deprivation and for the prevention of

premature neuronal degeneration



Keywords: adenosine/aged/BRAIN/calcium/central nervous

system/CT/DEFICIENT/essential/fruit/gene/GENE-EXPRESSION/genes/geneti

c/GLUTAMATE RECEPTORS/heat/ION CHANNELS/K+

CHANNELS/LETHALITY/mechanisms/myocardial/myocardial

infarct/NERVOUS-SYSTEM/prevention/PROTEIN/RNA-EDITING

ENZYME/sodium/stroke

Ruigomez, A., Johansson, S., Wallander, M.A. and Rodriguez, L.A.G. (2002), Incidence

of chronic atrial fibrillation in general practice and its treatment pattern. Journal

of Clinical Epidemiology, 55 (4), 358-363.



Abstract: The object of this article was to estimate the incidence rate of chronic atrial

fibrillation (AF) in a general practice setting, to identify factors predisposing to

its occurrence, and to describe treatment patterns in the year following the

diagnosis. The method used was a population-based cohort study using the

General Practice Research Database (GPRD) in the UK. We identified patients

aged 40-89 years with a first ever recorded diagnosis of AF. The diagnosis was

validated through a questionnaire sent to the general practitioners. A nested case-

control analysis was performed to assess risk factors for AF using 1,035

confirmed incident cases of chronic AF and a random sample of 5,000 controls

from the original source population. The incidence rate of chronic AF was 1.7

per 1,000 person- years, and increased markedly with age. The age adjusted rate

ratio among males was 1.4 (95% CI 1.2-1.6). The major risk factors were age,

high BMI, excessive alcohol consumption, and prior cardiovascular comorbidity,

in particular, valvular heart disease and heart failure. Digoxin was used in close

to 70% of the patients, and close to 15% did not receive any antiarrhythmic

treatment. Close to 40% did not receive either warfarin or aspirin in the 3 months

period after the diagnosis. Among the potential candidates for anticoagulation

only 22% of those aged 70 years or older were prescribed warfarin in comparison

to 49% among patients aged 40-69 years. Chronic AF is a disease of the elderly,

with women presenting a lower incidence rate than men specially in young age.

Age, weight, excessive alcohol consumption, and cardiovascular morbidity were

the main independent risk factors for AF. Less than half of patients with chronic

AF and no contraindications for anticoagulation received warfarin within the first

trimester after the diagnosis. (C) 2002 Elsevier Science Inc. All rights reserved



Keywords: AF/age/aged/alcohol/alcohol consumption/antiarrhythmic

treatment/anticoagulation/ANTICOAGULATION/ANTITHROMBOTIC

THERAPY/aspirin/atrial/atrial fibrillation/automated

database/cardiovascular/cardiovascular morbidity/chronic/chronic atrial

fibrillation/COHORT/cohort

study/comorbidity/control/diagnosis/disease/elderly/ENGLAND/epidemiology/E

PIDEMIOLOGY/fibrillation/general practice/heart/heart disease/heart

failure/incidence/men/morbidity/population/population-based/PREVALENCE/ri

sk/risk factors/RISK-FACTORS/Spain/STROKE

PREVENTION/treatment/warfarin/WARFARIN USE/weight/women



Ono, A. and Fujita, T. (2003), Stroke prevention in patients with atrial fibrillation.

Journal of Clinical Neuroscience, 10 (1), 71-73.



Abstract: We evaluated the antithrombotic therapy and eligibility for anticoagulation

before stroke in 30 patients with atrial fibrillation (AF) admitted to a district

hospital in Kochi, Japan from 1992 to 1998. The mean age was 77 +/- 10 years

old. Subtypes of ischemic stroke were classified as possibly cardioembolic in 26

(87%) patients and lacunar in four (13%). Eight (26.7%) patients died in the

acute phase and 15 (50%) were disabled at discharge. Most patients were eligible

for anticoagulation before stroke because of previously known AF (80%), high

risk for stroke (80%), absence of contraindications (83.3%), and good clinical

compliance (90%). The prescription rate of warfarin was, however, less than

20% even In high risk patients who needed anticoagulation. In conclusion,

underuse of warfarin and high eligibility for anticoagulation in stroke patients

with AF suggest that the chance of stroke prevention may be lost in many

patients with AF in clinical practice. (C) 2002 Elsevier Science Ltd. All rights

reserved



Keywords: acute/AF/age/ANTICOAGULATION/anticoagulation/antiplatelet

therapy/antithrombotic/antithrombotic therapy/atrial/atrial

fibrillation/cardioembolic/clinical

practice/CLINICAL-PRACTICE/COMMUNITY/fibrillation/high

risk/hospital/INTENSITY/ischemic/ISCHEMIC

STROKE/Japan/MULTICENTER/old/PREVALENCE/prevention/REGISTRY/r

isk/SCOTLAND/stroke/stroke patients/stroke

prevention/therapy/TRIAL/warfarin/WARFARIN USE



Abbott, R.D., Curb, J.D., Rodriguez, B.L., Masaki, K.H., Popper, J.S., Ross, G.W. and

Petrovitch, H. (2003), Age-related changes in risk factor effects on the incidence

of thromboembolic and hemorrhagic stroke. Journal of Clinical Epidemiology,

56 (5), 479-486.



Abstract: We examined the changes in risk factor effects on the incidence of

thromboembolic and hemorrhagic stroke as they may occur with age. Findings

were based on repeated risk factor measurements at four examinations over a

26-year period in 7589 men in the Honolulu Heart Program. After each

examination, 6 years of follow-up were available to assess risk factor effects on

the incidence of stroke over a broad range of ages (45-93 years). As compared

with normotensive men, the risk of thromboembolic stroke in the presence of

hypertension declined from a 7-fold excess in men aged 45 to 54 years to a

1.4-fold excess in men aged greater than or equal to75 (P 180 mmHg) may be

at higher risk for hemodynamic instability and neurological events during carotid

stenting. The greater the change in SBP, the more severe the neurological event

seems to be, but further studies in a greater number of patients are needed to

evaluate the potential causes of SBP fluctuations in an effort to avoid

neurological events



Keywords: age/angioplasty/ANGIOPLASTY/asymptomatic/balloon/blood

pressure/carotid/carotid artery/carotid artery stenosis/carotid stent/carotid

stenting/causes/changes/complications/EMBOLIZATION/ENDARTERECTOM

Y/high

risk/hypotension/HYPOTENSION/men/PLACEMENT/PREDICTORS/PREVE

NTION/risk/secondary/self-expanding

stent/stenosis/stent/stenting/stroke/systolic blood/systolic blood

pressure/THERAPIES/THERAPY/transient/transient ischemic attack/USA



Castriota, F., Cremonesi, A., Manetti, R., Liso, A., Oshola, K., Ricci, E. and Balestra, G.

(2002), Impact of cerebral protection devices on early outcome of carotid

stenting. Journal of Endovascular Therapy, 9 (6), 786-792.



Abstract: Purpose: To evaluate the impact of cerebral protection devices on the

procedural safety and outcome of carotid stent procedures. Methods: From June

1997 to July 2001, 275 consecutive patients (208 men; mean age 71 +/- 7.4 years)

underwent percutaneous angioplasty and/or stenting of the extracranial carotid

artery. In the first 125 (45.4%) patients, the procedures were performed without

cerebral protection. After January 2000, protection devices were routinely used

(150 [54.6%] patients), including the Angioguard filter, GuardWire occlusion

system, TRAP Vascular Filtration System, EPI Filter Wire, NeuroShield, Parodi

Anti-Embolism System, and Medicorp occlusive balloon. Results: The

percutaneous procedures were effective in 273 (99.3%) patients. No death or

major stroke occurred in either group. In the unprotected group, 5 (4.0%)

complications occurred: 3 (2.4%) minor strokes, 1 (0.8%) transient ischemic

attack (TIA), and 1 (0.8%) subarachnoid hemorrhage. In the patients treated

under cerebral protection, there were 2 (1.3%) complications: 1 (0.7%) minor

stroke and 1 (0.7%) subarachnoid hemorrhage. There were 4 (3.2%)

periprocedural embolic complications in the unprotected group versus 1 (0.7%)

in the protected patients. Conclusions: Our data suggest that percutaneous

dilation and stenting of the carotid arteries protected by cerebral protection

devices is feasible and effective. In a consecutive series, the use of the cerebral

protection systems reduced the acute neurological event rate related to embolic

complications by 79%



Keywords: acute/age/ANGIOPLASTY/arteries/ARTERY STENOSIS/balloon/balloon

occlusion systems/carotid/carotid angioplasty/carotid arteries/carotid

artery/carotid stent/carotid stenting/cerebral/cerebral protection/cerebral

protection devices/complications/death/EFFICACY/embolic

complications/EMBOLIC EVENTS/EXPERIENCE/filter systems/flow reversal

systems/hemorrhage/ischemic/Italy/men/outcome/PLACEMENT/PREVENTIO

N/protection/safety/stent/stenting/stroke/subarachnoid

hemorrhage/THERAPIES/THERAPY/TIA/transient/transient ischemic

attack/USA/use



Adami, C.A., Scuro, A., Spinamano, L., Galvagni, E., Antoniucci, D., Farello, G.A.,

Maglione, F., Manfrini, S., Mangialardi, N., Mansueto, G.C., Mascoli, F.,

Nardelli, E. and Tealdi, D. (2002), Use of the Parodi anti-embolism system in

carotid stenting: Italian trial results. Journal of Endovascular Therapy, 9 (2),

147-154.

Abstract: Purpose: To investigate the safety and efficacy of the Parodi anti-embolism

system (PAES) in establishing flow reversal in the internal carotid artery (ICA)

as a means of protecting against embolic phenomena during carotid stenting.

Methods: Seven centers participated in a nonrandomized, prospective trial of

carotid angioplasty and stenting under PAES protection in 30 patients (22 men;

mean age 72 years, range 49-88) with 15 symptomatic (>70%) and 15

asymptomatic (>80%) stenotic ICAs. Safety was defined as achieving sufficient

brain oxygenation during flow reversal as determined by level of awareness and

motor control. The presence of new or enhanced neurological deficits and death

were endpoints. Performance was based on angiographic evidence of successful

retrograde flow. Results: The PAES was positioned in all 30 patients, but

technical error and access-related difficulties prevented establishment of reversed

flow in 2. Among the 28 (93%) patients treated under PAES protection, 1 patient

developed aphasia after flow reversal, necessitating balloon deflation between

subsequent stages of the procedure. Three other adverse events included 1 case

of bradycardia and 2 cases of hypotension, with dysarthria and facial paresis in

one and temporary loss of consciousness in the other. All events resolved with

appropriate therapy, and there was no change from baseline in the neurological

status or brain scans at 24 hours. There were no strokes or neurological deficits at

30 days. Conclusions: The PAES appears to be a safe and effective means of

providing protection from embolic complications during carotid stenting



Keywords: adverse

events/age/angioplasty/asymptomatic/awareness/balloon/BALLOON

ANGIOPLASTY/brain/brain oxygenation/carotid/carotid angioplasty/carotid

artery/carotid stenting/CEREBRAL PROTECTION/cerebral

protection/complications/control/death/DEVICES/EFFICACY/EVENTS/flow

reversal/hypotension/internal carotid

artery/men/paresis/PLACEMENT/PREVENTION/protection/safety/status/stenti

ng/stroke/THERAPIES/THERAPY/trial/Wallstent



Mekaru, S., Fukumoto, I. and Makishi, T. (1995), Studies on Double-Side Shearing with

Parallel and Straight Cutting Edges (Prevention of Tool Breakage by Beveled

Punches with High Slenderness Ratio). Journal of Engineering for

Industry-Transactions of the Asme, 117 (1), 67-71.



Abstract: In the present investigation the cutting edge of a slender punch was bevelled in

an attempt to prevent bending or breakage in use. Tests with Kovar sheet showed

that use of a bevelled punch significantly reduces the risk of bending or breakage,

a particular problem when clearance on both sides of the punch is unbalanced.

This is because the punch guides itself in the later stage of the stroke. Tool life

tests shearing Kovar sheet with the bevelled punch produced a smaller burr on

the product than with the conventional punch. The application of such punches is

found to be most suitable for thin materials such as are used in the manufacture

of IC and LSI parts



Keywords: NEW-YORK/risk/stroke

Penfold, D., Styles, W.M. and Bulpitt, C.J. (1983), North-Hammersmith Stroke

Prevention Project. Journal of Epidemiology and Community Health, 37 (4),

310-314



Keywords: BRITISH/COMMUNITY/HEALTH



Wolfe, C.D.A., Taub, N.A., Woodrow, J., Richardson, E., Warburton, F.G. and Burney,

P.G.J. (1993), Does the Incidence, Severity, Or Case Fatality of Stroke Vary in

Southern England. Journal of Epidemiology and Community Health, 47 (2),

139-143.



Abstract: Study objectives-To determine differences in incidence and case fatality of

stroke in district health authorities with differing standardised mortality ratios

(SMR) for stroke in residents aged under 65 years in whom death from stroke is

considered 'avoidable'. Design-Registration of first ever strokes in three district

health authorities. Patients were assessed and followed up over one year by one

of three observers. Setting-West Lambeth, Lewisham and North Southwark, and

Tunbridge Wells District Health Authorities in south east England.

Participants-Patients under the age of 75 years having a first ever in a lifetime

stroke between 15 August 1989 and 14 August 1990. Measurements and main

results-Age specific incidence rates and survival time from stroke to death.

Severity was assessed in terms of the level of consciousness and the presence of

speech, urinary, and motor impairment within the first 24 hours of the stroke.

Altogether 386 strokes were registered. There was a significant difference in the

incidence rate between district health authorities in those aged under 65 (p25 kg/m(2)).

Conclusions - Taken together, the combination of cigarette smoking, excessive

body fat, and lack of exercise accounted for a major proportion of stroke cases in

the population studied. It appears that these easily identifiable factors related to

lifestyle are a major and possibly predominant cause of stroke, at least until the

age of 75



Keywords: age/aged/body mass

index/BRITISH/COMMUNITY/ENGLAND/exercise/HEALTH/lifestyle/MEN/

obesity/OVERWEIGHT/prevention/risk/RISK-FACTORS/sex/smoking/stroke/st

roke prevention/WOMEN



Hart, C.L., Hole, D.J. and Smith, G.D. (2001), The relation between questions indicating

transient ischaemic attack and stroke in 20 years of follow up in men and women

in the Renfrew/Paisley Study. Journal of Epidemiology and Community Health,

55 (9), 653-656.



Abstract: Study objective-Transient ischaemic attack (TIA) is often a precursor to stroke,

so identification of people experiencing TIA could assist in stroke prevention by

indicating those at high risk of stroke who would benefit most from intervention

for other stroke risk factors. The objective of this study was to investigate

whether answers to a simple questionnaire for TIA could predict the occurrence

of stroke in the following 20 years. Design-Prospective cohort study, conducted

between 1972 and 1976, with 20 years of follow up. Setting Renfrew and Paisley,

Scotland. Participants-7052 men and 8354 women aged 45-64 years at the time

of screening completed a questionnaire and attended a physical examination. The

questionnaire asked participants if they had ever, without warning, suddenly lost

the power of an arm, suddenly lost the power of a leg, suddenly been unable to

speak properly or suddenly lost consciousness. These four questions were taken

as indicators of TIA and were related to subsequent stroke mortality or hospital

admission. Main results-For women, each question was significantly related to

stroke risk, whereas for men only the question on loss of power of arm was

significantly related to stroke risk. Men and women answering two or more

questions positively had double the relative rate of stroke compared with men

and women answering none of the questions positively, even after adjusting for

other risk factors for stroke. Conclusions-A simple questionnaire for TIA could

help predict stroke over 20 years of follow up. Targeting men and women who

report TIA with early treatment could help to prevent strokes from occurring



Keywords: aged/ASSOCIATION/BRITISH/CEREBRAL ISCHEMIA/cohort

study/COMMUNITY/DISEASE/ENGLAND/HEALTH/high

risk/hospital/ischaemic/ISCHEMIC

ATTACKS/men/MORTALITY/POPULATION/prevention/PROGNOSIS/RENF

REW/RISK/risk factors/risk factors for stroke/screening/stroke/stroke

mortality/stroke prevention/TIA/transient/transient ischaemic

attack/treatment/women



Ebrahim, S., May, M., Ben Shlomo, Y., McCarron, P., Frankel, S., Yarnell, J. and Smith,

G.D. (2002), Sexual intercourse and risk of ischaemic stroke and coronary heart

disease: the Caerphilly study. Journal of Epidemiology and Community Health,

56 (2), 99-102.



Abstract: Objective: To examine the relation between frequency of sexual intercourse

and risk of ischaemic stroke and coronary heart disease. Design: Cohort study

with 20 year follow up., Setting: The town of Caerphilly, South Wales and five

adjacent villages. Subjects: 914 men aged 45-59 years at time of recruitment in

1979 to 1983. Main outcome measures: Ischaemic stroke and coronary heart

disease, all first events and fatal events. Results: Of the 914 men studied, 197

(21.5%) reported sexual intercourse less often than once a month, 231 (25.3%)

reported sexual intercourse twice or more a week, and the remaining 486 (53.2%)

men fell into the intermediate category. Frequency of sexual intercourse was not

associated with all first ischaemic stroke events: age adjusted odds ratios (95%

CI) for intermediate and low frequency of sexual intercourse of 0.61 (0.32 to

1.16) and 0.71 (0.34 to 1.49) respectively compared with the reference category

of high frequency. A graded relation with fatal coronary heart disease events was

observed in events recorded up to 10 years. The age adjusted relative risk (95%

CI) of fatal coronary heart disease contrasting low frequency of sexual

intercourse (that is, less than monthly) with the highest group (at least twice a

week) was 2.80 (1.13 to 6.96, test for trend, p=0.04) which was not attenuated by

adjustment for a wide range of potential confounders. Longer follow up to 20

years showed attenuation of this risk with odds of 1.69 (95% CI 0.90 to 3.20),

contrasting low frequency of sexual intercourse with the highest group.

Conclusions: The differential relation between frequency of sexual intercourse,

stroke and coronary heart disease suggests that confounding is an unlikely

explanation for the observed association with fatal coronary heart disease events.

Middle aged men should be heartened to know that frequent sexual intercourse is

not likely to result in a substantial increase in risk of strokes, and that some

protection from fatal coronary events may be an added bonus

Keywords: age/aged/BENIGN/BRITISH/COMMUNITY/coronary heart

disease/DEATH/disease/England/EXERTION/HEADACHES/HEALTH/heart/h

eart disease/HYPERTENSION/INFARCTION/ischaemic/ischaemic

stroke/LONDON/low

frequency/MEN/ORGASM/outcome/PHYSICAL-ACTIVITY/PREVENTION/p

rotection/recruitment/relative risk/risk/risk of ischaemic stroke/stroke



Lawlor, D.A., Bedford, C., Taylor, M. and Ebrahim, S. (2003), Geographical variation

in cardiovascular disease, risk factors, and their control in older women: British

Women's Heart and Health Study. Journal of Epidemiology and Community

Health, 57 (2), 134-140.



Abstract: Objectives: To measure the geographical variation in prevalence of

cardiovascular disease, risk factors, and their control in a nationally

representative sample of older British women. Methods: Baseline survey using

general practitioner record review, a self completed questionnaire, research nurse

interview, and physical examination in a randomly selected sample of women

aged 60-79 drawn from 23 towns in England, Scotland, and Wales. Results: Of

7173 women invited and eligible to participate, information was obtained on

4286 (60%). One in five women had a doctor diagnosis of any one of myocardial

infarction, angina, heart failure, stroke, or peripheral vascular disease. Fifty per

cent of women were hypertensive, 12% smoked, and over one quarter were

obese. Fifty per cent had a total cholesterol level greater than 6.5 mmol/l, though

only 3% had low high density lipoprotein concentrations. Cardiovascular disease

prevalence varied by geographical region being highest in Scotland: age adjusted

prevalence (95% confidence intervals) 25.0% (21.5% to 28.8%) and lowest in

South England: age adjusted prevalence (95% confidence intervals) 15.4%

(13.5% to 17.6%). The geographical variations in cardiovascular disease

prevalence were attenuated by adjustment for risk factors and socioeconomic

position; further adjustment for health service use (as indicated by aspirin or

statin use) reduced the differences further. However, variation remained even

after full adjustment for these factors: odds ratio (95% confidence intervals)

comparing Midlands and Wales to South England 1.15 (0.82 to 1.61) and

comparing Scotland to South England 1.53 (1.08 to 2.14). Of women with

cardiovascular disease, 12% were current smokers, a third had uncontrolled

hypertension, a third were obese, and 90% had a blood cholesterol over 5 mmol/l.

Only 41% were taking antiplatelet drugs and 22% were taking a statin.

Conclusions: Older British women have a higher prevalence of cardiovascular

disease and risk factors than previously documented. The workload

consequences of attempting to control risk factors and ensure optimal secondary

prevention for older British women are considerable. Geographical variations in

cardiovascular disease prevalence in older women are somewhat, but not fully,

explained by variations in major risk factors, socioeconomic position, and health

service utilisation



Keywords: age/aged/angina/antiplatelet/antiplatelet

drugs/aspirin/BRITISH/CARDIOLOGY/cardiovascular/cardiovascular

disease/cholesterol/CLINICAL-PRACTICE/COMMUNITY/control/DEPRIVAT

ION/diagnosis/disease/drugs/ENGLAND/HEALTH/heart/heart failure/high

density

lipoprotein/HYPERTENSION/INEQUALITIES/infarction/LONDON/MORTAL

ITY/myocardial/myocardial infarction/peripheral vascular

disease/prevalence/PREVENTION/RECOMMENDATIONS/research/review/ris

k/risk factors/secondary/secondary

prevention/statin/stroke/survey/TASK-FORCE/use/vascular/vascular

disease/women



Massberg, S., Sausbier, M., Klatt, P., Bauer, M., Pfeifer, A., Siess, W., Fassler, R., Ruth,

P., Krombach, F. and Hofmann, F. (1999), Increased adhesion and aggregation

of platelets lacking cyclic guanosine 3 ',5 '-monophosphate kinase I. Journal of

Experimental Medicine, 189 (8), 1255-1263.



Abstract: Atherosclerotic vascular lesions are considered to be a major cause of ischemic

diseases, including myocardial infarction and stroke. Platelet adhesion and

aggregation during ischemia- reperfusion are thought to be the initial steps

leading to remodeling and reocclusion of the postischemic vasculature. Nitric

oxide (NO) inhibits platelet aggregation and smooth muscle proliferation A

major downstream target of NO is cyclic guanosine 3',5'-monophosphate kinase I

(cGKI). To test the intravascular significance of the NO/cGKI signaling pathway

in vivo, we have studied platelet-endothelial cell and platelet- platelet

interactions during ischemia/reperfusion using cGKI- deficient (cGKI(-/-)) mice.

Platelet cGKI but not endothelial or smooth muscle cGKI is essential to prevent

intravascular adhesion and aggregation of platelets after ischemia. The defect in

platelet cGKI is not compensated by the cAMP/cAMP kinase pathway

supporting the essential role of cGKI in prevention of ischemia-induced platelet

adhesion and aggregation



Keywords: aggregation/CGMP/cyclic guanosine 3 '/5 '-monophosphate-dependent

protein kinase/DEPENDENT PROTEIN-KINASE/diseases/endothelial

cell/ENDOTHELIAL-CELLS/fluorescence

microscopy/infarction/INHIBITION/INTACT HUMAN

PLATELETS/ischemia/ischemic/MICE

LACKING/microcirculation/muscle/myocardial/myocardial

infarction/NEW-YORK/nitric

oxide/NITRIC-OXIDE/PHOSPHORYLATION/PLASMINOGEN-ACTIVATO

R/platelet

aggregation/platelets/prevention/reperfusion/smooth/stroke/vascular/vasculature/

VASODILATOR-STIMULATED PHOSPHOPROTEIN



MacGregor, E.A. and Hackshaw, A. (2002), Prevention of migraine in the pill-free

interval of combined oral contraceptives: A double-blind, placebo-controlled

pilot study using natural oestrogen supplements. Journal of Family Planning and

Reproductive Health Care, 28 (1), 27-31.

Abstract: Context. Migraine in the pill-free interval of combined oral contraceptives is

reported by many women, but there is little published information on possible

mechanisms and treatments. Objective. To determine whether the use of natural

oestrogen patches affected the occurrence and severity of migraine during the

pill-free interval. Design. A double-blind, placebo- controlled, randomised,

crossover study. Setting. The City of London Migraine Clinic. Participants.

Fourteen women with migraine during the pill-free interval. Interventions. 50

mug oestradiol patches (Evorel(TM)) used during the pill-free interval for two

cycles versus placebo for two cycles (total four cycles). Main outcome measures.

Number of pill-free intervals (Zero, one or two) during which migraine occurred;

number of days of migraine; severity of migraine; number of clays of migraine

accompanied by nausea, vomiting and/or photophobia. Results. Complete data

were available for 12 women and for two cycles for one woman. Use of 50 mug

oestrogen patches during the pill-free interval showed a trend towards reducing

the frequency and severity of migraine. Discussion. These results were not as

good as expected. However, we had originally aimed for 20 eligible women to

participate in the trial, but only 14 were recruited and only 12 completed the

study with full data for analysis. Conclusion. The results of this pilot study

suggest that use of 50 mug oestrogen patches during the pill-free interval may

reduce the frequency and severity of migraine at that time. This study should be

repeated with larger numbers of women and a higher dose of oestrogen



Keywords: ATTEMPTED

PROPHYLAXIS/CARE/CYCLE/England/ESTRADIOL/ESTROGEN-WITHD

RAWAL MIGRAINE/HEALTH/HEALTH-CARE/mechanisms/MENSTRUAL

MIGRAINE/migraine/oral

contraceptives/outcome/RISK/severity/STROKE/trial/use/women/YOUNG-WO

MEN



Antani, M.R., Beyth, R.J., Covinsky, K.E., Anderson, P.A., Miller, D.G., Cebul, R.D.,

Quinn, L.M. and Landefeld, C.S. (1996), Failure to prescribe warfarin to patients

with nonrheumatic atrial fibrillation. Journal of General Internal Medicine, 11

(12), 713-720.



Abstract: OBJECTIVE: To determine how often warfarin was prescribed to patients

with nonrheumatic atrial fibrillation in our community in 1992 when randomized

trials had demonstrated that warfarin could prevent stroke with little increase in

the rate of hemorrhage, and to determine whether warfarin was prescribed less

frequently to older patients-the patients at highest risk of stroke but of most

concern to physicians in terms of the safety of warfarin. DESIGN:

Cross-sectional study. Appropriateness of warfarin was classified for each

patient based on the independent judgments of three physicians applying relevant

evidence and guidelines. SETTING: Two teaching hospitals and five

community-based practices. PATIENTS: Consecutive patients with

nonrheumatic atrial fibrillation (n = 189). MEASUREMENTS AND MAIN

RESULTS: Warfarin was prescribed to 44 (23%) of the 189 patients. Warfarin

was judged appropriate in 98 patients (52%), of whom 36 (37%) were prescribed

warfarin. Warfarin was prescribed to 11 (14%) of 76 patients aged 75 years or

older with hypertension, diabetes mellitus, or past stroke, the group at highest

risk of stroke. In a multivariable logistic regression model controlling for

appropriateness of warfarin and other patient characteristics, patients aged 75

years or older were less likely than younger patients to be treated with warfarin

(odds ratio 0.25; 95% confidence interval 0.10, 0.65). CONCLUSIONS:

Warfarin was prescribed infrequently to these patients with nonrheumatic atrial

fibrillation, especially the older patients and even the patients for whom warfarin

was judged appropriate. These findings indicate a substantial opportunity to

prevent stroke



Keywords: aged/ANTICOAGULATION/ANTITHROMBOTIC THERAPY/atrial

fibrillation/CARE/CLINICAL-TRIALS/COMPLICATIONS/DESIGN/diabetes/

diabetes

mellitus/fibrillation/guidelines/hemorrhage/hypertension/INTERNAL/MEASUR

EMENT/nonrheumatic/PATIENT/physician

behavior/PHYSICIANS/PRACTICE GUIDELINES/PREDICTION/prescription

practices/PREVALENCE/PREVENTION/quality of

care/randomized/randomized trials/risk/safety/STROKE/stroke

prevention/trials/warfarin



Beyth, R.J., Antani, M.R., Covinsky, K.E., Miller, D.G., Chren, M.M., Quinn, L.M. and

Landefeld, C.S. (1996), Why isn't warfarin prescribed to patients with

nonrheumatic atrial fibrillation? Journal of General Internal Medicine, 11 (12),

721-728.



Abstract: OBJECTIVE: To determine the opinions of selected physicians in our

community about use of warfarin for patients with nonrheumatic atrial

fibrillation, and to determine the relation of the physicians' opinions to their

practices. DESIGN: Survey of physicians, using eight hypothetical clinical

vignettes to characterize physicians' opinions about use of warfarin in patients

with nonrheumatic atrial fibrillation, according to patient age, risk of bleeding,

and risk of stroke. SETTING: Two teaching hospitals and five community-based

practices. PARTICIPANTS: Eighty physicians who cared for 189 consecutive

patients with nonrheumatic atrial fibrillation. MEASUREMENTS AND MAIN

RESULTS: The survey response rate was 73%. Nearly all responding physicians

(90%) recommended warfarin for at least one vignette. However, physicians

recommended warfarin less often for vignettes depicting 85-year-old patients

than for matched vignettes depicting 88-year-old patients (odds ratio [OR] 0.03;

95% confidence interval [CI] 0.01, 0.08), and less often for cases with specified

risk factors for bleeding than for matched cases without the risk factors (OR 0.01;

95% CI 0.004, 0.03); warfarin was recommended more often for cases with a

recent stroke than for matched cases without this history (OR 8.2; 95% CI 3.6,

18). In practice, warfarin was prescribed more often (p less than or equal to .05)

by physicians reporting good personal experience and by those who had

favorable opinions about its use. However, even physicians with good experience

and favorable opinions did not prescribe warfarin to half of their patents for

whom warfarin was independently judged appropriate. CONCLUSIONS:

Physicians' opinions frequently opposed warfarin for older patients with

nonrheumatic atrial fibrillation, and for those with bleeding risk factors.

Physicians' opinions, as well as other barriers to warfarin therapy, most likely

contribute to its infrequent prescription



Keywords: age/ANTICOAGULATION/ANTITHROMBOTIC

THERAPY/ASPIRIN/atrial

fibrillation/ATTITUDES/CARE/DESIGN/fibrillation/history/INTERNAL/JUD

GMENT/MEASUREMENT/medical decision

making/nonrheumatic/OMISSION/PHYSICIAN/physician

opinions/PREDICTION/prescription practices/risk/risk factors/stroke/STROKE

PREVENTION/therapy/TRIAL/warfarin



Augustovski, F.A., Cantor, S.B., Thach, C.T. and Spann, S.J. (1998), Aspirin for

primary prevention of cardiovascular events. Journal of General Internal

Medicine, 13 (12), 824-835.



Abstract: OBJECTIVE: The use of aspirin for primary prevention of cardiovascular

events in the general population is controversial. The purpose of this study was

to create a versatile model to evaluate the effects of aspirin in the primary

prevention of cardiovascular events in patients with different risk profiles.

DESIGN:A Markov decision-analytic model evaluated the expected length and

quality of life for the cohort's next 10 years as measured by quality-adjusted

survival for the options of taking or not taking aspirin. SETTING: Hypothetical

model of patients in a primary care setting. PATIENTS: Several cohorts of

patients with a range of risk profiles typically seen in a primary care setting were

considered. Risk factors considered included gender, age, cholesterol levels,

systolic blood pressure, smoking status, diabetes, and presence of left ventricular

hypertrophy. The cohorts were followed for 10 years. Outcomes were

myocardial infarction, stroke, gastrointestinal bleed, ulcer, and death. MAIN

RESULTS: For the cases considered, the effects of aspirin varied according to

the cohort's risk profile. By taking aspirin, the lowest-risk cohort would be the

most harmed with a loss of 1.8 quality-adjusted life days by taking aspirin; the

highest risk cohort would achieve the most benefit with a gain of 11.3

quality-adjusted life days. Results without quality adjustment favored taking

aspirin in all the cohorts, with a gain of 0.73 to 8.04 days. The decision was

extremely sensitive to variations in the utility of taking aspirin and to aspirin's

effects on cardiovascular mortality. The model was robust to other probability

and utility changes within reasonable parameters. CONCLUSIONS: The

decision of whether to take aspirin as primary prevention for cardiovascular

events depends on patient risk. It is a harmful intervention for patients with no

risk factors, and it is beneficial in moderate and high-risk patients. The benefits

of aspirin in this population are comparable to those of other widely accepted

preventive strategies. It is especially dependent on the patient's risk profile,

patient preferences for the adverse effects of aspirin, and on the level of

beneficial effects of aspirin on cardiovascular-related mortality

Keywords: aspirin/blood pressure/cardiovascular disease/cardiovascular

events/cholesterol/COST-EFFECTIVENESS/decision

analysis/DISEASE/HEALTH-

PROFESSIONALS/hypertrophy/MORTALITY/myocardial

infarction/MYOCARDIAL-INFARCTION/NONVALVULAR

ATRIAL-FIBRILLATION/PATIENT/PREFERENCES/prevention/primary

care/primary prevention/PROPHYLAXIS/risk/risk factors/RISK PROFILE/risk

stratification/smoking/STROKE



Shorr, R.I., Johnson, K.C., Wan, J.Y., Sutton-Tyrrell, K., Pahor, M., Bailey, J.E. and

Applegate, W.B. (1998), The prognostic significance of asymptomatic carotid

bruits in the elderly. Journal of General Internal Medicine, 13 (2), 86-90.



Abstract: OBJECTIVE: To determine the association between asymptomatic carotid

bruits and the development of subsequent stroke in older adults with isolated

systolic hypertension. DESIGN: Retrospective cohort study. SETTING: The

Systolic Hypertension in the Elderly Program (SHEP), a 5-year randomized trial

testing the efficacy of treating systolic hypertension in noninstitutionalized

persons aged 60 years or older. From the original 4,736 SHEP participants, we

identified a cohort of 4,442 persons who had no prior history of stroke, transient

ischemic attack, or myocardial infarction at randomization. MEASUREMENTS

AND MAIN RESULTS: The end point for this ancillary study was the

development of a stroke. The average follow-up was 4.2 years. Carotid bruits

were found in 284 (6.4%) of the participants at baseline. Strokes developed in 21

(7.4%) of those with carotid bruits and in 210 (5.0%) of those without carotid

bruits. The unadjusted risk of stroke among persons with carotid bruits was 1.53

(95% confidence interval [CI] 0.98, 2.40). Adjusting for age, gender, race, blood

pressure, smoking, lipid levels, self-reported aspirin use, and treatment group

assignment, the relative risk of stroke among persons with asymptomatic carotid

bruits was 1.29 (95% CI 0.80, 2.06). Among SHEP enrollees aged 60 to 69 years,

there was a trend (p = .08) toward increased risk (relative risk [RR] 2.05: 95% CI

0.92, 4.68) of subsequent stroke in persons with, compared to those without,

carotid bruits. However, among enrollees aged 70 years or over, there was no

relation between carotid bruit and subsequent stroke (RR 0.98; 95% CI 0.55,

1.76). In no other subgroup of SHEP enrollees did the presence of carotid bruit

independently predict stroke. CONCLUSIONS: Although we cannot rule out a

small increased risk of stroke associated with bruits in asymptomatic SHEP

enrollees aged 60 to 69 years, the utility of carotid bruits as a marker for

increased risk of stroke among asymptomatic elderly with isolated systolic

hypertension aged 70 years or older is limited



Keywords: adults/AGE/aged/aspirin/asymptomatic/blood pressure/carotid/carotid

bruits/CLINICAL- SIGNIFICANCE/cohort study/CORONARY

HEART-DISEASE/DESIGN/development/elderly/history/hypertension/infarctio

n/isolated systolic hypertension/MEASUREMENT/myocardial

infarction/NECK/POPULATION/PREVENTION/PROGRAM/race/relative

risk/RISK/SHEP/smoking/STROKE/stroke/SYSTOLIC

HYPERTENSION/Systolic Hypertension in the Elderly Program

(SHEP)/transient/transient ischemic attack/treatment



Warshafsky, S., Packard, D., Marks, S.J., Sachdeva, N., Terashita, D.M., Kaufman, G.,

Song, K., Deluca, A.J., Peterson, S.J. and Frishman, W.H. (1999), Efficacy of

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for prevention of

stroke. Journal of General Internal Medicine, 14 (12), 763-774.



Abstract: OBJECTIVE: To determine if 3-hydroxy-3-methylglutaryl coenzyme A

(HMG-CoA) reductase inhibitors (statins) are effective in preventing fatal and

nonfatal strokes in patients at increased risk of coronary artery disease. DESIGN:

Mete-analysis of randomized controlled trials. Clinical trials were identified by a

computerized search of MEDLINE (1983 to June 1996), by an assessment of the

bibliographies of published studies, mete- analyses and reviews, and by

contacting pharmaceutical companies that manufacture statins. Trials were

included in the analysis if their patients were randomly allocated to a statin or

placebo group, and reported data on stroke events. Thirteen of 28 clinical trials

were selected for review. Data were extracted for details of study design, patient

characteristics, interventions, duration of therapy, cholesterol measurements, and

the number of fatal and nonfatal stroke events in each arm of therapy. Missing

data on stroke events were obtained by contacting the investigators of the clinical

trials. MAIN RESULTS: Among 19,921 randomized patients, the late of total

stroke in the placebo group was 2.38% (90% nonfatal and 10% fatal). In contrast,

patients who received statins had a 1.67% stroke rate. Using an exact stratified

analysis, the pooled odds ratio (OR) for total stroke was 0.70 (95% confidence

interval [CI] 0.57, 0.86; p = .0005). The pooled OR for nonfatal stroke was 0.64

(95% CI 0.51, 0.79; p = .00001), and the pooled OR for fatal stroke was 1.25

(95% CI 0.71, 2.24; p = .4973). In separate analyses, reductions in total and

nonfatal stroke risk were found to be significant only for trials of secondary

coronary disease prevention. Regression analysis showed no statistical

association between the magnitude of cholesterol reduction and the relative risk

for any stroke outcome. CONCLUSIONS:The available evidence clearly shows

that HMG-CoA reductase inhibitors reduce the morbidity associated with strokes

in patients at increased risk of cardiac events. Data from 13 placebo-controlled

trials suggest that on average one stroke is prevented for every 143 patients

treated with statins over a 4-year period



Keywords: cardiac/CAROTID ATHEROSCLEROSIS/cholesterol/clinical

trials/coronary artery disease/coronary disease/CORONARY-ARTERY

DISEASE/DESIGN/disease/ELEVATED APOLIPOPROTEIN-B/EXPANDED

CLINICAL-EVALUATION/HEART-DISEASE/HMG-CoA reductase

inhibitors/LIPID- LOWERING THERAPY/meta-analysis/MODERATE

HYPERCHOLESTEROLEMIA/morbidity/outcome/prevention/randomized/rand

omized controlled trials/relative risk/review/risk/SCANDINAVIAN

SIMVASTATIN SURVIVAL/SECONDARY

PREVENTION/SERUM-CHOLESTEROL LEVELS/statin/statins/stroke/stroke

outcome/stroke prevention/therapy/trials

Lafata, J.E., Martin, S.A., Kaatz, S. and Ward, R.E. (2000), The cost-effectiveness of

different management strategies for patients on chronic warfarin therapy. Journal

of General Internal Medicine, 15 (1), 31-37.



Abstract: OBJECTIVE:To examine the cost-effectiveness of moving from usual care to

more organized management strategies for patients on chronic warfarin therapy.

DESIGN:Using information available in the scientific literature, supplemented

with data from a large health system and, when necessary, expert opinion, we

constructed a 5-year Markov model to evaluate the health and economic

outcomes associated with each of three different anticoagulation management

approaches: usual care, anticoagulation clinic testing with a capillary monitor,

and patient self-testing with a capillary monitor. PATIENTS:Three hypothetical

cohorts of patients beginning long-term warfarin therapy were used to generate

model results. MAIN RESULTS:Model results indicated that moving from usual

care to anticoagulation clinic testing would result in a total of 1.7

thromboembolic events and 2.0 hemorrhagic events avoided per 100 patients

over 5 years. Another 4.0 thromboembolic events and 0.8 hemorrhagic events

would be avoided by moving to patient self-testing. When direct medical care

costs and those incurred by patients and their caregiver, in receiving care were

considered, patient self-testing was the most cost- effective alternative, resulting

in an overall cost saving. CONCLUSIONS:Results illustrate the potential health

and economic benefits of organized care management approaches and capillary

monitors in the management of patients receiving warfarin therapy



Keywords: anticoagulation/anticoagulation management/BLEEDING

COMPLICATIONS/cost/cost effectiveness/cost-effectiveness/cost-effectiveness

analysis/costs/decision analytic

model/DECISION-ANALYSIS/DISABILITY/health/LIFE/MONITOR/NONVA

LVULAR ATRIAL-FIBRILLATION/ORAL

ANTICOAGULANT-THERAPY/PREVENTION/RISK-FACTORS/STROKE

PATIENTS/therapy/thromboembolic events/warfarin



Weisbord, S.D., Whittle, J. and Brooks, R.C. (2001), Is warfarin really underused in

patients with atrial fibrillation? Journal of General Internal Medicine, 16 (11),

743-749.



Abstract: CONTEXT: There is agreement that warfarin decreases stroke risk in patients

with atrial fibrillation (AF), but prior studies suggest that warfarin is markedly

underused, for unclear reasons. OBJECTIVE: To determine if warfarin is

underused In the treatment of patients with atrial fibrillation. DESIGN:

Cross-sectional. SETTING: Tertiary care VA hospital. PATIENTS: All patients

with a hospital or outpatient diagnosis of AF between 10/1/95 and 5/31/98.

DATA COLLECTION:. One or more physician investigators reviewed pertinent

records for each patient. When any of the 3 investigators thought warfarin might

be indicated, the patient's primary care provider completed a survey regarding

why warfarin was not used. RESULTS: Of 1,289 AF patients, 844 (65%) had

filled at least 1 warfarin prescription. Of the 445 remaining, 19 had died, 5 had

inadequate medical records, and 54 received warfarin elsewhere, leaving 367

patients. Of these, 160 had no documented AF, 53 had only a history of AF, and

49 had only transient AF. Of the remaining 105 patients, 17 refused warfarin

therapy and 72 had documented contraindications to warfarin use including

bleeding risk or history, fall risk, alcohol abuse, or other compliance problems.

The reasons for not using warfarin among the 16 patients remaining included

provider oversight (n = 4) and various reasons suggesting provider knowledge

deficits. CONCLUSION: In contrast to prior studies that suggested that warfarin

is markedly underused, we found that few patients with AF and no

contraindication to anticoagulation were not receiving warfarin. We believe that

differing study methodologies, including the use of physician review and

provider survey, may explain our markedly different rate of warfarin

underutilization, although local institutional factors cannot be excluded. The

findings suggest that primary providers may be far more compliant with the

standard of care for patients with atrial fibrillation than previously believed



Keywords: AF/alcohol/ANTICOAGULATION/atrial

fibrillation/bleeding/COMMUNITY/CONTEXT/DESIGN/diagnosis/fibrillation/

history/hospital/HOSPITALS/institutional/knowledge/MANAGEMENT/medical

/NATIONAL PATTERNS/PATIENT/PHYSICIAN ATTITUDES/physician

practice/PREVALENCE/primary/primary care/QUALITY/quality of

care/review/risk/stroke/STROKE

PREVENTION/survey/THERAPY/transient/treatment/use/warfarin



Landon, B.E., Wilson, I.B., Wenger, N.S., Cohn, S.E., Fichtenbaum, C.J., Bozzette, S.A.,

Shapiro, M.F. and Cleary, P.D. (2002), Specialty training and specialization

among physicians who treat HIV/AIDS in the United States. Journal of General

Internal Medicine, 17 (1), 12-22.



Abstract: Objective: To assess the association of specialty training and experience in the

care of HIV disease with HIV-specific knowledge, referral patterns, and

HI-V-related education activities. Design. Cross-sectional survey. Setting: The

United States. Participants: Physicians caring for patients in the HIV Costs and

Service Utilization Study, a study of a probability sample of HIV-infected

individuals in the United States. Measurements and main results: Measures

included physicians' reports of specialty training and HIV caseload, scores on an

HIV-specific knowledge test, referral patterns, and attendance rates at

HIV-related educational activities. Approximately 72% (379) of the eligible

physicians completed a survey. Of these, 152 (40%) had infectious disease (ID)

training, and 213 (56%) were generalists; 4% of ID-trained physicians and 37%

of generalist physicians did not consider themselves HIV experts. The median

current caseloads were 150 and 200 patients for ID experts and generalist experts,

respectively. In contrast, the median caseload for non-expert generalists was 5.

Mean scores on the knowledge scale were similar for ID and generalist experts

(9.0 items correct out of 11 vs 8.5; P=not significant), but lower for generalist

non-experts (6.5 items correct; P50 were more

likely to have a high knowledge score (defined as 80% or more correct, odds

ratio [OR], 2.8; P=.04 and OR, 5.7; P90 mm Hg 24-h post dose), the

dose was doubled for a further 4 weeks. After 8 weeks felodipine-metoprolol

reduced supine BP significantly more than enalapril (19.7/12.0 mmHg and

11.1/7.2 mm Hg, respectively). The mean differences in change in BP between

treatments were 8.6/4.8 mm Hg in favour of felodipine- metoprolol (P = 0.001/P

60 years) may increase the risk of stroke. However, a J-shaped

relationship between both mortality and morbidity and blood pressure has been

reported in the untreated controls of the Hypertension in Elderly Patients in

primary care (HEP) study. In the European Working Party on High Blood

Pressure in the Elderly trial (EWPHE) there was a U-shaped relationship

between total mortality and treated systolic pressure, but a similar U-shaped

relationship was observed with diastolic pressure in patients on placebo. In

addition, patients with the lowest pressure during treatment showed the greatest

falls in body weight and haemoglobin concentrations, suggesting that the

increased mortality seen with lower blood pressure levels may have been an

expression of a deterioration in general health. Moreover, a U-shaped

relationship between blood pressure and mortality has been observed in the very

old (aged 80+ years). Conclusions: While it is premature to conclude, on the

basis of present evidence, that reducing blood pressure to the lower part of the

normal range is harmful in older patients, it appears prudent, nonetheless, not to

lower blood pressure excessively with treatment in this age group



Keywords: AGE/CORONARY HEART-DISEASE/DIASTOLIC

BLOOD-PRESSURE/ELDERLY/EPIDEMIOLOGY/EUROPEAN-

WORKING-PARTY/FLOW

RESERVE/FOLLOW-UP/HYPERTENSION/ISCHEMIC HEART

DISEASE/MORTALITY/MYOCARDIAL-INFARCTION/PRIMARY

PREVENTION TRIAL/STROKE/TREATED HYPERTENSION



Vonlutterotti, N., Camargo, M.J.F., Campbell, W.G., Mueller, F.B., Timmermans, P.B.,

Sealey, J.E. and Laragh, J.H. (1992), Angiotensin-Ii Receptor Antagonist Delays

Renal Damage and Stroke in Salt-Loaded Dahl Salt-Sensitive Rats. Journal of

Hypertension, 10 (9), 949-957.



Abstract: Objective: To study the effects of blockade of the renin- angiotensin system

upon the development of hypertension, end- organ damage and mortality in Dahl

salt-sensitive (DSS) rats using an angiotensin 11 receptor antagonist, losartan.

Design and methods: DSS rats (n = 186) were fed 8% NaCl from 6 to 16 weeks

of age. One group received losartan whilst the control group was untreated.

Changes in blood pressure and plasma renin activity (PRA), as well as renal and

cerebrovascular damage and survival were assessed during the study. Results:

Losartan blunted the blood pressure rise only transiently. Salt loading suppressed

PRA in both groups until week 4 and thereafter it rose more markedly in the

treated group. With no treatment renal lesions were first detected at 2 weeks, and

strokes at 6 weeks. However, losartan transiently decreased the incidence and

delayed the progression of renal damage and cerebrovascular lesions (strokes)

and increased survival. PRA correlated with renal damage and the incidence of

strokes in both groups. Blood pressure only partially affected survival, but did

not correlate with stroke incidence. Conclusions: These results indicate that

whereas the rise in blood pressure is dependent upon sodium loading, morbidity

and mortality in salt-loaded DSS rats are associated with activation of the

renin-angiotensin system and are only partially related to blood pressure



Keywords: ACTIVE ANTIHYPERTENSIVE

AGENT/BLOOD-PRESSURE/CALCIUM-ANTAGONISTS/CAPTOPRIL/CER

EBROVASCULAR

LESIONS/ENALAPRIL/HYPERTENSION/HYPERTROPHY/PLASMA-RENI

N/PREVENTION/RENAL LESIONS/RENIN ANGIOTENSIN SYSTEM/SALT

LOADING/SMOOTH-MUSCLE CELLS/SPONTANEOUSLY

HYPERTENSIVE RATS/SURVIVAL



Johannesson, M. and Fagerberg, B. (1992), A Health Economic Comparison of Diet and

Drug-Treatment in Obese Men with Mild Hypertension. Journal of Hypertension,

10 (9), 1063-1070.

Abstract: Objective: To compare dietary and antihypertensive drug treatment in obese

men with mild hypertension in economic terms. Design: A 6-week run-in period

followed by randomization to either diet or drug treatment, lasting for 1 year.

Blood pressure was measured blindly and serum lipid concentrations assessed at

run-in and after 1 year. A computer-based model was used in five

cost-effectiveness simulations with different assumptions as to the effect upon

coronary heart disease risk from the changes in diastolic blood pressure and

cholesterol, both total and high-density lipoprotein. A cost-benefit analysis was

also performed, calculated as willingness to pay for treatment, as assessed by

questionnaire, minus total cost. Setting: Outpatient clinic in city hospital. Patients:

Sixty- four men aged 40-69 years with body mass index greater-than-or- equal-to

26 kg/m2 and a diastolic blood pressure 90-104 mmHg when untreated were

recruited (screening after advertisement in newspaper). Exclusion criteria were

diabetes mellitus, organ damage secondary to hypertension, and diseases that

might have interfered with compliance and the interpretation of results. Sixty-one

patients completed the study. Interventions: Dietary treatment was based upon

weight reduction and sodium restriction. Drug treatment used a stepped-care

approach, with atenolol as the drug of first choice. Main outcome measures: Life

years gained and willingness to pay. Results: Drug treatment was the preferred

option in three of the five cost- effectiveness simulations. The cost-benefit

analysis did not show any difference between the two groups. Conclusions: Non-

pharmacological treatment seemed to be less cost-effective than drug treatment.

However, more studies and further methodological development are needed to

verify this finding



Keywords: BLOOD- PRESSURE/CORONARY HEART-DISEASE/COST BENEFIT

ANALYSIS/COST-EFFECTIVENESS ANALYSIS/ECONOMIC

EVALUATION/HEALTH

ECONOMICS/HYPERTENSION/METOPROLOL/MORTALITY/NONPHAR

MACOLOGICAL TREATMENT/PRIMARY

PREVENTION/STROKE/TRIALS/WILLINGNESS TO PAY



Whelton, P.K., Perneger, T.V., Brancati, F.L. and Klag, M.J. (1992), Epidemiology and

Prevention of Blood Pressure-Related Renal- Disease. Journal of Hypertension,

10 S77-S84.



Abstract: Aim: To examine the relationship between blood pressure and end-stage renal

disease. Method: Review of recent reports on blood pressure in relation to renal

function. Background: The incidence and prevalence of treated end-stage renal

disease are increasing progressively in economically developed countries. To

combat this problem, the treatment of established end-stage renal disease must be

complemented by strategies to treat and prevent risk factors for the development

of renal failure. Results: Severe hypertension and malignant hypertension are

well accepted as risk factors for renal insufficiency. Recent reports suggest a

strong relationship between blood pressure and renal function, throughout the

entire range of blood pressure. Most blood pressure-related renal disease can

probably be attributed to mild hypertension or a high normal blood pressure.

Conclusions: Additional clinical trials are needed to assess the value of different

antihypertensive drugs and different levels of blood pressure control in

preserving renal function in subjects at risk of blood pressure-related renal

disease. Primary prevention of hypertension may be an important complement to

the treatment of established hypertension in reducing the burden of renal disease

in the community



Keywords: AGE/ANTIHYPERTENSIVE TREATMENT/CARDIOVASCULAR

DISEASE/CORONARY HEART-DISEASE/DECLINE/DIABETIC

NEPHROPATHY/END-STAGE RENAL

FAILURE/EPIDEMIOLOGY/HYPERTENSION/KIDNEY

DISEASE/PREVENTION/PROGRESSION/RISK-FACTORS/STROKE

MORTALITY/TRENDS



King, R.A., Smith, R.M., Krishnan, R. and Cleary, E.G. (1992), Effects of Enalapril and

Hydralazine Treatment and Withdrawal Upon Cardiovascular Hypertrophy in

Stroke-Prone Spontaneously Hypertensive Rats. Journal of Hypertension, 10 (9),

919-928.



Abstract: Ojective: To test the hypothesis that effects of angiotensin converting enzyme

(ACE) inhibitors upon resistance vessel structure are responsible for their ability

to cause long-term reduction in blood pressure. Design: Stroke-prone

spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats were

treated with enalapril or hydralazine from 4 to 15 weeks of age. Effects upon

tail-cuff blood pressure, left ventricular hypertrophy and structural indices of the

superior mesenteric artery (SMA) and its resistance vessels were assessed at 11

weeks of treatment and up to 11 weeks post-treatment. Methods: Left ventricular

hypertrophy was assessed by left ventricular weight: body weight ratios.

Evidence of vascular structural change was obtained from tissue weight:body

weight ratios, levels of RNA, DNA and expression of alpha-actin and elastin

messenger (m)RNA. Results: The effects of enalapril and hydralazine upon left

ventricular hypertrophy in SHRSP were consistent with their respective effects

upon blood pressure. Both drugs prevented the development of medial

hypertrophy in SMA and resistance vessels. This was accompanied by

substantial reductions in RNA: DNA ratios. Alpha-actin mRNA levels were not

affected by either drug but elastin mRNA levels were reduced by both drugs.

During the first 12 days post-treatment there was evidence of structural change in

SMA accompanying the increases in blood pressure but importantly not in the

resistance vessels. Conclusion: The effects of enalapril upon left ventricular

hypertrophy and mesenteric arterial hypertrophy are totally consistent with

responses to blood pressure and the persistence of structural changes

post-treatment does not underlie the ability of the ACE inhibitors to persistantly

suppress hypertension



Keywords: ACID/ALPHA-ACTIN MESSENGER RNA/BLOOD-

PRESSURE/CAPTOPRIL/CARDIAC-HYPERTROPHY/COLLAGEN-SYNTH

ESIS/CONVERTING ENZYME-INHIBITION/ELASTIN MESSENGER

RNA/ENALAPRIL/HYDRALAZINE/HYPERTENSION/LONG-TERM/MESE

NTERIC ARTERIAL HYPERTROPHY/PREVENTION/STROKE-PRONE

SPONTANEOUSLY HYPERTENSIVE RAT/VASCULAR

STRUCTURE/VESSELS



Stier, C.T., Adler, L.A., Levine, S. and Chander, P.N. (1993), Stroke Prevention by

Losartan in Stroke-Prone Spontaneously Hypertensive Rats. Journal of

Hypertension, 11 S37-S42.



Abstract: Background: Chronic angiotensin converting enzyme (ACE) inhibitor therapy

with enalapril, captopril or ceranopril prevents the development of

cerebrovascular lesions in stroke- prone spontaneously hypertensive rats (SHRSP)

given a 1% NaCl solution to drink, with little or no effect on systolic blood

pressure. Objectives: To determine the effect of the orally active angiotensin

(Ang) II receptor antagonist losartan on blood pressure and stroke in SHRSP.

Methods: Losartan or vehicle was chronically administered to saline-drinking

SHRSP, and systolic blood pressure was monitored. The effect of losartan on

arterial blood pressure measured by radiotelemetry in enalapril-treated SHRSP

was also examined. Results: Oral losartan at 30mg/kg per day delayed the

development of severe hypertension and prevented stroke in saline-drinking

SHRSP. Losartan therapy at a dose of 10 mg/kg per day did not affect the

systolic blood pressure elevation but prevented the occurrence of cerebrovascular

lesions at least until 28 weeks of age. Radiotelemetric monitoring of arterial

blood pressure in enalapril-treated, saline-drinking SHRSP over a 3-month

period verified the maintenance of severe hypertension without any strokes.

Treatment with oral losartan at a dose of 30 mg/kg did not affect the blood

pressure of SHRSP chronically treated with enalapril. Conclusions: These results

are consistent with the theory that Ang II has an effect on the pathophysiology of

cerebrovascular lesion development in saline-drinking SHRSP. These findings

indicate that losartan has a protective action, similar to that previously observed

with ACE inhibitors, against the development of cerebrovascular lesions in

SHRSP in the absence of a blood pressure fall



Keywords: ANGIOTENSIN/ANGIOTENSIN-II RECEPTOR ANTAGONIST/BLOOD

PRESSURE/BLOOD-PRESSURE/CT/DUP-753/HYPERTENSION/II

RECEPTOR ANTAGONISTS/STROKE/STROKE-PRONE

SPONTANEOUSLY HYPERTENSIVE RATS



Minami, N. and Head, G.A. (1993), Relationship Between Cardiovascular Hypertrophy

and Cardiac Baroreflex Function in Spontaneously Hypertensive and Stroke-

Prone Rats. Journal of Hypertension, 11 (5), 523-533.



Abstract: Objective: To determine whether the reduced baroreceptor-heart rate reflex

sensitivity in genetically hypertensive rats is related to the level of cardiac or

vascular hypertrophy. Design: Young spontaneously hypertensive rats (SHR),

stroke- prone hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats were

treated chronically with the angiotensin converting enzyme (ACE) inhibitor

perindopril in different regimens in order to produce a wide-ranging combination

of cardiac and vascular hypertrophy. Methods: All strains were treated with

perindopril (0.1, 0.3, 1 or 3 mg/kg per day) in their drinking water from 4 until 9

weeks of age. Additional groups of SHR were treated with perindopril (3 mg/kg

per day) from 4 until 12 weeks and from 4 until 14 weeks of age. At 13 weeks of

age all animals were chronically instrumented with arterial and venous catheters.

One week later, steady-state sigmoidal mean arterial pressure-heart rate reflex

curves were obtained in the conscious rats by the injection of pressor and

depressor agents before and after the administration of atenolol (1 mg/kg,

intravenously) to determine the vagal component. The minimum and the

maximum blood pressure produced by nitroprusside and methoxamine,

respectively, after simultaneous ganglion and beta-adrenoceptor blockade were

used as an index of whole body vascular hypertrophy. The left ventricular to

body weight ratio was measured at the end of the experiment. Results: At 14

weeks of age, mean arterial pressure, the maximum and minimum autonomically

blocked blood pressure and the left ventricular to body weight ratio were 34, 20,

9 and 17% higher, respectively, in SHR, and 56, 35, 27 and 39% higher,

respectively, in SHRSP than in WKY rats. Perindopril treatment

dose-dependently reduced both cardiac and vascular hypertrophy but to different

extents. The highest doses reduced mean arterial pressure and the autonomically

blocked maximum and minimum blood pressure in both hypertensive strains to

the levels of untreated WKY rats but approximately 50% of the cardiac

hypertrophy was still present. The left ventricular to body weight ratio was

normalized in SHR only with the longer term perindopril treatments. A

comparison of the baroreflex function curves in untreated SHR and SHRSP

showed that the vagal component of the heart rate range was markedly reduced

compared to that in WKY rats. Treated SHRSP had a normal mean arterial

pressure and a normal autonomically blocked maximum and minimum blood

pressure, but their vagal heart rate range was only 63% of that in WKY rats. The

heart rate range in SHR treated from 4 to 9 weeks of age was only marginally

greater than that of untreated SHR, despite prevention of hypertension and

vascular hypertrophy. In SHR treated from 4 until 12 weeks of age, which

prevented cardiac hypertrophy, the vagal heart rate range was markedly greater.

With perindopril from the age of 4 to 14 weeks, the vagal baroreflex heart rate

range was similar to that of WKY rats. Thus the improvement in the vagal heart

rate range was more closely related to the prevention of cardiac hypertrophy (r =

0.73, P20 weeks) untreated WKY rats and untreated

SHRSP; SHRSP treated with perindopril, and age- and sex-matched control

SHRSP; and SHRSP treated with hydralazine and hydrochlorothiazide and age-

and sex-matched control SHRSP. The effects of treatment of the SHRSP with

perindopril for 30 days on vascular smooth muscle polyploidy and growth

kinetics were measured and compared with the effects of equivalent

antihypertensive doses of hydralazine and hydrochlorothiazide. Methods:

Vascular smooth muscle polyploidy was measured using flow-cytometry DNA

analysis of freshly harvested cells. Growth curves were performed on cultured

aortic cells. Plasma renin activity was measured by an antibody-trapping method,

plasma angiotensin II (Ang II) by radioimmunoassay and plasma ACE activity

by a colorimetric method. Cardiac hypertrophy was evaluated by measuring the

heart weight:body weight and left ventricle + septum weight:body weight ratios.

Results: The SHRSP had markedly and significantly elevated G(2) + M phase of

the cell cycle. Treatment with perindopril resulted in a significant reduction in

polyploidy in the SHRSP, whereas treatment with hydralazine and

hydrochlorothiazide had no effect on the percentage of cells in the G(2) + M

phase of the cell cycle. The regression of polyploidy after treatment with

perindopril was associated with a significant reduction in the concentration of

Ang II and ACE activity, and with a significant regression of cardiac

hypertrophy. Increased mitogenesis of cultured vascular smooth muscle cells

from the SHRSP was not altered by treatment with perindopril. Conclusions:

ACE inhibition reduces vascular smooth muscle polyploidy in large conduit

arteries. This type of vascular protection is mediated by the reduced Ang II and

possibly by increased kinins level, rather than by the hypotensive effect alone



Keywords: ABNORMALITIES/angiotensin/angiotensin II/ANGIOTENSIN-II/CELL

CYCLE/CELL

HYPERTROPHY/DNA/ENGLAND/GENETIC-HYPERTENSION/GROWTH-

CHARACTERISTICS/heart/HYPERPLASIA/HYPERPLOIDY/HYPERTENSI

ON/hypertrophy/muscle/PERINDOPRIL/POLYPLOIDY/PREVENTION/rats/R

ESISTANCE VESSELS/SHRSP/smooth/SMOOTH MUSCLE

CELLS/treatment/vascular/WISTAR-KYOTO RATS

Lee, R.M.K.W., Wang, H. and Smeda, J.S. (1996), Perindopril treatment in the

prevention of stroke in experimental animals. Journal of Hypertension, 14

S29-S33.



Abstract: Objective To determine the effect of perindopril treatment and treatment

withdrawal in the prevention of stroke in male stroke-prone spontaneously

hypertensive rats (SPSHR). Design After weaning at 4 weeks of age, male

SPSHR were given a Japanese-style rat diet which induces stroke in these

animals. Beginning at 6 weeks of age, SPSHR were treated with either distilled

water (control) or different daily dosages of perindopril (1 or 4 mg/kg) by gavage

for 24 weeks followed by treatment withdrawl. Additional subgroups were

treated with the 4 mg/kg dose for different durations (8, 12 or 24 weeks) before

treatment withdrawal. Treatment effects on blood pressure, heart rate and body

weight were studied during the treatment period and after the withdrawal of the

treatment. Myogenic and mechanical properties of the middle cerebral arteries

were studied in control SPSHR that had developed stroke, in treated SPSHR at

the end of the treatment period, and at certain intervals after the withdrawal of

the treatment. Methods Systolic blood pressure, heart rate and body weight of

control and treated SPSHR were determined at regular intervals before, during

and after the treatment withdrawal periods until they died from stroke, or until 42

or 43 weeks of age when the study was terminated. Functional studies of the

cerebral arteries were carried out using a pressurized artery system. At necropsy,

macroscopic and microscopic examinations were made of the kidneys and brain.

Results Untreated SPSHR usually died of stroke-related complications by 14

weeks of age. The middle cerebral arteries from these animals had lost their

ability to contract in response to pressure increase. Chronic treatment of SPSHR

with perindopril when initiated at 6 weeks of age attenuated the sharp blood

pressure rise, and prevented the development of stroke during the treatment

period. This was associated with the preservation of the myogenic response of

the middle cerebral arteries to pressure increase, and the prevention of tissue

damage in the kidneys and brain. After withdrawl of the treatment, SPSHR

treated for a longer period (12 or 24 weeks) also survived longer than those

treated for a shorter period (8 weeks). The subsequent loss of myogenic response

in the middle cerebral arteries was associated with the development of stroke and

death in these treatment withdrawl groups. Conclusion Chronic treatment with

perindopril is beneficial for the prevention of stroke in SPSHR, through the

preservation of the myogenic response properties of the cerebral arteries, and the

attenuation of tissue damage in the brain and kidneys



Keywords: age/blood pressure/BLOOD-PRESSURE/brain/cerebral/cerebral

artery/complications/control/CONVERTING-ENZYME-INHIBITOR/developm

ent/diet/ENALAPRIL/ENGLAND/heart/HEMORRHAGIC

STROKE/HYPERTENSION/HYPERTROPHY/LONG-TERM/myogenic

response/perindopril/prevention/rat/rats/RESISTANCE

ARTERIES/SPONTANEOUSLY HYPERTENSIVE RATS/stroke/stroke-prone

spontaneously hypertensive rats/treatment/TREATMENT

WITHDRAWAL/VASCULAR STRUCTURE

Anderson, C.S. (1996), Contribution of prevention to vascular cerebral disease

management. Journal of Hypertension, 14 S25-S28.



Abstract: Background Epidemiological studies suggest that significant reductions in the

incidence of stroke, as with coronary heart disease, can be expected by reducing

the prevalence or shifting the distribution of risk factors across the entire

population. Thus, identifying risk factors and intervening to control or modify

them remains the most important means of further reducing the incidence and

case fatality of stroke in developed countries, and controlling the emerging

epidemic of cardiovascular disease in developing countries. All people should be

encouraged to stop smoking, reduce weight, and increase physical activity and

the consumption of fruit and vegetables. Methods The high-risk strategy involves

the identification and management of people at high risk of developing stroke.

Therapies of proven benefit in the prevention of stroke among certain individuals

are blood pressure lowering therapy, antiplatelet therapy, anticoagulation therapy

and carotid endarterectomy. Evidence is mounting that aggressive treatment of

hypercholestrolaemia and hyperglycaemia is also effective in reducing the risk of

stroke, but the role of aspirin and carotid endarterectomy in the primary

prevention of stroke remains uncertain. This article will review strategies for the

prevention of stroke, except blood pressure lowering therapy, which is discussed

elsewhere, and address some of the questions about which individuals have the

most to gain from various interventions



Keywords: anticoagulation/antiplatelet therapy/aspirin/ATRIAL-FIBRILLATION/blood

pressure/cardiovascular disease/carotid/carotid endarterectomy/case

fatality/cerebral/clinical trials/control/coronary heart

disease/endarterectomy/ENGLAND/fruit/heart/high-risk

strategy/HONOLULU-HEART-PROGRAM/HYPERTENSION/incidence/MEN

/physical activity/PHYSICAL-ACTIVITY/population

strategy/prevention/primary prevention/risk/risk

factors/RISK-FACTORS/SMOKING/STROKE/stroke

incidence/therapy/treatment/vascular



MacMahon, S. (1996), Blood pressure and the prevention of stroke. Journal of

Hypertension, 14 S39-S46.



Abstract: Relationship between blood pressure and stroke Data from prospective

observational studies indicate that usual levels of blood pressure are directly and

continuously related to the risk of initial stroke. A prolonged difference in usual

blood pressure levels of just 9/5 mmHg is associated with approximately a

one-third difference in stroke risk, with similar proportional effects in

hypertensives and normotensives. Recent data from studies of individuals with a

history of cerebrovascular disease indicate a similar association between blood

pressure and the risk of recurrent stroke. Effects of treatment on stroke The

results of randomized trials of blood pressure-lowering drugs in hypertensive

patients suggest that much or all of the long-term potential stroke avoidance

associated with prolonged blood pressure differences can be achieved within just

a few years of beginning treatment. Overall, in 17 randomized trials of

antihypertensive treatment a net blood pressure reduction of 10-12 mmHg

systolic and 5-6 mmHg diastolic conferred a reduction in stroke incidence of

38% (SD 4), with similar reductions in fatal and non-fatal stroke. Because the

proportional effects of treatment were similar in higher and lower risk patient

groups, the absolute effects of treatment on stroke varied in direct proportion to

the background risk of stroke. The greatest potential benefits were observed

among those with a history of cerebrovascular disease; however, the results of

the trials conducted in patients with a history of stroke or transient ischaemic

attack, although promising, were not definitive. New trials are required to

determine more reliably the effects of blood pressure lowering in patients with

cerebrovascular disease



Keywords: antihypertensive treatment/blood pressure/cerebrovascular/cerebrovascular

disease/CORONARY

HEART-DISEASE/drugs/ENGLAND/epidemiology/history/HYPERTENSION/i

ncidence/JAPAN/MEN/MORBIDITY/MORTALITY/MULTIVARIATE-ANAL

YSIS/observational studies/prevention/randomized/randomized trials/recurrent

stroke/risk/RISK-FACTORS/stroke/stroke

incidence/SURVIVORS/transient/treatment/TRIAL/TRIALS



Sleight, P. (1996), Primary prevention of coronary heart disease in hypertension. Journal

of Hypertension, 14 S35-S38.



Abstract: Mortality from myocardial infarction Primary prevention of coronary heart

disease in hypertension is important because the mortality among those who have

suffered a myocardial infarction is around 50% within 1 month of the infarction.

Although the mortality of those who reach hospital has about halved over the last

decade (to about 8%), prevention is the only way to affect coronary mortality

overall. Overall prevention of coronary heart disease There are several proven

strategies, involving both drugs and lifestyle changes. Stopping smoking is the

most powerful, but exercise and reduction of dietary fats and salt are also

important; the latter will need co-operation with the food industry. Treating

hypertensives with a coronary risk Lipid-lowering drugs will be needed for some,

but not all hypertensives, depending on the coronary risk Some drug treatments

which lower blood pressure (e.g. short-acting formulations of nifedipine) may

not reduce the coronary risk; further data or newer preparations are awaited.

Potassium- sparing diuretics (particularly in elderly patients) and/or

beta-blockers remain the first choice for primary prevention. If a calcium channel

blocker is needed, verapamil or diltiazem are useful in patients with no left

ventricular dysfunction



Keywords:

aspirin/BLOOD-PRESSURE/exercise/hypertension/lifestyle/lipids/MEN/mortali

ty/salt/smoking/statins/STROKE

Menard, J. and Chatellier, G. (1996), Integration of trial, meta-analysis and cohort

results with treatment guidelines. Journal of Hypertension, 14 S129-S133.



Abstract: Importance of guidelines Guidelines to medical practice are of vital

importance because of the fast and uncontrolled introduction of new technologies,

increasing amounts of information, including contradictory results, high levels of

inappropriate care and increased financial pressure. Thus guidelines can help

solve common problems in all health care systems worldwide. Preparation of

guidelines In preparing guidelines, a synthesis of results from the literature

prepared by a single expert must be compared with syntheses done by others, and

a consensus recommendation may then be issued. Such a recommendation will

not be based exclusively on the results of controlled trials, even when they have

indisputable internal validity. There is still a need for a value judgement within a

particular psychological and socio-economic context. Freedom for physician It is

important to preserve the physician's freedom to prescribe drugs or not in

conjunction with informed choice by the patient concerning the risks of any

long-term drug intervention, even if this freedom of choice does not fit with the

expectations of 'managed' care or third-party payers



Keywords: BLOOD- PRESSURE/cohort studies/CORONARY

HEART-DISEASE/HYPERTENSION/MEN/meta-analysis/PRIMARY-PREVE

NTION TRIAL/RECOMMENDATIONS/STROKE/treatment guidelines/trials



Lees, K.R. and Dyker, A.G. (1996), Blood pressure control after acute stroke. Journal of

Hypertension, 14 S35-S38.



Abstract: Background Although long-term blood pressure control is known to prevent

stroke, acute blood pressure reduction after stroke is associated with worse

neurological and functional outcome. Vasoactive drug treatment after stroke

Chronic blood pressure reduction for secondary prevention of stroke is presently

being tested within the PROGRESS trial. This study uses angiotensin- converting

enzyme (ACE) inhibitor-based treatment (perindopril) versus placebo. ACE

inhibitors may reduce blood pressure without adversely affecting cerebral blood

flow. We have recently reported elsewhere that perindopril 4 mg once daily,

initiated within 2-7 days of acute ischaemic stroke, reduces blood pressure

without adverse effects on cerebral blood flow as measured by Doppler

ultrasound. Nevertheless the optimal policy with regard to blood pressure

management in the first 48 h after acute stroke remains uncertain. Conclusions A

clinical trial is proposed to establish whether it is better to maintain pre-existing

antihypertensive therapy or to discontinue this temporarily



Keywords: acute/ACUTE ISCHEMIC STROKE/angiotensin/blood pressure/blood

pressure control/cerebral/cerebral blood flow/control/CONVERTING

ENZYME-INHIBITION/Doppler/Doppler

ultrasound/ENGLAND/FLOW/HYPERTENSION/ischaemic stroke/NMDA

ANTAGONIST CNS-1102/perindopril/prevention/secondary

prevention/STREPTOKINASE/stroke/therapy/treatment/TRIAL/VOLUNTEER

S



Chalmers, J., Macmahon, S., Bousser, M.G., Cutler, J., Donnan, G., Hansson, L., Harrap,

S., Liu, L.S., Mancia, G., Menard, J., Omae, T., Reid, J., Rodgers, A., Warlow,

C., Culpan, A., Currie, R., Flett, S., Neal, B., Milne, A., Davis, S., Gong, L.S.,

Sega, R., Yamaguchi, T., Terent, A., Lees, K., Williams, F., Wang, J.G., Wang,

W., Biousse, V., Tzourio, C., Crespi, S., Fujimoto, K., Marttala, K., Fenton, J.

and McIlvenna, Y. (1996), PROGRESS - Perindopril protection against recurrent

stroke study: Status in July 1996. Journal of Hypertension, 14 S47-S51.



Abstract: Objectives The primary objective of PROGRESS is to determine reliably the

efficacy of lowering blood pressure for the prevention of stroke in patients with a

history of cerebrovascular disease. Design PROGRESS is a randomized,

double-blind, placebo-controlled trial investigating the effects on the incidence

of stroke and other major cardiovascular events and dementia of treatment with

the angiotensin-converting enzyme inhibitor perindopril, alone or in combination

with the diuretic indapamide. Methods The study population comprises 6000

normotensive or hypertensive patients with a history of stroke or transient

ischaemic attack within the previous 5 years. The study is being conducted in

over 160 centres in seven regions: Australia and New Zealand, The People's

Republic of China, France and Belgium, Italy, Japan, Sweden and the United

Kingdom. Computerized randomization to active treatment or placebo is

performed by fax direct to Auckland, New Zealand. The primary study outcome

is total stroke and secondary outcomes include fatal or non-fatal stroke, total

major cardiovascular events and deaths, cognitive function and disability.

Patients will be followed for a minimum of 4 years after randomization. Results

By 16 July 1996, 162 local clinical centres had been registered across the seven

regions, and 1682 patients, 49% with a history of hypertension, had been

randomly assigned to receive active treatment or placebo, with 65% allocated to

the combination of perindopril and indapamide or double placebo, and 35% to

perindopril alone or single placebo. Three months after randomization, the blood

pressure difference between the treatment and control groups among the first 182

patients randomized was 11.9 mmHg (systolic) and 3.9 mmHg (diastolic). Six

strokes and two non-stroke cardiovascular deaths have been recorded after a total

of 3174 patient-months of follow-up. Conclusions Observations made so far

confirm that full recruitment into the study is feasible and that treatment with

perindopril and indapamide is well tolerated in the study population. The blood

pressure differences between control and treatment groups recorded so far

suggest that the study should have the power to achieve its primary objectives,

provided compliance with treatment is satisfactory and 6000 patients are

successfully recruited and followed for 4-5 years



Keywords: angiotensin-converting enzyme inhibitors/Australia/blood

pressure/cardiovascular events/cerebrovascular/cerebrovascular disease/cognitive

function/control/dementia/DISEASE/ENGLAND/history/hypertension/incidence

/indapamide/perindopril/prevention/randomized/randomized clinical

trial/recruitment/recurrent stroke/stroke/transient/treatment/United Kingdom



Chalmers, J., MacMahon, S., Bousser, M.G., Cutler, J., Donnan, G., Hansson, L., Harrap,

S., Liu, L.S., Mancia, G., Menard, J., Omae, T., Reid, J., Rodgers, A. and

Warlow, C. (1996), Blood pressure lowering for the secondary prevention of

stroke: Rationale and design for PROGRESS. Journal of Hypertension, 14

S41-S45.



Abstract: Background Usual blood pressure levels have been shown to be directly and

continuously associated with the risks of initial and recurrent stroke. Blood

pressure lowering has been demonstrated to reduce the risk of a first stroke in

hypertensive patients, but there is uncertainty about the effects of reducing blood

pressure in patients with a history of cerebrovascular disease, for whom stroke

risks are particularly high, The primary objective of the Perindopril Protection

Against Recurrent Stroke Study (PROGRESS) is to determine the effects of

blood pressure reduction on stroke risk in patients with a history of

cerebrovascular disease. Design and treatment PROGRESS is a randomized,

double-blind, placebo-controlled clinical trial of an angiotensin converting

enzyme (ACE) inhibitor-based blood pressure lowering treatment regimen.

Before randomization, there is a 4-week run-in phase on open-label treatment,

after which patients are assigned to continued treatment or to placebo. Following

randomization, the trial treatments comprise perindopril (4 mg daily) plus

indapamide (2.5 mg daily) or matching placebos for patients without an

indication for or contraindication to treatment with a diuretic, and perindopril

alone or matching placebo for all other patients. The scheduled duration of

treatment and follow- up is a minimum of 4 years. Patients The study will

involve 6000 patients with a proven transient ischaemic attack (including

amaurosis fugax) or stroke (cerebral infarct, cerebral haemorrhage or stroke of

unknown type) in the past 5 years. The patients selected will have no known

definite indication for or contraindication to treatment with an ACE inhibitor and

no disability likely to prevent regular attendance at study clinics. Patients will be

recruited from collaborating clinical centres in Australia, Belgium, China, France,

Italy, Japan, New Zealand, Sweden and the United Kingdom. Major outcomes

Stroke is the primary study outcome, and secondary outcomes include fatal or

disabling strokes, total major cardiovascular events, cardiovascular deaths and

dementia



Keywords: angiotensin converting enzyme inhibitors/cardiovascular events/cognitive

function/CORONARY

HEART-DISEASE/dementia/HYPERTENSION/ischaemia/secondary

prevention/stroke/SURVIVORS/TRIAL/TRIALS



Sever, P.S. and Mackay, J.A. (1996), The hypertension trials. Journal of Hypertension,

14 S29-S33.

Abstract: Established antihypertensive treatment Previous studies have clearly

demonstarted the benefits of antihypertensive therapy, particularly in reducing

the incidence of stroke. However, there is still concern that the full potenial for

reversing coronary heart disease in the hypertensive patient has not been realized

by treatment with established agents, the diuretics and the beta-blockers. Trials

on newer agents A question that still remains to be answered is whether

treatment regimens based on alternative drugs, including calcium channel

blocking agents and angiotensin converting enzyme inhibitors, will confer an

advantage over older drugs. This question is at last being addressed in long-term

morbidity and mortality trials with these newer agents



Keywords: BLOOD-PRESSURE/CORONARY

HEART-DISEASE/hypertension/MEN/morbidity/MORBIDITY/MORTALITY/

mortality/PRIMARY PREVENTION/STROKE/trials



Strandgaard, S. (1996), Hypertension and stroke. Journal of Hypertension, 14 S23-S27.



Abstract: Hypertension and stroke Hypertension is a major risk factor for stroke, and

stroke prevention is the most important achievement of modern antihypertensive

treatment. In controlled trials, a few years of this treatment can eliminate the

entire excess stroke risk associated with hypertension. tn observational studies,

stroke risk appears to be not always fully reversible when the blood pressure is

lowered with drugs. Hypertension is associated with an increased incidence of

both haemorrhagic, ischaemic and lacunar stroke. It is likely that

antihypertensive treatment prevents all these types of strokes as well as transient

ischaemic attacks. Acute stroke In acute stroke, a transient rise in blood pressure

is common, in some cases superimposed on chronic hypertension. No major

controlled trials have reported findings on whether blood pressure should be

towered acutely in such patients. On the basis of observational studies and

haemodynamic considerations it seems prudent to leave all but the highest blood

pressures in acute stroke to settle spontaneously. Ischaemic stroke Ischaemic

stroke may occasionally be precipitated by overzealous blood pressure reduction.

This has been reported in particular in the initial treatment of very severe

hypertension, and occasionally in the elderly hypertensive. It may also occur in

the rare cases where transient cerebral ischaemia is haemodynamically induced.

(C) Rapid Science Publishers



Keywords: acute/ACUTE ISCHEMIC STROKES/ANTIHYPERTENSIVE

THERAPY/antihypertensive treatment/blood

pressure/BLOOD-PRESSURE/cerebral/cerebral

ischaemia/COMPUTED-TOMOGRAPHY/CORONARY

HEART-DISEASE/drugs/elderly/ENGLAND/HYPERTENSION/incidence/INF

ARCTION/ischaemia/lacunar stroke/MORTALITY/observational

studies/prevention/RISK/risk factor/stroke/stroke prevention/transient/transient

ischaemic attacks/TREAT/treatment/TRIALS

De Henauw, S., De Bacquer, D., Fonteyne, W., Stam, M., Kornitzer, M. and De Backer,

G. (1998), Trends in the prevalence, detection, treatment and control of arterial

hypertension in the Belgian adult population. Journal of Hypertension, 16 (3),

277-284.



Abstract: Objectives To discuss changes during the past decades in the prevalence and in

the patterns of detection, treatment and control of arterial hypertension in the

general Belgian population aged 25-64 years. Design Data from two cross-

sectional cardiovascular disease risk factor surveys of the general population

aged 25-64 years during the first and second halves of the 1980s (the Belgian

Inter-university Research on Nutrition and Health study of 1980-1984 and the

World Health Organization Multinational Monitoring of Trends and

Determinants in Cardiovascular Diseases study of 1985-1992) are compared.

Participants Age-stratified and sex-stratified random samples from the general

population yielded 9372 participants in the former study and 4904 participants in

the latter. Methods In both studies, blood pressure measurements and other

variables were collected in the same standardized way and by the same observers.

Results For both sexes, overall age- standardized prevalences of hypertension

(subjects with systolic blood pressure greater than or equal to 160 mmHg or

diastolic blood pressure greater than or equal to 95 mmHg or currently being

administered antihypertensive drug treatment) were found to be (P 160 mmHg with DBP 60 years of age. Despite these

findings, however, recent analysis suggests that most hypertension treatment

decisions continue to be based on DBP measurements instead of SBP. To combat

this treatment gap, we must disseminate this information and motivate physicians

and other providers to include reduction of SBP in their treatment plans. We

must also encourage the development of antihypertensive drugs that lower SBP

more effectively than those that are currently available. J Hypertens 17 (suppl

5):S49-S54 (C) 1999 Lippincott Williams & Wilkins



Keywords: age/antihypertensive drugs/blood

pressure/BLOOD-PRESSURE/cardiovascular/cardiovascular

disease/cardiovascular disease risk factors/clinical

trials/community/development/diabetes/diabetes mellitus/diastolic blood

pressure/DISEASE/diuretic-based

antihypertensives/drugs/elderly/FRAMINGHAM/guidelines/heart/heart

failure/HEART-FAILURE/history/hypertension/incidence/infarction/isolated

systolic hypertension/morbidity/mortality/myocardial/myocardial

infarction/NIDDM/PLACEBO/PREVENTION/RISK/SHEP/stroke/treatment/tria

l/trials/UNITED-STATES

Edwards, R., Unwin, N., Mugusi, F., Whiting, D., Rashid, S., Kissima, J., Aspray, T.J.

and Alberti, K.G.M.M. (2000), Hypertension prevalence and care in an urban

and rural area of Tanzania. Journal of Hypertension, 18 (2), 145-152.



Abstract: Objective To describe the prevalence, detection, treatment and control of

hypertension in an urban and rural area of Tanzania. Design Two linked

cross-sectional population-based surveys. Setting A middle-income urban district

of Dar es Salaam (Ilala) and a village in the relatively prosperous rural area of

Kilimanjaro (Shari). Participants Seven hundred and seventy adults (>15 years)

in Ilala and 928 adults in Shari were studied. Results Hypertension prevalence

(blood pressure greater than or equal to 140 and/or 90 mmHg, or known

hypertensives receiving antihypertensive treatment) was 30% (95% confidence

interval, 25.1-34.9%) in men and 28.6% (24.3- 32.9%) in women in Ilala, and

32.2% (27.7-36.7%) in men and 31.5% (27.8-35.2%) in women in Shari.

Age-standardized hypertension (to the New World Population) prevalence was

37.3% (32.2-42.5%) among men and 39.1% (34.2-44.0%) in women in Ilala, and

26.3% (22.4-30.4%) in men and 27.4% (24.4-30.4%) in women in Shari. In both

areas, just under 20% of hypertensive subjects were aware of their diagnosis,

approximately 10% reported receiving treatment and less than 1% were

controlled (blood pressure 6.5 mmol/l (n = 986), the risk of

death increased progressively with systolic blood pressure, whereas among

non-smoking normocholesterolaemic men (n = 504) the association was J-shaped,

i.e. higher mortality at less than or equal to 110 mmHg than between 111- 150

mmHg and a more consistent rise from 151-160 mmHg, The curves were

essentially similar for cardiovascular mortality. The results were supported by

analyses where major cardiovascular risk factors were controlled. Conclusion

During a truly long-term follow-up, the relationship between systolic blood

pressure and mortality was initially flat up to 131-140 mmHg although a linear

relationship is suggested in men with other cardiovascular risk factors, (C) 2001

Lippincott Williams & Wilkins



Keywords: age/blood pressure/body mass index/cancer/cardiovascular/cardiovascular

disease/cardiovascular disease risk factors/cardiovascular diseases/cardiovascular

mortality/cardiovascular risk/cardiovascular risk factors/CARDIOVASCULAR-

DISEASES/cholesterol/COHORTS/coronary heart

disease/CORONARY-HEART-DISEASE/death/disease/disease

risk/diseases/FINLAND/health/heart/heart

disease/HYPERTENSION/J-curve/MANAGEMENT/men/MIDDLE-AGED

MEN/mortality/PREVENTION/REGISTER/risk/risk factor/risk

factors/serum/smoking/stroke/systolic blood/systolic blood pressure/VALIDITY



Larosa, J.C. (2002), Use of statin drugs in women. Journal of Hypertension, 20

S70-S72.



Abstract: Risk factors associated with the progression of coronary disease are the same

in women and men, although there are some quantitative differences. Diabetic

women, for example, are exquisitely sensitive to the development of

atherosclerosis. There is no clinical trial devoted to the study of cholesterol

lowering in women. A meta-analysis of recent statin trials with clinical endpoints,

however, demonstrates that cholesterol lowering is as beneficial in women as it is

in men. Hormone replacement therapy has not been demonstrated in a clinical

trial to be of benefit even though there is considerable observational,

epidemiology and basic science evidence that indicates that it might be. It is

important that the risk of coronary disease and stroke, particularly in older

women, be recognized. Patients at risk should receive cholesterol- lowering

treatment with statin drugs to prevent both atherosclerotic morbidity and

mortality. (C) 2002 Lippincott Williams Wilkins



Keywords:

ATHEROSCLEROSIS/atherosclerosis/cholesterol/cholesterol-lowering/clinical

trial/coronary artery disease/coronary disease/CORONARY

HEART-DISEASE/development/disease/drugs/epidemiology/ESTROGEN

REPLACEMENT/HYPERTENSION/men/meta-analysis/METAANALYSIS/mo

rbidity/morbidity and

mortality/mortality/MYOCARDIAL-INFARCTION/POSTMENOPAUSAL

WOMEN/PREVENTION/PROGRESSION/risk/RISK-FACTORS/statin/statins/

stroke/therapy/treatment/trial/trials/women/YOUNG-ADULTS



West, M.J., White, H.D., Simes, R.J., Kirby, A., Watson, J.D., Anderson, N.E., Hankey,

G.J., Wonders, S., Hunt, D. and Tonkin, A.M. (2002), Risk factors for

non-haemorrhagic stroke in patients with coronary heart disease and the effect of

lipid-modifying therapy with pravastatin. Journal of Hypertension, 20 (12),

2513-2517.



Abstract: Objective To determine the relative importance of recognised risk factors for

non-haemorrhagic stroke, including serum cholesterol and the effect of

cholesterol-lowering therapy, on the occurrence of non-haemorrhagic stroke in

patients enrolled in the LIPID (Long-term Intervention with Pravastatin in

Ischaemic Disease) study. Design The LIPID study was a placebo- controlled,

double-blind trial of the efficacy on coronary heart disease mortality of

pravastatin therapy over 6 years in 9014 patients with previous acute coronary

syndromes and baseline total cholesterol of 4-7 mmol/l. Following identification

of patients who had suffered non-haemorrhagic stroke, a pre-specified secondary

end point, multivariate Cox regression was used to determine risk in the total

population. Time-to-event analysis was used to determine the effect of

pravastatin therapy on the rate of non-haemorrhagic stroke. Results There were

388 non-haemorrhagic strokes in 350 patients. Factors conferring risk of future

non-haemorrhagic stroke were age, atrial fibrillation, prior stroke, diabetes,

hypertension, systolic blood pressure, cigarette smoking, body mass index, male

sex and creatinine clearance. Baseline lipids did not predict non-haemorrhagic

stroke. Treatment with pravastatin reduced non-haemorrhagic stroke by 23% (P=

0.016) when considered alone, and 21% (P= 0.024) after adjustment for other

risk factors. Conclusions The study confirmed the variety of risk factors for

non-haemorrhagic stroke. From the risk predictors, a simple prognostic index

was created for nonhaemorrhagic stroke to identify a group of patients at high

risk. Treatment with pravastatin resulted in significant additional benefit after

allowance for risk factors. (C) 2002 Lippincott Williams Wilkins



Keywords: acute/acute coronary syndromes/age/atrial/atrial fibrillation/Australia/blood

pressure/body mass index/CARE/cholesterol/CHOLESTEROL

LEVELS/cholesterol-lowering/cigarette smoking/coronary heart

disease/diabetes/disease/disease mortality/EVENTS/fibrillation/heart/heart

disease/high

risk/HYPERTENSION/LIPID/lipids/MEN/mortality/non-haemorrhagic

stroke/population/pravastatin/predictors/PRIMARY

PREVENTION/PROJECT/REDUCTION/risk/risk

factors/secondary/serum/sex/smoking/stroke/systolic blood/systolic blood

pressure/therapy/transient ischaemic attack/trial/TRIALS/USA



Bastuji-Garin, S., Deverly, A., Moyse, D., Castaigne, A., Mancia, G., de Leeuw, P.W.,

Ruilope, L.M., Rosenthal, T. and Chatellier, G. (2002), The Framingham

prediction rule is not valid in a European population of treated hypertensive

patients. Journal of Hypertension, 20 (10), 1973-1980.



Abstract: Background Stratification of population groups according to cardiovascular

risk level is recommended for primary prevention. Objective To assess whether

the Framingham models could accurately predict the absolute risk of coronary

heart disease (CHD) and stroke in a large cohort of middle-aged European

patients with hypertension, and rank individual patients according to actual risk.

Design A prospective cohort study comparing the actual risk with that predicted

by either the Framingham equations or models derived from the INSIGHT study.

Patients and setting From the INSIGHT prospective trial, conducted in eight

countries of Western Europe and Israel, we selected 4407 European patients

younger than 75 years without previous cardiovascular events. Interventions

None. Main outcome measures Major cardiovascular events. Results In this

population (45% men, mean age 64.1 years), 124 (2.8%) patients had CHD and

96 (2.2%) had strokes after a median follow-up of 3.7 years. Overestimation of

absolute CHD risk by the Framingham equation was observed in all countries

(from 2% in the UK to 7% in France), whereas predicted risk of stroke was close

to the actual risk. However, patients in the highest risk quintile within each

country had a threefold greater risk of a cardiovascular event than those in the

lowest quintile. Conclusions The Framingham models should not be used to

predict absolute CHD risk in the European population as a whole. However,

these models may be used within each country, provided that cut-off points

defining high-risk patients have been determined within each country. J

Hypertens 20:1973-1980 (C) 2002 Lippincott Williams Wilkins



Keywords: 7 COUNTRIES/absolute

risk/age/CARDIOLOGY/cardiovascular/cardiovascular event/cardiovascular

events/CARDIOVASCULAR RISK/CHD/cohort study/coronary heart

disease/CORONARY-HEART-DISEASE/disease/Europe/European

cohort/Framingham equation/GLOBAL BURDEN/heart/heart disease/high

risk/HYPERTENSION/INTERNATIONAL NIFEDIPINE

GITS/INTERVENTION/Israel/men/MORTALITY/outcome/population/predicti

on/PREVENTION/primary/primary prevention/prospective cohort study/risk/risk

factors/risk prediction/stroke/TREATMENT INSIGHT/trial/Western Europe

de Simone, G., Palmieri, V., Bella, J.N., Celentano, A., Hong, Y.L., Oberman, A.,

Kitzman, D.W., Hopkins, P.N., Arnett, D.K. and Devereux, R.B. (2002),

Association of left ventricular hypertrophy with metabolic risk factors: the

HyperGEN study. Journal of Hypertension, 20 (2), 323-331.



Abstract: Objective To determine whether combinations of metabolic risk factors

(obesity, diabetes and hypercholesterolemia) influence the magnitude of left

ventricular (LV) mass and prevalence of LV hypertrophy. Design

Cross-sectional, relational. Methods A total of 1627 hypertensive (85.9% treated,

1036 women, 1041 African Americans) and 342 normotensive (180 women, 183

African Americans) participants in the Hypertension Genetic Epidemiology

Network (HyperGEN) Study, without prevalent cardiovascular disease, were

studied. Echocardiographic LV mass, normalized by height(2.7) or fat-free mass

or body surface area (BSA) and the ratio of stroke volume to pulse pressure as a

percentage of predicted (as a crude estimate of arterial compliance) were

analyzed in relation to obesity [by body mass index (BMI)], central fat

distribution (by waist circumference), diabetes (by ADA criteria) and

hypercholesterolemia. Results Obesity, hypercholesterolemia, and diabetes were

more frequent among hypertensives than normotensives (all P R and R --> T conversion were 0.04 s(-1) and 1.0 s(-1), respectively. The

clearly rate-limiting T --> R conversion renders the R state a minor form of

DnaK that cannot account for the chaperone effects. Because DnaK in the

absence of the co-chaperones is chaperone-ineffective, the T state has also to be

excluded. Apparently, the slow, ATP-driven conformational change T --> R is

the key step in the DnaK/DnaJ/GrpE chaperone cycle underlying the chaperone

effects such as the prevention of protein aggregation, disentangling of

polypeptide chains and, in the case of eukaryotic Hsp70 homologs, protein

translocation through membranes or uncoating of clathrin-coated vesicles. (C)

1997 Academic Press Limited



Keywords: aggregation/ATPASE DOMAIN/CLATHRIN/DnaJ/DnaK/DNAK

CHAPERONE/ENGLAND/ESCHERICHIA-COLI/GRPE/GrpE/HEAT-SHOCK

PROTEINS/HSP70/HYDROLYSIS/KINETICS/mechanism of action/molecular

chaperones/PEPTIDE BINDING/prevention/stroke



Zimmermann, R., Kastens, J., Linz, W., Wiemer, G., Scholkens, B.A. and Schaper, J.

(1999), Effect of long-term ACE inhibition on myocardial tissue in hypertensive

stroke-prone rats. Journal of Molecular and Cellular Cardiology, 31 (8),

1447-1456.



Abstract: The aim of the study was to investigate the influence of long- term ACE

inhibition with ramipril on myocardial hypertrophy and its molecular background

in spontaneously hypertensive stroke- prone rats (SHR-SP). Therefore,

1-month-old pre-hypertensive SHR-SP were randomized into three groups and

exposed lifelong via drinking water to 1 mg/kg/day ramipril (anti-hypertensive

dose, RHI), 10 mu g/kg/day ramipril (non anti-hypertensive dose, RLO) or

placebo. After 15 months cardiac tissue was collected from ten rats each for

immunohistochemistry and Northern blot analysis of structural proteins. proteins

of the extracellular matrix and several growth factors. Results showed that RHI,

but not RLO, treatment prevented development of myocyte hypertrophy (ANP).

Furthermore, unlike placebo-treated rats, the ramipril-treated animals had no

evidence of degeneration and loss of structural proteins (alpha-actinin),

inflammatory infiltrates (CD45) and deposition of extracellular matrix proteins

(collagen, fibronectin, vimentin). Only in RHI- treated animals, mRNA levels for

TGF-beta(1) as well as of collagen alpha(1)(I) and fibronectin were

downregulated compared to placebo-treated animals. In contrast, VEGF mRNA

levels increased significantly in both groups of ramipril- treated animals v.

placebo-treated SHR-SP. Thus, the reported life prolonging effect of high doses

of ramipril which is associated with prevention of hypertension and hypertrophy

is accompanied by prevention of the development of necrosis and fibrosis. The

role of VEGF, however, seems to be independent of this effect. (C) 1999

Academic Press



Keywords: ACE inhibitors/ANGIOTENSIN-II/collagen/development/ENDOTHELIAL

GROWTH-FACTOR/ENGLAND/EXTRACELLULAR-MATRIX/fibrosis/gene

expression/GENE-EXPRESSION/hypertension/hypertrophy/LEFT-

VENTRICULAR

HYPERTROPHY/LIFE-SPAN/MESSENGER-RNA/myocardial/necrosis/NITRI

C-OXIDE/prevention/randomized/rats/SHRSP/stroke/stroke-prone

rats/TRANSFORMING GROWTH-FACTOR-

BETA-1/treatment/VASCULAR-PERMEABILITY FACTOR/VEGF



Yang, C.C., Tsai, W.J., Chuo, H.T., Shiau, F.S. and Deng, J.F. (1995), Mushroom

Poisoning in Taiwan. Journal of Natural Toxins, 4 (2), 185-194.

Abstract: Mushroom gathering is not uncommon in Taiwan; however, incidence of

poisoning following mushroom ingestion has not been reported. We have been

recently acquainted with several incidents of mushroom poisoning and wish to

clarify the exact incidence of mushroom poisoning in Taiwan. We therefore

conducted a review study to analyze the data of all suspected mushroom

poisonings reported to the PCC-Taiwan from July 1986 through December 1993.

During that time period, totally 39 cases, belonging to 17 incidents, of suspected

mushroom poisoning were recorded. All cases, except two cases with unrelated

diagnosis of carbamate poisoning and stroke, and two cases with inadequate

clinical data, were included in this study. The diagnosis of mushroom poisoning

in the other 14 incidents were confirmed either by identification of the poisonous

mushrooms or by the clear causal link between presentation of symptoms and

consumption of mushrooms. Of the 35 cases of defined mushroom poisoning, all

presented with GI symptoms as their earliest manifestation, with incubation

period ranging from 30 minutes to 6 hours. Diarrhea was the most common GI

symptom (80%), followed by vomiting (74.3%), abdominal pain (62.9%), and

nausea (45.7%). Other symptoms being less recorded were dizziness, fever,

chilliness, hypotension, unconsciousness, weakness, cold sweating, abdominal

fullness, drowsiness, hallucination, etc. Eight out of the 14 incidents of

mushroom poisoning occurred in the summer, while the other 6 incidents

occurred in the spring (4) or in the fall (2). According to the limited data

obtained in this study, mushroom poisoning is not common in Taiwan and most

cases were manifested with GI symptoms only. Treatment is mainly supportive

and the outcome is good, with no deaths being reported. As most cases are

poisoned following consumption of wild mushrooms, careful discrimination and

ingestion of wild mushrooms are mandatory in further prevention of mushroom

poisoning in Taiwan



Keywords: diagnosis/incidence/prevention/stroke/THERAPY/TOXIN



Schmidt, R., Roob, G., Kapeller, P., Schmidt, H., Berghold, A., Lechner, A. and Fazekas,

F. (2000), Longitudinal change of white matter abnormalities. Journal of Neural

Transmission-Supplement, (59), 9-14.



Abstract: A three year follow-up of 273 participants (mean age 60+/-6.1 years) of the

Austrian Stroke Prevention Study provides first information on the rate, clinical

predictors, and cognitive consequences of MRI white matter hyperintensity in

elderly individuals without neuropsychiatric disease. Lesion progression was

found in a total of 49 (17.9%) individuals. It was minor in 27 (9.9%) and marked

in 22 (8.1%) participants. Diastolic blood pressure (odds ratio 1.07/mmHg) and

early confluent or confluent white matter hyperintensities at baseline (odds ratio

2.62) were the only significant predictors of white matter hyperintensity

progression. Lesion progression had no influence on the course of

neuropsychologic test performance over the observational period

Keywords: age/Austria/AUSTRIAN STROKE PREVENTION/blood

pressure/elderly/FOLLOW-UP/HYPERINTENSITIES/MRI/NEW-YORK/predi

ctors/white matter



Schmidt, H., Fazekas, F., Kostner, G.M. and Schmidt, R. (2000), Genetic aspects of

microangiopathy-related cerebral damage. Journal of Neural

Transmission-Supplement, (59), 15-21.



Abstract: Microangiopathy related cerebral damage (MARCD) includes early confluent

and confluent white matter hyperintensities (WMH) and lacunar lesions. It is

expected to be the result of interactions between multiple genetic and

environmental factors. The estimated proportion of genetic factors contributing

to the interindividual variation seen in WMH volume is 73%. This estimate

points to a significant genetic component in WMH development. In the setting of

the Austrian Stroke Prevention Study we search for genes being associated with

the presence, severity and progression of MARCD using the candidate gene

approach. Defining susceptibility genes may allow to better identify individuals

at high risk for MARCD and to target preventive measures



Keywords: ABNORMALITIES/APOLIPOPROTEIN-E/Austria/AUSTRIAN STROKE

PREVENTION/cerebral/CHOLESTEROL

TRANSPORT/development/DISEASE/gene/genes/genetic/high

risk/HYPERINTENSITIES/MR/NEW-YORK/risk/RISK-FACTORS/severity/T

RAITS/white matter/WHITE-MATTER LESIONS



Schmidt, R., Fazekas, F., Enzinger, C., Ropele, S., Kapeller, P. and Schmidt, H. (2002),

Risk factors and progression of small vessel disease-related cerebral

abnormalities. Journal of Neural Transmission-Supplement, (62), 47-52.



Abstract: A three year follow-up of 273 participants (mean age 60 years) of the Austrian

Stroke Prevention Study provides first information on the rate and clinical

predictors of progression of small vessel disease related cerebral abnormalities

including white matter changes and lacunes. White matter hyperintensity

progression was found in 17.9% of individuals over the 3 year period. New

lacunes occurred in 2.2% of subjects. The overall frequency of progression of

small vessel disease related brain changes was 19%. Diastolic blood pressure and

early confluent or confluent white matter hyperintensities at baseline predicted

lesion progression. Genetic association studies in the setting of the Austrian

Stroke Prevention Study described that polymorphisms in the renin angiotensin

system (RAS) increase the susceptibility for progression of cerebral small vessel

disease. Homozygosity for the T allele of the M235T polymorphism of the

angiotensinogen gene was associated with a 3.19-fold increased risk for lesion

progression independently of arterial hypertension. These data suggest that drugs

influencing the RAS system may allow to intervene with an unfavorable course

of cerebral small vessel disease

Keywords: age/angiotensin/angiotensinogen/arterial/arterial hypertension/Austria/blood

pressure/brain/cerebral/disease/drugs/gene/hypertension/NEW-YORK/POLYM

ORPHISM/predictors/renin angiotensin system/risk/small vessel

disease/STROKE/white matter



Erkinjuntti, T. (2002), Diagnosis and management of vascular cognitive impairment and

dementia. Journal of Neural Transmission-Supplement, (63), 91-109.



Abstract: Vascular dementias (VaDs) are the second most common cause of dementia.

Cerebrovascular disease (CVD) and stroke relates to high risk of cognitive

impairment, but also relate to Alzheimer's disease (AD): Vascular cognitive

impairment (VCI) and dementias extend beyond the traditional multi-infarct

dementia. Pathophysiology of VaD incorporates interactions between vascular

etiologies (CVD and vascular risk-factors), changes in the brain (infarcts, white

matter lesions, atrophy), host factors (age, education) and cognition. Variation in

defining the cognitive syndrome, in vascular etiologies, and allowable brain

changes in current criteria have resulted in variable estimates of prevalence, of

groups of subjects, and of the types and distribution of putative causal brain

lesions. Should new criteria be developed? Ideally in constructing new criteria

the diagnostic elements should be tested with prospective studies with

clinical-pathological correlation: replace dogma with data. Meanwhile focus on

more homogenous subtypes of VaD, and on imaging criteria could be a solution.

Subcortical ischemic vascular disease and dementia (SIVD) incorporate small

vessel disease as the chief vascular etiology, lacunar infarct and ischaemic white

matter lesions as primary type of brain lesions, subcortical location as the

primary location of lesions, and subcortical syndrome as the primary clinical

manifestation. It incorporates two clinical entities "Binswanger's disease" and

"the lacunar state". AD with VaD (mixed dementia) has been underestimated as a

prevalent cause in the older population. In addition to simple co-existence, VaD

and AD have closer interaction: several vascular risk factors and vascular brain

changes relate to clinical manifestation of AD, and they share also common

pathogenetic mechanisms. Vascular cognitive impairment (VCI) is a category

aiming to replace the "Alzhemerized" dementia concept in the setting of CVD,

and substitute it with a spectrum that includes subtle cognitive deficits of

vascular origin, poststroke dementia, and the complex group of the vascular

dementias. As far there is no standard treatment for VaDs, and still little is

known on the primary prevention (brain at risk for CVD) and secondary

prevention (CVD brain at risk for VCI/VaD). There is no standard symptomatic

treatment for VaD. Recently symptomatic cholinergic treatment has shown

promise in AD with VaD, as well as probable VaD. Future focus should be

directed to the distinct etiological and pathological factors: the vascular and the

AD burden of the brain



Keywords: AD/age/Alzheimer's

disease/ALZHEIMERS-DISEASE/brain/CLINICAL-DIAGNOSIS/cognition/co

gnitive impairment/dementia/diagnostic/disease/education/etiology/Finland/high

risk/HOSPITALIZED COHORT/interaction/ischaemic/ischemic/LONG-TERM

SURVIVAL/MAJOR SUBTYPES/management/mechanisms/mixed

dementia/MULTI-INFARCT DEMENTIA/MULTIINFARCT

DEMENTIA/NEW-YORK/NINDS-AIREN/population/POPULATION-BASED

COHORTS/prevalence/prevention/primary/primary prevention/prospective

studies/risk/risk factors/RISK-FACTORS/secondary/secondary prevention/small

vessel disease/stroke/treatment/vascular/vascular cognitive impairment/vascular

disease/vascular risk/vascular risk factors/white matter/white matter lesions



Schmidt, H., Fazekas, F. and Schmidt, R. (2002), Microangiopathy-related cerebral

damage and angiotensinogen gene: from epidemiology to biology. Journal of

Neural Transmission-Supplement, (62), 53-59.



Abstract: Microangiopathy-related cerebral damage (MARCD) is a common finding in

the elderly. It may lead to cognitive impairment and gait disturbances. Arterial

hypertension and age are the best accepted risk factors for MARCD. Genes

involved in blood pressure regulation, like genes encoding the proteins of the

renin-angiotensin system (RAS) therefore represents good candidate genes for

MARCD. Plasma angiotensinogen level is a major determinant of the RAS

activity. Positive correlation between angiotensinogen gene expression and RAS

activity, as well as blood pressure were observed. Common mutations described

in the AGT promoter were able to alter AGT expression in cell culture. We

described that 4 frequent mutations at the AGT promoter are combined in 5

haplotypes coded as A (-6:g, - 20:a, -152:g, -217:g), B (-6:a, -20:c, -152:g,

-217:g), C (- 6:a, -20:c, -152:a, -217:g), D (-6:a, -20:a, -152:g, -217:g), and E

(-6:a, -20:a, -152:g, -217:a). The B haplotype was significantly associated with

MARCD in the cohort of the Austrian Stroke Prevention Study (p = 0.005). The

association was independent of hypertension, which pinpointed to a possible role

of the local RAS in this relationship. Investigation of the promoter activity of the

AGT gene in astrocytes suggests that expression of this gene may be modulated

by the haplotype



Keywords: age/angiotensinogen/AORTIC SMOOTH-MUSCLE/AT(1)

RECEPTOR/Austria/AUSTRIAN STROKE PREVENTION/blood

pressure/cerebral/cognitive

impairment/culture/elderly/epidemiology/EXPRESSION/gene/gene

expression/genes/HYPERTENSION/NEW-YORK/PROMOTER/PROTEIN-KI

NASE/renin angiotensin system/renin-angiotensin system/risk/risk factors/TATA

BOX/TRANSCRIPTION INITIATION SITE/WHITE MATTER LESIONS



van Dijk, E.J., Prins, N.D., Vermeer, S.E., Koudstaal, P.J. and Breteler, M.M.B. (2002),

Frequency of white matter lesions and silent lacunar infarcts. Journal of Neural

Transmission-Supplement, (62), 25-39.



Abstract: White matter lesions and silent lacunar infarcts are related to and may result

from cerebral small vessel disease. Reported frequencies of these lesions vary

largely among studies. Differences in imaging techniques, rating scales, cut-off

points in lesion severity grading and study populations contribute to the variation,

in addition to differences in risk factor profiles across studies. In this paper, we

will firstly discuss general methodological issues that may influence reported

frequencies of white matter lesions and silent lacunar infarctions, and then

review published data. We will focus on the results from population-based

studies and only briefly comment on patient series of stroke and dementia



Keywords: ALZHEIMERS-DISEASE/ANATOMIC

CHARACTERISTICS/AUSTRIAN STROKE

PREVENTION/CARDIOVASCULAR

HEALTH/cerebral/dementia/DIAGNOSTIC-CRITERIA/disease/ELDERLY

PEOPLE/Netherlands/NEW-YORK/population-based/review/risk/risk

factor/severity/SIGNAL HYPERINTENSITIES/small vessel

disease/stroke/TRANSIENT ISCHEMIC ATTACK/VASCULAR

RISK-FACTORS/VISUAL RATING-SCALES/white matter/white matter

lesions



Guo, Z.H., Lee, J., Lane, M. and Mattson, M.P. (2001), Iodoacetate protects

hippocampal neurons against excitotoxic and oxidative injury: involvement of

heat-shock proteins and Bcl-2. Journal of Neurochemistry, 79 (2), 361-370.



Abstract: Mild metabolic stress may increase resistance of neurons in the brain to

subsequent, more severe insults, as demonstrated by the ability of ischemic

pre-conditioning and dietary restriction to protect neurons in experimental

models of stroke- and age-related neurodegenerative disorders. In the present

study we employed iodoacetic acid (IAA), an inhibitor of

glyceraldehyde-3-phosphate dehydrogenase, to test the hypothesis that inhibition

of glycolysis can protect neurons. Pre-treatment of cultured hippocampal neurons

with IAA can protect them against cell death induced by glutamate, iron and

trophic factor withdrawal. Surprisingly, protection occurred with concentrations

of IAA (2-200 nm) much lower than those required to inhibit glycolysis.

Pre-treatment with IAA results in suppression of oxyradical production and

stabilization of mitochondrial function in neurons after exposure to oxidative

insults. Levels of the stress heat-shock proteins HSP70 and HSP90, and of the

anti-apoptotic protein Bcl-2, were increased in neurons exposed to IAA. Our data

demonstrate that IAA can stimulate cytoprotective mechanisms within neurons,

and suggest the possible use of IAA and related compounds in the prevention

and/or treatment of neurodegenerative conditions



Keywords: AMYLOID BETA-PEPTIDE/apoptosis/brain/CALCIUM

HOMEOSTASIS/cerebral ischemia/death/DIETARY

RESTRICTION/ENGLAND/experimental/glutamate/heat-shock proteins 70 and

90/HSP70/ischemic/LIPID-PEROXIDATION/MANGANESE

SUPEROXIDE-DISMUTASE/membrane lipid

peroxidation/MITOCHONDRIAL DYSFUNCTION/mitochondrial

transmembrane potential/neurons/PARKINSONS-

DISEASE/PEROXYNITRITE

PRODUCTION/prevention/protection/stress/stroke/TRANSIENT FOREBRAIN

ISCHEMIA/treatment/TROPHIC FACTOR WITHDRAWAL/use



MacGregor, D.G., Avshalumov, M.V. and Rice, M.E. (2003), Brain edema induced by

in vitro ischemia: causal factors and neuroprotection. Journal of Neurochemistry,

85 (6), 1402-1411.



Abstract: Decreased cerebral blood flow, hence decreased oxygen and glucose, leads to

ischemic brain injury via complex pathophysiological events, including

excitotoxicity, mitochondrial dysfunction, increased intracellular Ca2+ , and

reactive oxygen species (ROS) generation. Each of these could also contribute to

cerebral edema, which is the primary cause of patient mortality after stroke. In

vitro brain slices are widely used to study ischemia. Here we introduce a slice

model to investigate ischemia-induced edema. Significant water gain was

induced in coronal slices of rat brain by 5 min of oxygen and glucose deprivation

(OGD) at 35degreesC, with progressive edema formation after return to

normoxic, normoglycemic medium. Edema increased with increasing injury

severity, determined by OGD duration (5-30 min). Underlying factors were

assessed using glutamate-receptor antagonists (AP5/CNQX), blockade of

mitochondrial permeability transition [cyclosporin A (CsA) versus FK506],

inhibition of Na+ /Ca2+ exchange (KB-R7943), and ROS scavengers (ascorbate,

Trolox((R)) , dimethylthiourea, Tempol((R)) ). All agents except KB-R7943 and

FK506 significantly attenuated edema when applied after OGD; KB-R7943 was

effective when applied before OGD. Significantly, complete prevention of

ischemia-induced edema was achieved with a cocktail of AP5/CNQX, CsA and

Tempol((R)) applied after OGD, which demonstrates the involvement of

multiple, additive mechanisms. The efficacy of this cocktail further shows the

potential value of combination therapies for the treatment of cerebral ischemia



Keywords: blood flow/brain/brain injury/brain slices/Ca2+/CEREBELLAR GRANULE

CELLS/cerebral/cerebral blood flow/cerebral edema/cerebral

ischemia/combination/CORTICAL

SLICES/CYCLOSPORINE-A/ENGLAND/excitotoxicity/formation/glucose/GL

UTAMATE NEUROTOXICITY/HYPOXIC/HYPOGLYCEMIC

INJURY/INTRACELLULAR

CALCIUM/ischemia/ischemic/mechanisms/mitochondria/MITOCHONDRIAL

PERMEABILITY TRANSITION/mortality/NA+/CA2+

EXCHANGE/neuroprotection/oxidative stress/OXYGEN-GLUCOSE

DEPRIVATION/prevention/primary/rat/RAT HIPPOCAMPAL

SLICES/severity/stroke/treatment/USA



Koponen, S., Kurkinen, K., Akerman, K.E.O., Mochly-Rosen, D., Chan, P.H. and

Koistinaho, J. (2003), Prevention of NMDA-induced death of cortical neurons by

inhibition of protein kinase C zeta. Journal of Neurochemistry, 86 (2), 442-450.



Abstract: Excitotoxicity through stimulation of N -methyl-d-aspartate (NMDA)

receptors contributes to neuronal death in brain injuries, including stroke. Several

lines of evidence suggest a role for protein kinase C (PKC) isoforms in NMDA

excitotoxicity. We have used specific peptide inhibitors of classical PKCs (alpha,

beta, and gamma), novel PKCs delta and epsilon, and an atypical PKCzeta in

order to delineate which subspecies are involved in NMDA-induced cell death.

Neuronal cell cultures were prepared from 15-day-old mouse embryos and plated

onto the astrocytic monolayer. After 2 weeks in vitro the neurons were exposed

to 100 mum NMDA for 5 min, and 24 h later the cell viability was examined by

measuring the lactate dehydrogenase release and bis-benzimide staining. While

inhibitors directed to classical (alpha, beta, and gamma) or novel PKCs (delta or

epsilon) had no effect, the PKCzeta inhibitor completely prevented the

NMDA-induced necrotic neuronal death. Confocal microscopy confirmed that

NMDA induced PKCzeta translocation, which was blocked by the PKCzeta

inhibitor. The NMDA-induced changes in intracellular free Ca2+ were not

affected by the peptides. In situ hybridization experiments demonstrated that

PKCzeta mRNA is induced in the cortex after focal brain ischemia. Altogether,

the results indicate that PKCzeta activation is a downstream signal in

NMDA-induced death of cortical neurons



Keywords: activation/brain/brain ischemia/CEREBELLAR GRANULE

CELLS/CEREBRAL-ARTERY OCCLUSION/changes/cortical

neurons/death/DELTA-PKC/ENGLAND/excitotoxicity/Finland/focal/INDUCE

D APOPTOSIS/inhibitor

peptide/ISCHEMIA/ischemia/METHYL-D-ASPARTATE/neurons/NF-KAPPA-

B/NMDA/protein kinase C/PROTEOLYTIC

ACTIVATION/RAT-BRAIN/receptors/results/SPREADING

DEPRESSION/stimulation/stroke



Callahan, A.S. and Berger, B.L. (1997), Balloon angioplasty of intracranial arteries for

stroke prevention. Journal of Neuroimaging, 7 (4), 232-235.



Abstract: Stroke from surgically inaccessible intracranial atherostenosis remains a

formidable clinical challenge. While antithrombotic or antiplatelet therapy may

prevent distal embolism, there is no effective program for plaque stabilization

preventing progression of atherosclerotic stenosis. In patients with isolated

circulations (single vertebral with absent posterior communicating arteries, single

carotid with contralateral internal carotid artery occlusion, or single carotid with

an absent anterior communicating artery), occlusion of the stenotic vessel may

produce a low flow-mediated stroke. Fifteen patients with atherosclerotic

intracranial stenoses were treated by balloon angioplasty after medical therapy

with warfarin failed. Treated territories included the distal internal carotid,

proximal middle cerebral, distal vertebral, and basilar arteries. Dilation was

successful in all vessels, with residual stenoses averaging less than 30%. Two

complications included one paramedian pontine stroke and a single vessel

rupture that proved fatal. There was no recurrence of transient ischemic attacks

and no restenosis at the angioplasty site over a follow-up period of more than 24

months. In this small series, balloon angioplasty of intracranial vessels provided

a therapeutic option for secondary stroke prevention in highly selected patients.

Further studies will be necessary to establish the efficacy and safety of

endovascular treatment in larger series



Keywords: angioplasty/antiplatelet therapy/balloon angioplasty/carotid/carotid

artery/cerebral/complications/embolism/ischemic/plaque/prevention/recurrence/s

afety/stroke/stroke prevention/therapy/transient/treatment/warfarin



Boyajian, R.A. and Otis, S.M. (2002), Integration and added value of the modern

noninvasive vascular laboratory in vascular diseases management. Journal of

Neuroimaging, 12 (2), 148-152.



Abstract: Background and Purpose. Today's vascular laboratory technology offers broad

applications throughout vascular medicine. We explore the diagnostic work-up

and management of selected peripheral vascular diseases by benchmarking the

institutional mix of invasive and noninvasive technology utilization and

associated cost burdens. Methods. Specialized diagnostic studies for prevention

of stroke and pulmonary embolism, and diagnosis and management of femoral

pseudoaneurysm were reviewed for our 355-physician clinic and hospital

practice. The proportions and costs for invasive and noninvasive diagnostic

procedures were tabulated for carotid stenosis, deep venous thrombosis (DVT),

and iatrogenic femoral pseudoaneurysm. Current technology utilization mix cost

burdens were compared to projected cost burdens for hypothetical equivalent

medical value (ie, the same total test volume) in the theoretical absence of

noninvasive laboratory services. Results, The technology utilization mix was

dominated by noninvasive duplex ultrasonography for all 3 vascular disease

workups. The technology utilization mix benchmarks were 92% noninvasive for

carotid stenosis, 98% noninvasive for DVT, and 100% noninvasive for

pseudoaneurysm. Under hypothetical constant test volume normalized to

utilization level for the 2-year period, the maximal range in cost burdens between

current reliance on noninvasive diagnoses versus projected 100% reliance on

invasive procedures for the 3 vascular applications is approximately $6 million.

Conclusion. Benchmark indices reveal near total adoption of noninvasive

technology for vascular diagnostic workups at our center. The benefits to

institutions of benchmarking their technology utilization mix and costs are

discussed in relation to identifying potential for cost- containment from

modifying technology utilization practices



Keywords: benchmarking/carotid/carotid stenosis/cost/cost

control/COST-EFFECTIVENESS/costs/DEEP VENOUS

THROMBOSIS/DIAGNOSIS/diagnostic/diagnostic technology

utilization/disease/diseases/duplex/DVT/embolism/hospital/institutional/manage

ment/medical/noninvasive vascular laboratory/peripheral vascular

diseases/prevention/PSEUDOANEURYSM/pulmonary/pulmonary

embolism/PULMONARY-EMBOLISM/stenosis/stroke/thrombosis/ultrasonogra

phy/vascular/vascular disease/venous thrombosis

Felberg, R.A., Christou, L., Demchuk, A.M., Malkoff, M. and Alexandrov, A.V. (2002),

Screening for intracranial stenosis with transcranial Doppler: The accuracy of

mean flow velocity thresholds. Journal of Neuroimaging, 12 (1), 9-14.



Abstract: Background. Patients with 50% intracranial arterial stenosis may require more

intensive therapies for stroke prevention. Transcranial Doppler (TCD) is a

convenient noninvasive screen for intracranial stenosis. The accuracy of different

mean flow velocity (MFV) thresholds for determining the degree of stenosis

remains uncertain. Methods. The authors prospectively compared the accuracy of

TCD criteria and MFV thresholds to magnetic resonance, computed tomography,

and digital subtraction angiography in patients with symptoms of recent or

remote stroke or transient ischemic attack. Stenosis on angiography was

measured as 0%, 900 mg per day) doses of

aspirin in patients after a transient ischaemic attack or non-disabling stroke. The

purpose of this study was to resolve the issue. Thus a minimeta-analysis was

performed on data from 10 randomised trials of aspirin only upsilon control

treatment in 6171 patients after a transient ischaemic attack or nondisabling

stroke. The data on the trials were listed in an appendix of the report on the

second cycle of the Antiplatelet Trialists' Collaboration. There was virtually no

difference in relative risk reduction for low, medium, and high doses of aspirin

(13%, 9%, and 14% respectively). This equivalence corresponds with the results

of the UK-TIA trial in a direct comparison of 300 and 1200 mg. The Dutch TIA

trial showed no difference in efficacy of 30 and 283 mg. It is concluded that

aspirin at any dose above 30 mg daily prevents 13% (95% confidence interval

4-21) of vascular events and that there is a need for more efficacious drugs

Keywords: aspirin/BRITISH/cerebral ischaemia/CONTROLLED

TRIAL/ischaemia/ISCHEMIA/meta-analysis/relative risk/risk/SECONDARY

PREVENTION/STROKE/TIA/transient/treatment/trials/vascular



Rudd, A.G., Wolfe, C.D.A. and Howard, R.S. (1997), Prevention of neurological disease

in later life. Journal of Neurology Neurosurgery and Psychiatry, 63 S39-S52



Keywords: AGED BRITISH MEN/BLACK-WHITE

DIFFERENCES/BLOOD-PRESSURE/BRITISH/CARE/CAROTID

ENDARTERECTOMY/CEREBROVASCULAR- DISEASE/CHRONIC

ATRIAL-FIBRILLATION/COMMUNITY-STROKE-PROJECT/CORONARY

HEART-DISEASE/ENGLAND/MODERATE

ALCOHOL-CONSUMPTION/RISK-FACTORS



O'Connell, J.E., Gray, C.S., French, J.M. and Robertson, I.H. (1998), Atrial fibrillation

and cognitive function: case-control study. Journal of Neurology Neurosurgery

and Psychiatry, 65 (3), 386-389.



Abstract: Atrial fibrillation is an important and independent risk factor for

cerebrovascular disease and vascular dementia. There is increasing evidence that

atrial fibrillation is associated with an increased risk of asymptomatic or silent

cerebral infarction and as a result may confer an increased risk of progressive

cognitive impairment on a person. In this study we sought to determine whether

this hypothesis could be explored in a prospective case controlled design.

Twenty seven patients with non-valvular atrial fibrillation (NVAF) and no

history of stroke, transient ischaemic attack, dementia, and thyrotoxicosis were

compared with 54 age and sex matched controls in sinus rhythm. All cases

underwent clinical examination, ECG, and psychological assessment using a

battery of nine neuropsychological tests. Between group analysis and a

comparison of mean test scores of paired controls with cases were undertaken.

The presence of atrial fibrillation was consistently associated with poorer

performances on all the subtests of the neuropsychological battery. There was no

association between duration of atrial fibrillation and performance. These results

provide evidence to justify further examination of the hypothesis in a larger

prospective study to determine whether antithrombotic therapy may protect

against cognitive decline in patients at maximal risk of silent cerebral ischaemia

and associated cognitive decline



Keywords: age/antithrombotic therapy/atrial fibrillation/BRITISH/cerebral

infarction/cerebral ischaemia/cerebrovascular disease/cognitive

function/DEMENTIA/ENGLAND/fibrillation/history/IMPAIRMENT/ischaemia

/POPULATION/PREVENTION/prospective

study/risk/sex/STROKE/transient/vascular



Yamamoto, H. and Bogousslavsky, J. (1998), Mechanisms of second and further strokes.

Journal of Neurology Neurosurgery and Psychiatry, 64 (6), 771-776.

Abstract: Objectives-The mechanisms underlying recurrent stroke may be complex and

multifactorial, but they have not been studied systematically. The aim was to

analyse the different patterns and pathophysiological mechanisms of second and

further strokes. Methods-Recurrent stroke patterns and mechanisms were studied

in 102 patients admitted with second or further strokes to the stroke centre in

Lausanne University Hospital. Results- The patients with an initial

cardioembolic stroke experienced recurrent stroke of the same type most often,

followed by those with initial non-lacunar non-cardioembolic stroke, brain

haemorrhage, and lacunar stroke (77%, 65%, 58%, and 48% respectively). Forty

two per cent of the recurrent strokes in patients with an initial brain haemorrhage

were ischaemic, whereas patients with ischaemic stroke only occasionally

suffered brain haemorrhage (5%). In patients with brain haemorrhage, the lobar

location predominated in both the first and all episodes (69% and 78%

respectively), suggesting a small, occult arteriovenous malformation or cerebral

amyloid angiopathy rather than hypertensive small artery disease. The functional

disability of patients after an initial lacunar stroke was significantly better than in

patients with other stroke subtypes (p 60 months) were included. Patients were categorized as

asymptomatic if they were free of cerebrovascular incidents for at least 24

months (n = 18). Symptomatic patients had suffered ischemic strokes or transient

ischemic attacks within the previous 3 days (n = 35). Platelet function was

assessed using the PFA-100 system that allows for quantitative assessment of

platelet function, reporting platelet aggregatability as the time required to close a

small aperture in a biologically active membrane. Results Collagen/epinephrine

closure times were significantly shorter in symptomatic patients than in

asymptomatic patients (p 40% of contracting myocardium estimated to be at risk for severe

ischemia during angioplasty. The cardiac (liters/min per m2) and stroke work

(g.m/m2) indexes decreased from mean baseline values of 2.5 +/- 0.52 and 52 +/-

15 to 1.7 +/- 0.47 and 27 +/- 12 (mean +/- SD), respectively, during

nonsupported balloon inflations but decreased only to 2.1 +/- 0.52 (p 80 years of age with MI (P not significant); to

three of seven patients (43%) 80

years of age with stroke (P not significant); to two of four patients (50%) (70

years of age with PAD, to seven of 17 patients (41%) 70 to 80 years of age with

PAD, and to 10 of 25 patients (40%) >80 years of age with PAD (P not

significant); and to six of 15 patients (40%) 80 years of age with no CAD,

stroke, or PAD (P not significant). None of the other patients with MI, stroke,

PAD, or no CAD, stroke, or PAD was treated with diet or lipid- lowering drugs.

CONCLUSIONS: Measurement of serum LDL cholesterol and of appropriate

use of lipid-lowering drugs and diet in older patients with MI, stroke, PAD, and

no CAD, stroke, or PAD is underutilized in an academic, hospital-based

geriatrics practice



Keywords: age/cholesterol/coronary artery disease/CORONARY

HEART-DISEASE/DESIGN/diet/drug

therapy/drugs/GUIDELINES/LDL/lipids/MEASUREMENT/myocardial

infarction/MYOCARDIAL-INFARCTION/PRAVASTATIN/PREVENTION/str

oke/women



Obisesan, T.O., Hirsch, R., Kosoko, O., Carlson, L. and Parrott, M. (1998), Moderate

wine consumption is associated with decreased odds of developing age-related

macular degeneration in NHANES-1. Journal of the American Geriatrics Society,

46 (1), 1-7.



Abstract: OBJECTIVE: To determine the association between alcohol intake and the

risk of developing age-related macular degeneration (AMD). DESIGN: Case

control study. PARTICIPANTS: The sample consisted of 3072 adults 45 to 74

years of age with macular changes indicative of AMD who participated in a

nationally representative sample of the first National Health Nutrition and

Examination Survey (NHANES-1) between 1971 and 1975: (a) the

ophthalmology data set and (b) the medical history questionnaire. MAIN

OUTCOME MEASURES: Alcohol intake and the risk of developing AMD were

measured. AMD was determined by staff at the National Eye Institute by

fundoscopy examination using standardized protocol. RESULTS: Overall, 184

individuals (6%) had AMD. We observed a statistically significant but negative

association between AMD and the type of alcohol consumed in a bivariate model

(OR 0.86; 95% CI 0.73, 0.99). In the same model, age maintained a consistently

strong association with AMD (OR 1.08; 95% CI 1.06-1.11; P 20 cm/s (RR 1.7, p = 0.008) and complex aortic plaque (RR

2.1%, p 350 mg/dL (P 85 years (p 85 years (p 17 vs. 137 + 22 mm Hg for standing, p 16 vs. 144 +/- 22 mm Hg for lying, p 2 days' duration who may

benefit from immediate cardioversion with self-administered

low-molecular-weight heparin (enoxaparin) as a bridge antithrombotic therapy to

warfarin, after a negative transesophageal echo-cardiography (TEE) screening

for thrombus. Assuming no difference in stroke or bleeding rates, our cost

minimization model shows that the TEE- guided enoxaparin treatment costs are

$1353 lower per patient than an Intravenous unfraction-ated heparin approach.

Sensitivity analyses for stroke and bleeding reveal that the treatment-cost

economic dominance of the TEE-guided enoxaparin approach may be enhanced

by an expected improvement in clinical outcome



Keywords: ANTICOAGULANT-THERAPY/antithrombotic/antithrombotic

therapy/atrial fibrillation/bleeding/cardioversion/COMPLICATIONS/cost/cost

analysis/costs/DEEP-VEIN

THROMBOSIS/DISEASE/echocardiography/ECONOMIC-ANALYSIS/ELECT

IVE CARDIOVERSION/fibrillation/heparin/low molecular weight

heparin/low-molecular-weight

heparin/MANAGEMENT/outcome/PREVENTION/screening/stroke/SURGERY

/therapy/thrombus/transesophageal

echocardiography/treatment/UNFRACTIONATED HEPARIN/warfarin



Guralnik, J.M., Ferrucci, L., Balfour, J.L., Volpato, S. and Di Iorio, A. (2001),

Progressive versus catastrophic loss of the ability to walk: Implications for the

prevention of mobility loss. Journal of the American Geriatrics Society, 49 (11),

1463-1470.



Abstract: OBJECTIVES: Loss of mobility is an important functional outcome that can

have devastating effects on quality of life and the ability of older persons to

remain independent in the community. Although a large amount of research has

been done on risk factors for disability onset, little work has focused on the pace

of disability progression. This study characterizes the development of severe

walking disability over time and evaluates risk factors and subsequent mortality

as they relate to mobility disability with progressive or catastrophic onset.

DESIGN: Population-based prospective cohort study with annual follow-up

assessments for up to 7 years SETTING: Three communities of the Established

Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: There

were 5,355 persons not disabled at baseline and the first follow-up who had

adequate data available to classify mobility disability during subsequent

follow-ups. MEASUREMENTS: Severe mobility disability was defined as the

need for help from a person to walk across a room or inability to walk across a

room. Those developing severe mobility disability were classified as having

progressive mobility disability if they had been unable to walk half a mile in

either of the prior 2 years. They were classified as having catastrophic mobility

disability if they reported having been able to walk half a mile in two previous

annual interviews. RESULTS: The overall incidence of severe mobility disability

was 11.6 cases/1,000 person years. Those age 85 and older or having three or

ii-tore chronic conditions at baseline were significantly more likely to develop

progressive disability than catastrophic disability. Stroke, hip fracture, and

cancer occurring during follow-up were associated with very high risk of severe

mobility disability. For stroke and hip fracture, the risk was twice as high for

catastrophic disability as for progressive disability, but this difference did not

reach statistical significance. Risk for catastrophic disability from cancer was

significantly greater than for progressive disability. Half of catastrophic

disability subjects had stroke, hip fracture, or cancer in the year immediately

preceding this disability. Incident heart attack did not predict severe mobility

disability. Among those who developed severe mobility disability, type of

disability did not influence subsequent survival for the first 3 years, but beyond 3

years those with catastrophic disability had a relative risk of death of 0.4 (95%

confidence interval 0.2-0.9) compared with those with progressive disability.

CONCLUSION: The observation that risk factors and mortality outcomes were

both different for progressive and catastrophic mobility disability supports the

value of ascertaining the pace of disability development as a useful

characterization of disability. Further progress in developing prevention and

treatment strategies may be made by taking the pace of disability development

into account



Keywords: ADULTS/age/aging/cancer/chronic disease/cohort

study/community/death/DECLINE/DESIGN/development/DISABILITY/disabili

ty/FUNCTIONAL OUTCOMES/functional status/heart/high risk/HIP

FRACTURE/HOSPITALIZATION/incidence/MEASUREMENT/mobility/mort

ality/OBJECTIVES/OLDER

PERSONS/outcome/PATTERNS/PREDICTORS/prevention/prospective cohort

study/quality of life/relative risk/research/risk/risk

factors/stroke/treatment/TRIAL



Lonn, E., Roccaforte, R., Yi, Q.L., Dagenais, G., Sleight, P., Bosch, J., Suhan, P., Micks,

M., Probstfield, J., Bernstein, V. and Yusuf, S. (2002), Effect of long-term

therapy with ramipril in high-risk women. Journal of the American College of

Cardiology, 40 (4), 693-702.



Abstract: OBJECTIVES We evaluated the effects of long-term therapy with the

angiotensin-converting enzyme (ACE) inhibitor ramipril on major cardiovascular

(CV) outcomes in high-risk women. BACKGROUND The effect of long-term

ACE inhibitor therapy in high-risk women without heart failure and with

preserved left ventricular (LV) systolic function has not been previously reported.

METHODS The Heart Outcomes Prevention Evaluation (HOPE) trial is a large,

randomized clinical trial that evaluated. ramipril and vitamin E in high-risk

patients. We present the preplanned analysis of the effects of ramipril in women

in the HOPE study. The study randomized 2,480 women aged 55 years with

vascular disease or diabetes and at least one additional CV risk factor and

without heart failure or a known low LV ejection fraction to ramipril (10 mg/day)

or placebo. The primary outcome was the composite of myocardial infarction,

stroke or CV death. Average follow-up was 4.5 years. RESULTS Treatment with

ramipril resulted in reduced primary end point rates (11.3% vs. 14.9% in the

placebo arm; relative risk [RR] 0.77, 95% confidence interval [CI] 0.62 to 0.96;

p = 0.019), fewer strokes (3.1% vs. 4.8%; RR 0.64, 95% CI 0.43 to 0.96; p =

0.029) and fewer CV deaths (4.2% vs. 6.996; RR 0.62, 95% CI 0.44 to 0.88; p =

0.0068). There were trends toward reduced rates of myocardial infarction, heart

failure and all-cause death. The beneficial effect of ramipril was similar in

women and men. CONCLUSIONS Treatment with ramipril reduces the CV risk

in high-risk women without heart failure and with preserved LV systolic function.

(C) 2002 by the American College of Cardiology Foundation



Keywords: ACE inhibitor/aged/cardiovascular/clinical trial/CLINICAL-

TRIALS/death/diabetes/DISEASE/ESTROGEN/heart/heart failure/high

risk/infarction/INHIBITORS/left ventricular/LEFT-VENTRICULAR

DYSFUNCTION/men/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/NEW-YORK/OBJECTIVES/outcom

e/POSTMENOPAUSAL WOMEN/primary/ramipril/randomized/randomized

clinical trial/RECEPTOR GENE-EXPRESSION/relative

risk/RENIN-ANGIOTENSIN SYSTEM/REPLACEMENT THERAPY/risk/risk

factor/stroke/therapy/trends/trial/vascular/vascular disease/vitamin/vitamin

E/women



Friedman, S.M., Munoz, B., West, S.K., Rubin, G.S. and Fried, L.P. (2002), Falls and

fear of falling: Which comes first? A longitudinal prediction model suggests

strategies for primary and secondary prevention. Journal of the American

Geriatrics Society, 50 (8), 1329-1335.



Abstract: OBJECTIVES: Previous cross-sectional studies have shown a correlation

between falls and fear of falling, but it is unclear which comes first. Our

objectives were to determine the temporal relationship between falls and fear of

falling, and to see whether these two outcomes share predictors. DESIGN: A 20-

month, population-based, prospective, observational study. SETTING: Salisbury,

Maryland. Each evaluation consisted of a home-administered questionnaire,

followed by a 4- to 5-hour clinic evaluation. PARTICIPANTS: The 2,212

participants in the Salisbury Eye Evaluation project who had baseline and

20-month follow-up clinic evaluations. At baseline, subjects were aged 65 to 84

and community dwelling and had a Mini-Mental State Examination score of 18

or higher. MEASUREMENTS: Demographics, visual function, comorbidities,

neuropsychiatric status, medication use, and physical performance-based

measures were assessed. Stepwise logistic regression analyses were performed to

evaluate independent predictors of falls and fear of falling at the follow-up

evaluation, first predicting incident outcomes and then predicting fall or

fear-of-falling status at 20 months with baseline falling and fear of falling as

predictors. RESULTS: Falls at baseline were an independent predictor of

developing fear of falling 20 months later (odds ratio (OR) = 1.75; P 60 years

old. Age at first event ranged from 29 to 86 years (mean 61 +/- 14 years). Most

(n = 37; 72%) events occurred in those >50 years, although 14 (28%) younger

patients (less than or equal to50 years) also had events. Multivariate analysis

showed stroke and other peripheral vascular events to be independently

associated with congestive symptoms and advanced age, as well as with atrial

fibrillation (in 45 [88%] of 51 patients), at the initial evaluation. The cumulative

incidence of these events among patients with atrial fibrillation was significantly

higher in non-anticoagulated patients as compared with patients receiving

warfarin (31% vs. 18%; p 1 g/d. Nevertheless, in

persons with CKD, even those with proteinuria below the dipstick positive level

(approximately 300 mg/d or urine protein to creatinine ratio of 0.22), aggressive

BP control also may be warranted because of the high risk of nonrenal

cardiovascular disease. Multiple antihypertensive drugs will be required in the

vast majority of patients with diabetes and/or reduced kidney function to attain

BP goal. Resin-angiotensin system (RAS) modulator therapy is indicated among

persons with diabetes mellitus and CKD. Available data support the use of

angiotensin receptor blockers in persons with type 2 diabetes and overt

nephropathy for preservation of kidney function. Among persons with type I

diabetes with or without overt nephropathy, type 2 diabetes without overt

nephropathy and in nondiabetic CKD, the available clinical data support the use

of angiotensin-converting enzyme inhibitors as the RAS modulator of choice.

Low therapeutic target BP levels 75%) RCS, a strategy not unlike that adopted for primary CENDX



Keywords: ARTERY DISEASE/carotid

stenosis/ENDARTERECTOMY/morbidity/mortality/NATURAL-HISTORY/OC

CLUSION/prevention/RESTENOSIS/RISK/risk

factors/SERIES/STROKE/stroke prevention/TERM FOLLOW-UP/transient

ischemic attack/vascular disease



Lennard, N., Smith, J., Dumville, J., Abbott, R., Evans, D.H., London, N.J.M., Bell,

P.R.F. and Naylor, A.R. (1997), Prevention of postoperative thrombotic stroke

after carotid endarterectomy: The role of transcranial Doppler ultrasound.

Journal of Vascular Surgery, 26 (4), 579-584.



Abstract: Purpose: To determine the incidence of particulate embolization after carotid

endarterectomy (CEA), the effect of dextran-40 infusion in patients with

sustained postoperative embolization, and the impact of transcranial Doppler

(TCD) monitoring plus adjuvant dextran therapy on the rate of postoperative

carotid thrombosis. Methods: Prospective study in 100 patients who underwent

CEA with 6-hour postoperative monitoring using a TCD that was modified to

allow automatic, intermittent recording from the ipsilateral middle cerebral artery

waveform (10 minute sample every 30 minutes). An incremental dextran-40

infusion was commenced if 25 or more emboli were detected in any 10- minute

period. Results: Overall, 48% of patients had one or more emboli detected in the

postoperative period, particularly in the first 2 hours. However, sustained

embolization that required Dextran therapy developed in only five patients, In

each case, the rate of embolization rapidly diminished. Conclusions: A small

proportion of patients have sustained embolization after CEA, which in previous

studies has been shown to be highly predictive of thrombotic stroke. Intervention

with dextran reduced and subsequently stopped all the emboli in those in whom

it was used and contributed to a 0% perioperative morbidity and mortality rate in

this series



Keywords: ARTERY THROMBOSIS/carotid/carotid endarterectomy/cerebral/cerebral

artery/DIAGNOSIS/emboli/endarterectomy/incidence/morbidity/mortality/stroke

/therapy/thrombosis/transcranial Doppler ultrasound



Frawley, J.E., Hicks, R.G., Beaudoin, M. and Woodey, R. (1997), Hemodynamic

ischemic stroke during carotid endarterectomy: An appraisal of risk and cerebral

protection. Journal of Vascular Surgery, 25 (4), 611-619.



Abstract: Purpose: The purpose of this study was to validate the commonly accepted

indicators of risk of ischemic stroke that indicate the necessity for cerebral

protection during carotid endarterectomy (CEA), and to examine the efficacy of

high-dose thiopentone sodium (thiopental) as a cerebral protection method in

patients who are at high risk of intraoperative ischemic stroke. Method: In a

prospective study of 37 CEAs pet-formed for symptomatic stenosis >70%,

functional and clinical indicators of risk of ischemic stroke during carotid cross-

clamping were identified. Functional indicators of risk were the development of

ischemic electroencephalogram (EEG) changes and stump pressure 70% reduction in

diameter) and for 16 healthy control subjects. The 18 patients with ICA flow

lesion and no visible infarction on MRI who underwent CEA were evaluated

before and 7 days after surgery (CEA group). The 16 control subjects had never

had a cerebral event, and brain MRI and carotid duplex scan study results were

normal in all (control group). Results: Preoperative ICA volume flow was

severely decreased to less than 150 mL/min in all 18 patients, in comparison with

our laboratory normal value of matched age group of 250 to 300 mL/min. After

CEA, ICA volume flow was increased to greater than 300 mL/min in all patients

(P = .00). For patients in the CEA group, preoperative N- acetylaspartate/creatine

and choline/creatine ratios in the MCA territory were slightly decreased

compared with the healthy subjects in the control group but were within normal

limits. However, the postoperative values of N-acetylaspartate/creatine and

choline/creatine ratios in the ipsilateral MCA territory were significantly

increased as compared with the preoperative values (P 80%) was managed in 70 patients (61%), and symptomatic lesions (>50%)

were treated in 44 patients (39%). Results. CAS was technically successful in all

patients. Mean severity of stenosis before CAS was 87% +/- 6%, compared with

9% +/- 4% after CAS. Two patients (1.9%) died, 1 of reperfusion-intracerebral

hemorrhage and 1 of myocardial infarction 10 days after discharge; and 1 patient

(0.95%) had a stroke (retinal infarction), for a 30-day stroke and death rate of

2.85%. Two patients (1.9%) had transient neurologic events. No cranial nerve

deficits were noted. No neurologic complications have been noted in the last 27

patients (26%). Conclusions. A 30-day stroke and death rate of 2.85% in our

experience demonstrates acceptability of CAS as an alternative to repeat

operation or primary CEA in patients at high risk or in patients with

radiation-induced stenosis. We recommend further clinical investigation of CAS

and participation in clinical trials by vascular surgeons. (J Vasc Surg 2003;37:

1234-9.)



Keywords: age/ANGIOPLASTY/carotid/carotid endarterectomy/carotid stenosis/clinical

trials/complications/death/ENDARTERECTOMY/hemorrhage/high

risk/infarction/INITIAL

EXPERIENCE/MANAGEMENT/men/myocardial/myocardial

infarction/neurologic

complications/PLACEMENT/PREVENTION/primary/RESTENOSIS/results/rev

iew/risk/severity/STENOSIS/stenting/STROKE/SURGERY/therapy/transient/tri

als/USA/use/vascular/women



Reed, A.B., Gaccione, P., Belkin, M., Donaldson, M.C., Mannick, A., Whittemore, A.D.

and Conte, M.S. (2003), Preoperative risk factors for carotid endarterectomy:

Defining the patient at high risk. Journal of Vascular Surgery, 37 (6),

1191-1199.



Abstract: Purpose: The efficacy of carotid endarterectomy (CEA) for prevention of

stroke has been demonstrated in randomized trials; however, the optimal

approach in patients excluded from these trials or who have other significant

comorbid conditions remains controversial, particularly with the advent of

percutaneous interventions. We examined the influence of putative risk factors

on outcome of CEA in a single-center experience. Methods: A retrospective

analysis of 1370 consecutive CEA performed from 1990 to 1999 was undertaken.

Preoperative risk factors examined included age older than 80 years, congestive

heart failure, chronic obstructive pulmonary disease, renal failure (serum

creatinine concentration > 2.0 mg/dL), contralateral carotid artery occlusion,

recurrent ipsilateral carotid artery stenosis, ipsilateral hemispheric symptoms

within 6 weeks, and recent coronary bypass grafting (CABG). The Fisher exact

test was used to identify baseline variables associated with perioperative (30 days)

risk for stroke or death. Multivariate analysis with Poisson regression was used

to study the effect of all univariate criteria in combination. Results. In the overall

cohort, there were 32 adverse events (2.3%), including 11 deaths (0.8%), 6

disabling strokes (0.4%), and 10 nondisabling strokes (0.7%). There was no

significant difference in incidence of perioperative stroke or death between

patients with one or more risk factors (n = 689) and those with no risk factors

(low risk, n = 681). Thirty-day mortality was significantly greater in patients

with two or more risk factors compared with patients with no risk factors (2.8%

vs 0.3%; P = .04), but no significant difference was noted in perioperative stroke

rate (2.3% vs 1.0%). Univariate analysis demonstrated that contralateral carotid

occlusion (n = 75) was the only significant predictor of adverse outcome (5

events, 6.7%) among the variables tested; this was confirmed with multivariate

analysis (relative risk, 4.3; 95% confidence interval, 1.2-12.3; P = .01). Five-year

survival for patients with two or more risk factors was notably diminished

compared with that for patients with no risk factors (38.7% +/- 5.9% vs 75.0%

+/- 2.6%; P 10(5) cfu/ml of urine on >25% of an

individual's collected cultures. Women with persistent BU more frequently were

incontinent of bowel and bladder (OR 5.3, 6.3, respectively), more likely to be

functionally disabled (OR 3.2), to carry a diagnosis of dementia (OR 2.4), and

less likely to have suffered a stroke (OR 0.40). Cancer (OR 6.5) was the only risk

factor for persistent BU in men. The number of antibiotic courses prescribed,

frequency of hospitalizations, and mortality rates were not significantly different

between the two BU groups in either men or women. Conclusions. Persistent BU

is common in nursing home residents. The association of bowel and bladder

incontinence and functional disability with persistent bacteriuria suggests that

treatment or prevention of these risk factors may prevent or decrease the

incidence of bacteriuria. There was no evidence of significant adverse outcomes

resulting directly from the bacteriuric state. Higher mortality in the bacteriuric

group was the result of underlying functional debility and severity of illness

rather than the presence or persistence of BU

Keywords: ASSOCIATION/ELDERLY INSTITUTIONALIZED

MEN/INFECTIONS/MORTALITY/POPULATION/SURVIVAL



Freidl, W., Schmidt, R., Stronegger, W.J. and Reinhart, B. (1997), The impact of

sociodemographic, environmental, and behavioral factors and cerebrovascular

risk factors as potential predictors of the Mattis Dementia Rating Scale. Journals

of Gerontology Series A-Biological Sciences and Medical Sciences, 52 (2),

M111-M116.



Abstract: Background. Age and education have been found to affect the Mattis Dementia

Rating Scale (MDRS) score of elderly normals, but there have been no studies

assessing the influence of environmental and behavioral factors on this scale.

Their role as potential predictors of the MDRS total score was investigated.

Methods. The MDRS was administered to 1,927 normal elderly subjects in the

setting of a stroke prevention study. Results were correlated with 16

sociodemographic, environmental, and behavioral factors, and cerebrovascular

risk factors. Study statistics resulted from multiple logistic regression analysis.

Results. Results indicated that higher age and arterial hypertension were

associated with poorer cognitive performance, while better education and

moderate general life stress exerted a positive effect on the participants' test

results. Conclusions. Thus, besides the well-established factors of age and

educational level, moderate general life stress and hypertension were identified

as relevant predictors in determining the MDRS test performance of elderly

normals



Keywords: AGE/arterial hypertension/cerebrovascular/COGNITIVE

IMPAIRMENT/DIAGNOSIS/EDUCATION/elderly/environmental and

behavioral

factors/hypertension/INDIVIDUALS/MENTAL-STATE-EXAMINATION/POP

ULATION/predictors/prevention/risk/risk

factors/SENSITIVITY/SOCIETY/SPECIFICITY/stress/stroke/stroke prevention



Fuchs, Z., Blumstein, T., Novikov, I., Walter-Ginzburg, A., Lyanders, M., Gindin, J.,

Habot, B. and Modan, B. (1998), Morbidity, comorbidity, and their association

with disability among community-dwelling oldest-old in Israel. Journals of

Gerontology Series A-Biological Sciences and Medical Sciences, 53 (6),

M447-M455.



Abstract: Background. The impact of chronic conditions on the development of

disability has not yet been comprehensively studied among the elderly

population living in Israel. This study evaluates the prevalence of disability and

morbidity among the community- dwelling oldest-old population and examines

the association between medical conditions, comorbidity, and disability in basic

and instrumental activities of daily living (ADLs, IADLs). Method. The data are

based on a national random stratified sample of 1,820 Israeli Jewish individuals

75-94 years old. of whom 1,487 lived in the community. Results. Nineteen

percent of the population was disabled in ADLs and 36% in IADLs. Disability

rose with age and was higher for women and among individuals of Middle

Eastern and North African origin. Stepwise logistic regression indicates that the

variables associated with disability in ADLs and IADLs were older age, Middle

Eastern or North African origin, living with others, and the following conditions:

stroke, hip fracture, diabetes, osteoporosis, anemia, and heart attack. In addition,

lower education and suffering from urinary or kidney diseases, respiratory

disease, and/or Parkinson's disease were related to disability in ADLs; being a

woman and suffering from heart diseases other than heart attack were related to

disability in IADLs. Comorbidity was related to increased disability only for

individuals with three or more conditions. Conclusions. The identification of

medical conditions and sociodemographic variables related to limitations in

functioning may serve as a basis for health promotion and disease prevention in

elders by attempting to reduce the incidence and disabling consequences of

known disabling conditions



Keywords:

ABILITY/age/comorbidity/development/diseases/education/elderly/ELDERS/F

UNCTIONAL STATUS/HEALTH/health

promotion/heart/incidence/LIMITATIONS/MEDICAL

CONDITIONS/morbidity/osteoporosis/prevention/SOCIETY/stroke/women



Aronow, W.S. (2001), Treatment of older persons with hypercholesterolemia with and

without cardiovascular disease. Journals of Gerontology Series A-Biological

Sciences and Medical Sciences, 56 (3), M138-M145.



Abstract: Hypercholesterolemia is a risk factor for new coronary events in older men and

women. Secondary prevention trials have demonstrated in persons with coronary

artery disease (CAD) and hypercholesterolemia that statin drugs reduced in older

persons all-reuse mortality, cardiovascular mortality, coronary events, coronary

revascularization. stroke, and intermittent claudication. Statins have also been

shown to slow progression of coronary atherosclerotic plaques in persons with

CAD, to reduce restenosis after coronary stent implantation, and to decrease

myocardial ischemia in persons with CAD. Older men and women with CAD,

prior atherothrombotic brain infarction, peripheral arterial disease, or extracranial

carotid arterial disease and a serum low-density lipoprotein (LDL) cholesterol

level higher than 125 mg/dl despite diet should be treated with statin drug

therapy to loner the serum LDL cholesterol level below 100 mg/dl. Primary

prevention trials have shown that statins were also effective in reducing

cardiovascular events in older persons with hypercholesterolemia. On the basis

of data from the Air Force/Texas Coronary Atherosclerosis Prevention Study, the

physician should consider using statins in persons aged 65-80 years without

cardiovascular disease with a serum LDL cholesterol level above 130 mg/dl and

serum high- density lipoprotein cholesterol level below 50 mg/dl



Keywords: aged/AGED GREATER-THAN-OR-EQUAL-TO-62

YEARS/arterial/ASSOCIATION TASK-FORCE/ATHEROTHROMBOTIC

BRAIN INFARCTION/brain/brain infarction/cardiovascular/cardiovascular

disease/cardiovascular events/cardiovascular

mortality/carotid/cholesterol/coronary artery disease/CORONARY

HEART-DISEASE/coronary revascularization/coronary

stent/DENSITY-LIPOPROTEIN CHOLESTEROL/diet/disease/drug

therapy/drugs/ELDERLY PATIENTS/high density

lipoprotein/hypercholesterolemia/infarction/ischemia/LDL/LDL

cholesterol/LDL-cholesterol/low density

lipoprotein/men/mortality/myocardial/peripheral arterial disease/PERIPHERAL

ARTERIAL-DISEASE/prevention/PREVIOUS MYOCARDIAL-

INFARCTION/RECURRENT EVENTS

CARE/restenosis/revascularization/risk/risk

factor/SCANDINAVIAN-SIMVASTATIN-SURVIVAL/serum/SOCIETY/statin

/statins/stent/stroke/therapy/trials/women



Murphy, D.J., Gahm, G.J., Santilli, S., North, P., Oliver, S.C.N. and Shapiro, H. (2002),

Seniors' preferences for cancer screening and medication use based on absolute

risk reduction. Journals of Gerontology Series A-Biological Sciences and

Medical Sciences, 57 (2), M100-M105.



Abstract: Background. This study as conducted to determine the influence of patient

perceptions of absolute risk on choices for cancer screening and use of

medications to present heart attack, stroke, and hip fracture. Methods. At the end

of routine office visits, we surveyed all eligible consecutive patients who visited

four geriatricians in a Denver practice between November 8, 1993, and February

9, 1994. Results. We saw a total of 675 outpatients during the study period and

completed the interview with 409 patients (75% female, mean age 81.78%

Caucasian). We found a strong correlation between (i) increased probability of

detecting cancer and greater preference for cancer screening tests (p 0.1). For the combined in-hospital endpoint of

death or non-fatal stroke at 4 weeks, there was a 12% (6) proportional risk

reduction with aspirin (545 [5.3%] vs 614 [5.9%]; 2p=0.03), an absolute

difference of 6.8 (3.2) fewer cases per 1000. At discharge, 3153 (30.5%)

aspirin-allocated patients and 3266 (31.6%) placebo-allocated patients were dead

or dependent, corresponding to 11.4 (6.4) fewer per 1000 in favour of aspirin

(2p=0.08). Interpretation There are two major trials of aspirin in acute ischaemic

stroke. Taken together, CAST and the similarly large IST show reliably that

aspirin started early in hospital produces a small but definite net benefit, with

about 9 (SD 3) fewer deaths or non-fatal strokes per 1000 in the first few weeks

(2p=0.001), and with 13 (5) fewer dead or dependent per 1000 after some weeks

or months of followup (2pmol/L rise in plasma

ascorbic acid concentration, equivalent to about 50 g per day increase in fruit and

vegetable intake, was associated with about a 20% reduction in risk of all-cause

mortality (p856 pg/mL) were associated with a 2.7-fold increase in risk (95% CI

1.6-4.9, p=0.001). This effect was independent of traditional cardiovascular risk

factors and at least additive to that of C- reactive protein. There was no

significant association between MIC-1 polymorphism and vascular events.

Interpretation MIC-1 could be a novel target for cardiovascular disease

prevention



Keywords: age/APPARENTLY HEALTHY-

MEN/ATHEROSCLEROSIS/atherothrombosis/C-REACTIVE

PROTEIN/cardiovascular/cardiovascular disease/cardiovascular disease

prevention/cardiovascular event/cardiovascular events/cardiovascular

risk/cardiovascular risk factors/case-control

study/control/DISEASE/ENGLAND/EXPRESSION/gene/GROWTH-FACTOR-

BETA/infarction/INFLAMMATION/LONDON/macrophage/MEMBER/MIC-1/

myocardial/myocardial infarction/polymorphism/prevention/risk/risk

factors/serum/smoking/status/stroke/TGF-BETA

SUPERFAMILY/vascular/women



Cherry, N., Gilmour, K., Hannaford, P., Heagerty, A., Khan, M.A., Kitchener, H.,

McNamee, R., Elstein, M., Kay, C., Seif, M. and Buckley, H. (2002), Oestrogen

therapy for prevention of reinfarction in postmenopausal women: a randomised

placebo controlled trial. Lancet, 360 (9350), 2001-2008.



Abstract: Background Results of observational studies suggest that hormone

replacement therapy (HRT) could reduce the risk of coronary heart disease

(CHD), but those of randomised trials do not indicate a lower risk in women who

use oestrogen plus progestagen. The aim of this study was to ascertain whether

or not unopposed oestrogen reduces the risk of further cardiac events in

postmenopausal women who survive a first myocardial infarction. Methods The

study was a randomised, blinded, placebo controlled, secondary prevention trial

of postmenopausal women, age 50-69 years (n=1017) who had survived a first

myocardial infarction. Individuals were recruited from 35 hospitals in England

and Wales. Women received either one tablet of oestradiol valerate (2 mg; n=513)

or placebo (n=504), daily for 2 years. Primary outcomes were reinfarction or

cardiac death, and all-cause mortality. Analyses were by intention-to-treat.

Secondary outcomes were uterine bleeding, endometrial cancer, stroke or other

embolic events, and fractures. Findings Frequency of reinfarction or cardiac

death did not differ between treatment groups at 24 months (rate ratio 0.99, 95%

Cl 0.70-1.41, p=0.97). Similarly, the reduction in all-cause mortality between

those who took oestrogen and those on placebo was not significant (0.79,

0.50-1.27, p=0.34). The relative risk of any death (0.56, 0.23-1.33) and cardiac

death (0.33, 0.11-1.01) was lowest at 3 months post- recruitment. Interpretation

Oestradiol valerate does not reduce the overall risk of further cardiac events in

postmenopausal women who have survived a myocardial infarction



Keywords: age/all-cause

mortality/ATHEROSCLEROSIS/bleeding/cancer/cardiac/CHD/CORONARY

EVENTS/coronary heart

disease/death/disease/ENGLAND/ESTROGEN-REPLACEMENT/fractures/HE

ALTH/heart/heart disease/HEART-DISEASE/HORMONE REPLACEMENT

THERAPY/hospitals/HRT/infarction/INITIATION/LONDON/mortality/myocar

dial/myocardial infarction/observational studies/outcomes/postmenopausal

women/prevention/PROGRESSION/recruitment/relative

risk/RISK/secondary/SECONDARY

PREVENTION/stroke/therapy/treatment/trial/trials/use/women



Collins, R., Armitage, J., Parish, S., Sleight, P. and Peto, R. (2002), MRC/BHF Heart

Protection Study of cholesterol lowering with simvastatin in 20536 high-risk

individuals: a randomised placebo-controlled trial. Lancet, 360 (9326), 7-22.



Abstract: Background Throughout the usual LDL cholesterol range in Western

populations, lower blood concentrations are associated with lower cardiovascular

disease risk. In such populations, therefore, reducing LDL cholesterol may

reduce the development of vascular disease, largely irrespective of initial

cholesterol concentrations. Methods 20 536 UK adults (aged 40- 80 years) with

coronary disease, other occlusive arterial disease, or diabetes were randomly

allocated to receive 40 mg simvastatin daily (average compliance: 85%) or

matching placebo (average non-study statin use: 17%). Analyses are of the first

occurrence of particular events, and compare all simvastatin- allocated versus all

placebo-allocated participants. These "Intention-to-treat"comparisons assess the

effects of about two-thirds (85% minus 17%) taking a statin during the scheduled

5-year treatment period, which yielded an average difference in LDL cholesterol

of 1.0 mmol/L (about two-thirds of the effect of actual use of 40 mg simvastatin

daily). Primary outcomes were mortality (for overall analyses) and fatal or

non-fatal vascular events (for subcategory analyses), with subsidiary assessments

of cancer and of other major morbidity. Findings All-cause mortality was

significantly reduced (1328 [12.9%] deaths among 10 269 allocated simvastatin

versus 1507 [14.7%] among 10 267 allocated placebo; p=0.0003), due to a

highly significant 18% (SE 5) proportional reduction in the coronary death rate

(587 [5.7%] vs 707 [6.9%]; p=0.0005), a marginally significant reduction in

other vascular deaths (194 [1.9%] vs 230 [2.2%]; p=0.07), and a non-significant

reduction in non- vascular deaths (547 [5.3%] vs 570 [5.6%]; p=0-4). There were

highly significant reductions of about one-quarter in the first event rate for

non-fatal myocardial infarction or coronary death (898 [8.7%] vs 1212 [11.8%];

p 2.9) +/- aspirin 75 mg

daily. Where patients had received two or three of these treatments successively,

the periods of time on each treatment were added and the number of patients

with recurrence(s) on each treatment were compared by Fisher's exact probability

test. 'High' anticoagulation (INRs > 2.9) +/- aspirin 75 mg daily was more

effective than aspirin 75 mg daily in preventing further thromboembolic events

(P = 0.0053). In addition, when comparing 'high' anticoagulation +/- aspirin 75

mg daily versus 'low' anticoagulation (INRs 2.0-2.9) +/- aspirin 75 mg daily,

there was a trend in favour of 'high' anticoagulation (P = 0.066). No statistically

significant difference could be demonstrated when comparing 'low'

anticoagulation +/- aspirin 75 mg daily with aspirin 75 mg daily (P = 0.092).

These results suggest that aggressive anticoagulation with or without low-dose

aspirin is effective in preventing further thromboembolic events in APS



Keywords: ANTICARDIOLIPIN/ANTICARDIOLIPIN

ANTIBODIES/ANTICOAGULANT/ANTICOAGULANTS/anticoagulation/anti

phospholipid syndrome/aspirin/ASSOCIATION/CEREBRAL

INFARCTION/EMBOLIC EVENTS/ENGLAND/ISCHEMIC

STROKE/LUPUS/prevention/secondary prevention/SYSTEMIC

LUPUS-ERYTHEMATOSUS/thrombosis/treatment/VALVULAR

HEART-DISEASE/VASCULOPATHY/VENOUS THROMBOSIS/warfarin

Brey, R.L. and Levine, S.R. (1996), Treatment of neurologic complications of

antiphospholipid antibody syndrome. Lupus, 5 (5), 473-476.



Abstract: Thrombosis associated with antiphospholipid antibodies (aPL) occurs in both

venous and the arterial circulation. The most common arterial thrombo-occlusive

event is cerebral infarction. We briefly review treatment strategies aimed at

patients with cerebrovascular disease and aPL. Besides general treatment issues,

we discuss primary prevention and secondary prevention. Most regimens include

antithrombotics or immune modulation. Prospective studies (currently underway)

are required to better estimate the rate of recurrent thrombo-occlusive events on

standardized therapy before one therapy can be recommended over another with

reasonable evidence



Keywords: ADULTS/ANTICARDIOLIPIN ANTIBODIES/anticardiolipin

antibody/ANTICOAGULANT/antiphospholipid

syndrome/aspirin/CEREBRAL-ISCHEMIA/EVENTS/LUPUS/lupus

anticoagulant/secondary prevention/stroke/STROKE/SYSTEMIC

LUPUS-ERYTHEMATOSUS/thrombosis/THROMBOSIS/treatment/warfarin/Y

OUNG-PEOPLE



Hunskaar, S. and Backe, B. (1992), Attitudes Towards and Level of Information on

Perimenopausal and Postmenopausal Hormone Replacement Therapy Among

Norwegian Women. Maturitas, 15 (3), 183-194.



Abstract: In order to investigate women's attitudes towards and level of information on

perimenopausal and postmenopausal hormone replacement therapy (HRT) 1019

women over 17 years of age constituting a representative sample of the

Norwegian female population were interviewed in 1990 as part of a monthly

national opinion poll (response rate 96.5%). Women's magazines proved to be

the most important source of information on hormone therapy. Only in the

over-45 age group were doctors mentioned frequently as information sources. A

high self- assessed information level was associated with a positive attitude

towards hormone therapy. Those who had obtained information from a doctor

were more positive than those who had not. More than half of those who

expressed an opinion believed that hormone therapy increased the risk of heart

infarction, stroke, breast cancer and cancer in general. There was a strong

association between a negative attitude, towards using hormones and belief in an

increased risk of serious disease. The women were more positive towards the use

of HRT for the prevention of osteoporosis and for postmenopausal urogenital

complaints than for the alleviation of climacteric symptoms



Keywords: ATTITUDE TO HEALTH/ESTROGENS/HORMONE REPLACEMENT

THERAPY/HRT/MENOPAUSE/VIEWS



Daly, E., Vessey, M.P., Barlow, D., Gray, A., McPherson, K. and Roche, M. (1996),

Hormone replacement therapy in a risk-benefit perspective. Maturitas, 23 (2),

247-259.

Abstract: The relative cost-effectiveness of different treatment strategies for hormone

replacement therapy (HRT) was assessed within the framework of a computer

model. Where data were lacking, it was necessary to make assumptions about the

effects of HRT, particularly in relation to combined oestrogen- progestogen

therapy and cardiovascular disease; however, sensitivity analyses were

performed to assess the impact of changing these assumptions on the

cost-effectiveness equation. It appears that net expenditure by the NHS will

depend critically on the direct costs of treatment, rather than on any indirect costs

incurred or saved as a result of side-effects. In terms of mortality, a reduction in

cardiovascular disease risk would have greatest impact and would overshadow

any small increase in breast cancer risk which may be associated with long-term

use. If the cardioprotective effect of oestrogen is real, our results suggest that

long-term prophylactic treatment of hysterectomised women would be relatively

cost-effective. Treatment of symptomatic menopausal women for any period of

time appears to offer very good value for money. The lack of data relating to

combined oestrogen-progestogen therapy and cardioprotection, and the major

importance of the latter in the equation of benefits and risks, make it more

difficult to draw conclusions about the cost-effectiveness of treating non-

hysterectomised asymptomatic women for prophylactic reasons



Keywords: cardiovascular

disease/CARDIOVASCULAR-DISEASE/COST-EFFECTIVENESS

ANALYSIS/cost-effectiveness analysis/disease risk/GENERAL-

PRACTICE/health care costs/hormone replacement

therapy/HRT/menopause/mortality/MYOCARDIAL-INFARCTION/POSTMEN

OPAUSAL

ESTROGEN/PREVENTION/QALYS/STROKE/treatment/VERTEBRAL

FRACTURES/WOMEN



Ushiroyama, T., Ikeda, A. and Ueki, M. (2002), Effect of continuous combined therapy

with vitamin K-2 and vitamin D-3 on bone mineral density and

coagulofibrinolysis function in postmenopausal women. Maturitas, 41 (3),

211-221.



Abstract: Objectives: To investigate the therapeutic effect of combined use of vitamin K,

and D, on vertebral bone mineral density in postmenopausal women with

osteopenia and osteoporosis. Subjects and methods: We enrolled 172 women

with vertebral bone mineral density .10). The odds of aortic

atherosclerosis (of any degree) were 2.87 times greater (95% confidence interval

[CI], 1.41-5.83; P=,004) and the odds of complex atherosclerosis (protruding

atheroma 24 mm thick, mobile debris, or plaque ulceration) were 2.71 times

greater (CI, 1.13-6.53; P=,03) in the AF group than in the non AF group. Age

was a significant predictor of aortic atherosclerosis (P 30 mm) rose from 4.8% in men aged 65-69 years to

10.8% in those aged 80-83 years. The overall prevalence of large (> 50 mm)

aneurysms was 0.69%. In a multivariate logistic model Mediterranean-born men

had a 40% lower risk of AAA (> 30 mm) compared with men born in Australia

(odds ratio [OR], 0.6; 95% CI, 0.4-0.8), while ex-smokers had a significantly

increased risk of AAA (OR, 2.3; 95% CI, 1.9-2.8), and current smokers had even

higher risks. AAA was significantly associated with established coronary and

peripheral arterial disease and a waist:hip ratio greater than 0.9; men who

regularly undertook vigorous exercise had a lower risk (OR, 0.8; 95% CI,

0.7-1.0). Conclusion: Ultrasound screening for AAA is acceptable to men in the

likely target population. AAA shares some but not all of the risk factors for

occlusive vascular disease, but the scope for primary prevention of AAA in later

life is limited



Keywords:

ADULTS/aged/aneurysm/aorta/Australia/BEHAVIORS/exercise/lifestyle/MEN/

peripheral arterial

disease/population/population-based/PREVALENCE/prevention/primary/primar

y prevention/RISK/risk factors/screening/SMOKING

CESSATION/STROKE/ultrasound/vascular/vascular

disease/WESTERN-AUSTRALIA/WOMEN



Heller, R.F., Fisher, J.D., D'Este, C.A., Lim, L.L.Y., Dobson, A.J. and Porter, R. (2000),

Death and readmission in the year after hospital admission with cardiovascular

disease: the Hunter Area Heart and Stroke Register. Medical Journal of Australia,

172 (6), 261-265.



Abstract: Objectives: To compare outcomes one year after hospital admission for

patients initially discharged with a diagnosis of acute myocardial infarction

(AMI), other ischaemic heart disease (other IHD), congestive heart failure (CHF)

or stroke. Design: Cohort study. Setting: Hunter Area Heart and Stroke Register,

which registers all patients admitted with heart disease or stroke to any of the 22

hospitals in the Hunter Area Health Service in New South Wales. Patients: 4981

patients with AMI, other IHD, CHF or stroke admitted to hospital as an

emergency between 1 July 1995 and 30 June 1997 and followed for at least one

year. Main outcome measures: Death from any cause or emergency hospital

readmission for cardiovascular disease. Results: In-hospital mortality varied from

1% of those with other IHD to 22% of those with stroke. Almost a third of all

patients discharged alive (and 38% of those aged 70 or more) had died or been

readmitted within one year. This varied from 22% of those with stroke to 49% of

those with CHF. The causes of death and readmission were from a spectrum of

cardiovascular disease, regardless of the cause of the original hospital admission.

Conclusions: Data from this population register show the poor outcome,

especially with increasing age, among patients admitted to hospital with

cardiovascular disease. This should alert us to determine whether optimal

secondary prevention strategies are being adopted among such patients



Keywords: acute/acute myocardial infarction/ACUTE

MYOCARDIAL-INFARCTION/AGE/aged/Australia/cardiovascular/cardiovasc

ular disease/congestive heart

failure/death/diagnosis/disease/FAILURE/heart/heart disease/heart

failure/hospital/hospitals/INDEX/infarction/ischaemic heart

disease/MODE/MORTALITY/myocardial/myocardial

infarction/outcome/population/prevention/RISK/secondary

prevention/stroke/VALIDATION/WOMEN



Hankey, G.J. (2000), Transient ischaemic attacks and stroke. Medical Journal of

Australia, 172 (8), 394-400.



Abstract: Stroke is the third most common cause of death and a major cause of disability

in Australia. Effective prevention is the most powerful strategy for reducing the

burden of stroke. Major modifiable causal risk factors for stroke include

hypertension, cigarette smoking, diabetes, atrial fibrillation, and carotid stenosis.

Atrial fibrillation, in particular, is undertreated in the community; almost all

patients should be prescribed warfarin or aspirin, depending on their absolute

risk of stroke and risk of bleeding complications. Patients with suspected acute

stroke should be referred immediately to a specialist stroke unit for urgent

assessment and care by an interested, organised, multidisciplinary team of stroke

experts. They should undergo immediate computed tomography brain scan and,

if intracranial haemorrhage is excluded, be given aspirin (160-300 mg).

Rehabilitation and secondary prevention of recurrent stroke should begin on day

one after stroke



Keywords: absolute risk/acute/acute stroke/aspirin/atrial

fibrillation/AUCKLAND/Australia/bleeding/brain/CARE/carotid/CAROTID

ENDARTERECTOMY/carotid stenosis/CEREBRAL INFARCTION/cigarette

smoking/community/complications/computed

tomography/death/diabetes/disability/fibrillation/haemorrhage/HEMORRHAGE/

hypertension/intracranial-haemorrhage/METAANALYSIS/prevention/recurrent

stroke/risk/risk factors/risk factors for stroke/secondary

prevention/smoking/STENOSIS/stroke/stroke unit/SURGERY/TRIALS/warfarin



Hender, K.M., Anderson, J.N. and Chong, W. (2001), Carotid stenting or

endarterectomy for stroke prevention? Medical Journal of Australia, 175 (8),

430-431



Keywords: ANGIOPLASTY/Australia/endarterectomy/prevention/stenting/stroke/stroke

prevention



Sturm, J.W., Davis, S.M., O'Sullivan, J.G., Vedadhaghi, M.E. and Donnan, G.A. (2002),

The Avoid Stroke as Soon as Possible (ASAP) general practice stroke audit.

Medical Journal of Australia, 176 (7), 312-316.



Abstract: Objectives: To determine the prevalence of stroke risk factors in a general

practice population and to identify pharmacotherapies currently used in

management of stroke risk factors. Design: Multicentre, observational study by

321 randomly selected general practitioners who each collected data on 50

consecutive patients attending their surgery. Patients and setting: 16 148 patients

aged 30 years or older attending general practices across Australia during 2000.

Outcome measures: Prevalence of hypertension, current smoking, diabetes,

hypercholesterolaemia, atrial fibrillation, recent history of stroke or TIA; extent

of pharmacotherapy use in risk-factor management. Results: 70% of patients had

one or more risk factors and 34% had two or more. Hypertension was the risk

factor with greatest prevalence (44%), followed by hypercholesterolaemia (43%)

and current smoking (17%). The prevalence of risk factors generally increased

with age, except for current smoking, where a decrease with age was seen. The

most common pharmacotherapies were cardiovascular agents, followed by

antiplatelet agents. Two-thirds of patients with hypertension were taking

cardiovascular drugs, most commonly angiotensin-converting enzyme inhibitors.

Conclusions: Stroke risk factors are highly prevalent in general practice patients

and GPs are ideally placed for opportunistic case-finding. There is considerable

scope for improving management of stroke risk factors. The Avoid Stroke as

Soon as Possible (ASAP) general practice stroke audit provides a baseline

against which progress in risk-factor management can be measured



Keywords: age/aged/angiotensin converting enzyme inhibitors/angiotensin-converting

enzyme inhibitors/antiplatelet/antiplatelet agents/atrial/atrial

fibrillation/audit/Australia/cardiovascular/COMMUNITY/diabetes/drugs/fibrillat

ion/general

practice/history/hypercholesterolaemia/hypertension/management/METAANAL

YSIS/population/prevalence/PREVENTION/risk/risk factor/risk

factors/smoking/stroke/surgery/TIA/TRIALS/use



Hankey, G.J. and Eikelboom, J.W. (2003), Antiplatelet drugs. Medical Journal of

Australia, 178 (11), 568-574.



Abstract: Antiplatelet drugs protect against myocardial infarction, stroke, cardiovascular

death and other serious vascular events in patients with a history of previous

vascular events or known risk factors for cardiovascular disease. Aspirin reduces

the risk of serious vascular events in patients at high risk of such an event by

about a quarter and is recommended as the first-line antiplatelet drug.

Clopidogrel reduces the risk of serious vascular events among high-risk patients

by about 10% compared with aspirin. It is as safe as aspirin, but much more

expensive. It is an appropriate alternative to aspirin for long-term secondary

prevention in patients who cannot tolerate aspirin, have experienced a recurrent

vascular event while taking aspirin, or are at very high risk of a vascular event

(greater than or equal to 20% per year). Addition of. clopidogrel to aspirin

reduces the risk of serious vascular events among patients with non-ST-segment

elevation acute coronary syndromes by 20%, and patients undergoing

percutaneous coronary intervention by 30%, compared with aspirin alone.

Addition of a glycoprotein IIb/IIIa receptor antagonist to aspirin reduces the risk

of vascular events among patients with non-ST-segment elevation acute coronary

syndromes by 10% and among patients undergoing percutaneous coronary

intervention by 30%, compared with aspirin alone; it appears to provide

incremental benefit in patients also treated with clopidogrel. Addition of

dipyridamole to aspirin seems to be more effective than aspirin alone for

preventing recurrent stroke, but its overall effect in preventing serious vascular

events in patients with ischaemic stroke and transient ischaemic attack has not

been determined



Keywords: ACETYLSALICYLIC-ACID/acute/acute coronary

syndromes/antiplatelet/antiplatelet drug/ARTERY

STENTS/ASPIRIN/Australia/cardiovascular/cardiovascular

disease/CLOPIDOGREL/death/dipyridamole/disease/drug/drugs/glycoprotein

IIb/IIIa receptor antagonist/high risk/history/infarction/ischaemic/ischaemic

stroke/myocardial/myocardial infarction/PERCUTANEOUS CORONARY

INTERVENTION/prevention/RANDOMIZED CONTROLLED

TRIALS/recurrent stroke/RISK/risk factors/secondary/SECONDARY

PREVENTION/stroke/STROKE PREVENTION/THROMBOTIC

THROMBOCYTOPENIC PURPURA/transient/transient ischaemic

attack/vascular/vascular event/vascular events



[Anon]. (1989), Aspirin for Prevention of Myocardial-Infarction and Stroke. Medical

Letter on Drugs and Therapeutics, 31 (799), 77-80



Keywords: DRUG



[Anon]. (2000), Aggrenox: A combination of antiplatelet drugs for stroke prevention.

Medical Letter on Drugs and Therapeutics, 42 (1071), 11-12



Keywords: antiplatelet/antiplatelet

drugs/combination/DRUG/drugs/prevention/stroke/stroke prevention



Bodo, M., Thuroczy, G., Nagy, I., Peredi, J., Sipos, K., Harcos, P., Nagy, Z., Voros, J.,

Zoltay, L. and Ozsvald, L. (1995), A Complex Cerebrovascular Screening

System (Cerberus). Medical Progress Through Technology, 21 (2), 53-66.



Abstract: Stroke is unique among neurological diseases since it has a high incidence rate,

severe burden of illness, high economic cost, and it may be preventable [1].

Described here is a system for screening the cerebral and vascular status of

individuals to detect the initial stages of vascular disorders. The computer based

polygraphic system (CERBERUS) questions subjects about risk factors, stresses,

neurologic symptoms and monitors impedance pulse waves of the head and

extremities, EEG, and EGG. The system has been tested in 691 cases. Doppler

control studies were carried out on approximately 300 of these cases. Additional

somatic measures and psychological tests related to stroke risk factors were

carried out for wide biological basis of possible correlation of CERBERUS data

base. The high incidence of cerebrovascular disturbance was established by

CERBERUS data, further confirmed by additional data gathered, and moreover

was compared by traditional medical records. The polygraphic system is more

sensitive at detecting physiological asymmetries of blood flow than even a

Doppler measurements. This suggests that it may be a significantly improved

means for the differential diagnosis of neurological disease and the screening of

subjects for arteriosclerosis, transient ischemic attack and stroke prevention to be

offered at the lowest level of medical service



Keywords:

ARTERIOSCLEROSIS/BLOOD-FLOW/diagnosis/diseases/EEG/incidence/ISC

HEMIA/POLYGRAPHIC

MEASURING/prevention/RHEOENCEPHALOGRAPHY/risk/RISK

FACTORS/SCREENING/STRESS/STROKE/STROKE

PREVENTION/transient/transient ischemic attack/vascular



Korin, J.D. and Avalos, J.C.S. (1996), Prophylaxis of venous thrombosis, yes but ..

Medicina-Buenos Aires, 56 (3), 299-307.

Abstract: Prevention of venous thromboembolism (VTE) can be achieved through

mechanic or pharmacological means. For the latter, unfractionated low dose

heparin, low molecular weight heparins and oral anticoagulants are successfully

and widely employed. Results of controlled and uncontrolled studies favour the

use of prophylactic heparin in different clinical and surgical conditions such as

myocardial infarction, stroke, orthopedic or prolonged surgery and surgical

interventions in patients older than forty. Useful parameters to evaluate the

results of VTE prophylaxis are discussed as well as timing, duration,

effectiveness, side effects and costs of therapy. Although the benefits of VTE

prohylaxis in high risk patients are clear, it is not routinely employed in

Argentina



Keywords: anticoagulants/COST-EFFECTIVENESS/DEEP-VEIN

THROMBOSIS/LOW-MOLECULAR-WEIGHT/myocardial

infarction/PREVENTION/STANDARD

HEPARIN/stroke/SURGERY/THROMBOEMBOLISM/thrombosis/TOTAL

HIP-REPLACEMENT/UNFRACTIONATED HEPARIN/WARFARIN



Ennis, I.L., Gende, O.A. and Cingolani, H.E. (1998), Prevalence of hypertension in 3154

young students. Medicina-Buenos Aires, 58 (5), 483-491.



Abstract: Blood pressure (BP) levels were evaluated in 3154 students (mean age 21

years old) of La Plata University, School of Medicine. BP was registered three

times in each student and the mean was used for all the analyses. Systolic (SBP)

and diastolic pressure (DBP) were significantly higher in men. Mean SEP was

126 +/- 13 mm Hg for men and 115 +/- 11 mm Hg for women. Mean DBP was

77 +/- 10 mm Hg and 74 +/- 9 mmHg for men and women, respectively. The

global prevalence of HBP (BP greater than or equal to 140 and / or 90 mm Hg)

was 12% when both sexes were considered together, but it was significantly

higher in men than in women (20% and 6% respectively; p 240 mg/dl, and a CT scan showing no evidence of small

vessel disease are, respectively, the characteristics most frequently encountered

in patients who suffer an ischemic stroke despite preventive treatment with

125-500 mg/day of ASA. Moreover, this treatment does not reduce initial and

long-term stroke severity



Keywords: age/aspirin/atrial fibrillation/cholesterol/coronary heart

disease/CT/fibrillation/heart/history/hypercholesterolemia/INFARCTION/ische

mic/ischemic stroke/LOW-DOSE ASPIRIN/myocardial

infarction/PATIENT/prevention/risk/risk

factors/serum/severity/SPAIN/stroke/stroke prevention/TIA/transient/transient

ischemic attack/treatment



del Pino, A.M., de Abajo, F.J., Montero, D., Madurga, M. and Martin-Serrano, G.

(2000), Ticlopidine use in Spain: a pharmacy-based drug utilization study.

Medicina Clinica, 115 (6), 211-213.



Abstract: BACKGROUND: In 1997 a program was set up to improve the use of

ticlopidine. In the present study we assess whether this objective was achieved.

PATIENTS AND METHODS: We carried out a pharmacy-based cross-sectional

study. RESULTS: Out Of 346 patients interviewed, 56% presented an off-label

indication for ticlopidine. In 23% of patients the daily dose used was lower or

higher than the recommended. Only 28% patients had the fortnightly blood

monitoring performed at the time of interview. CONCLUSIONS: The use of

ticlopidine in Spain is not consistent with the summary of product characteristics

and the program set up to improve it did not achieve a satisfactory result



Keywords: drug utilization/ISCHEMIC

STROKE/monitoring/PATIENT/pharmacy/PREVENTION/Spain/ticlopidine/use

Chamorro, A., Alonso, P., Arrizabalaga, J., Carne, X. and Camps, V. (2001), Limitations

of evidence-based medicine: the case of stroke. Medicina Clinica, 116 (9),

343-349



Keywords:

ASPIRIN/EUROPE/EVENTS/PREVENTION/Spain/stroke/THERAPY/TRIAL



Banegas, J.R.B., Ganan, L.D., Rodriguez-Artalejo, F., Enriquez, J.G., Perez-Regadera,

A.G. and Alvarez, F.V. (2001), Smoking-attributable deaths in Spain in 1998.

Medicina Clinica, 117 (18), 692-694.



Abstract: BACKGROUND: Between 1993 and 1997, smoking prevalence remained

stable in Spain yet age-adjusted death rates by smoking-related diseases

decreased. Our study aimed to estimate the burden of smoking-attributable

mortality in Spain in 1998. POPULATION AND METHOD: Spain's smoking

prevalence, mortality and relative risks for death from the Cancer Prevention

Study II were used to estimate smoking-attributable mortality in the population

aged 35 years and over. RESULTS: In 1998, 55,613 deaths were attributable to

smoking. One out of 4 deaths in males and one out of 40 deaths in females were

attributable to tobacco. Two thirds of the attributable mortality corresponded to

deaths due to lung cancer, chronic obstructive pulmonary disease, ischemic heart

disease and stroke. CONCLUSIONS: Smoking actually represents a remarkable

burden of avoidable deaths in Spain. Smoking-attributable mortality appears to

continue increasing in the last years



Keywords: aged/attributable risk/cancer/death/disease/diseases/heart/heart

disease/ischemic/ischemic heart disease/lung

cancer/mortality/POPULATION/prevalence/smoking/Spain/stroke/tobacco



Rubio, P.P., Gaju, R.T., Alcala, E.N. and Alenta, H.P. (2002), Cost-effectiveness of

hypertension treatment in Catalonia (Spain). Medicina Clinica, 118 (6), 211-216.



Abstract: BACKGROUND: We assessed the cost-effectiveness of pharmacological

treatments for hypertension to prevent coronary heart disease and stroke in

Catalonia (Spain). METHODS: Cost- effectiveness was measured as the cost in

Spanish Ptas per life year gained (LYG) in 1998 in individuals aged 40 to 69

years with moderate/severe hypertension ( greater than or equal to 105 mmHg)

and mild hypertension (95-104 mmHg). We evaluated hydrochlorothiazide

(diuretic), propranolol (beta-blocker), nifedipine (calcium antagonist), captopril

(angiotensin- converting-enzyme inhibitor) and prazosin (alpha-adrenergic

blocker). RESULTS: Cost-effectiveness ranged from 706,100 to 446,780 ptas.

per LYG in men and from 635,100 to 810,270 ptas. per LYG in women with

moderate/severe hypertension and from 108,770 to 682,460 ptas. per LYG in

men and from 101,000 to 12,699,000 ptas. per LYG in women with mild

hypertension. Incremental cost-effectiveness analysis showed that

hydrochlorothiazide and propranolol were the most cost- effective treatments in

individuals with moderate/severe hypertension while hydrochlorothiazide and

nifedipine were most cost-effective in those with mild hypertension.

CONCLUSION: In this study, greatest-to-lowest cost-effectiveness of assessed

treatments was as follows: hydrochlorohiazide, propranolol, nifedipine, prazosin

and captopril in moderate/severe hypertension and hydrochlorothiazide,

nifedipine, propranolol, prazosin and captopril in mild hypertension



Keywords: aged/angiotensin/angiotensin converting enzyme

inhibitor/beta-blocker/blocker/BLOOD- PRESSURE/calcium/calcium

antagonist/captopril/cardiovascular disease prevention/COA REDUCTASE

INHIBITORS/coronary heart disease/CORONARY HEART-DISEASE/cost/cost

effectiveness/cost-effectiveness/cost-effectiveness analysis/disease/evaluative

studies/heart/heart disease/hydrochlorothiazide/hypertension/hypertension

treatment/men/PREVENTION/propranolol/Spain/stroke/THERAPY/treatment/w

omen



Martinez, V.B., Blasco, P.J.M., Juanatey, J.R.G., Ezquerra, E.A., Acuna, J.M.G.,

Maqueda, I.G., Garcia, A.F., Parra, R.V. and Ortega, J.A.R. (2002),

Antithrombotic treatment in hypertensive patients with chronic atrial fibrillation.

CARDIOTENS 99 study. Medicina Clinica, 118 (9), 327-331.



Abstract: BACKGROUND: Our main goals were to know the actual degree of oral

anticoagulation and antiaggregation in hypertensive patients with atrial

fibrillation in the daily clinical practice in Spain and to analyze any differences

between primary care physicians and cardiologists. PATIENTS AND METHOD:

32,051 outpatients attended the same day by 1,159 physicians (21% cardiologists)

were prospectively included in a database taking into account a history of

hypertension and atrial fibrillation, demographic data and ongoing treatments.

RESULTS: Hypertension was detected in 10,555 patients and 999 of them had

both hypertension and atrial fibrillation (9.46%: 435 males [44%] and 564

females [56%]). 53% patients were attended by primary care physicians and the

rest by cardiologists. 33% of hypertensive patients with atrial fibrillation were on

oral anticoagulation: 41% of them attended by cardiologists and 26% by primary

care physicians (p 80 years-old) were found

to receive less anticoagulants and more antiaggregants both in primary health-

care and cardiology health-care



Keywords: age/aged/anticoagulants/anticoagulation/ANTICOAGULATION/atrial/atrial

fibrillation/cardiology/chronic/chronic atrial fibrillation/clinical

practice/elderly/elderly

patients/FAILURE/fibrillation/GUIDELINES/health/health

care/history/hypertension/NATIONAL PATTERNS/oral

anticoagulation/PATIENT/prevalence/PREVENTION/primary/primary

care/primary health care/Spain/STROKE/THERAPY/treatment/WARFARIN

USE



Gutierrez, P.C., Bejarano, J.M.L., Juanatey, J.R.G., Nunez, A.G., Fernandez, F.J.P. and

Sarda, A.N. (2003), Different approach in high-cardiovascular-risk women,

compared to men: a multidisciplinary study-Spain. Medicina Clinica, 120 (12),

451-455.



Abstract: Background and objective: There is a broad range of cardiovascular high-risk

patients, who might benefit from general and pharmacological interventions. The

aim of the study was to evaluate the differences in the characteristics of cv risk in

women with respect to men, and if there are differences in the treatment between

men and women. Patients and method: We collected the data from cv high-risk

patients from cardiology, internal medicine, neurology, endocrinology and

primary care. We considered high-risk patients those with coronary artery

disease, stroke, peripheral vascular disease, or diabetes plus one or more

additional risk factor. Parameters recorded were age, gender, glucose, glycated

haemoglobin, blood pressure, smoking habit, lipid profile, microalbuminuria, and

pharmacological treatment. We performed an age-adjusted, multivariate analysis.

Results: Out of 5,207 patients, 1,307 were considered as high risk (56.1% Men

and 43.9% Women). The median age was 67.3 Years (66.1 Y men, 68.8 Y

women). In the coronary heart disease group, women received less antiplatelet

therapy (69.4% Vs 80.4%; Or = 1.592) And less cholesterol- lowering agents

(Despite higher prevalence of hypercholesterolemia, 52.8% Vs 39.1%). In

diabetics patients with additional risk factors, women received less antiplatelet

therapy (42.9% Vs 36.6%, Or = 1.486) And lipid-lowering therapy (53.5% Vs

41.4%), And more diuretics (41.4% Vs 26.5%; Or = 0.588). Conclusions: There

is a different profile of cv risk in women, with more diabetes and less smoking

habit. In this study, a trend to less treat high-risk women with respect to high-risk

men is observed



Keywords: age/antiplatelet/antiplatelet therapy/approach/blood

pressure/cardiology/cardiovascular/cardiovascular diseases/cholesterol/coronary

artery disease/coronary heart disease/diabetes/DISEASE/diuretics/drug

therapy/gender/glucose/heart/heart disease/HEART-FAILURE/high

risk/hypercholesterolemia/internal/internal medicine/lipid lowering/lipid

lowering therapy/lipid profile/lipid-lowering/men/microalbuminuria/multivariate

analysis/neurology/peripheral vascular disease/pharmacological

treatment/prevalence/PREVENTION/primary/primary care/RANDOMIZED

TRIALS/risk/risk factor/risk factors/sex

factors/smoking/Spain/stroke/therapy/treatment/vascular/vascular disease/women



Armstrong, L.E., Epstein, Y., Greenleaf, J.E., Haymes, E.M., Hubbard, R.W., Roberts,

W.O. and Thompson, P.D. (1996), Heat and cold illnesses during distance

running. Medicine and Science in Sports and Exercise, 28 (12), R1-R10.

Abstract: Many recreational and elite runners participate in distance races each year.

When these events are conducted in hot or cold conditions, the risk of

environmental illness increases. However, exertional hyperthermia, hypothermia,

dehydration, and other related problems may be minimized with pre-event

education and preparation. This position stand provides recommendations for the

medical director and other race officials in the following areas: scheduling;

organizing personnel, facilities, supplies, equipment, and communication;

providing competitor education; measuring environmental stress; providing

fluids; and avoiding potential legal liabilities. This document also describes the

predisposing conditions, recognition, and treatment of the four most common

environmental illnesses: heat exhaustion, heatstroke, hypothermia, and frostbite.

The objectives of this position stand are: 1) To educate distance running event

officials and participants about the most common forms of environmental illness

including predisposing conditions, warning signs, susceptibility, and incidence

reduction. 2) To advise race officials of their legal responsibilities and potential

Liability with regard to event safety and injury prevention. 3) To recommend that

race officials consult local weather archives and plan events at times likely to be

of low environmental stress to minimize detrimental effects on participants. 4)

To encourage race officials to warn participants about environmental stress on

race day and its implications for heat and cold illness. 5) To inform race officials

of preventive actions that may reduce debilitation and environmental illness. 6)

To describe the personnel, equipment, and supplies necessary to reduce and treat

cases of collapse and environmental illness



Keywords: ACCLIMATION/EXERCISE/EXERTIONAL

HEATSTROKE/HYPERTHERMIA/INJURY/PHYSICAL-FITNESS/RESPONS

ES/RUNNERS/STROKE/TOLERANCE



Shephard, R.J. (2001), Absolute versus relative intensity of physical activity in a

dose-response context. Medicine and Science in Sports and Exercise, 33 (6),

S400-S418.



Abstract: Purpose: To examine the importance of relative versus absolute intensities of

physical activity in the context of population health. Methods: A standard

computer-search of the literature was supplemented by review of extensive

personal files. Results: Consensus reports (Category D Evidence) have

commonly recommended moderate rather than hard physical activity in the

context of population health. Much of the available literature provides Category

C Evidence. It has often confounded issues of relative intensity with absolute

intensity or total weekly dose of exercise. In terms of cardiovascular health, there

is some evidence: for a threshold intensity of effort, perhaps as high as 6 METs,

in addition to a minimum volume of physical activity. Decreases in blood

pressure and prevention of stroke seem best achieved by moderate rather than

high relative intensities of physical activity, Many aspects of metabolic health

depend on the total volume of activity; moderate relative intensities of effort are

more effective in mobilizing body fat, but harder relative intensities may help to

increase energy expenditures postexercise. Hard relative intensities seem needed

to augment bone density, but this may reflect an associated increase in volume of

activity. Hard relative intensities of exercise induce a transient

immunosuppression. The optimal intensity of effort, relative or absolute, for

protection against various types of cancer remains unresolved. Acute effects of

exercise on mood state also require further study; long-term benefits seem

associated with a moderate rather than a hard relative intensity of effort.

Conclusions: The importance of relative versus absolute intensity of effort

depends on the desired health outcome, and many issues remain to be resolved.

Progress will depend on more precise epidemiological methods. of assessing

energy expenditures and studies that equate total energy expenditures between

differing relative intensities. There is a need to focus on gains in quality-adjusted

life expectancy



Keywords: ACUTE MYOCARDIAL- INFARCTION/ALL-CAUSE

MORTALITY/assessment of energy expenditure/blood

pressure/cancer/cardiovascular/cardiovascular health/CORONARY

HEART-DISEASE/DENSITY-LIPOPROTEIN CHOLESTEROL/DEPENDENT

DIABETES-MELLITUS/DIFFERENT EXERCISE INTENSITIES/dose of

exercise/EXERCISE/HARVARD ALUMNI HEALTH/health/intensity/life

expectancy/MIDDLE-AGED MEN/outcome/physical

activity/population/population health/POSTEXERCISE OXYGEN-

CONSUMPTION/prevention/protection/PUBLIC-HEALTH

PERSPECTIVE/review/stroke/transient



Kohl, H.W. (2001), Physical activity and cardiovascular disease: evidence for a dose

response. Medicine and Science in Sports and Exercise, 33 (6), S472-S483.



Abstract: Purpose: To summarize and synthesize existing literature providing evidence

of a dose-response relation between physical activity and cardiovascular disease

endpoints. Methods: MEDLINE search of indexed English-language literature

through August 2000. Findings supplemented by existing consensus documents

and other published literature. Only studies with greater than two physical

activity exposure categories were included, and studies not focusing on the

clinical manifestation of the outcome (incidence or mortality) were excluded.

Results: Existing studies were classified by outcome used: all cardiovascular

disease (CVD), coronary (ischemic) heart disease (CHD), and stroke. The vast

majority of the literature in this area has relied on prospective observational

studies and has been conducted in European men or populations of men of

primarily European descent. Follow-up intervals ranged from 3 to 26 yr, and

most studies related a single initial measure of physical activity to the outcome of

interest, sometimes many years in the future. No randomized trials of physical

activity and cardiovascular disease as a clinical outcome exist. Taken together,

the available evidence indicates that cardiovascular disease incidence and

mortality, and specifically ischemic heart disease, are causally related to physical

activity in an inverse, dose-response fashion. These findings have been

demonstrated in a variety of populations and using a variety of physical activity

assessment methods. Contrarily, equivocal evidence for stroke incidence and

mortality prohibits a similar conclusion. No strong evidence for dose-response

relation between physical activity and stroke as a CVD outcome is available.

Conclusion: Physical inactivity is prominent in the causal constellation for

factors predisposing to cardiovascular disease, particularly ischemic heart disease.

Methodologic advances in physical activity assessment; additional studies on

changes in the antecedent variable, physical activity, as it relates to the outcome;

and more studies among women and ethnically diverse populations are needed to

clarify these relations



Keywords: cardiovascular/cardiovascular disease/CHD/consensus/coronary heart

disease/CORONARY HEART-DISEASE/DEATH/disease/disease

incidence/dose response/EXERCISE/FOLLOW- UP/HARVARD ALUMNI

HEALTH/heart/heart disease/incidence/ischemic/ischemic heart

disease/ISCHEMIC STROKE RISK/LEISURE-TIME/men/MIDDLE-AGED

MEN/MORTALITY/observational studies/outcome/physical activity/PRIMARY

PREVENTION/randomized/randomized trials/stroke/stroke

incidence/trials/WOMEN



Oja, P. (2001), Dose response between total volume of physical activity and health and

fitness. Medicine and Science in Sports and Exercise, 33 (6), S428-S437.



Abstract: Purpose: Studies published in 1990s were evaluated for the possible dose

response between the total volume of physic:al activity and the fitness and health

outcomes, and for the characteristics of the dose response relations. Methods:

Nineteen observational studies and 15 randomized trials were identified. The

scope of the studies was on primary prevention among inactive, healthy,

middle-aged and elderly men and women. MET-min.wk(-1) was used as the

primary volume measure. No studies addressing specifically the volume-outcome

dose response were identified. Results: The cross-sectional and follow-up studies

suggested a graded dose response of the volume of physical activity with

all-cause mortality, stroke and several coronary heart disease risk factors. The

benefits were apparent among both men and women. Nonrandomized and

uncontrolled randomized trials exhibited no clear dose response relationship,

whereas the randomized controlled trials showed a crude graded dose response

between the exercise volume as measured by MET-min.wk(-1) and VO2max but

not between volume and disease risk factors. An apparently clearer dose

response was seen between the intensity of physical activity and the VO2max

response. These data do not allow for quantitative characterization of the

observed dose response relations between physical activity volume and health

and fitness. Conclusion: Fairly strong evidence indicates a crude dose response

between the total volume of weekly physical activity and cardiorespiratory

fitness but only weak evidence for a dose response of activity volume and health

measurers



Keywords: all-cause mortality/CARDIORESPIRATORY

FITNESS/CARDIOVASCULAR- DISEASE/coronary heart

disease/CORONARY HEART-DISEASE/disease/disease

risk/elderly/ENERGY-EXPENDITURE/EXERCISE/EXERCISE

INTENSITY/Finland/HARVARD ALUMNI HEALTH/health/heart/heart

disease/intensity/LIPOPROTEIN CHOLESTEROL

LEVELS/men/MET-minutes/middle-aged men/MIDDLE-AGED

MEN/mortality/observational studies/physical

activity/prevention/primary/primary prevention/randomized/randomized

controlled trials/RANDOMIZED TRIAL/randomized trials/risk/risk

factors/RISK-FACTORS/stroke/trials/women



Do Lee, C. and Blair, S.N. (2002), Cardiorespiratory fitness and stroke mortality in men.

Medicine and Science in Sports and Exercise, 34 (4), 592-595.



Abstract: Purpose: We examined the association between cardiorespiratory fitness and

stroke mortality in men. Methods: This is a prospective cohort study. We

followed 16,878 men, ages 40-87 yr, who had a complete medical evaluation

including a maximal treadmill exercise test and self-reported health habits, There

were 32 stroke deaths during an average of 10 yr of follow-up (167,961 man-yr).

Results: After adjustment for age and examination year, there was an inverse

association between cardiorespiratory fitness and stroke mortality (P = 0.005 for

trend). This association remained after further adjustment for cigarette smoking,

alcohol intake, body mass index, hypertension, diabetes mellitus, and parental

history of coronary heart disease (P = 0.02 for trend). High-fit men (most fit 40%)

had 68% (95% CI: 0.12, 0.82) and moderate-fit men had 63% (95% CI: 0.17,

0.83) lower risk of stroke mortality when compared with low-fit men (least fit

20%). respectively. Conclusions: Moderate and high levels of cardiorespiratory

fitness were associated with lower risk of stroke mortality in men in the Aerobics

Center Longitudinal study population



Keywords: age/alcohol/ALL-CAUSE MORTALITY/body mass index/cigarette

smoking/cohort study/coronary heart disease/CORONARY

HEART-DISEASE/diabetes/diabetes mellitus/disease/disease

prevention/epidemiology/evaluation/EXERCISE/exercise

test/FOLLOW-UP/health/HEALTHY/heart/heart

disease/history/hypertension/medical/men/mortality/OVERWEIGHT

MEN/physical activity/PHYSICAL-ACTIVITY/population/prospective cohort

study/risk/RISK-FACTORS/smoking/stroke/stroke deaths/stroke

mortality/TIME/WOMEN



LeMaster, J.W., Reiber, G.E., Smith, D.G., Heagerty, P.J. and Wallace, C. (2003), Daily

weight-bearing activity does not increase the risk of diabetic foot ulcers.

Medicine and Science in Sports and Exercise, 35 (7), 1093-1099.



Abstract: Daily Weight-Bearing Activity Does Not Increase the Risk of Diabetic Foot

Ulcers. Med. Sci. Sports Exerc., Vol. 35, No. 7, pp. 1093-1099, 2003. Purpose:

This study had two purposes: to identify characteristics associated with

participants' usual weight-bearing activity, and to determine whether weight-

bearing activity increased the risk of foot ulcer among persons with diabetes and

prior foot ulcer. Methods: We conducted a prospective cohort study of 400

participants with diabetes and a prior history of foot ulcer. Participants were from

the Veterans Affairs Puget Sound Health Care System and Group Health

Cooperative in Seattle, WA, and were originally assembled for a randomized

controlled trial of footwear. Feet were examined and demographic and health

history information was collected at enrollment. Daily weight-bearing activity

was reported at enrollment and every 17 wk thereafter for 2 yr. All incident foot

lesions were recorded. Results: Weight-bearing activity was significantly higher

among women. Activity was lower among participants who were older,

unmarried, or who had a history of congestive heart failure, respiratory disease,

stroke, or depression. Activity decreased significantly over the study period but

remained similar in those with or without insensate feet. After adjustment for

foot-related and health- status characteristics, moderately active participants

(4.5-7.4 weight-bearing h(.)d(-1)) were at substantially but nonsignificantly

reduced risk of foot ulcer compared with "least active" participants (2% per year), we observed a huge variation of the proportion of

patients classified at high risk (from 0 to 17%). There was a poor agreement

between risk models and the decision to treat taken by the physician. These

results suggest that risk-based guidelines should be validated before their

diffusion



Keywords: age/BLOOD-PRESSURE/cardiovascular/cardiovascular

disease/cardiovascular risk/CORONARY

HEART-DISEASE/evaluation/FOLLOW-UP/FRAMINGHAM/GUIDELINES/h

igh

risk/hypercholesterolemia/hypertension/management/population/prediction/PRI

MARY PREVENTION/PROBABILITY/PROFESSIONALS/PROFILE/risk/risk

models/statistical/STROKE/use/World Health Organization



Collen, M.F. (2002), Vicissitudes of preventive medicine and a new challenge. Methods

of Information in Medicine, 41 (3), 224-229.



Abstract: Objectives. Significant changes in mortality patterns are part of the changing

population demographics. This paper explores their implications for health

evaluation and screening programs. Methods. A review of selected age-adjusted

mortality rates from the National Vital Statistics Reports of the USA was

undertaken and their change over the lost five decades analyzed. Results: The

review shows a continued decline in mortality rates from leading causes of death,

such as heart disease, cancer, stroke, pneumonia and influenza, and a sharp rise

in the death rates from Alzheimer's disease. Available means for detection of

Alzeimer's disease are summarized. Conclusion: Given the emerging possibilities

for the treatment and prevention of the progression of Alzheimer's disease, tests

for early detection of Alzheimer's should be included in health screening

examinations



Keywords: AGE/Alzheimer's

disease/ALZHEIMER-DISEASE/cancer/causes/COGNITIVE

IMPAIRMENT/COMMUNITY/death/DEMENTIA/dementia/detection/disease/e

valuation/FOLLOW-UP/health/heart/heart

disease/METAANALYSIS/mortality/PLACEBO-CONTROLLED

TRIAL/pneumonia/POPULATION/PREVALENCE/prevention/preventive

medicine/review/screening/stroke/treatment/vital statistics



Cooper, J.K. (1997), Preventing heat injury: Military versus civilian perspective.

Military Medicine, 162 (1), 55-58.



Abstract: Guidelines for preventing heat injury (HI) among military personnel are not

directly applicable to civilian personnel. Military guidelines call for relatively

large volumes of prophylactic water consumption and physical activity

limitations depending on the met bulb globe temperature. However, in civilian

populations, there is an increased prevalence of HI risk factors: older age,

medication use, especially anticholinergic and psychotropic medications, obesity,

previous HI, and skin disorders. Although dehydration is a major contributor to

HI in military situations, it is unlikely in classical heat stroke among civilians.

Civilian guidelines are based on the heat index, Activity levels must be restricted

more for civilians, and prophylactic water consumption (beyond replacing loss

from sweat) is not necessary. This review discusses the pathophysiology of heat

injury, contrasts the military and civilian approach to prevention of HI, and

describes appropriate field intervention for HI



Keywords: age/CARE/EXERCISE/FLUID/guidelines/heat

stroke/HYPERTHERMIA/ILLNESS/obesity/physical

activity/POLICIES/POLICY/prevention/PRIMARY-CARE/risk/risk

factors/stroke/STROKE PATIENTS



Linz, W., Wiemer, G., Schaper, J., Zimmermann, R., Nagasawa, K., Gohlke, P., Unger,

T. and Scholkens, B.A. (1995), Angiotensin-Converting Enzyme-Inhibitors,

Left-Ventricular Hypertrophy and Fibrosis. Molecular and Cellular Biochemistry,

147 (1-2), 89-97.



Abstract: From pharmacological investigations and clinical studies, it is known that

angiotensin converting enzyme (ACE) inhibitors exhibit additional local actions,

which are not related to hemodynamic changes and which cannot be explained

only by interference with the renin angiotensin system (RAS) by means of an

inhibition of angiotensin II (ANG II) formation. Since ACE is identical to

kininase II, which inactivates the nonapeptide bradykinin (BK) and related kinins,

potentiation of kinins might be responsible for these additional effects of ACE

inhibitors. a) In rats made hypertensive by aortic banding, the effect of ramipril

in left ventricular hypertrophy (LVH) was investigated. Ramipril in the

antihypertensive dose of 1 mg/kg/day for 6 weeks prevented the increase in

blood pressure and the development of LVH. The low dose of ramipril (10 mu

g/kg/day for 6 weeks) had no effect on the increase in brood pressure or on

plasma ACE activity but also prevented LVH after aortic banding. The

antihypertrophic effect of the higher and lower doses of ramipril, as well as the

antihypertensive action of the higher dose of ramipril, was abolished by

coadministration of the kinin receptor antagonist icatibant. In the regression

study the antihypertrophic actions of ramipril were not blocked by the kinin

receptor antagonist. Chronic administration of BK had similar beneficial effects

in a prevention study which were abolished by icatibant and N-G-

nitro-L-arginine (L-NNA). In a one year study the high and low dose of ramipril

prevented LVH and fibrosis. Ramipril had an early direct effect in hypertensive

rats on the mRNA expression for myocardial collagen I and III, unrelated to its

blood pressure lowering effect. b) In spontaneously hypertensive rats (SHR) the

preventive effects of chronic treatment with ramipril on myocardial LVH was

investigated. SHR were treated in utero and, subsequently, up to 20 weeks of age

with a high dose (1 mg/kg/day) or with a low dose (10 mu g/kg/day) of ramipril.

Animals on a high dose remained normotensive, whereas those on a low dose

developed hypertension in parallel to vehicle- treated controls. Left ventricular

mass was reduced only in high-dose-treated, but not in low-dose treated animals

but both groups revealed an increase in myocardial capillary length density. In

SHR stroke prone animals cardiac function and metabolism was improved by

ramipril and abolished by coadministration of icatibant. In contrast to the

prevention studies, in a regression study ramipril reduced cardiac hypertrophy

also by low dose treatment. c) In rats chronic nitric oxide (NO) inhibition by

N-G-nitro-L-arginine-methyl ester (L-NAME) treatment induced hypertension

and LVH. Ramipril protected against blood pressure increase and partially

against myocardial hypertrophy. These experimental findings in different models

of LVH characterise ACE inhibitors as remarkable antihypertrophic and

antifibrotic substances



Keywords: ACE INHIBITORS/angiotensin/angiotensin II/AUTOCRINE- PARACRINE

ACTIONS/blood pressure/BRADYKININ/CARDIAC-

HYPERTROPHY/development/ENDOTHELIAL-CELLS/FIBRILLAR

COLLAGEN/FIBROSIS/formation/GUANOSINE-MONOPHOSPHATE/hypert

ension/HYPERTENSIVE RATS/hypertrophy/LEFT VENTRICULAR

HYPERTROPHY/MYOCARDIAL FIBROSIS/NITRIC-OXIDE

SYNTHASE/PRESSURE OVERLOAD

HYPERTROPHY/prevention/PROSTACYCLIN/RAMIPRIL/RAT

LEFT-VENTRICLE/rats/SHR/SMOOTH-MUSCLE CELLS/stroke/treatment



Hirano, T., Yamori, Y., Kanai, N., Umetsu, T. and Nishio, S. (1992), The Effects of

Beraprost Na, A Stable Prostacyclin Analog, on Animal-Models of Stroke.

Molecular and Chemical Neuropathology, 17 (1), 91-102.



Abstract: We evaluated the effects of beraprost Na (Sodium (+/-)- (1R*,2R*,

3aS*,8bS*)-2,3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S

*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butylate,

beraprost), a stable and orally active prostacyclin (PGI2) analog with potent

antiplatelet and vasodilating properties, on two stroke models, namely sudden

death induced by arachidonate (AA) in rabbits and spontaneeous stroke in

stroke-prone spontaneously hypertensive rats (SHRSP). In the AA-induced

sudden death model, 30 min after beraprost administration (1 or 3 mg/kg, po),

AA was injected into the rabbit internal carotid artery, and incidence of

convulsion and sudden death were assessed. Beraprost decreased both incidence

of convulsion and mortality of rabbits. In SHRSP, orally administered beraprost

(100-mu-g/kg, twice a day from 56-385 d of age) improved survival rate and

decreased incidence of stroke. Preventive effects of beraprost on the two stroke

models may have been caused mainly by the improvement of cerebral circulation.

These results indicate that beraprost may have potential in the treatment and/or

prevention of the cerebral circulatory disorders



Keywords: ANTIPLATELET EFFECT/ARACHIDONATE-INDUCED SUDDEN

DEATH/BERAPROST

NA/CATS/CELLS/CEREBRAL-ISCHEMIA/INVITRO/PLATELETS/PRONE/

PROSTACYCLIN ANALOG/RATS/SHRSP/SODIUM/STROKE

MODELS/TICLOPIDINE/TRK-100/VASODILATION



Waters, C.M. (1996), Mechanisms of neuronal cell death - An overview. Molecular and

Chemical Neuropathology, 28 (1-3), 145-151.



Abstract: Neuronal cell death is both a vital component of the embryogenesis of the

nervous system and forms the basis of all neurodegenerative diseases. This

overview explores the fundamental mechanisms underlying neuronal cell death

at a cellular and molecular level. The significance of the mode of neuronal death

is compared with respect to physiological (developmental) and pathological

neuronal loss



Keywords: Alzheimer disease/apoptosis/APOPTOSIS/BCL-2

PROTOONCOGENE/C-JUN/development/diseases/DNA/EXPRESSION/GENE

CED-3/glutamate/ICE bcl-2/interleukin converting

enzyme/necrosis/neurons/Parkinson

disease/PREVENTION/PROTEIN/stroke/SYMPATHETIC

NEURONS/TRANSGENIC MICE/trophic factors



Halperin, J.L. and Rothlauf, E.B. (1993), Stroke Prevention in Atrial-Fibrillation. Mount

Sinai Journal of Medicine, 60 (4), 289-294.



Abstract: Atrial fibrillation (AF) is a risk factor for ischemic stroke. In randomized trials,

AF raised the risk of stroke nearly sixfold, cumulating in a 35% risk over a

lifetime. Anticoagulation with warfarin reduces the danger of ischemic stroke,

but carries hemorrhagic risks, making this agent unsuitable for treating many

patients. Platelet inhibitor therapy with aspirin was highly effective for patients

younger than 75 years of age in one study, but the reason for lower efficacy in

older individuals is perplexing. These trials support a thrombotic mechanism for

most strokes in patients with AF, but leave physicians in a quandary as to

selection of optimum prophylaxis. Secondary analysis of patients given placebo

identified predictors of thromboembolism, including a history of hypertension,

congestive heart failure, and prior stroke or transient ischemic attack, and

echocardiographic findings of left ventricular dysfunction or left atrial

enlargement. The absence of these risk factors selects a fairly large subgroup of

AF patients at comparatively low risk of stroke, for whom the danger and

inconvenience of chronic anticoagulation may not be warranted. It is becoming

clear that specific clinical and echocardiographic features allow individualized

antithrombotic approaches within the broad category of patients with AF, to

enhance therapeutic benefit while minimizing hemorrhagic risk



Keywords: ANTICOAGULATION/THERAPY



Nassisi, D. (1997), Acute stroke: Emergency management and future interventions.

Mount Sinai Journal of Medicine, 64 (4-5), 241-248.

Abstract: Stroke is a major cause of death and disability. Early intervention in the

emergency department has become increasingly important in improving stroke

outcome as effective therapies are used. Current emergency evaluation and

management of ischemic (thromboembolic) stroke, intracerebral hemorrhage,

cerebellar stroke, subarachnoid hemorrhage, and transient ischemic attacks is

discussed. Recent developments in stroke therapeutics including thrombolytics,

low-molecular-weight heparins, excitatory amino acid antagonists, free radical

scavengers, gangliosides, and leukocyte inhibitors are reviewed



Keywords: ACUTE ISCHEMIC

STROKE/CIRCULATION/EMERGENCY/evaluation/EXPERIENCE/hemorrha

ge/INFARCTION/intracerebral hemorrhage/ischemic/MOLECULAR-WEIGHT

HEPARIN/NEW-YORK/PREVENTION/PROGRESSION/stroke/stroke

outcome/SUBARACHNOID HEMORRHAGE/subarachnoid

hemorrhage/SURGERY/THROMBOLYTIC

THERAPY/thrombolytics/transient/transient ischemic attacks/TRIAL



Tuhrim, S. (2002), Management of stroke and transient ischemic attack. Mount Sinai

Journal of Medicine, 69 (3), 121-130.



Abstract: Stroke is a major cause of death and disability. The resulting burden on society

continues to grow, despite recent advances in acute stroke therapy. Thrombolysis

reduces stroke morbidity but is only applicable to a small percentage of stroke

patients. Acute stroke units, which allow for the greatest overall improvement in

outcome, provide the best facilities for acute intervention. Despite recent

advances in acute management, such as endarterectomy and anticoagulation,

primary and secondary preventive measures to control stroke risk factors, along

with appropriate specific interventions, are the key to reducing the overall burden

of stroke



Keywords: acute/acute stroke/acute stroke therapy/anticoagulation/ASPIRIN/ATRIAL-

FIBRILLATION/BLOOD-PRESSURE/cause of

death/CHOLESTEROL/CIRCULATION/control/CORONARY

HEART-DISEASE/death/disability/endarterectomy/FRAMINGHAM/HIGH-RIS

K PATIENTS/ischemic/management/MOLECULAR-WEIGHT

HEPARIN/morbidity/MORTALITY/NEW-YORK/outcome/prevention/primary/

risk/risk factors/secondary/SECONDARY PREVENTION/stroke/stroke

patients/stroke units/therapy/transient/transient ischemic attack/treatment



Elkind, M.S.V. (2003), Stroke in the elderly. Mount Sinai Journal of Medicine, 70 (1),

27-37.



Abstract: Stroke is one of the oldest but least understood diseases, and it is one of the

major public health problems facing the elderly. Recent epidemiological

investigations have found that the incidence of stroke has been underestimated

by about 50%, and that the burden of disease is highest in minority populations.

Recent clinical and basic neuroscience research indicates that stroke is neither

unpredictable nor irreversible. Many risk factors for stroke are readily

identifiable, and evidence-based treatment may be used to reduce the likelihood

of stroke among those at risk. Rapid diagnosis and evaluation of stroke and

transient ischemic attack and their treatment, including surgery, anticoagulation,

antiplatelet and other medical therapies, reduce the chance of recurrence. More

aggressive treatment of blood pressure, even among patients who are not

necessarily hypertensive, may also reduce the risk of future strokes. Once

ischernic stroke has occurred, emergent therapy using thrombolysis may

significantly reduce disability, even among the elderly. This review presents an

update on definitions of stroke and its subtypes, stroke epidemiology, and the

results of recent studies of stroke prevention and acute treatment



Keywords: acute/ACUTE ISCHEMIC STROKE/acute

treatment/ALTEPLASE/anticoagulation/antiplatelet/ASPIRIN/ATRIAL-FIBRIL

LATION/blood pressure/cerebrovascular disorders/CIRCULATION/clinical

trials/diagnosis/disability/disease/diseases/elderly/epidemiology/evaluation/healt

h/HIGH-RISK PATIENTS/incidence/ischemic/LOBAR INTRACEREBRAL

HEMORRHAGE/medical/NEW-YORK/PLASMINOGEN-

ACTIVATOR/PREVENTION/public health/RANDOMIZED CONTROLLED

TRIAL/recurrence/research/results/review/risk/risk factors/risk factors for

stroke/SECULAR TRENDS/stroke/stroke

prevention/surgery/therapy/thrombolysis/transient/transient ischemic

attack/treatment/USA



Weisburger, J.H. (1998), Worldwide prevention of cancer and other chronic diseases

based on knowledge of mechanisms. Mutation Research-Fundamental and

Molecular Mechanisms of Mutagenesis, 402 (1-2), 331-337.



Abstract: International research, particularly as part of US/Japan programs, has led to

major advances in knowledge of causes of heart disease, stroke, many types of

cancer and diabetes, showing that individual lifestyle is associated with these

diseases. In Japan, a major health problem is high blood pressure and stroke, and

cancer of the stomach, from excessive use of salt and salted, pickled foods, and

the relative low intake of protective fruits and vegetables. We identified a likely

gastric carcinogen, 2-chloro-4-methylthiobutanoate, in salted, pickled fish. In the

Western world, heart disease and cancer of the breast, colon, rectum, prostate,

pancreas, ovary and endometrium relate to a nutritional tradition too high in total

fat and fried or broiled meats, and too low in fiber, vegetables and fruits. The

cooked meats contain genotoxic chemicals, heterocyclic amines, causative

elements in heart disease and the nutritionally linked cancers. Decreasing total

fat intake, from 40 to 20% of calories and a greater use of starches such as rice,

pasta, potatoes and whole grain bread, as well as daily intake of five to nine

vegetables and fruits would be beneficial. Adults should consume 2.5 l of fluids

per day. Green or black tea and fruit juices have health promoting properties.

Regular exercise contributes to good health, and to the avoidance of obesity, a

major problem in the USA and of increasing importance in Japan. Avoidance of

a risky lifestyle would likely prevent diseases important not only for the

individual and his family, but with major impact in lowering medical care costs.

Tobacco and cigarette use, particularly on a Western diet, involve a high risk of

heart attacks, and cancers of the lung, pancreas, kidney, urinary bladder, and

cervix, accounting for 35% of medical care expenditures. (C) 1998 Elsevier

Science B.V. All rights reserved



Keywords: 2-chloro-4-methylthiobutanoate/2-CHLORO-4-METHYLTHIOBUTANOIC

ACID/blood pressure/cancer prevention/cardiovascular

disease/costs/diabetes/diet/diseases/exercise/fats/fiber/FISH/fruit/FRUIT/health/h

eart/heterocyclic amine/high blood

pressure/knowledge/lifestyle/obesity/prevention/risk/salt/stroke/tea/tobacco/vege

table



Kawasaki-Yatsugi, S., Ichiki, C., Yatsugi, S., Shimizu-Sasamata, M. and Yamaguchi, T.

(1998), YM90K, an AMPA receptor antagonist, protects against ischemic

damage caused by permanent and transient middle cerebral artery occlusion in

rats. Naunyn-Schmiedebergs Archives of Pharmacology , 358 (5), 586-591.



Abstract: The neuroprotective effect of YM90K, a potent AMPA receptor antagonist,

was examined in rats with permanent and transient occlusion of middle cerebral

artery (MCA) using intraluminal suture occlusion method. In rats with permanent

MCA occlusions, two types of occluders were used to compare the efficacy of

YM90K. When a 4-0 (diameter: 0.19 mm) suture was used, YM90K (20 mg

kg(-1) h(-1) i.v. infusion for 4 h) significantly reduced infarct volume (P 50%) in elderly men and women (60-79 years) was

10.5 and 5.5%. In nonstenotic carotid artery disease the lumen diameter turned

out to be a useful indirect measure of the vascular status



Keywords: aged/atherosclerosis/carotid/CAROTID

ATHEROSCLEROSIS/development/DISEASE/elderly/POPULATION

STUDIES/PREVALENCE/RISK/ULTRASOUND/vascular/women



Foulkes, M.A., Sacco, R.L., Mohr, J.P., Hier, D.B., Price, T.R. and Wolfe, P.A. (1994),

Parametric Modeling of Stroke Recurrence. Neuroepidemiology, 13 (1-2), 19-27.



Abstract: Stroke recurrence has been investigated primarily with respect to prognostic

factors predictive of recurrence. Several parametric functions are considered in

modeling the distribution of ischemic stroke recurrences recorded within the

Stroke Data Bank. A linear hazard function is shown to be the best-fitting

function among those considered. This method of parametric modeling may lead

to a more informed approach to treatment of ischemic stroke and secondary

prevention and may enhance future investigations of prognostic factors as well



Keywords: DATA-BANK/INFARCTION/ISCHEMIC STROKE/MATHEMATICAL

MODELING/prevention/RECURRENCE/RISK/secondary

prevention/stroke/treatment



Woo, J., Ho, S.C., Lau, S., Lau, J. and Yuen, Y.K. (1994), Prevalence of Cognitive

Impairment and Associated Factors Among Elderly Hong-Kong Chinese Aged

70 Years and Over. Neuroepidemiology, 13 (1-2), 50-58.



Abstract: The prevalence of cognitive impairment was determined in a random age- and

sex-stratified sample of 2,011 elderly Hong Kong Chinese, aged 70 years and

over, consisting of subjects living in the community and in institutions. The

Information/ Orientation Section of the Clifton Assessment Procedure was used

as the screening instrument using a cutoff point of 7. The overall age-adjusted

prevalence was 5% for men and 22% for women, and 15% for both sexes

combined. Univariate analysis identified the following associated factors in order

of magnitude of the odds ratio: age; history of Parkinson's disease; functional

disability; female sex; low educational level; low social class; history of stroke,

and low monthly income. Other diseases, such as heart disease, hypertension,

chronic lung diseases or diabetes, were not associated factors. In multivariate

analysis, all the above factors remained significant with the exception of a

history of stroke. The prevalence figures are comparable to other Caucasian and

Chinese studies, and the associated factors identified suggest that there may be

room for prevention



Keywords: aged/ALZHEIMERS-DISEASE/CHINESE/COGNITIVE

IMPAIRMENT/COMMUNITY/DEMENTIA/diseases/ELDERLY/HEALTH/he

art/history/hypertension/PEOPLE/prevention/RISK FACTORS/stroke/TOTAL

POPULATION/women



Castillon, P.G., Artalejo, F.R., Banegas, F.B., Guallar, E. and Calero, J.D. (1997),

Cerebrovascular disease mortality in Spain, 1955-1992: An age- period-cohort

analysis. Neuroepidemiology, 16 (3), 116-123.



Abstract: The purpose of this study was to assess the contributions of period and birth

cohort effects to changes in cerebrovascular disease (CVD) mortality in Spain

over the period 1955-1992. Poisson regression models were fitted to age- and

sex-specific CVD mortality rates obtained from National Vital Statistics, In the

period 1955-1975, CVD mortality remained stable, In the period 1975-1992:

CVD mortality declined by 54% (rate ratio, RR: 0.46; 95% confidence interval,

Cl: 0.43-0.49) in males and 62% (RR: 0.38; 95% Cl: 0.34-0.42) in females, The

cohort effect was very small up to the generation born in 1905, moving clearly

downward thereafter. CVD mortality for subjects born in the period 1945-1949

was lower than for those born in the period 1905-1909 by 68% (RR: 0.32; 95%

Cl: 0.16-0.63) in males and 82% (RR: 0.18; 95% Cl: 0.07-0.45) in females,

Among the possible partial explanations for these effects are the decline in

ischemic heart disease and rheumatic fever mortality, the drop in salt and alcohol

intake, the reduction in smoking among males and blood pressure among females,

and the widespread use of antihypertensive treatments in Spain over the last 20

years



Keywords: age/age-period-cohort analysis/alcohol/blood

pressure/cerebrovascular/cerebrovascular disease/cerebrovascular disease

mortality/DECLINE/HEART/HYPERTENSION/ischemic/ischemic heart

disease/mortality/PRIMARY PREVENTION/salt/smoking/Spain/STROKE

MORTALITY/TRENDS



Sitzer, M., Skutta, M., Siebler, M., Sitzer, G., Siegrist, J. and Steinmetz, H. (1998),

Modifiable stroke risk factors in volunteers willing to participate in a prevention

program. Neuroepidemiology, 17 (4), 179-187.



Abstract: The current trends in stroke incidence require continued efforts to improve

primary prevention. Compared to large-scale public health approaches, more

limited programs targeting volunteers may offer some advantages. We invited all

12,824 members of a health insurance company program who lived within 50 km

from one of two study sites to participate in a vascular screening program aimed

at reducing modifiable risk factors. 1,837 persons registered and

participated(14.3%, mean age 53 +/- 12 years, 50% men). Using the Framingham

stroke risk profile for persons aged 55 years or above (n = 961, 52.3%), 97 stroke

events can be predicted for this age group within 10 years. The majority of these

97 events will occur in those with mean resting blood pressure values greater

than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg

(diastolic; 420 persons, mean age 64 +/- 7 years, 60 expected events), or with a

particularly high age- and sex-adjusted risk (288 persons, mean age 68 +/- 7

years, 60 expected events). Our pilot study provides an estimate of the

prevalence of modifiable vascular risk factors among volunteer participants of a

prevention program. Possible benefits of this approach will be investigated in a

second step using a randomized intervention



Keywords: age/aged/atherosclerosis/blood pressure/cardiovascular

diseases/cerebrovascular diseases/CORONARY

HEART-DISEASE/EDUCATION/health/health

education/HEALTH-PROGRAM/hypertension/HYPERTENSION/incidence/IN

TERVENTION/MINNESOTA/NORTH-KARELIA PROJECT/PHYSICAL-

ACTIVITY/prevention/primary prevention/PROBABILITY/program

evaluation/risk/risk factors/stroke/TRENDS/vascular



Chaturvedi, S. (1999), Public health impact of carotid endarterectomy.

Neuroepidemiology, 18 (1), 15-21.



Abstract: Despite the completion of several multi-center clinical trials comparing

medical management and carotid endarterectomy, there is still controversy as to

when carotid endarterectomy is appropriate. The volume of this surgery appears

to be increasing. However, available performance data indicate that the surgical

proficiency required for the clinical trials is not achieved uniformly in actual

practice. Therefore, benefits of carotid endarterectomy, when considered from a

public health perspective, are limited by the following: (1) endarterectomy is an

expensive stroke prevention modality; (2) endarterectomy addresses the needs of

only a relatively small subset of stroke patients, and (3) endarterectomy for

asymptomatic patients, without clearer evidence that these individuals benefit,

may decrease the cost-effectiveness of this surgical procedure



Keywords: carotid/carotid endarterectomy/carotid stenosis/clinical trials/cost

effectiveness/cost-effectiveness/DISEASE/endarterectomy/health/PERFORMA

NCE/prevention/RACE/STENOSIS/STROKE/stroke

prevention/surgery/transient ischemic attack/trials



Abel, G.A., Chen, X., Boden-Albala, B. and Sacco, R.L. (1999), Social readjustment and

ischemic stroke: Lack of an association in a multiethnic population.

Neuroepidemiology, 18 (1), 22-31.

Abstract: Clinical experience has suggested that stressful life events and ongoing

stressful illness, collectively termed 'social readjustment', may precipitate stroke.

We investigated the association between a simple in-office evaluation of such

stressors and stroke in an urban, multiethnic study population. Cases were

patients from the Northern Manhattan Stroke Study with first ischemic stroke;

controls were derived through random digit dialing with n:m matching for age,

gender, and race-ethnicity. Social readjustment was measured through in- person

interview using Amster and Krauss' Geriatric Social Readjustment Rating Scale

(GSRRS), a one-time, 35-item, checklist type weighted questionnaire of stressful

life events occurring in the previous 6 months. Conditional logistic regression

was used to analyze the GSRRS and its quartiles as well as stressful events

subgroups, adjusting for education, hypertension, cardiac disease, diabetes, and

number of weekly visits as a measure of socialization. Six hundred and fifty- five

cases of ischemic stroke and 1,087 controls were utilized. The mean age of the

cases was 69.8 years, with 55.4% women, 51.0% Hispanics, 28.4% blacks, and

19.1% whites. GSRRS scores ranged from 0 to 812; the mean score was 205.5

for the cases and 206.2 for the controls. The analysis showed no association

between stroke and a 20-point increase on the GSRRS (OR = 1.01,95% CI =

0.99-1.01). There was also no effect for the second, third or highest versus lowest

quartile. No association was found in age, gender or race-ethnic subgroups, or

when analyzing negative events, severely threatening events, or ongoing stressful

illnesses separately. While this study does not preclude social readjustment as a

stroke risk factor, it suggests that the one-time assessment often done in the

medical office setting has little relevance for stroke prevention planning



Keywords: CARDIOVASCULAR REACTIVITY/cerebrovascular

disease/CORONARY-ARTERY

DISEASE/education/epidemiology/evaluation/HEART-DISEASE/Hispanics/hyp

ertension/ischemic stroke/life events/LIFE EVENTS/MIDDLE-AGED

MEN/MYOCARDIAL-INFARCTION/prevention/PSYCHOLOGICAL

STRESS/risk/RISK-FACTORS/social readjustment/stress/stroke/stroke

prevention/SUSCEPTIBILITY/women



Nakayama, T., Yokoyama, T., Yoshiike, N., Zaman, M.M., Date, C., Tanaka, H. and

Detels, R. (2000), Population attributable fraction of stroke incidence in middle-

aged and elderly people: Contributions of hypertension, smoking and atrial

fibrillation. Neuroepidemiology, 19 (4), 217-226.



Abstract: We determined the population attributable fraction (PAF) of stroke due to

hypertension (HT), atrial fibrillation (Af) and smoking in a Japanese community.

Residents of Shibata (n = 2,302) who were surveyed initially in 1977 were

followed until 1997. Two hundred and thirteen first strokes occurred. Among

those 40-64 years of age, the risk ratio (RR) of Af was 11.24, followed by

untreated HT (3.61), uncontrolled HT (3.69) and smoking (1.84). The PAFs,

however, were 14.9% for smoking, 13.5% for untreated HT, 8.6% for

uncontrolled HT and 3.6% for Af. Among those over 65 years, only Af was

significant (RR 3.89) and the PAF was 6.0%. Determination of PAFs is also

essential for designing effective stroke prevention programs in communities.

Copyright (C) 2000 S. Karger AG, Basel



Keywords: age/aged/atrial fibrillation/BLOOD-PRESSURE/CEREBRAL

INFARCTION/cerebrovascular

disease/CIGARETTE-SMOKING/community/elderly/epidemiology/essential/fib

rillation/hypertension/incidence/JAPANESE PROVINCIAL CITY/longitudinal

studies/MISCLASSIFICATION/MORTALITY/OLD/population/PREVENTION

/RELATIVE RISK/risk/RISK-FACTORS/smoking/stroke/stroke

incidence/stroke prevention



Voko, Z., Koudstaal, P.J., Bots, M.L., Hofman, A. and Breteler, M.M.B. (2001), Aspirin

use and risk of stroke in the elderly: The Rotterdam Study. Neuroepidemiology,

20 (1), 40-44.



Abstract: The objective of the study was to assess the. association between aspirin use

and the risk of stroke in a population- based study in the elderly. The study was

carried out within the framework of the Rotterdam Study, a prospective

population- based cohort study. In the total study population there was a weak,

nonsignificant association. between aspirin use and the risk of stroke (adjusted

relative risk 1.29, 95% CI 0.91-1.83). Stratification by history of vascular

diseases revealed that aspirin considerably increased the ri sk of first-ever stroke

in subjects free from vascular disease (adjusted relative risk 7.80; 95% CI

1.03-3.13). In persons with vascular disease, no association was observed

between aspirin use and risk of stroke (adjusted relative risk 0.99, 95% CI

0.56-1.73). Our findings suggest that aspirin use may increase the risk of stroke

in elderly subjects free from vascular disease. Copyright (C) 2001 S. Karger AG,

Basel



Keywords: aspirin/CARDIOVASCULAR HEALTH/cerebrovascular disorders/cohort

studies/cohort study/DETERMINANTS/disease/diseases/elderly/elderly

subjects/GENERAL- POPULATION/history/INCIDENT

STROKE/INFARCTION/Netherlands/population/PREVALENCE/primary

prevention/RABBIT MODEL/relative risk/risk/stroke/THROMBOEMBOLIC

STROKE/THROMBOLYSIS/use/vascular/vascular disease



Spence, J.D., Howard, V.J., Chambless, L.E., Malinow, M.R., Pettigrew, L.C., Stampfer,

M. and Toole, J.F. (2001), Vitamin intervention for stroke prevention (VISP)

trial: Rationale and design. Neuroepidemiology, 20 (1), 16-25.



Abstract: Elevated plasma levels of homocyst(e)ine [H(e)] are surprisingly common and

strongly associated with endothelial dysfunction and a marked increase in

vascular risk. Treatment with a combination of folic acid, pyridoxine (vitamin

B-6) and cobalamin (vitamin B-12) reduces plasma H(e) levels in most cases,

restores endothelial function, and regresses carotid plaque, but there is no

evidence that such treatment will reduce clinical events. The Vitamin

Intervention for Stroke Prevention (VISP) study is a double-masked, randomized,

multicenter clinical trial designed to determine if, in addition to best

medical/surgical management, high-dose folic acid, vitamin Bg, and Vitamin

B12 supplements will reduce recurrent stroke compared to lower doses of these

vitamins. Patients at least 35 years old with a nondisabling ischemic stroke

within 120 days, and screening plasma H(e) > the 25th percentile of benchmark

population data are eligible. Secondary endpoints are myocardial infarction or

fatal coronary heart disease. This paper describes the design and rationale of the

study. Copyright (C) 2001 S. Karger AG, Basel



Keywords: carotid/cerebral infarction prevention/cerebrovascular disorders/clinical

trial/clinical trials/CLINICAL-TRIALS/combination/coronary heart

disease/CORONARY-ARTERY DISEASE/design/disease/ENDOTHELIAL

DYSFUNCTION/endothelial function/folic acid/heart/heart

disease/homocyst(e)ine/HOMOCYSTINURIA/HYPERHOMOCYSTEINEMIA/

infarction/ischemic/ischemic stroke/management/myocardial/myocardial

infarction/NEURAL-TUBE DEFECTS/OCCLUSIVE

DISEASE/plaque/PLASMA TOTAL

HOMOCYSTEINE/population/prevention/randomized/recurrent

stroke/risk/RISK FACTOR/screening/stroke/stroke

prevention/treatment/trial/vascular/vascular risk/VASCULAR-DISEASE/vitamin

therapy/vitamins



Kennedy, B.S., Kasl, S.V., Brass, L.M. and Vaccarino, V. (2002), Trends in hospitalized

stroke for blacks and whites in the United States, 1980-1999. Neuroepidemiology,

21 (3), 131-141.



Abstract: Background: Racial differences in stroke mortality are widely recognized, but

it is unclear whether or not these differences are due mainly to blacks having a

greater stroke incidence or higher case fatality rates compared to those of whites.

Objectives: The aim of this study was to describe the race- specific US trends in

hospital discharge rates and in-hospital mortality among stroke patients for the

period 1980-1999. It was hypothesized that the hospital discharge rates and in-

hospital mortality among stroke patients would be greater for blacks than for

whites. Methods: Data from the National Hospital Discharge Survey for the

period 1980-1999 were used to identify stroke subjects according to the codes of

the International Classification of Diseases, ninth revision (codes 430-434 and

436). Direct standardization and Poisson regression were used to compare

hospitalized stroke morbidity and mortality rates between blacks and whites. The

main outcome measures were the number of stroke discharges and in-hospital

deaths for black and white stroke patients. Results: Between the years 1980 and

1999, the hospital discharge rates for stroke increased for blacks (n = 8,700) and

decreased for whites (n = 46,154); the in-hospital mortality rates decreased for

both black and white stroke patients. Generally, the risk of a stroke

hospitalization was greater for blacks than for whites by more than 70%, whereas

both groups were similar in terms of in-hospital mortality rates among stroke

patients. Conclusions: Differences between blacks and whites in terms of stroke

mortality are more likely due to differences in stroke incidence rather than case

fatality. These data imply that greater attention should be given to

primary/secondary prevention and that additional research is needed to

understand the reasons for these patterns. Copyright (C) 2002 S. Karger AG,

Basel



Keywords: 2000 CENSUS/ACUTE CEREBRAL INFARCTION/blacks/case

fatality/CT/ETHNICITY/FIRST-EVER/FOLLOW-UP/hemorrhagic

stroke/hospital/hospital mortality/hospitalization/in-hospital

mortality/incidence/INCIDENCE RATES/ischemic stroke/morbidity/morbidity

and mortality/MORTALITY/NORTHERN

MANHATTAN/outcome/prevention/RACE/RACE/ETHNICITY/research/risk/st

roke/stroke incidence/stroke mortality/stroke patients/trends/United States/US



Chimowitz, M., Howlett-Smith, H., Calcaterra, A., Lessard, N., Stern, B., Lynn, M.,

Hertzberg, V., Cotsonis, G., Swanson, S., Tutu-Gxashe, T., Griffin, P., Kosinski,

A., Chester, C., Asbury, W., Rogers, S., Chimowitz, M., Stern, B., Frankel, M.,

Howlett-Smith, H., Hertzberg, V., Lynn, M., Levine, S., Chaturvedi, S., Benesch,

C., Woolfenden, A., Sila, C., Zweifler, R., Lyden, P., Barnett, H., Easton, D.,

Fox, A., Furlan, A., Gorelick, P., Hart, R., Meldrum, H., Sherman, D., Cloft, H.,

Hudgins, P., Tong, F., Caplan, L., Anderson, D., Miller, V., Sperling, L.,

Weintraub, W., Marshall, J., Manoukian, S., Chimowitz, M., Stern, B., Frankel,

M., Samuels, O., Howlett-Smith, H., Lessard, N., Lane, B., Braimah, J.,

Sailor-Smith, S., Asbury, B., Chester, C., Chaturvedi, S., Levine, S., Wiseman,

D., Andersen, J., Sampson-Haggood, A., Kasner, S., Liebeskind, D., Cucchiara,

B., Chalela, J., McGarvey, M., Luciano, J., Shaw, S., Corrozi, M., Rockwell, K.,

Benesch, C., Zentner, J., Bean, S., Cole, D., Sila, C., Katzan, I., Rudd, N., Horvat,

M., Bragg, L., Begany, K., Mazzoli, G., Woolfenden, A., Teal, P., Johnston, C.,

Synnot, D., Busser, J., Lyden, P., Jackson, C., Werner, J., Kelly, N., McClean, T.,

Gonzales, J., Adams, C., Romano, J., Forteza, A., Hidalgo, A., Concha, M.,

Koch, S., Ferreira, A., Wityk, R., Aldrich, E., Lane, K., Rice, S., White, L., Traill,

T., Hemphill, C., Smith, W., Hewlett, L., Reed, C., Fields, S., Nehira, J.,

Wechsler, L., Gebel, J., Goldstein, S., Jovin, T., DeCesare, S., Harbison, B.,

Bernstein, R., Zweifler, R., Mendizabal, J., Alday, D., Yunker, R., Umana, E.,

Neal, T., Cruz-Flores, S., Selhorst, J., Leira, E., Holzemer, E., Armbruster, J.,

Walden, H., Olsen, T., Chan, R., Pullicino, P., Harrington, S., Hopkins, L., Crone,

K., Seyse, S., Hanna, J., Winkelman, M., Liskay, A., Schella, M., Lewayne, N.,

Gullion, L., Thakore, N., Tong, D., Garcia, M., Kemp, S., Shen, H., Tuholski, M.,

LaFranchise, E., Reel, S., Maddox, R., Rice, D., Mitsias, P., Papamitsakis, N.,

Reuther, J., Marchese, P., Kaatz, S., McCord, J., Bruno, A., Sears, A., Pettigrew,

T., Unwin, D., Johnson, M., Graybeal, D., Redhead, A., Stanford, J., Croft, C.,

Lee, R., Culebras, A., Vertino, M., Dean, M., Ayers, J., Zaleski, J., Silliman, S.,

Ray, W., Ballew, K., Darracott, D., Robinson, K., Malcolm, K., Johnston, K.,

Haley, E., Nathan, B., Maupin, K., Grandinetti, C., Adams, A., Libman, R.,

Benson, R., Bhatnagar, R., Gonzaga-Camfield, R., Grant, Y., Kwiatkowski, T.,

Alagappan, K., Saver, J., Kidwell, C., Liebeskind, D., Leary, M., Ferguson, K.,

Llanes, J., Melamed, F., Cohen, S., Krauss, T., Jolly, T., Date, L., Abedi, G.,

Song, A., Wells, M., Dandapani, B., Waddill, A., Parker, L., Vicari, R., Howard,

M., Tuhrim, S., Wright, P., Augustine, S., Ali, J., Halperin, J., Rothlauf, E.,

Kelley, R., Pajeau, A., Jinkins, P., Wang, Y., Booth, A., Middlebrook, M., Grotta,

J., Campbell, M., Shaw, S., Boudreaux, R., Hickey, J., Munson, R., Homer, D.,

McGinn, T., Small, B., Feinberg, A., Shim, B., Nichols, F., Sahm, M., Kutlar, A.,

Belden, J., Diconzo-Fanning, D., Carr, A., Allan, W., Spiro, R., Thaler, D.,

Scandura, T., Douglass, L., Libenson, M., Kase, C., Licata-Gehr, E., Ansell, J.,

McDonough, M., Babikian, V., Allen, N. and Brophy, M. (2003), Design,

progress and challenges of a double-blind trial of warfarin versus aspirin for

symptomatic intracranial arterial stenosis. Neuroepidemiology, 22 (2), 106-117.



Abstract: Background and Relevance: Atherosclerotic stenosis of the major intracranial

arteries is an important cause of transient ischemic attack (TIA) or stroke. Of the

900,000 patients who suffer a TIA or stroke each year in the USA, intracranial

stenosis is responsible for approximately 10%, i.e. 90,000 patients. There have

been no prospective trials evaluating antithrombotic therapies for preventing

recurrent vascular events in these patients. The main objective of this trial is to

compare warfarin [international Normalized Ratio (INR) 2-3] with aspirin (1,300

mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in

patients presenting with TIA or stroke caused by stenosis of a major intracranial

artery. Study Design: Prospective, randomized, double-blind, multicenter trial.

The sample size required will be 403 patients per group, based on stroke and

vascular death rates of 33% per 3 years in the aspirin group vs. 22% per 3 years

in the warfarin group, a p value of 0.05, power of 80%, a 24% rate of 'withdrawal

of therapy', and a 1% rate of 'lost to follow-up'. Conduct of Trial. Patients with

TIA or nondisabling stroke caused by greater than or equal to50% stenosis of a

major intracranial artery documented by catheter angiography are randomized to

warfarin or aspirin. Patients are contacted monthly by phone and examined every

4 months until a common termination date. Mean follow-up in the study is

expected to be 3 years. Conclusion: This study will determine whether warfarin

or aspirin is superior for patients with symptomatic intracranial arterial stenosis.

Furthermore, it will identify patients whose rate of ischemic stroke in the

territory of the stenotic intracranial artery on best medical therapy is sufficiently

high to justify a subsequent trial comparing intracranial angioplasty/stenting with

best medical therapy in this subset of patients. Copyright (C) 2003 S. Karger AG,

Basel



Keywords:

ANGIOGRAPHY/ANTICOAGULANTS/antithrombotic/arterial/arteries/aspirin/

ATRIAL- FIBRILLATION/cerebral angiography/clinical

trial/death/FOLLOW-UP/hemorrhagic/HYPOTHESES/INFARCTION/INR/intra

cranial/intracranial atherosclerosis/ischemic/ischemic stroke/medical/MIDDLE

CEREBRAL-ARTERY/OCCLUSIVE

DISEASE/randomized/stenosis/stroke/STROKE

PREVENTION/therapy/TIA/transient/transient ischemic attack/TRANSIENT

ISCHEMIC ATTACKS/trial/trials/USA/vascular/vascular events/warfarin

Piguet, O., Grayson, D.A., Creasey, H., Bennett, H.P., Brooks, W.S., Waite, L.M. and

Broe, G.A. (2003), Vascular risk factors, cognition and dementia incidence over

6 years in the Sydney older persons study. Neuroepidemiology, 22 (3), 165-171.



Abstract: The specific contributions of factors associated with an increased risk of stroke

to cognitive decline and vascular dementia in elderly people remain somewhat

unclear. We investigated the prevalence of vascular risk factors (RFs) and their

role on the incidence of dementia, cognitive decline and death over a 6-year

period in a sample of 377 non-demented community dwellers aged 75 years and

over at the time of study entry. Presence and history of vascular RFs and

cognitive decline over 6 years were ascertained using direct interviews, medical

and cognitive examinations. Hypertension and history of heart disease were very

common affecting about 50% of the participants. At 6 years, 114 (30%)

participants had died, and 63 (16.7%) met diagnostic criteria for dementia.

Hypertension was significantly associated with a greater cognitive decline but

not with dementia. Smoking and stroke diagnosis showed a significant positive

association with death. Reported hypercholesterolaemia was found to be

associated with a protective effect for the development of dementia, for cognitive

decline and for death over the 6-year period. All other associations were

non-significant. Figures of dementia incidence are similar to previous studies in

contrast to the lack of anticipated effects of the vascular RFs. The results indicate

that in very old participants, the impact of vascular RFs changes with time and

may no longer contribute to the development of dementia and cognitive decline.

Copyright (C) 2003 S. Karger AG, Basel



Keywords: aged/ALZHEIMERS-DISEASE/Australia/changes/cognition/cognitive

decline/community/death/dementia/development/DIAGNOSIS/diagnostic/diseas

e/elderly/EPIDEMIOLOGY/HEALTH/heart/heart

disease/history/hypercholesterolaemia/incidence/LIFE/medical/old/POPULATIO

N/prevalence/PREVENTION/results/risk/risk factors/stroke/vascular/vascular

dementia/vascular risk/vascular risk factors/WHITE-MATTER LESIONS



Hurst, R.W. (1996), Interventional neuroradiology of the head and neck. Neuroimaging

Clinics of North America, 6 (2), 473-&.



Abstract: Interventional neuroradiologic techniques continue to assume increasing

importance in the management of disorders of the head and neck. Their

usefulness includes not only treatment for neoplastic and vascular conditions

with embolization but also test occlusion for diagnostic information. Future

developments also may extend the usefulness of interventional techniques to

additional conditions, including prevention and treatment for ischemic stroke



Keywords: BALLOON TEST OCCLUSION/CAROTID-CAVERNOUS

FISTULAS/CEREBRAL BLOOD-FLOW/CLASSIFICATION/ischemic

stroke/MAXILLARY ARTERY/POSTERIOR

EPISTAXIS/prevention/stroke/TRANSARTERIAL EMBOLIZATION/treatment

Cho, L. and Yadav, J.S. (2002), Embolization in atherosclerosis. Neuroimaging Clinics

of North America, 12 (3), 365-+.



Abstract: New evidence has highlighted the frequency and importance of atherosclerotic

embolization to the microvasculature. Several factors determine the clinical

significance of embolization. These include the characteristics of the embolus

itself, the frequency of emboli in the same vascular bed, and the collateral supply

and perfusion pressure of the recipient vascular bed. Until recently, we have had

limited ability to diagnose microvascular obstruction in living patients. With the

availability of imaging technology such as MRI, myocardial contrast

echocardiography, and transcranial Doppler (TCD), the frequency and the

importance of microvascular obstruction has been better understood in the last

two decades. Embolization that leads to arterial occlusion occurs more frequently

in the cerebral circulation than in the coronary circulation and can have a

devastating effect on the patient. Consequently, the detection and prevention of

embolic events are crucial to stroke prevention. Although much work has been

done to prevent large emboli, not much is known about prevention or

consequence of microembolic events. Microembolic events are common in high-

risk patients with carotid stenosis and in patients undergoing carotid

endarterectomy (CEA), carotid stenting, or coronary artery bypass graft surgery

(CABG). This article reviews the latest technology in detecting and preventing

microembolization during carotid stenting and CABG



Keywords:

arterial/atherosclerosis/bypass/CABG/CARDIAC-SURGERY/CARDIOPULMO

NARY BYPASS/carotid/CAROTID ENDARTERECTOMY/carotid

stenosis/carotid stenting/cerebral/CEREBRAL

MICROEMBOLISM/CREATINE-KINASE

ELEVATION/detection/Doppler/echocardiography/emboli/embolization/embolu

s/endarterectomy/high risk/INTENSITY TRANSIENT

SIGNALS/MRI/myocardial/MYOCARDIAL-INFARCTION/PERCUTANEOU

S CORONARY INTERVENTIONS/prevention/REVASCULARIZATION

PROCEDURES/risk/stenosis/stenting/stroke/stroke

prevention/surgery/TCD/transcranial/transcranial Doppler/TRANSCRANIAL

DOPPLER ULTRASOUND/vascular



Di Tullio, M.R. and Homma, S. (2002), Transesophageal echocardiography aortic

plaque imaging. Neuroimaging Clinics of North America, 12 (3), 445-+.



Abstract: Transesophageal echocardiography (TEE) has been used widely as a

diagnostic tool during the past two decades to detect cardiac abnormalities that

are not visible, or are inadequately visualized, by transthoracic echocardiography

or by other noninvasive diagnostic imaging techniques. Recently, the use of TEE

to detect cardioembolic sources in patients with acute ischemic stroke or

peripheral embolism has increased dramatically. It is estimated that

approximately one fourth of all TEE performed in the United States is done for

this reason. TEE is far more sensitive than transthoracic echocardiography for

cardioembolic source detection and has in fact contributed to the actual discovery

of new potential embolic sources. Among them, the presence of large atheromas

in the proximal portion of the aorta has been recognized as an important risk

factor for stroke in patients older than 60 years, and TEE has become one of the

cornerstones of the diagnostic work-up in this subset of patients. This article

focuses on the use of TEE to search for atherosclerotic plaques in the aorta and

its contribution to the assessment of the associated embolic risk and the

prevention of embolic complications



Keywords: acute/acute ischemic

stroke/aorta/ARCH/ATHEROMAS/cardiac/cardioembolic/complications/DEBRI

S/detection/diagnostic/diagnostic

imaging/echocardiography/embolism/FOLLOW-UP/ischemic/ISCHEMIC

STROKE/MORPHOLOGY/MR/plaque/prevention/RISK/risk

factor/stroke/SYSTEMIC EMBOLI/THORACIC AORTA/transthoracic

echocardiography/United States/use/VASCULAR EVENTS



Yamamoto, I., Kanno, H. and Fujii, S. (1998), Indication for carotid endarterectomy.

Neurologia Medico-Chirurgica, 38 275-278.



Abstract: From recent randomized studies, carotid endarterectomy (CEA) is highly

beneficial to the patients with a symptomatic high-grade carotid artery stenosis

(70-99%), but the surgical indication for an asymptomatic carotid artery disease

remains unsolved. Sixty-three atheromatous plaques (symptomatic 51,

asymptomatic 12) were obtained from 57 patients who underwent CEA. The

presence of an intraplaque hemorrhage was noted in 75% from symptomatic

plaques, compared with 33% from asymptomatic ones. A plaque disruption

occurred over protruding mounds of intraplaque hemorrhage and was noted in

76% and 42% from symptomatic and asymptomatic ones, respectively. However,

asymptomatic plaques, which were angiographically demonstrated as carotid

ulcer of types B and C, had a high incidence of intraplaque hemorrhage as well

as plaque disruption. Three patients followed with asymptomatic contralateral

carotid artery disease developed a stroke following ipsilateral revascularization

and all three specimens showed the presence of plaque hemorrhage and

disruption. It is concluded that before prophylactic CEA is considered, an

intraplaque hemorrhage and/or plaque disruption should be detected by less

invasive procedures such as ultrasonography



Keywords: ARTERY/asymptomatic/carotid/carotid artery/carotid artery disease/carotid

artery stenosis/carotid

endarterectomy/CEREBRAL-ISCHEMIA/endarterectomy/hemorrhage/incidence

/intraplaque hemorrhage/INTRAPLAQUE

HEMORRHAGE/JAPAN/NATURAL-HISTORY/PLAQUE/plaque

disruption/PREVENTION/randomized/STENOSIS/stroke/surgical

indication/ultrasonography

Vangijn, J. (1992), Aspirin - Dose and Indications in Modern Stroke Prevention.

Neurologic Clinics, 10 (1), 193-207



Keywords:

ACETYLATION/CEREBRAL-ISCHEMIA/CONFIDENCE-INTERVALS/HEA

LTHY- SUBJECTS/INTEROBSERVER

AGREEMENT/MYOCARDIAL-INFARCTION/PLATELET

CYCLOOXYGENASE INHIBITION/PROSTACYCLIN/THROMBOXANE

PRODUCTION/TRANSIENT ISCHEMIC ATTACKS



Barnett, H.J.M. (1992), Stroke Prevention by Surgery for Symptomatic Disease in

Carotid Territory. Neurologic Clinics, 10 (1), 281-292



Keywords: ARTERIES/BILATERAL

OCCLUSION/ENDARTERECTOMY/INTERNATIONAL RANDOMIZED

TRIAL/MEDICALLY TREATED PATIENTS/MORTALITY/RISK/TRENDS



Thompson, D.W. and Furlan, A.J. (1996), Clinical epidemiology of stroke. Neurologic

Clinics, 14 (2), 309-&.



Abstract: The effect of stroke as a major health issue in the United States is well

established. Well-designed epidemiologic studies have contributed important

information about the natural history of stroke and its associated risk factors.

These cerebrovascular profiles have provided the foundation for many of the

current ischemic stroke trials, but the cause and prevention of the hemorrhagic

subtypes remain elusive



Keywords: BLACKS/CEREBRAL

ANEURYSMS/health/history/INFARCTS/INTRACRANIAL

ANEURYSMS/ischemic stroke/prevention/risk

factors/stroke/SUBARACHNOID HEMORRHAGE/THROMBOEMBOLIC

STROKE/trials



Alexander, D.N. (1998), Geriatric neurorehabilitation. Neurologic Clinics, 16 (3), 713-+.



Abstract: Rehabilitation of the elderly patient with a neurologic disease consists

primarily of the coordinated actions of an interdisciplinary team of physicians.

Key aspects of this process are remediation to reduce neurologic impairments,

prevention of secondary complications and comorbidities, compensation to offset

and adapt to residual disabilities, and maintenance of function over the long term



Keywords: complications/elderly/ELDERLY

PEOPLE/prevention/RECOVERY/REHABILITATION/STROKE



Diener, H.C. (2000), Stroke prevention - Antiplatelet and antithrombolytic therapy.

Neurologic Clinics, 18 (2), 343-+.

Abstract: In patients with TLA or ischemic stroke of noncardiac origin antiplatelet drugs

are able to decrease the risk of stroke by 11-15%, and the risk of stroke, MI, and

vascular death by 15- 22%, but not mortality. Low doses of aspirin (50-325 mg)

are as effective as high doses and cause less gastrointestinal side effects. Severe

bleeding complications are not dose-dependent. The combination of aspirin with

slow release dipyridamole is superior to aspirin alone for stroke prevention.

Ticlopidine is superior to aspirin but has slightly more serious adverse effects

(neutropenia). It will be replaced by clopidgrel which has a better safety profile.

Anticoagulation with an INR between 3.0 and 4.5 is too dangerous. Whether

anticoagulation with lower INR is safe and effective is not yet known



Keywords: ACETYLSALICYLIC-ACID/adverse

effects/anticoagulation/antiplatelet/antiplatelet

drugs/aspirin/bleeding/CEREBRAL-ISCHEMIA/CEREBROVASCULAR-DISE

ASE/complications/death/DIPYRIDAMOLE/DRUGS/Germany/INR/ischemic/is

chemic stroke/LOW-DOSE

ASPIRIN/mortality/neutropenia/prevention/RANDOMIZED

TRIAL/risk/safety/SECONDARY PREVENTION/stroke/stroke

prevention/therapy/THROMBOTIC THROMBOCYTOPENIC

PURPURA/TICLOPIDINE/vascular



Benson, R.T. and Sacco, R.L. (2000), Stroke prevention - Hypertension, diabetes,

tobacco, and lipids. Neurologic Clinics, 18 (2), 309-+.



Abstract: This article reviews the most recent epidemiologic evidence supporting topics

such as hypertension, diabetes, tobacco, and Lipids as risks for stroke. Where

available, American Stroke Association (ASA) and National Stroke Association

(NSA) consensus statement guidelines for the treatment of these risk factors are

given



Keywords: CARDIOVASCULAR EVENTS/CAROTID

ATHEROSCLEROSIS/CIGARETTE-SMOKING/consensus/CORONARY

HEART-DISEASE/DENSITY-LIPOPROTEIN

CHOLESTEROL/diabetes/guidelines/hypertension/INDEPENDENT RISK

FACTOR/ISCHEMIC

STROKE/lipids/MYOCARDIAL-INFARCTION/prevention/risk/risk

factors/SERUM-CHOLESTEROL/SMOKING

CESSATION/stroke/tobacco/treatment



Staub, L. and Morgenstern, L.B. (2000), Stroke in Hispanic Americans. Neurologic

Clinics, 18 (2), 291-+.



Abstract: The Hispanic American population is the fastest growing minority group with

increasing representation among the older age strata. Current ethnic-specific

cerebrovascular disease data regarding stroke outcomes and risk factor status

reveal significant differences compared with other race/ethnic groups. The

authors discuss the literature on stroke incidence and mortality among Hispanic

populations. Traditional risk factors, access to care and stroke mechanism

differences are also discussed. Advances in Hispanic American specific stroke

prevention and treatment efforts demand further investigation to better define

Hispanic American stroke prevention and acute treatment strategies



Keywords: acute/acute treatment/AFRICAN-AMERICANS/age/CEREBRAL

INFARCTION/cerebrovascular/cerebrovascular

disease/disease/EPIDEMIOLOGY/ETHNIC-DIFFERENCES/Hispanic

Americans/incidence/MORTALITY/NORTHERN MANHATTAN

STROKE/population/prevention/RACE/risk/risk factor/risk

factors/RISK-FACTORS/SOCIOECONOMIC- STATUS/status/stroke/stroke

incidence/stroke prevention/treatment/WHITE



Palacio, S. and Hart, R.G. (2002), Neurologic manifestations of cardiogenic embolism -

An update. Neurologic Clinics, 20 (1), 179-+.



Abstract: Stroke should be considered a syndrome and not a single disease, and this is

especially true when stroke is the result of cardiogenic embolism. Increasing

evidence about new potential sources of embolism and the recognition of

different risk groups with established causes of cardioembolic strokes in recent

years continue to challenge clinicians in diagnosis and management. The

frequent coexistence of noncardioembolic etiologies of stroke (approximately

20%) in patients with potential cardioembolic sources makes management

decisions even more difficult.(26) On the other hand, cardioembolic strokes are

largely preventable, making early recognition paramount. The big challenge is

first to establish a firm cause-effect relationship and then to stratify the risk of

individual patients to choose the best therapy. When weighing treatment

alternatives, it is the absolute risk reduction in stroke by a therapy, determined in

part by the absolute rate of stroke with each specific cardioembolic source, that is

crucial. Basic concepts about cardiogenic embolism to the brain have been

comprehensively reviewed elsewhere.(10, 11,16) This article focuses on new

data and concepts from the past 5 years



Keywords: absolute risk/ACUTE

MYOCARDIAL-INFARCTION/brain/cardioembolic/causes/CRYPTOGENIC

STROKE/diagnosis/disease/embolism/INFECTIVE

ENDOCARDITIS/management/NONVALVULAR

ATRIAL-FIBRILLATION/PATENT FORAMEN OVALE/risk/SECONDARY

PREVENTION/SEPTAL ABNORMALITIES/stroke/STROKE

PREVENTION/therapy/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/TRANSIENT ISCHEMIC ATTACK/treatment



Nighoghossian, N., Perinetti, M., Barthelet, M., Adeleine, P. and Trouillas, P. (1995),

Transesophageal Echocardiography in Patients Less-Than-60 Years of Age

Without Obvious Cardiac Source of Embolism. Neurological Research, 17 (5),

368-372.

Abstract: Minor potential cardioembolic sources of stroke such as atrial septal

aneurysms (ASA) or patent foramen ovale (PFO) are important risk factors for

cryptogenic stroke. We aim to determine the prevalence of these abnormalities

through an exhaustive etiological workup including transesophageal

echocardiography and cervical arteries assessment in stroke patients younger

than 60 years of age who had no evidence of a significant source of embolism.

We classified 118 stroke patients into four groups according to transesophageal

echocardiography (TEE) and cervical arteries assessment findings. Group A,

consisted of 30 (25.4%) patients who had an arteriopathy likely related to stroke

without any cardiac abnormality; Group B, 49 (41%) patients who had only a

potential cardiac source; Group C, 9 (7.6%) patients who had an obvious arterial

source of stroke and incidental cardiac abnormalities, and Group D, 30 (25.4%)

patients who had neither cardiac nor arterial source. Data were analysed with X(2)

test for the comparison of risk factors between groups. Variance analysis was

used to compare age between groups. Significance was assessed as p 200

cm/sec time averaged mean in the middle cerebral or intracranial internal carotid

arteries) have a very significant reduction in stroke with chronic transfusion.

Hydroxyurea and bone marrow transplantation may in the future be used for

stroke prevention, but there are no data at present. There is no primary stroke

prevention strategy for adults and prevention of recurrent stroke has not been

well studied. Transfusion is an option, as well as empiric use of antiplatelet

agents, warfarin, or surgery, but there are virtually no data on risk/benefit for

these treatments in adults. All SCD patients with intracranial hemorrhage should

be considered for angiography to look for surgically correctable lesions.

CONCLUSION- The neurologist should bear in mind that, although stroke is

common in SCD, other etiologies and causes for neurological dysfunction may

be present and should be considered in patients with SCD who present with

neurological symptoms



Keywords: adults/ANEMIA/antiplatelet/antiplatelet agents/arteries/carotid/carotid

arteries/cerebral/cerebral infarction/children/CHILDREN/clinical

trial/COMPLICATIONS/disease/Doppler/epidemiology/hemorrhage/incidence/i

ntracranial

hemorrhage/morbidity/mortality/neurologist/PREVENTION/primary/randomize

d/RECURRENT STROKE/REVIEW/RISK/screening/sickle cell

disease/stroke/stroke prevention/surgery/transcranial/TRANSCRANIAL

DOPPLER/transfusion/TRANSFUSION

THERAPY/trial/ULTRASONOGRAPHY/use/warfarin



Sivenius, J., Laakso, M., Penttila, I.M., Smets, P., Lowenthal, A. and Riekkinen, P.J.

(1991), The European Stroke Prevention Study - Results According to Sex.

Neurology, 41 (8), 1189-1192.



Abstract: The European Stroke Prevention Study was a multicenter trial comparing the

effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid

tid with placebo in the prevention of stroke or death after one or more attacks of

recent transient ischemic attack or stroke of atherothrombotic origin. From the

2,500 patients in the intention-to-treat analysis, the proportion of women was

42%, and from the 1,861 patients in the explanatory analysis it was 44%. The

endpoint incidence was significantly higher in men than in women. The endpoint

reduction was statistically significant in men in both types of analyses with total

endpoints (stroke or death) and in the risk of stroke, while in women it was

statistically significant only in the intention-to-treat analysis with total endpoints.

However, there was a marked percentage reduction of endpoints in both men and

women in explanatory analysis. The risk reduction of strokes was 49% for men

and 41% for women, and the reduction of total endpoints was 39% in men and

30% in women. Thus, antiplatelet therapy is effective in the prevention of stroke

or death in both sexes



Keywords: ACID/ASPIRIN/BRUITS/CEREBRAL-ISCHEMIA/CONTROLLED

TRIAL/DIFFERENCE/PLATELET- AGGREGATION/RISK/SECONDARY

PREVENTION/TRANSIENT ISCHEMIC ATTACKS



Grotta, J.C., Norris, J.W., Kamm, B., Adams, H.P., Anderson, B.A., Bellavance, A.,

Byer, J.A., Couch, J.R., Dobkin, B.H., Fisher, M.J., Hanna, G.R., Hershey, L.A.,

Kase, C.S., Lacy, J.R., Levy, L.L., Mayman, C., Meyer, J.S., Olinger, C.P.,

Prysephillips, W., Robertson, J.T., Rothrock, J.F., Sadowsky, C.H., Swanson,

P.D., Taylor, J. and Weisberg, L.A. (1992), Prevention of Stroke with

Ticlopidine - Who Benefits Most. Neurology, 42 (1), 111-115.



Abstract: We examined the baseline characteristics of patients in the Ticlopidine Aspirin

Stroke Study (TASS) to determine if the effects of the two treatments in

preventing stroke differed in various subgroups. Patients with the following

characteristics did less well on aspirin: elevated creatinine, hypertension or

diabetes requiring treatment, or treatment with anticoagulant or antiplatelet drugs

prior to their qualifying TIA or stroke. Women and patients with vertebrobasilar

symptoms did particularly well on ticlopidine. We performed arteriography in

1,188 patients with carotid qualifying events. The frequency of stroke in patients

with abnormal arteriograms ipsilateral to their symptoms was slightly higher than

in those with normal carotid arteries. Ticlopidine was more effective in patients

without carotid stenosis. Ticlopidine is more effective than aspirin in preventing

strokes in patients having warning TIAs. The patients who benefit most from

ticlopidine may be women, those who have vertebrobasilar symptoms, those with

cerebral ischemic symptoms while on aspirin or anticoagulant therapy, and

patients with diffuse atherosclerotic disease rather than high-grade carotid

stenosis



Keywords: ASPIRIN/CEREBRAL-ISCHEMIA/CONTROLLED TRIAL/TIA



Miller, V.T., Rothrock, J.F., Pearce, L.A., Feinberg, W.M., Hart, R.G. and Anderson,

D.C. (1993), Ischemic Stroke in Patients with Atrial-Fibrillation - Effect of

Aspirin According to Stroke Mechanism. Neurology, 43 (1), 32-36.



Abstract: Ischemic strokes occurring in patients with nonrheumatic atrial fibrillation are

due to a variety of mechanisms, not exclusively to cardiogenic embolism.

Without knowledge of antithrombotic therapy assignment, we categorized

strokes in the Stroke Prevention in Atrial Fibrillation Study as presumed

cardioembolic or noncardioembolic. We then compared patient clinical and

echocardiographic variables, as well as the efficacy of aspirin prophylaxis, for

each stroke type. Of 71 ischemic strokes, we categorized 46 (65%) as

cardioembolic, 13 (18%) as noncardioembolic, and 12 (17%) as of uncertain

cause. Patients developing noncardioembolic strokes, relative to cardioembolic

strokes, were more commonly men (p = 0.005) and were more likely to have left

ventricular wall motion abnormalities by two-dimensional echocardiography (p =

0.002). Aspirin reduced the occurrence of strokes categorized as

noncardioembolic significantly more than it did those categorized as

cardioembolic (p = 0.01). These results emphasize the value of considering

stroke mechanisms in therapeutic trials of antithrombotic agents and suggest a

differential effect of aspirin according to mechanism



Keywords: REGISTRY/RISK



Pessin, M.S., Estol, C.J., Lafranchise, F. and Caplan, L.R. (1993), Safety of

Anticoagulation After Hemorrhagic Infarction. Neurology, 43 (7), 1298-1303.



Abstract: Cerebral hemorrhagic infarction visualized on CT, secondary to embolic stroke

in an anticoagulated individual, is usually associated with clinically stable or

improving neurologic signs; fear of transforming the hemorrhagic infarction into

a hematoma, however, usually prompts cessation of anticoagulation until the

blood has cleared on CT, despite the recognized risk of recurrent embolism

during this non-anticoagulated period. We now report our experience with 12

patients with hemorrhagic infarction who remained anticoagulated. Eleven men

and one woman, ages 33 to 77, developed hemorrhagic infarction while on

heparin, warfarin, or both, for prevention of recurrent embolism. Patients were

either continued on uninterrupted anticoagulation from stroke onset (n = 6), or

anticoagulation was withheld for several days and then resumed (n = 4), or it was

withheld for 5 and 14 days (n = 2) after stroke onset and then continued

uninterrupted despite the CT appearance of hemorrhagic infarction. Eleven

patients had a definite cardioembolic source for stroke (atrial fibrillation, seven;

ventricular thrombus, two; and ventricular dyskinesia, two). One patient had

carotid occlusion with local intra-arterial embolism. Hemorrhagic infarcts varied

in size and were located in the middle cerebral artery territory in 11 patients and

posterior cerebral artery territory in one. All patients remained clinically stable or

improved on anticoagulation. Serial CTs showed fading hemorrhagic areas.

When the risk of recurrent embolism is high, anticoagulation may be safely used

in some patients with hemorrhagic infarction



Keywords: ATRIAL- FIBRILLATION/CARDIAC ORIGIN/CT/EMBOLIC

CEREBRAL INFARCTION/RISK/STROKE



Weisberg, L.A. (1993), The Efficacy and Safety of Ticlopidine and Aspirin in Non-

Whites - Analysis of A Patient Subgroup from the Ticlopidine Aspirin Stroke

Study. Neurology, 43 (1), 27-31.



Abstract: We analyzed the efficacy of ticlopidine and aspirin in the non- white subgroup

of patients from the Ticlopidine Aspirin Stroke Study. In this double-blind,

randomized, multicenter study, patients received either ticlopidine 250 mg (312

non-white patients) or aspirin 650 mg (291 non-white patients) twice a day. The

1-year cumulative event rate per 100 patients for nonfatal stroke or death from

any cause was 5.5 for ticlopidine and 10.6 for aspirin-an apparent 48.1%

reduction in risk with ticlopidine relative to aspirin. The 1-year cumulative event

rate for fatal or non-fatal stroke was 3.7 for ticlopidine and 9.4 for aspirin-an

apparent 60.8% reduction in risk with ticlopidine relative to aspirin. The

cumulative event rates for both endpoints also were lower in ticlopidine-treated

patients after the 2nd and 3rd years. These reductions were not significantly

different between treatment groups, but were of the same order of magnitude as

previously found for the total series, which did attain statistical significance (p =

0.048), and the frequency of adverse events was not significantly different

between the two treatment groups. Severe neutropenia, the most serious adverse

event associated with ticlopidine use, did not occur in non-white patients. These

results suggest that ticlopidine is superior to aspirin for stroke prevention in

non-whites



Keywords:

DECLINE/DISEASE/HYPERTENSION/MORTALITY/PREVENTION/TRAN

SIENT ISCHEMIC ATTACKS/TRIAL/UNITED-STATES

Depippo, K.L., Holas, M.A., Reding, M.J., Mandel, F.S. and Lesser, M.L. (1994),

Dysphagia Therapy Following Stroke - A Controlled Trial. Neurology, 44 (9),

1655-1660.



Abstract: Objective: To determine the effect, of graded levels of intervention by a

dysphagia therapist on the occurrence of pneumonia, dehydration,

calorie-nitrogen deficit, recurrent upper airway obstruction, and death following

stroke. Design: A randomized control trial, Setting: Inpatient stroke rehabilitation

unit. Patients: All patients met the following eligibility criteria: (1) stroke defined

by clinical history and neurologic examination with compatible CT or MRI, (2)

ages 20 to 90 years inclusive, (3) no known history of significant oral or

pharyngeal anomaly, (4) laboratory values below end point criteria, (5) failure on

the Burke Dysphagia Screening Test, and (6) modified barium swallow

evaluation evidence of dysphagia (patients who aspirated greater than or equal to

50% of all consistencies presented, even using compensatory swallowing

techniques, were excluded). Of 123 eligible patients, eight refused study

participation. One hundred fifteen patients were randomized. Interventions:

Three graded levels of dysphagia therapist control of diet consistency and

reinforcement of compensatory swallowing techniques were provided during the

inpatient rehabilitation stay. Main outcome measures: Pneumonia, dehydration,

calorie-nitrogen deficit, recurrent upper airway obstruction, and death. Results:

The log rank statistic showed no significant difference between the three

treatment groups for the distribution of time until end point during the inpatient

stay or to 1 year post-stroke. Conclusion: Limited patient and family instruction

regarding use of diet modification and compensatory swallowing techniques

during inpatient rehabilitation is as effective as therapist control of diet

consistency and daily rehearsal of compensatory swallowing techniques for the

prevention of medical complications associated with dysphagia following stroke



Keywords:

ASPIRATION/complications/CT/DEATH/diet/evaluation/history/prevention/RE

LATIVE RISK/stroke/SWALLOW/treatment/VIDEOFLUOROSCOPY



Raps, E.C. and Galetta, S.L. (1995), Stroke Prevention Therapies and Management of

Patient Subgroups. Neurology, 45 (2), S19-S24.



Abstract: Stroke is the third leading cause of death in the United States. Efforts directed

at reversing acute cerebral ischemia are promising but are hampered by multiple

logistic and physiologic barriers. Prevention of stroke, therefore, remains of

critical importance. Primary prevention is accomplished through reduction of

risk factors and the appropriate use of warfarin or aspirin in patients with cardiac

sources of emboli such as atrial fibrillation. Secondary prevention is designed to

reduce the risk of stroke in patients with known stroke precursors, including

transient ischemia, reversible ischemic deficits, and completed stroke. Aspirin

and ticlopidine are two antiplatelet agents with an established role in secondary

stroke prevention. In a major North American clinical trial, ticlopidine

demonstrated superior efficacy to aspirin for the prevention of recurrent stroke,

particularly in the first year following a stroke. Dipyridamole has not been shown

to be useful for stroke prevention. The role of warfarin in the prevention of

recurrent noncardiogenic stroke remains controversial and is currently under

investigation. Stroke prevention remains an important challenge, and therapy

should be individualized to achieve optimal results



Keywords: antiplatelet agents/aspirin/atrial fibrillation/cerebral

ischemia/CEREBRAL-ISCHEMIA/CHRONIC

ATRIAL-FIBRILLATION/DIPYRIDAMOLE/DISEASE/EFFICACY/emboli/fi

brillation/FRAMINGHAM/ischemia/PLACEBO/prevention/RANDOMIZED

TRIAL/risk/risk factors/stroke/stroke prevention/ticlopidine/TICLOPIDINE

ASPIRIN STROKE/transient/WARFARIN



Chimowitz, M.I., Kokkinos, J., Strong, J., Brown, M.B., Levine, S.R., Silliman, S.,

Pessin, M.S., Weichel, E., Sila, C.A., Furlan, A.J., Kargman, D.E., Sacco, R.L.,

Wityk, R.J., Ford, G. and Fayad, P.B. (1995), The Warfarin-Aspirin

Symptomatic Intracranial Disease Study. Neurology, 45 (8), 1488-1493.



Abstract: We conducted a retrospective, multicenter study to compare the efficacy of

warfarin with aspirin for the prevention of major vascular events (ischemic

stroke, myocardial infarction, or sudden death) in patients with symptomatic

stenosis of a major intracranial artery. Patients with 50 to 99% stenosis of an

intracranial artery (carotid; anterior, middle, or posterior cerebral; vertebral; or

basilar) were identified by reviewing the results of consecutive angiograms

performed at participating centers between 1985 and 1991. Only patients with

TIA or stroke in the territory of the stenotic artery qualified for inclusion in the

study. Patients were prescribed warfarin or aspirin according to local physician

preference and were followed by chart review and personal or telephone

interview. Seven centers enrolled 151 patients; 88 were treated with warfarin and

63 were treated with aspirin. Median follow-up was 14.7 months (warfarin group)

and 19.3 months (aspirin group). Vascular risk factors and mean percent stenosis

of the symptomatic artery were similar in the two groups, yet the rates of major

vascular events were 18.1 per 100 patient-years of follow-up in the aspirin group

(stroke rate, 10.4/100 patient-years; myocardial infarction or sudden death rate,

7.7/100 patient-years) compared with 8.4 per 100 patient-years of follow-up in

the warfarin group (stroke rate, 3.6/100 patient-years; myocardial infarction or

sudden death rate, 4.8/100 patient-years). Kaplan-Meier analysis showed a

significantly higher percentage of patients free of major vascular events among

patients treated with warfarin (p = 0.01). The relative risk of a major vascular

event in those treated with warfarin was 0.46 (95% CI, 0.23 to 0.86) compared

with patients treated with aspirin. Major hemorrhagic complications occurred in

three patients on warfarin (including two deaths) during 166 patient-years of

follow-up and in none of the patients on aspirin during 143 patient-years of

follow- up. This study suggests a favorable risk/benefit ratio for warfarin

compared with aspirin for the prevention of major vascular events in patients

with symptomatic intracranial large-artery stenosis. A prospective, randomized

study is needed to confirm these findings

Keywords: ANTICOAGULANTS/aspirin/carotid/complications/ischemic

stroke/MIDDLE CEREBRAL-ARTERY/myocardial

infarction/PREVENTION/PROGNOSIS/relative risk/risk/risk

factors/STENOSIS/STROKE/TIA/TICLOPIDINE/TRANSIENT ISCHEMIC

ATTACKS/vascular/warfarin



Bowes, M.P., Rothlein, R., Fagan, S.C. and Zivin, J.A. (1995), Monoclonal-Antibodies

Preventing Leukocyte Activation Reduce Experimental Neurologic Injury and

Enhance Efficacy of Thrombolytic Therapy. Neurology, 45 (4), 815-819.



Abstract: We evaluated the ability of monoclonal antibodies directed against leukocyte

adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], CD18) to

enhance the efficacy of thrombolysis in a rabbit cerebral embolism stroke model.

Both tissue-type plasminogen activator (tPA) and anti-CD18 (alpha- CD18)

monoclonal antibody administered 5 minutes after embolization increased the

quantity of clots required to produce neurologic damage, although the

combination was no more effective than either substance alone. Neither

alpha-CD18 nor anti-ICAM-1 (alpha-ICAM-1) improved neurologic outcome at

postischemic delays of 15 or 30 minutes. However, the combination of

alpha-ICAM-1 (15 minutes after embolization) and tPA (2 hours after

embolization) significantly improved neurologic outcome even though neither

substance was effective alone at these postembolization delays. These findings

suggest that prevention of leukocyte adhesion increases the postischemic

duration at which thrombolytic therapy remains effective



Keywords: AIR-EMBOLISM/cerebral embolism/CEREBRAL-ISCHEMIA/EMBOLIC

STROKE/INTERCELLULAR-ADHESION MOLECULE/MYOCARDIAL

INJURY/POLYMORPHONUCLEAR

LEUKOCYTES/prevention/REPERFUSION

INJURY/SKELETAL-MUSCLE/stroke/SYSTEM

ISCHEMIC-INJURY/thrombolysis/thrombolytic therapy/TISSUE

PLASMINOGEN-ACTIVATOR



Adams, R.J. (1995), Management Issues for Patients with Ischemic Stroke. Neurology,

45 (2), S15-S18.



Abstract: This review briefly summarizes the acute management of cerebral infarction

and cardiac comorbidity in patients with stroke, with a focus on more general

aspects of care. Important aspects of the acute management of cerebral infarction

are its prompt recognition, use of appropriate emergency medical services,

including 911, initial treatment, and prevention of complications. Secondary

prevention begins with the diagnostic workup for the cause of the initial stroke.

Although the optimal workup depends on the patient, a minimal workup consists

of a history and physical examination sufficient to establish vascular risk factors

and the neurologic and medical status of the patient, basic laboratory tests, EGG,

chest x- ray, cranial CT, evaluation of carotid arteries, and a search for cardiac

sources and the presence of atrial fibrillation. Further workup may include a

search for coagulopathies, less common sources of embolism, and intracranial

intravascular disease. Better education of patients at risk is of vital importance.

Patients with cerebral infarction share vascular risk factors with those who have

coronary disease, and the presence of both coronary and cerebrovascular disease

is highly likely. The likelihood of finding coronary artery disease in patients with

transient ischemic attack and ischemic stroke with noninvasive testing, as well as

management recommendations for these patients are reviewed



Keywords: atrial fibrillation/carotid/carotid arteries/CEREBRAL-

ISCHEMIA/cerebrovascular

disease/CEREBROVASCULAR-DISEASE/chest/comorbidity/complications/cor

onary disease/CORONARY-ARTERY

DISEASE/CT/education/evaluation/fibrillation/history/ischemic

stroke/PREVALENCE/prevention/risk/risk factors/stroke/transient/transient

ischemic attack/treatment/vascular



Sacco, R.L. (1995), Risk-Factors and Outcomes for Ischemic Stroke. Neurology, 45 (2),

S10-S14.



Abstract: Stroke continues to have a great impact on public health in the United States.

Stroke is frequent, recurring, and is more often disabling than fatal. The annual

incidence of new strokes in the United States is nearly one half million, with over

3 million stroke survivors alive today. Identifying risk factors for initial ischemic

stroke, as well as characterizing the determinants of outcome (stroke recurrence

and mortality) after ischemic stroke, is the basis for stroke prevention strategies.

Modifiable and nonmodifiable risk factors for ischemic stroke have been

identified and include age; gender; race/ethnicity; heredity; hypertension; cardiac

disease, particularly atrial fibrillation; diabetes mellitus; hypercholesterolemia;

cigarette smoking; and alcohol abuse. New risk factors, such as hypercoagulable

states and patent foramen ovale, are currently being investigated. Follow-up

studies have quantified case- fatality rates, early recurrence risk, and long-term

mortality and recurrence risks. Despite advances in stroke prevention strategies

and treatments, stroke recurrence is still the major threat to any stroke survivor.

A major goal set by the Public Health Service in its National Health Promotion

and Disease Prevention Objectives for the year 2000 is ''to reduce stroke deaths

to no more than 20 per 100,000.'' Part of this can be achieved if the risk of stroke

recurrence is reduced. However, the frequency and determinants of stroke

recurrence are poorly understood. Data from epidemiologic studies can help

identify risk factors and outcomes after ischemic stroke, as well as the selection

of high-risk individuals for focused risk-factor modification. Current information

on these topics is discussed



Keywords: atrial fibrillation/ATRIAL-FIBRILLATION/BLACKS/case

fatality/CHANGING PATTERN/DATA-BANK/DECLINE/diabetes

mellitus/fibrillation/health/HYPERTENSION/incidence/ischemic

stroke/MORTALITY/patent foramen ovale/prevention/RECURRENCE/risk/risk

factors/smoking/stroke/stroke prevention/SURVIVAL/TRENDS

Bruno, A., Carter, S., Qualls, C. and Nolte, K.B. (1996), Incidence of spontaneous

intracerebral hemorrhage among Hispanics and non-Hispanic whites in New

Mexico. Neurology, 47 (2), 405-408.



Abstract: Objective: To compare the incidence of spontaneous intracerebral hemorrhage

(ICH) among Hispanics and non-Hispanic whites living in Bernalillo County,

NM. Background: There are differences in cerebrovascular disease incidence

between racial and ethnic groups. Knowing these differences is likely to optimize

stroke prevention and evaluation. Methods: Medical records review of all

possible cases of ICH occurring between January 1, 1993 and December 31,

1993 among residents of Bernalillo County, NM, in all local hospitals. Hospital

records were identified by ICD-9-CM. codes. Also, State Medical Examiner

records review for additional ICH cases occurring during the same time interval.

The 1990 U.S. census provided the population base. Results: There were 47

spontaneous ICHs among 267,965 non-Hispanic whites and 39 spontaneous

ICHs among 178,310 Hispanics. Incidence of ICH rises exponentially with age

in both groups. The age- and sex-adjusted total annual incidence of ICH per

100,000 people is 16.6 among non-Hispanic whites and 34.9 among Hispanics

(relative risk for Hispanics 2.10, 95% confidence interval 1.35 to 3.26, p =

0.001). The age-adjusted incidence rates among men and women are not

significantly different in either ethnic group. Conclusion: The incidence of

spontaneous ICH among Hispanic residents of Bernalillo County, NM, is

approximately twice that among non- Hispanic whites. The reasons for this

difference require further investigation



Keywords: ALCOHOL-USE/BLACKS/cerebrovascular

disease/CEREBROVASCULAR-DISEASE/Hispanics/intracerebral

hemorrhage/prevention/RISK-FACTORS/STROKE/stroke prevention



Leibson, C.L., Hu, T., Brown, R.D., Hass, S.L., OFallon, W.M. and Whisnant, J.P.

(1996), Utilization of acute care services in the year before and after first stroke:

A population-based study. Neurology, 46 (3), 861-869.



Abstract: There is a need for accurate population-based data on the utilization of medical

resources after stroke. The present study used the Rochester Stroke Registry to

identify all Rochester, Minnesota residents with confirmed first stroke

(hospitalized and nonhospitalized) during the period of 1987 to 1989 (n = 292).

Events were categorized by type of stroke and assigned Rankin severity.

Inpatient and outpatient acute care activity for the 12 months before and after

stroke for each individual were obtained from billing tapes provided by Mayo

Clinic, Olmsted Medical Group, and affiliated hospitals. These providers account

for >95% of acute care received by Rochester residents. The results showed that

despite high poststroke mortality, total charges in the year after stroke were 3.4

times those for the previous year. Although greater than 50% of utilization in the

year poststroke occurred within the first 30 days, mean monthly charges for acute

care remained significantly above prestroke levels for up to 5 months after the

event. Poststroke charges per person-day of follow-up were significantly higher

for individuals who were hospitalized for the event, who had subarachnoid

hemorrhage, whose stroke occurred after admission to the hospital for another

reason, and who died within 7 days. Significantly lower poststroke charges were

evident for persons with mild cerebral infarctions and persons whose stroke

occurred in a nursing home. Neither prestroke utilization, age category, nor sex

were predictive of poststroke charges. The unique population-based data

presented here have important implications for efforts toward stroke prevention,

intervention, and cost containment



Keywords: hemorrhage/INCIDENCE

RATES/mortality/prevention/RECORD/severity/stroke/stroke prevention



Miller, V.T., Pearce, L.A., Feinberg, W.M., Rothrock, J.F., Anderson, D.C. and Hart,

R.G. (1996), Differential effect of aspirin versus warfarin on clinical stroke types

in patients with atrial fibrillation. Neurology, 46 (1), 238-240.



Abstract: The Stroke Prevention in Atrial Fibrillation II study compared the efficacy and

safety of aspirin and warfarin in patients with atrial fibrillation. Three

neurologists, blinded to patient therapy, categorized the pathophysiology of

ischemic strokes that occurred in the trial based on predetermined clinical criteria.

Upon analyzing the patients being treated with these two drugs, warfarin proved

significantly more effective than aspirin in preventing cardioembolic strokes (p =

0.005) and strokes of uncertain pathophysiology (p = 0.01). There was no

significant difference in the efficacy for prevention of noncardioembolic strokes



Keywords: aspirin/atrial fibrillation/fibrillation/prevention/safety/stroke/warfarin



Holloway, R.G., Witter, D.M., Lawton, K.B., Lipscomb, J. and Samsa, G. (1996),

Inpatient costs of specific cerebrovascular events at five academic medical

centers. Neurology, 46 (3), 854-860.



Abstract: We estimated the hospital costs for patients with different cerebrovascular

events and applied patient and administrative variables to explain the variance of

the cost estimates with particular attention to the relationship between patient age

and cost. The study sample was drawn from an administrative data set of all

hospital discharges from five academic medical centers for the 1992 calendar

year. Using International Classification of Diseases (ICD-9-CM) primary

diagnosis codes, cases were classified into cerebrovascular subgroups:

subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), ischemic

cerebral infarction (ICI), and transient ischemic attack (TIA). The ICD-9-driven

data file was supplemented with billing data containing inpatient charges

reported in UB-82 format. Costs were imputed by applying Medicare

charge-to-cost ratios and regional wage adjustments to the billing data. We

estimated relationships between inpatient costs and a number of demographic

and administrative variables. A statistically significant difference was found

between cerebrovascular subgroups for both the mean cost per discharge (p 18 to 45 years were

identified from the Indiana University and Northwestern University Young

Adults Stroke Registries. Validated criteria were used to subtype ischemic stroke

as atherothrombotic (AT), cardioembolic (CE), small-vessel (SV), other

determined cause, or unknown cause. Ninety-two children and 116 young adults

were identified. Stroke subtypes in children/young adults (percentages) were as

follows: AT 0/16 (p 65 years, 3.7; 95%

CI, 1.1 to 12.3), and the intensity of oral anticoagulation (RR, 1.8 for each 0.5

international normalized ratio [INR] unit increase; 95% Cl, 1.5 to 2.3). The

optimal intensity of oral anticoagulant therapy was 2.5 to 3.5 INR; the best target

value was 3.0 INR. Conclusion: The risk of hemorrhage with anticoagulant

therapy is high in patients with ischemic stroke of arterial origin but is mainly

confined to early use and elderly patients



Keywords: age/anticoagulant/anticoagulant

therapy/anticoagulation/bleeding/cerebral/cerebral ischemia/death/elderly/elderly

patients/hemorrhage/incidence/INR/international normalized

ratio/ischemia/ischemic/ischemic

stroke/MYOCARDIAL-INFARCTION/Netherlands/OPTIMAL

INTENSITY/oral anticoagulant therapy/oral anticoagulation/prevention/relative

risk/risk/stroke/THERAPY/thromboembolic

events/thromboembolism/treatment/use/WARFARIN



Hassaballa, H., Gorelick, P.B., West, C.P., Hansen, M.D. and Adams, H.P. (2001),

Ischemic stroke outcome - Racial differences in the trial of danaparoid in acute

stroke (TOAST). Neurology, 57 (4), 691-697.



Abstract: Objective: To determine racial differences in baseline stroke risk factors and

other measures in the Trial of ORG 10172 in Acute Stroke Therapy (TOAST).

Differences in these factors could influence response to acute stroke therapy and

overall stroke outcome. Methods: The authors compared baseline demographic,

medical, stroke, physical examination, CT, laboratory, and neurologic factors

among 292 African-American and 801 white patients who enrolled in the

TOAST study. TOAST compared danaparoid (ORG 10172) with placebo among

acute ischemic stroke patients who were treated within 24 hours of stroke onset.

Results: African-Americans were younger and more frequently had hypertension,

diabetes mellitus, congestive heart failure, and prior strokes. In addition, African-

Americans had higher mean diastolic blood pressure, more lacunar strokes, and

more severe prestroke disability. There were no significant differences between

African-Americans and white patients in outcomes at 7 days, overall number of

adverse experiences, or occurrence of serious bleeds or hemorrhagic

transformations. However, there was a trend toward a higher rate of favorable

outcomes in white patients at 7 days. There was no significant difference in very

favorable outcome at 3 months between African-American and white patients,

but significantly more white patients had favorable outcome at 3 months.

Conclusion: Although African-Americans possess a number of factors that

should predict higher rates of poor stroke outcome after acute therapy, they have

the capacity to respond similarly to white patients after acute stroke therapy.

Perhaps younger age and presence of lacunar infarction are stronger predictors of

good outcomes than was appreciated previously



Keywords: acute/acute ischemic stroke/acute stroke/acute stroke therapy/African

American/African

Americans/AFRICAN-AMERICANS/age/ATRIAL-FIBRILLATION/blood

pressure/congestive heart failure/CT/diabetes/diabetes mellitus/diastolic blood

pressure/disability/ETHNIC-DIFFERENCES/heart/heart

failure/hypertension/infarction/ischemic/ischemic stroke/lacunar

infarction/medical/NORTHERN

MANHATTAN/ORG-10172/outcome/POPULATION/PREDICTORS/PREVEN

TION/PROGNOSIS/racial differences/risk/risk factors/SEVERITY/stroke/stroke

outcome/therapy/TICLOPIDINE/TOAST/trial



Muller, T.H. (2001), Inhibition of thrombus formation by low-dose acetylsalicylic acid,

dipyridamole, and their combination in a model of platelet-vessel wall interaction.

Neurology, 57 (5), S8-S11.



Abstract: Effects of low-dose acetylsalicylic acid (ASA, 50 mg/day), dipyridamole

(sustained-release preparation 400 mg/day), and their combination were

investigated in a model of human platelet-vessel wall interaction. In a

randomized, double-blind clinical pharmacology trial in 96 healthy subjects, the

inhibition of mural platelet thrombus was measured ex vivo using blood samples

collected both before and 2 hours after a 3.5-day treatment with ASA,

dipyridamole, ASA combined with dipyridamole, or placebo. Both the size and

the number of platelet thrombi adherent to a thrombogenic matrix after a 15-

minute flow experiment were identified by automated fluorescence microscopy.

ASA treatment alone reduced the mean size of all thrombi by about 45%, and

dipyridamole alone achieved an approximate 17% reduction in the mean size of

all thrombi. The combination of both agents had an additive effect. Formation of

the subpopulation of very large thrombi was reduced by ASA and dipyridamole

to a similar extent, with their combination producing an effect at least twice as

strong as that witnessed in a single treatment. These results suggest that ASA and

dipyridamole affect platelet thrombus growth by different mechanisms of action.

These findings provide the pharmacologic rationale for the combination of ASA

(suppressing the synthesis of prothrombotic thromboxane A(2)) and

dipyridamole (by feedback inhibition of platelet activation via local

accumulation of adenosine) as a highly effective and safe combination for

secondary prevention of stroke. They are consistent with the clinical findings of

the Second European Stroke Prevention Study (ESPS-2). In this large trial, the

addition of dipyridamole (400 mg/day in a sustained-release preparation) to

aspirin (50 mg/day) doubled the efficacy of aspirin in the secondary prevention

of stroke without increasing the risk for bleeding



Keywords: acetylsalicylic

acid/activation/ADENOSINE/aspirin/bleeding/combination/dipyridamole/fluores

cence microscopy/formation/Germany/human/pharmacology/platelet/platelet

activation/prevention/randomized/risk/secondary/secondary

prevention/stroke/thrombus/treatment/trial



Catella-Lawson, F. (2001), Vascular biology of thrombosis - Platelet-vessel wall

interactions and aspirin effects. Neurology , 57 (5), S5-S7.



Abstract: The antithrombotic effect of aspirin has long been recognized, and

administration of low doses (80-60 mg/day) for the prevention of ischemic

events in patients with coronary artery disease (CAD) is now generally

considered to be routine practice. The action of aspirin derives mostly from the

selective inhibition of cyclo-oxygenases (Cox). These enzymes (Cox-1 and

Cox-2) catalyze the synthesis of eicosanoids, which play an important part in

platelet-vessel wall interactions. Cox-1 catalyzes the synthesis of thromboxane

A(2), (Tx-A(2)), which causes platelet activation, vasoconstriction, and smooth

muscle proliferation. Tx-A(2) levels are elevated in conditions associated with

platelet activation, including unstable angina and cerebral ischemia. Conversely,

Cox-2 controls the synthesis of prostacyclin (PGI(2)), a local platelet regulator

with an effect opposite to that of Tx-A(2). PGI(2), is produced as a compensatory

response to increases in Tx-A(2) during ischemic events. Aspirin is a more

potent inhibitor of Cox-1 than of Cox-2, unlike other non-steroidal

anti-inflammatory drugs (NSAIDs), which have limited selectivity. Aspirin at

low doses selectively inhibits the formation of Tx-A(2) without inhibiting the

basal biosynthesis of cardioprotective PGI(2),. Furthermore, aspirin causes

complete enzyme inhibition, without the recovery of enzyme activity at trough

drug levels associated with conventional NSAIDs. The effect of aspirin in the

prevention of ischemic events has been well documented in many recent clinical

trials involving more than 50,000 patients with CAD. It is clear from these

studies that aspirin, alone or in combination with other antithrombotics,

significantly reduces the incidence of cardiovascular death, stroke, and

myocardial infarction



Keywords:

ACTIVATION/administration/angina/antithrombotic/antithrombotics/aspirin/BI

OSYNTHESIS/cardiovascular/cerebral/cerebral

ischemia/CEREBRAL-ISCHEMIA/clinical trials/combination/coronary artery

disease/CYCLOOXYGENASE-2/death/disease/drugs/formation/incidence/infarc

tion/INHIBITION/ischemia/ischemic/LOW-DOSE

ASPIRIN/muscle/myocardial/myocardial infarction/NONSTEROIDAL

ANTIINFLAMMATORY DRUGS/PHARMACOLOGY/platelet/platelet

activation/PREVENTION/smooth/STROKE/thrombosis/thromboxane

A(2)/trials/unstable angina



Fieschi, C. and Falcou, A. (2001), Advances in stroke management: Update - Keynote

address. Neurology, 57 (5), S82-S86.



Abstract: "Acute strokes are here to stay": this could be the sad conclusion after decades

of stroke research. Generalized prevention of ischemic stroke is not fully

successful. After the decline in stroke incidence observed by 1970, partly related

to better management of vascular risk factors, there has again been an increase in

stroke frequency all around the world. This phenomenon may be explained by

the lack of educational modalities for modification of lifestyle behavior, the

small impact of high-risk individual prevention strategy, and the lack of rationale

and guidelines for multiple approaches. In the meantime, the benefits of acute

intensive management of stroke have been demonstrated. There is now

considerable evidence that careful monitoring and management of general and

cerebral functions in a dedicated stroke unit or by a specialized stroke team are

superior to management in a neurologic or general ward. Currently, one way of

optimizing limited personnel resources is to connect the stroke unit of a main

hospital with peripheral hospitals via a computer network. Experts in the central

stroke unit can then make on-line evaluations of CT and ultrasound examinations

performed in the local hospital and recommend the best course of patient

management. This new approach of treating stroke as an emergency will also

require educational programs directed at the general public, general practitioners,

and primary and emergency department physicians, to teach the recognition of

stroke symptoms and the importance of treating stroke with the same urgency as

for myocardial infarction (MI)



Keywords: acute/ATRIAL-FIBRILLATION/behavior/BLOOD-

PRESSURE/cerebral/CLINICAL-PRACTICE/CT/guidelines/high

risk/hospital/hospitals/HYPERTENSION/incidence/infarction/ischemic/ischemic

stroke/lifestyle/management/monitoring/MORTALITY/myocardial/myocardial

infarction/POPULATION/PREVENTION/primary/research/risk/risk

factors/RISK-FACTORS/SECULAR TRENDS/stroke/stroke incidence/stroke

management/stroke team/stroke unit/symptoms/ultrasound/vascular/vascular

risk/vascular risk factors/WARFARIN



Wahl, A., Meier, B., Haxel, B., Nedeltchev, K., Arnold, M., Eicher, E., Sturzenegger, M.,

Seiler, C., Mattle, H.P. and Windecker, S. (2001), Prognosis after percutaneous

closure of patent foramen ovale for paradoxical embolism. Neurology, 57 (7),

1330-1332.

Abstract: The long-term risk and risk factors for recurrent embolism after percutaneous

closure of patent foramen ovale (PFO) were investigated in 152 consecutive

patients with presumed paradoxical embolism. During follow-up, the actuarial

freedom from recurrent embolism was 95.1% at 1 year, and 90.6% at 2 and 6

years. A residual shunt after percutaneous PFO closure was a predictor for

recurrence (RR 5.3; 95% CI 1.3 to 21.0; p = 0.02). Randomized trials comparing

medical treatment with percutaneous PFO closure in the prevention of recurrent

embolism are in progress



Keywords: CEREBROVASCULAR EVENTS/CRYPTOGENIC

STROKE/embolism/foramen ovale/medical/medical treatment/paradoxical

embolism/patent/patent foramen ovale/prevention/recurrence/residual/risk/risk

factors/shunt/SURGICAL CLOSURE/Switzerland/TERM RISK/treatment/trials



Catto, A.J. (2001), Genetic aspects of the hemostatic system in cerebrovascular disease.

Neurology, 57 (5), S24-S30.



Abstract: Despite considerable research into the pathogenesis of cerebrovascular disease

(CVD), acute stroke is the third most common cause of mortality in the Western

world. The clinical management of acute stroke is largely supportive, although

evidence is emerging for the benefit of early pharmacologic intervention. Even

when the benefits of these therapies are accounted for, a significant proportion of

patients remain disabled or die. Accordingly, stroke prevention is likely to offer

the most effective manner of reducing stroke incidence. However, effective

prevention depends on a reliable means of identifying and treating the risk

factors associated with stroke and possibly targeting preventive measures at

high-risk groups. Atherosclerosis is the process responsible for the development

of ischemic CVD, and evidence is accumulating to suggest that these disorders

are multifactorial, resulting from a complex series of interactions between genes

and the environment. The outward expression of the disease, or the disease

phenotype, is in part the product of gene-gene and gene- environment

interactions. Research methods harnessing molecular biology techniques,

including polymerase chain reaction (PCR) and sequencing have, in contrast to

coronary artery disease (CAD), been under-utilized when it comes to furthering

our understanding of the molecular epidemiology of CVD. This article reviews

the evidence that stroke has a genetic basis and that the hemostatic system is an

important risk factor for stroke. The genetic regulation of a number of these

hemostatic proteins is evaluated



Keywords: acute/acute stroke/BLOOD-

COAGULATION/cerebrovascular/cerebrovascular disease/COAGULATION-

FACTOR-V/COMMON POLYMORPHISM/coronary artery

disease/development/disease/England/epidemiology/FACTOR-XIII

GENE/gene/genes/genetic/high

risk/incidence/ischemic/ISCHEMIC-HEART-DISEASE/management/mortality/

MYOCARDIAL-INFARCTION/PLASMA-FIBRINOGEN

CONCENTRATION/PLASMINOGEN-ACTIVATOR

INHIBITOR-1/prevention/research/risk/risk factor/risk

factors/RISK-FACTORS/stroke/stroke incidence/stroke prevention/VENOUS

THROMBOSIS



Koennecke, H.C. and Leistner, S. (2001), Prophylactic antipyretic treatment with

acetaminophen in acute ischemic stroke: A pilot study. Neurology, 57 (12),

2301-2303.



Abstract: Fever is associated with poor outcome in acute stroke. Forty- two consecutive,

normothermic patients with acute ischemic stroke were, within 24 hours from

symptom onset, randomized to either receive 4 g acetaminophen daily (n = 20) or

matched placebo (n = 22). Fever of greater than 37.5 degreesC occurred in

36.4% of patients in the placebo group, compared with 5.0% in the

acetaminophen group (Fisher's exact test, p = 0.014). Prophylactic antipyretic

treatment with acetaminophen may be effective in the prevention of fever after

acute ischemic stroke



Keywords: acute/acute ischemic stroke/acute

stroke/Germany/HYPOTHERMIA/ischemic/ischemic

stroke/NEUROLOGY/outcome/prevention/randomized/stroke/TEMPERATURE

/treatment/USA



Dufouil, C., Kersaint-Gilly, A., Besancon, V., Levy, C., Auffray, E., Brunnereau, L.,

Alperovitch, A. and Tzourio, C. (2001), Longitudinal study of blood pressure

and white matter hyperintensities - The EVA MRI cohort. Neurology, 56 (7),

921-926.



Abstract: Objective: To investigate the relationship between baseline hypertension and

severity of white matter hyperintensities (WMH) at 4-year follow-up in a sample

of subjects aged 59 to 71 years old at entry. Methods: Subjects were participants

in the Epidemiology of Vascular Ageing study, a longitudinal study on vascular

aging and cognitive decline. At 4-year follow-up, 845 subjects had a cerebral

MRI. MRI examinations were read by a single rater to determine the severity of

WMH, ranging from absent to severe. Hypertension at each wave of the study

was defined as systolic blood pressure greater than or equal to 160 mm Hg,

diastolic blood pressure greater than or equal to 95 mm Hg, or use of

antihypertensive medication. Results: Hypertension at baseline was significantly

associated with an increased risk of having severe WMH at 4-year follow-up.

When taking into account both blood pressure levels and antihypertensive drug

intake, analysis showed that the risk of having severe WMH was significantly

reduced in subjects with normal blood pressure taking antihypertensive

medication compared with those with high blood pressure taking

antihypertensive agents. Cross-sectional relationships between hypertension and

WMH at 4-year follow-up showed that the frequency of severe WMH was

significantly higher in people who were hypertensive at both baseline and 4-year

follow-up than those who were hypertensive only at I-year follow-up.

Conclusions: Hypertension is a major risk factor for severe WMH. Subjects

taking antihypertensive drugs and who have controlled blood pressure had a

reduced risk of severe WMH. Longitudinal studies are needed to investigate

whether reduction of the development of WMH, by treatment and prevention of

hypertension, might reduce the subsequent risk of cognitive deterioration or

stroke



Keywords: aged/aging/ALZHEIMERS-DISEASE/antihypertensive

agents/antihypertensive drugs/blood pressure/BRAIN/CARDIOVASCULAR

HEALTH/cerebral/COGNITIVE FUNCTION/development/diastolic blood

pressure/drugs/FOLLOW-UP/high blood pressure/hypertension/ISOLATED

SYSTOLIC HYPERTENSION/LESIONS/longitudinal study/MRI/OLDER

ADULTS/prevention/risk/risk factor/RISK-

FACTORS/severity/STROKE/systolic blood/systolic blood

pressure/treatment/use/vascular/white matter



Demond, D.W., Moroney, J.T., Sano, M. and Stern, Y. (2002), Mortality in patients with

dementia after ischemic stroke. Neurology, 59 (4), 537-543.



Abstract: Objective: Although dementia is typically considered to be a consequence of a

variety of neurologic diseases, it can also serve as a risk factor for other adverse

outcomes. The authors investigated dementia as a predictor of long-term survival

among patients with ischemic stroke. Methods: Neurologic, neuropsychological,

and functional assessments were administered to 453 patients (mean age +/- SD,

72.0 +/- 8.3 years) 3 months after ischemic stroke. The authors diagnosed

dementia in 119 (26.3%) of the patients using modified Diagnostic and Statistical

Manual of Mental Disorders, Revised 3rd Edition, criteria requiring deficits in

memory and two or more additional cognitive domains as well as functional

impairment. Dementia as a predictor of long-term survival during up to 10 years

of follow-up was then investigated. Results: The mortality rate was 15.90 deaths

per 100 person- years among patients with dementia and 5.37 deaths per 100

person-years among nondemented patients. A Cox proportional hazards analysis

found that the relative risk (RR) of death was increased in association with

dementia (RR = 2.4; 95% CI = 1.6 to 3.4), adjusting for the following: a major

hemispheral stroke syndrome (RR = 1.4); a middle cerebral artery territory index

stroke (RR = 1.7); a Stroke Severity Scale score of greater than or equal to4,

representing more severe stroke (RR = 1.8); atrial fibrillation (RR = 1.8);

congestive heart failure (RR = 2.2); recurrent stroke occurring during follow-up

(RR = 3.9); arid demographic variables. The risk of death increased in

association with the severity of dementia, but it did not differ by dementia

subtype. Conclusions: Dementia is a significant independent risk factor for

reduced survival after ischemic stroke, adjusting for other recognized predictors

of mortality. The authors hypothesize that patients with dementia are at an

elevated risk of mortality because of their increased burden of cerebrovascular

disease, a tendency toward undertreatment for stroke prophylaxis among

clinicians, or patient noncompliance with treatment regimens

Keywords: 5-YEAR FOLLOW-UP/age/ALZHEIMERS-DISEASE/atrial/atrial

fibrillation/cerebral/cerebral artery/cerebrovascular/cerebrovascular

disease/congestive heart

failure/DEATH/dementia/disease/diseases/fibrillation/heart/heart

failure/INCIDENT DEMENTIA/ischemic/ischemic stroke/LONG-TERM

SURVIVAL/middle cerebral artery/mortality/mortality rate/MULTI-INFARCT

DEMENTIA/POPULATION/predictors/prophylaxis/recurrent stroke/relative

risk/risk/risk factor/RISK-FACTORS/SECONDARY

PREVENTION/severity/stroke/survival/treatment/VASCULAR DEMENTIA



Herman, S.T. (2002), Epilepsy after brain insult - Targeting epileptogenesis. Neurology,

59 (9), S21-S26.



Abstract: Seizures and epilepsy are common sequelae of acute brain insults such as

stroke, traumatic brain injury, and central nervous system infections. Early, or

acute symptomatic, seizures occur at the time of the brain insult and may be a

marker of severity of injury. A cascade of morphologic and biologic changes in

the injured area over months to years leads to hyperexcitability and

epileptogenesis. After a variable latency period, late unprovoked seizures and

epilepsy occur. The latent period may offer a therapeutic window for the

prevention of epileptogenesis and the development of unprovoked seizures and

epilepsy. Administration of anticonvulsant drugs following acute brain insults

has thus far failed to prevent late epilepsy. Proper choice of disease models and

target populations will aid in the development of putative antiepileptogenic

agents. The incidence, timing, and pathophysiology of common epileptogenic

brain injuries, including head trauma, cerebrovascular disease, brain tumors,

neurosurgical procedures, neurodegenerative conditions, status epilepticus, and

febrile seizures, are reviewed



Keywords: acute/brain/brain injury/central nervous

system/cerebrovascular/cerebrovascular

disease/development/disease/drugs/EPIDEMIOLOGY/epilepsy/FIRST

STROKE/HEAD-INJURY/HEMORRHAGE/incidence/pathophysiology/POPU

LATION/POSTTRAUMATIC

SEIZURES/PREVALENCE/PREVENTION/RISK/severity/status/STATUS

EPILEPTICUS/stroke/timing/traumatic brain injury



Chaturvedi, S. and Fessler, R. (2002), Angioplasty and stenting for stroke prevention -

Good questions that need answers. Neurology, 59 (5), 664-668.



Abstract: Extracranial and intracranial angioplasty and stenting of the cerebral vessels

are being performed more frequently. One clinical trial demonstrated equivalent

outcomes between extracranial carotid angioplasty and carotid endarterectomy,

but the results in both groups were suboptimal. Concerns remain about the

iatrogenic stroke rate after angioplasty, especially for asymptomatic patients.

Angioplasty, with or without stent placement, also offers a potential new

therapeutic approach for patients with intracranial stenosis and vertebrobasilar

lesions, although these procedures have been performed in uncontrolled fashion



Keywords: angioplasty/ARTERY-STENOSIS/asymptomatic/carotid/carotid

angioplasty/CAROTID ENDARTERECTOMY/cerebral/cerebral

vessels/CEREBRAL- ISCHEMIA/clinical trial/endarterectomy/INITIAL

EXPERIENCE/INTRACRANIAL

STENOSIS/PLACEMENT/prevention/stenosis/stent/stent

placement/stenting/stroke/stroke prevention/SURGERY/TRANSLUMINAL

ANGIOPLASTY/TRIAL/vessels



Coull, B.M., Williams, L.S., Goldstein, L.B., Meschia, J.F., Heitzman, D., Chaturvedi,

S., Johnston, K.C., Starkman, S., Morgenstern, L.B., Wilterdink, J.L., Levine,

S.R. and Saver, J.L. (2002), Anticoagulants and antiplatelet agents in acute

ischemic stroke - Report of the Joint Stroke Guideline Development Committee

of the American Academy of Neurology and the American Stroke Association (a

division of the American Heart Association). Neurology, 59 (1), 13-22



Keywords: acute/acute ischemic stroke/antiplatelet/antiplatelet

agents/ASPIRIN/CONTROLLED TRIAL/ischemic/ischemic

stroke/MOLECULAR-WEIGHT

HEPARIN/NEUROLOGY/PREVENTION/stroke



Reeves, M.J., Hogan, J.G. and Rafferty, A.P. (2002), Knowledge of stroke risk factors

and warning signs among Michigan adults. Neurology, 59 (10), 1547-1552.



Abstract: Objective: To assess the knowledge of stroke risk factors and warning signs in

a representative statewide sample of Michigan adults. Methods: Respondents to

the 1999 Michigan Behavioral Risk Factor Survey, a random-digit-dialed

statewide survey of >2,500 adults, were asked to report up to three risk factors

and warning signs-for stroke. Predictors of inadequate knowledge (defined as not

reporting any correct responses) of stroke risk factors and warning signs were

identified using multiple logistic regression. Results: Eighty percent reported at

least one correct risk factor for stroke, and 28% reported three. The most

frequently mentioned risk factors were hypertension (32%), smoking (29%), and

physical inactivity (26%). Sixty-nine percent reported at least one correct

warning sign of stroke, but only 14% reported three. The most frequently

mentioned warning signs were sudden weakness or numbness (46%) and sudden

slurred speech, disorientation, or difficulty understanding (30%). Predictors for

inadequate knowledge of both stroke risk factors and warning signs were similar

and included age, race, sex, education, hypertension, and smoking. Conclusions:

Knowledge of stroke risk factors and warning signs was moderate at best. One in

five respondents was not aware of any stroke risk factors, and almost one in three

was not aware of any stroke warning signs. Stroke knowledge was poorest

among groups that have the highest risk of stroke

Keywords: adults/age/AWARENESS/EDUCATION/hypertension/ISCHEMIC

STROKE/knowledge/multiple logistic

regression/PERCEPTIONS/POPULATION/PREVENTION/race/risk/risk

factor/risk factors/sex/smoking/stroke/sudden/survey/SYMPTOMS



Ruland, S., Raman, R., Chaturvedi, S., Leurgans, S. and Gorelick, P.B. (2003),

Awareness, treatment, and control of vascular risk factors in African Americans

with stroke. Neurology, 60 (1), 64-68.



Abstract: Objective: To investigate control of risk factors in African American patients

with previous stroke. Methods: The baseline history, physical examination, and

laboratory data for 1,086 subjects enrolled in the African American Antiplatelet

Stroke Prevention Study from 1995 to 1999 were studied. The level of awareness,

pharmacologic treatment, and control of diabetes mellitus (casual plasma glucose

level greater than or equal to200 mg/dL), hypertension (blood pressure greater

than or equal to140/90 min Hg), and hypercholesterolemia (serum total

cholesterol level greater than or equal to240 mg/dL) were determined. Results:

Forty percent of subjects reported a history of diabetes mellitus or use of diabetic

medication, and 2% of the remaining subjects had a serum glucose level of

greater than or equal to200 mg/dL. Of those subjects known to be diabetic, 33%

had a serum glucose level of greater than or equal to200 mg/dL. A history of

hypertension or use of antihypertensive medication was reported in 87% of

subjects, and 48% of the remaining subjects were found to have a blood pressure

of greater than or equal to140/90 min Hg on exam. Of those subjects known to

be hypertensive by history, 73% were on antihypertensive medication, but only

30% of the treated subjects had a blood pressure under 140/90 min Hg. A history

of hypercholesterolemia or use of a lipid-lowering agent was reported in 40% of

subjects, and 24% of the remaining subjects had a cholesterol level of greater

than or equal to240 mg/dL. Use of a lipid-lowering agent was reported in 43% of

subjects known to be hypercholesterolemic, and 38% of the

hypercholesterolemic subjects had a cholesterol level of 2:240 mg/dL.

Conclusion: Inadequate rates of awareness and control of cardiovascular disease

and stroke risk factors are seen in a clinical trial of African American stroke

patients and are comparable with those of previously published reports



Keywords: 3RD NATIONAL-HEALTH/African American/African

Americans/ATHEROSCLEROSIS RISK/awareness/blood

pressure/cardiovascular/cardiovascular disease/CHOLESTEROL/clinical

trial/control/diabetes/diabetes

mellitus/disease/glucose/history/hypercholesterolemia/HYPERTENSION/ISCH

EMIC STROKE/lipid lowering/lipid-lowering/NEUROLOGY/NORTHERN

MANHATTAN STROKE/NUTRITION EXAMINATION

SURVEY/PREVALENCE/PREVENTION/risk/risk factors/serum/stroke/stroke

patients/stroke risk factors/treatment/trial/US

POPULATION/USA/use/vascular/vascular risk/vascular risk factors

Gururaj, G., Satishchandra, P. and Subbakrishna, D.K. (1995), Epidemiologic Correlates

of Stroke Mortality - Observations from A Tertiary Institution. Neurology India,

43 (1), 29-34.



Abstract: Factors associated with stroke were studied by a combination of morbidity and

mortality analysis for the period 1986 to 1990, Strokes constituted 6.5-7.8

percent of total neurological registration over a five year period at NIMHANS,

Bangalore. The morbidity pattern revealed that stroke increases with increasing

age and was predominantly constituted by ischaemic strokes (73.1 percent),

Stroke in the young constituted 27.8 per cent of cas es, Analysis of one year

mortality series revealed that 32.5 percent of deaths were in the age group of less

than 40 years, Hypertension, alcoholism and smoking were the major risk factors

associated with stroke mortality to the extent of 32 percent, 12 percent and 11

percent of cases respectively, Aneurysms contributed for 10.0 percent of total

deaths among the various other conditions associated with stroke, The case

fatality rate was in the order of 25.1 percent, The present report emphasizes the

need for well designed analytical studies for identifying and qualifying risk

factors along with the focus on primary preventive measures through risk

approach for preventing morbidity and mortality from stroke in India



Keywords: case

fatality/EPIDEMIOLOGY/INDIA/MORBIDITY/MORTALITY/PREVENTION

/risk/RISK FACTORS/smoking/STROKE/YOUNG



Nagaraja, D., Gurmurthy, S.G., Taly, A.B., Subbakrishna, K. and Rao, B.S.S. (1998),

Risk factors for stroke: Relative risk in young and elderly. Neurology India, 46

(3), 183-184.



Abstract: Stroke is a leading cause of morbidity and mortality. A significant proportion

of stroke victims in India are below the age of 40 years and may have specific

risk factors. 101 patients (42 less than 40 years of age) of ischaemic stroke were

studied at NIMHANS to estimate the relative risk of various contributing factors.

Hypercholesterolaemia, hyperglycaemia and hypertension were more common in

elderly group, while smoking, alcohol and tobacco abuse were more prevalent in

younger age group (relative risk 1.2, 1.9 and 1.5 respectively), A better

understanding of these risk factors may play a key role in the prevention of

stroke in young



Keywords:

age/alcohol/CEREBROVASCULAR-DISEASE/elderly/hypertension/INDIA/mo

rbidity/mortality/prevention/relative risk/risk/risk

factors/smoking/stroke/tobacco/tobacco abuse/young stroke



Lechner, H. and Samastur, M. (1997), The Graz scale for the evaluation of high stroke

risk among normal volunteers. Neurology Psychiatry and Brain Research, 5 (1),

9-14.

Abstract: To identify those individuals in populations at high risk of stroke, a statistical

model has been developed. From a cohort of 1950 volunteers and 512 ischemic

stroke victims utilizing a case control design was developed after the participants

were matched for age and sex. For both groups equal information was available

on the association of well and less-well established cerebrovascular risk factors,

utilizing relevant laboratory data, and results of Doppler-Duplex scanning, EEG

and EGG. From the cohort 512 volunteers and patients were selected for the case

control design. The statistic model showed a specificity of 82% for recognizing

stroke and a sensitivity of 80.1% for detecting normal volunteers. Utilizing a

numeric scale ranging from 0-100, the population could be grouped according to

severity of its cerebrovascular risk for stroke. Utilizing this numeric scale, new

and more sensitive dimensions mere introduced for the evaluation of

cerebrovascular risk factors for stroke



Keywords:

age/BRAIN/cerebrovascular/control/EEG/evaluation/INFARCTION/ischemic/is

chemic stroke/POPULATION/PREVENTION/risk/risk

factors/severity/sex/stroke



Kornhuber, H.H. (1998), Prevention of cerebral microangiopathy and stroke. Neurology

Psychiatry and Brain Research, 5 (4), 205-208.



Abstract: Most cases of stroke are embolic and originate from the heart, not only

because of arrhythmia, but mainly from microangiopathy of the valves and aorta;

therefore hypertension is the dominant risk factor. In younger women nowadays

the combination of hormonal contraception and smoking is a factor. Stroke is

striking, but microangiopathy is more common. The metabolic syndrome

associated with abdominal obesity (insulin resistance, hyperinsulinemia,

hypertriglyceridemia and high blood pressure), estrogen deficiency after

menopause and old age are the main causes of microangiopathy. The main cause

of abdominal obesity and the metabolic syndrome is not caloric overnutrition,

but daily "normal" alcohol consumption. The obese on average eat less calories

than the lean. The fattening effect of alcohol is toxic, not caloric. A

cardioprotective effect of "normal" alcohol does not exist. The main points in

preventing microangiopathy and stroke are treatment of hypertension, estrogen

replacement, a "mediterranean" diet with fish, vegetables, green salads, fruit,

olive oil - and largely to avoid alcohol



Keywords: age/alcohol/ALCOHOL/blood pressure/BRAIN/cerebrovascular

disease/CORONARY HEART-DISEASE/diet/DIET/heart/high blood

pressure/hypertension/insulin

resistance/menopause/MORTALITY-RATES/obesity/OBESITY/prevention/risk

/smoking/stroke/treatment/valves/women



Lechner, H. and Hadjiev, D. (1998), Comparative epidemiological study on

cerebrovascular risk factors among Austrian and Bulgarian populations.

Neurology Psychiatry and Brain Research, 6 (3), 141-146.

Abstract: Cross-sectional and longitudinal population-based epidemiological studies

devoted to the cerebrovascular risk factors have been carried out in different

countries. Geographic variations in the risk-factor prevalence have been reported.

It has been found that hypertension, hypercholesterolaemia, overweight and

cigarette smoking are unevenly distributed in different regions of Europe and do

not share a common distribution pattern. It seems that the variations in stroke

incidence and mortality rates are due mainly to differences in the prevalence of

hypertension. Austrian-Bulgarian comparative population-based cross-sectional

epidemiological study was designed to assess the frequency of the

cerebrovascular risk factors among urban population of Austria and Bulgaria. For

this purpose a common protocol was used. Volunteers without clinical signs or

symptoms of cerebrovascular disease aged 49 to 74 years were enrolled in the

study. An uniform structured questionnaire, physical examinations, ECG and

battery of laboratory tests were employed. Hypertension was significant more

frequent among bulgarian population (61,2%) than among austrian population

(40,2%). The prevalence of cardiac abnormalities, cigarette smoking and

diabetes mellitus did not show significant differences between the two

populations. The less well- documented risk factor hypercholesterolaemia was

found in 41,7% among bulgarian population and in 31,7% among austrian cohort.

However the total cholesterol/HDL-cholesterol ratio was nearly the same among

the two populations. The concentrations of lipoprotein (a) were higher among

bulgarian townspeople. Physical inactivity was found to be more frequent among

austrian population, whereas elevated haematocrit prevailed among bulgarian

volunteers. It is worthy of note that the risk factor combinations were more

frequent among bulgarian population. The data obtained suggest that different

patterns of risk factors may exist. The high incidence and mortality rates from

stroke in Bulgaria could be explained by the high prevalence of hypertension and

excess salt intake. No doubt population-based epidemiological studies on the

cerebrovascular risk factors will contribute to elaboration of multimodal stroke

prevention programs



Keywords: aged/Austria/BRAIN/CASE-FATALITY/cerebrovascular/cerebrovascular

disease/cerebrovascular risk factors/cigarette

smoking/CIGARETTE-SMOKING/diabetes/diabetes mellitus/geographic

variations/haematocrit/hypertension/incidence/ISCHEMIC

STROKE/MORTALITY/PHYSICAL-ACTIVITY/population/population-based/

prevalence/PREVENTION/risk/risk factor/risk

factors/salt/smoking/stroke/STROKE INCIDENCE/stroke mortality/stroke

prevention/TRENDS/urban



Felber, S. and Fazekas, F. (1995), Magnetic-Resonance in Acute Stroke and Secondary

Prevention. Neuropsychiatrie, 9 (2), 56-61.



Abstract: Presently, magnetic resonance techniques are considered to supplement

computerized tomography in the diagnosis of acute stroke, because magnetic

resonance is not arbitrarily available and more expensive. However, during the

last decade, magnetic resonance has shown to be superior to computerized

tomography in virtually all features of acute stroke diagnosis. This includes the

early detection of ischemia and higher sensitivity towards lesions in the posterior

fossa, but also the reliable delineation of intracranial hemorrhage. In addition,

magnetic resonance is a multimodal technique and enables morphologic

diagnosis together with assessment of vascular pathology, diffusion perfusion

and metabolism within a single examination. These methods have already

become standard for stroke research in animals and are now increasingly

available at clinical scanners. In future, the primary use of computerized

tomography in stroke diagnosis will be justified only in a surrounding of

therapeutic nihilism. If therapeutic strategies, that have been shown successful in

animals, should be transferred to the treatment of patients, multimodal magnetic

resonance facilities have to be made available for the diagnosis of acute stroke in

humans



Keywords: BRAIN/diagnosis/hemorrhage/ischemia/MAGNET

RESONANCE/PERFUSION/SPECTROSCOPY/STROKE/TOMOGRAPHY/tre

atment/vascular



Niederkorn, K. and Schmidauer, C. (1995), The Significance of Neurosonographic

Methods in the Acute Treatment and Prevention of Stroke. Neuropsychiatrie, 9

(2), 49-51.



Abstract: In acute focal cerebrovascular events the rapid examination (within 24 hours)

of the extracranial brain arteries by means of Doppler and duplex sonography is

indicated to exclude high- grade stenoses and/or occlusions of these vessels.

Clinical symptoms suggesting occlusion of the middle cerebral artery of the

basilar artery with the potential need for cerebral thrombolysis require urgent

transcranial Doppler sonography. TCD is also indicated if vasospasm following

subarachnoid hemorrhage is suspected. Due to these facts stroke centers should

have 24-hour availability of the neurosonographic methods. These methods are

also a basic requirement for the evaluation of the vessels wall status of the brain

supplying arteries in the primary and secondary prevention of stroke



Keywords: CEREBRAL THROMBOLYSIS/DOPPLER SONOGRAPHY/DUPLEX

SONOGRAPHY/evaluation/focal/hemorrhage/prevention/RISK-FACTORS/seco

ndary prevention/STROKE/STROKE PREVENTION/SUBARACHNOID

HEMORRHAGE/thrombolysis/TRANSCRANIAL DOPPLER

SONOGRAPHY/vasospasm



Niederkorn, K., Podreka, I., Rumpl, E. and Wege, H. (2000), Carotid endarterectomy.

Neuropsychiatrie, 14 (1), 23-29.



Abstract: An annual stroke incidence of 1.9 - 4% has been reported for asymptomatic

carotid stenosis of more than 60% diameter reduction. In the ACAS

(Asymptomatic Carotid Artery Stenosis Study) trial the risk for stroke and death

over 5 years could be reduced from 11% to 5.1% by performing carotid

endarterectomy (CEA) in patients with greater than 60% Internal Carotid Artery

(ICA) stenosis. The existence of such a lesion, however, should not lead to a

mandatory CEA. Additional factors like degree of stenosis of more than 85%,

high vascular risk, clinically silent ipsilateral cerebral infarcts and rapid increase

of the degree of stenosis may be helpful to identify patients who are likely to

benefit from CEA. In symptomatic carotid stenosis with a diameter reduction of

70% and more, the results of the NASCET (North American Symptomatic

Carotid Endarterectomy Trial) study and of the ECST (European Carotid Surgery

Trial) study prove a significant risk reduction by CEA in relation to the

increasing degree of stenosis. This benefit is consistent over 8 years. The

NASCET results show that CEA allows a 10.1% absolute risk reduction over 5

years for 50 - 69% ICA stenosis. The indication for surgery in this group should

be established on the basis of the individual case. Patients with less than 50%

ICA stenosis did not benefit from surgery. In a recently published review of 2048

interventions, the method of percutaneous transluminal angioplasty with stenting

(PTAS) has a technical success rate of 98.6%. The morbidity was 4.4%, the

mortality 1.37%, the rate of re- stenosis at 6 months 4.8%. Prospective and

randomized trials are needed to evaluate this new method in comparison with

CEA. Until these multicenter trials are started. local series should be performed

in well defined indications on the basis of an interdisciplinary protocol approved

by the local ethics committee



Keywords: absolute risk/ANGIOGRAPHY/angioplasty/ARTERY

STENOSIS/asymptomatic/ASYMPTOMATIC PATIENTS/Austria/BALLOON

ANGIOPLASTY/carotid/carotid endarterectomy/carotid

stenosis/cerebral/death/endarterectomy/incidence/indication for

surgery/morbidity/mortality/North American/percutaneous transluminal carotis

angioplasty/PREVENTION/randomized/randomized

trials/review/risk/stenosis/STENT PLACEMENT/stenting/STROKE/stroke

incidence/surgery/trials/vascular/with stenting (PTAS)



Schmidt, R., Willeit, J. and Brainin, M. (2000), Stroke: Protective factors.

Neuropsychiatrie, 14 (1), 3-11.



Abstract: We reviewed the current literature on protective factors for stroke. Physical

activity and salt restriction have a proven effect with data for salt restriction

existing for stroke mortality only. There is evidence from observational but not

interventional studies for protective effects of fruit- and vegetable-rich nutrition,

optimal vitamin B-6, B-12 and folic acid plasma levels as well as

mild-to-moderate alcohol consumption. Cholesterol-lowering diet and drugs

other than statins yielded no reduction in stroke risk. Statins reduce strokes in

patients with myocardial infarction, yet interventional trials with stroke as the

primary outcome measure are still pending. Similar evidence exists in terms of

postmenopausal hormone replacement and blood donation in order to reduce the

body's iron pool. Vitamin E and beta-caroten supplements failed to decrease the

incidence of strokes in large trials. Similar findings have been reported for the

general use of acetylsalicylic acid. However, metaanalyses indicate that

acetylsalicylic acid may be beneficial in high- risk groups

Keywords: acetylsalicylic acid/ACUTE

MYOCARDIAL-INFARCTION/alcohol/Austria/CARDIOVASCULAR-DISEA

SE/CORONARY HEART-DISEASE/diet/drugs/fruit/high risk/HORMONE

REPLACEMENT THERAPY/incidence/infarction/MIDDLE-AGED

MEN/mortality/myocardial/myocardial

infarction/nutrition/outcome/PHYSICAL-ACTIVITY/PLASMA

HOMOCYSTEINE/postmenopausal hormone replacement/primary/primary

prevention/protection/protective factors/risk/RISK

FACTOR/salt/statins/stroke/stroke

mortality/trials/use/VASCULAR-DISEASE/VITAMIN-C



Horner, S., Schmidbauer, M., Schnaberth, G., Weiss, S., Niederkorn, K., Schmidt, R.,

Homann, C.N., Ott, E. and Hartung, H.P. (2000), Antiplatelet therapy in

secondary ischemic stroke prevention. Neuropsychiatrie, 14 (1), 12-22.



Abstract: The primary purpose of this overview is to provide an update on antiplatelet

drugs evaluated in clinical trials in order to evaluate treatment strategies in

secondary stroke prevention. Acetylsalicylic acid (ASS) has been the standard

reference agent in cerebrovascular disease and decreases events up to 25%.

High-dose versus low-dose trials confirmed the lack of dose-response

relationship. Based on the results of ESPS-2 the lowest effective dose of ASS is

50 mg daily. Impressive beneficial results have been reported from the ESPS-2

concerning the role of a combination therapy with a relative risk reduction (RR)

of 37% for the outcome of stroke with ASS plus dipyridamole (50/400 mg) in

comparison to 18% for ASS (50 mg) alone. TASS confirmed a higher benefit of

ticlopidine versus ASS with a RR of 21% (p = 0.024) for TIA and stroke,

however, ticlopidine therapy was associated with neutropenia. CAPRIE

compared the efficacy of clopidogrel (75 mg) versus ASS (325 mg) for a cluster

of ischemic events and showed a modest increase in effectiveness, an RR of 8.7

(p = 0.043) for clopidogrel. Tn summary, ASS (50 - 325 mg daily) can be

suggested for first choice in patients with primary stroke. An alternative to ASS

is ASS plus dipyridamole in patients with TIA, stroke recurrence or

thienopyridine intolerance. Clopidogrel is suggested in patients with combined

atherosclerotic diseases and replaces ticlopidine when ASS has failed or is not

tolerated



Keywords: ACETYLSALICYLIC-ACID/antiplatelet/antiplatelet agents/antiplatelet

drugs/ANTITHROMBOTIC

THERAPY/ASS/ATRIAL-FIBRILLATION/Austria/CEREBRAL-ISCHEMIA/c

erebrovascular/cerebrovascular disease/clinical

trials/CLOPIDOGREL/combination therapy/CONTROLLED

TRIAL/DIPYRIDAMOLE/disease/diseases/DRUGS/ischemic/ischemic

stroke/LOW-DOSE

ASPIRIN/neutropenia/outcome/prevention/primary/recurrence/relative

risk/risk/secondary stroke prevention/stroke/stroke prevention/stroke

recurrence/therapeutic guidelines/therapy/TIA/TICLOPIDINE/treatment/trials

Shenal, B.V., Harrison, D.W. and Demaree, H.A. (2003), The neuropsychology of

depression: A literature review and preliminary model. Neuropsychology Review,

13 (1), 33-42.



Abstract: Neurcipsychological research provides a useful framework to study emotional

problems, such as depression, and their correlates. This paper reviews several

prominent neuropsychological theories. Functional neuroanatomical systems of

emotion and depression are reviewed, including those that describe cerebral

asymmetries in emotional processing. Following the review, a model that is

composed of three neuroanatomical divisions (left frontal, right frontal, and right

posterior) and corresponding neuropsychological emotional sequelae within each

quadrant is presented. It is proposed that dysfunction in any of these quadrants

could lead to symptomatology consistent with a diagnosis of depression. The

proposed model combines theories of arousal, lateralization, and functional

cerebral space and lends itself to scientific methods of investigation. Accordingly,

research, prevention, and treatment programs in accordance with the proposed

model may promote an improved understanding of the neurcipsychological

mechanisms involved in depression



Keywords: AFFECTIVE STYLE/ASYMMETRY/cerebral/CEREBRAL

BLOOD-FLOW/correlates/depression/diagnosis/emotion/EMOTION/EXPRESS

ION/FACIAL AFFECT PERCEPTION/lateralization/literature

review/mechanisms/NEW-YORK/POSTSTROKE MOOD

DISORDERS/prevention/research/review/SEX-DIFFERENCES/STROKE

PATIENTS/theory/treatment/UNILATERAL BRAIN-DAMAGE/USA



Benjamin, M.S., Gillams, A.R. and Carter, A.P. (1997), Carotid MRA - What

advantages do the turbo field-echo and 3D phase-contrast sequences offer?

Neuroradiology, 39 (7), 469-473.



Abstract: Our purpose was to investigate some of the newer MR angiography (MRA)

techniques for studying the carotid arteries. Forty-two arteries in seven

asymptomatic, healthy volunteers were studied using five MRA sequences: two

conventional time-of-flight sequences, 2D time-of-flight (2DTOF) and 3D

time-of-flight (3DTOF); 2D and 3D magnetisation-prepared, segmented time-of-

flight sequences (2DTFE and 3DTFE); and a 3D phase contrast angiography

(3DPCA) sequence. A protocol that could be realistically employed in a routine

clinical situation was chosen. 2DTOF had significantly (P 35 percent

(P=0.01). The use of thrombolytic agents and captopril had no significant effect

on the risk of stroke. Conclusions During the five years after myocardial

infarction, patients have a substantial risk of stroke. A decreased ejection fraction

and older age are both independent predictors of an increased risk of stroke.

Anticoagulant therapy appears to have a protective effect against stroke after

myocardial infarction. (C) 1997, Massachusetts Medical Society



Keywords: acute/acute myocardial

infarction/age/anticoagulant/anticoagulants/aspirin/CAPTOPRIL/DILATED

CARDIOMYOPATHY/EMBOLISM/HEART-FAILURE/infarction/MANAGE

MENT/MASS/MORTALITY/MURAL THROMBI/myocardial/myocardial

infarction/predictors/PREVENTION/relative risk/risk/risk factors/risk factors for

stroke/stroke/TERM FOLLOW-UP/therapy/thrombolytic

agents/TWO-DIMENSIONAL ECHOCARDIOGRAPHY



Tu, J.V., Hannan, E.L., Anderson, G.M., Iron, K., Wu, K.Y., Vranizan, K., Popp, A.J.

and Grumbach, K. (1998), The fall and rise of carotid endarterectomy in the

United States and Canada. New England Journal of Medicine, 339 (20),

1441-1447.



Abstract: Background Randomized clinical trials have demonstrated the efficacy of

carotid endarterectomy in the prevention of stroke when the procedure is

performed in regional centers of surgical excellence. However, the relative

effects of these studies on the rates of carotid endarterectomy in the United States

and Canada have been unclear. Methods We calculated the annual rate of carotid

endarterectomy in the U.S. states of California and New York and in the

Canadian province of Ontario from 1983 through 1995. We also studied whether

patients in the early 1990s were selectively referred to hospitals with high

volumes of procedures and historically low in-hospital mortality rates. Results

Rates of carotid endarterectomy fell in all three regions from 1984 to 1989 (from

126 to 66 per 100,000 adults 40 years of age or older in California, from 65 to 40

per 100,000 in New York, and from 40 to 15 per 100,000 in Ontario), after the

publication of studies demonstrating that the rates of complications of carotid

endarterectomy were unacceptably high. However, the clinical trials of the 1990s,

which showed benefit from carotid endarterectomy, were associated with a

dramatic resurgence in the rates of the procedure from 1989 to 1995 (from 66 to

99 per 100,000 in California, from 40 to 96 per 100,000 in New York, and from

15 to 38 per 100,000 in Ontario). These increased rates were not associated with

proportionally greater numbers of referrals of patients to hospitals with low

mortality rates. Conclusions There have been a dramatic fall and a rise in the

rates of carotid endarterectomy in both the United States and Canada, which

correlate with the publication of first unfavorable and then favorable clinical

studies. The absence of selective referral of patients to centers with the lowest

mortality rates raises questions about whether the benefits of carotid

endarterectomy in the general population are similar to those demonstrated in the

clinical trials. (N Engl J Med 1998;339:1441-7.) (C) 1998, Massachusetts

Medical Society



Keywords: adults/age/carotid/carotid endarterectomy/clinical

trials/complications/endarterectomy/mortality/PREVENTION/STROKE/trials



Tonkin, A., Aylward, P., Colquhoun, D., Glasziou, P., Harris, P., MacMahon, S.,

Magnus, P., Newel, D., Nestel, P., Sharpe, N., Hunt, D., Shaw, J., Simes, R.J.,

Thompson, P., Thomson, A., West, M., White, H., Simes, S., Hague, W., Caleo,

S., Hall, J., Martin, A., Mulray, S., Barter, P., Beilin, L., Collins, R., McNeil, J.,

Meier, P., Willimott, H., Smithers, D., Wallace, P., Sullivan, D. and Keech, A.

(1998), Prevention of cardiovascular events and death with pravastatin in patients

with coronary heart disease and a broad range of initial cholesterol levels. New

England Journal of Medicine, 339 (19), 1349-1357.



Abstract: Background In patients with coronary heart disease and a broad range of

cholesterol levels, cholesterol-lowering therapy reduces the risk of coronary

events, but the effects on mortality from coronary heart disease and overall

mortality have remained uncertain. Methods In a double-blind, randomized trial,

we compared the effects of pravastatin (40 mg daily) with those of a placebo

over a mean follow-up period of 6.1 years in 9014 patients who were 31 to 75

years of age. The patients had a history of myocardial infarction or

hospitalization for unstable angina and initial plasma total cholesterol levels of

155 to 271 mg per deciliter. Both groups received advice on following a

cholesterol-lowering diet. The primary study outcome was mortality from

coronary heart disease. Results Death from coronary heart disease occurred in

8.3 percent of the patients in the placebo group and 6.4 percent of those in the

pravastatin group, a relative reduction in risk of 24 percent (95 percent

confidence interval, 12 to 35 percent; P 60

years imparted a slightly greater risk of intraoperative bleeding. Age >60 years.

hypertension, or recent cessation of aspirin may increase the risk of postoperative

bruising. A history of previous stroke increased the risk of postoperative

bleeding. There was no statistical difference in the incidence of hemorrhagic

complications among patients Currently treated with anti platelet/anticoagulant

agents, those who had stopped these medications before surgery, and those who

were not treated with these agents, No patient had permanent sequelae related to

hemorrhage. Two patients had postoperative systemic complications possibly

attributable to withholding anticoagulant/antiplatelet medications in preparation

for surgery. Conclusions: Although serious hemorrhagic complications may be

associated with oculoplastic procedures. the incidence of these complications is

low. The decision to withhold antiplatelet or anticoagulant medications before

surgery should be indiv vidualized. Selected procedures can be safely performed

without stopping these agents

Keywords: age/anticoagulant/antiplatelet/aspirin/ASPIRIN

THERAPY/bleeding/BLEPHAROPLASTY/BLINDNESS/complications/disease

/heart/heart

disease/hemorrhage/history/hypertension/incidence/INGESTION/MANAGEME

NT/medical/outcome/postoperative/PRIMARY PREVENTION/prospective

study/RANDOMIZED TRIALS/RISK/risk

factors/severity/sex/statistical/stroke/surgery/use/VASCULAR-DISEASE/WAR

FARIN



Carter, L.C., Tsimidis, K. and Fabiano, J. (1998), Carotid calcifications on panoramic

radiography identify an asymptomatic male patient at risk for stroke - A case

report. Oral Surgery Oral Medicine Oral Pathology Oral Radiology and

Endodontics, 85 (1), 119-122.



Abstract: Although stroke may be preventable, a major challenge is to find effective

methods of detection of stroke-prone patients. Most noncardiogenic strokes

occur as a result of atherosclerosis involving the proximal internal carotid artery,

calcifications of which can be detected on dental panoramic radiography. This

report describes the case of an asymptomatic patient whose dental radiographic

findings led to carotid endarterectomy. Calcifications were viewed bilaterally in

the soft tissues of the neck in the area of the carotid bifurcation on a screening

panoramic radiograph of an asymptomatic 75-year- old man. Subsequent duplex

Doppler ultrasound revealed extensive atherosclerotic changes bilaterally with

critical stenosis (90%+) in the right internal carotid artery. Carotid digital

subtraction angiography revealed a 95%+ stenosis at the origin of the right

internal carotid artery. The patient underwent right carotid endarterectomy

involving the internal, external, and common carotid arteries. Twelve months

later the patient was alive and well. Dental panoramic radiography represents a

useful imaging modality for detection of some asymptomatic stroke-prone

patients. Identification of calcifications in the area of a patient's carotid

vasculature should prompt expeditious referral to a physician for a

cerebrovascular and cardiovascular work-up as part of an active stroke

prevention strategy



Keywords: asymptomatic/atherosclerosis/carotid/carotid arteries/carotid artery/carotid

endarterectomy/detection/endarterectomy/HEART/prevention/risk/stroke/stroke

prevention



August, M. (2001), Cerebrovascular and carotid artery disease. Oral Surgery Oral

Medicine Oral Pathology Oral Radiology and Endodontics, 92 (3), 253-256



Keywords: carotid/carotid artery/carotid artery disease/disease/STROKE

PREVENTION



Shaper, A.G. (1996), Obesity and cardiovascular disease. Origins and Consequences of

Obesity, 201 90-107.

Abstract: The strong and consistent relationship observed between body weight and

blood pressure develops early in life, and overweight/obesity(1) in adult life is a

good predictor of hypertension. Weight reduction leads to a decrease in blood

pressure and prevention of weight increase lowers the incidence of hypertension,

but obesity is not necessarily the direct cause of raised blood pressure. Obesity is

not established as an independent risk factor for stroke beyond its association

with other risk factors. Obesity is a relatively weak risk factor for coronary heart

disease (CHD) but it is closely associated with almost ail other coronary risk

factors. Thus, becoming obese on a Western high fat diet, with development of

excess central fat, promotes atherogenesis through a wide range of biochemical

and hormonal parameters, including insulin sensitivity. The obesity-CHD

relationship is further confused by the weight loss associated with smoking and

smoking-related disease, and is confounded by risk factors that accompany the

development and maintenance of obesity. Weight loss in middle- aged

populations does not apparently lower CHD incidence, possibly because of lack

of specificity in methods of weight reduction. Irrespective of the mechanisms

involved, early prevention of atherogenic weight gain in young adulthood is an

important public health goal towards the control of hypertension and CHD



Keywords: AGED BRITISH MEN/BLOOD-PRESSURE/BODY-MASS

INDEX/CARE/MORTALITY/OVERWEIGHT/RISK

FACTOR/STROKE/UNITED-STATES/WEIGHT-LOSS/WOMEN



Ramnemark, A., Nyberg, L., Borssen, B., Olsson, T. and Gustafson, Y. (1998), Fractures

after stroke. Osteoporosis International, 8 (1), 92-95.



Abstract: Fractures are a serious complication after stroke. Among patients with femoral

neck fractures, a large subgroup have had a previous stroke. This study aimed to

investigate the incidence of fractures after stroke. Included in the study were

1139 patients consecutively admitted for acute stroke. Fractures occurring from

stroke onset until the end of the study or death were registered retrospectively.

Hip fracture incidence was compared with corresponding rates from the general

population. Patients were followed up for a total of 4132 patient-years (median

2.9 years). There were 154 fractures in 120 patients and median time between the

onset of stroke and the first fracture was 24 months. Women had significantly

more fractures than men chi(2) = 15.6; p 35

cm/s, mean velocity in middle cerebral artery (MCA) > 170 cm/s, resistive index

(RI) in OA 200 cm/s. Conclusion. Positive MRA

with a positive TCD in an asymptomatic patient in long-term follow-up suggests

a trend for developing clinical stroke. A 4- to 8-year follow-up of nine patients

with positive TCD, positive MRI, but not positive MRA did not show

development of clinical stroke. Nine Doppler findings are significant in

screening for clinically symptomatic vascular disease in sickle cell patients. It is

recommended that children with sickle cell disease be screened for

cerebrovascular disease with TCD. If one or two indicators of abnormality are

present, MRA is recommended. If the MRA is positive, the patient may be

considered for transfusion therapy or other treatment for prevention of stroke

Keywords: ANGIOGRAPHY/cerebral/cerebrovascular

disease/development/NEW-YORK/prevention/STROKE/therapy/treatment/ULT

RASONOGRAPHY/validity/vascular/vascular disease



Bulas, D.I., Jones, A., Seibert, J.J., Driscoll, C., O'Donnell, R. and Adams, R.J. (2000),

Transcranial Doppler (TCD) screening for stroke prevention in sickle cell anemia:

pitfalls in technique variation. Pediatric Radiology, 30 (11), 733-738.



Abstract: Background. The Stroke Prevention Trial in Sickle Cell Anemia (STOP)

identified children as being at high stroke risk if the time-averaged maximum

mean velocity (TAMMV) of the middle cerebral or intracranial internal carotid

arteries measured greater than or equal to 200 cm/s. These values were obtained

utilizing a 2-mHz dedicated nonimaging pulsed Doppler technique (TCD) and

manual measurements. Questions have been raised as to the comparability of

results obtained with different ultrasound machines and measurement techniques.

Objective. The purpose of this study was to compare nonimaging (TCD) and

transcranial duplex imaging (TCDI) findings in children potentially at risk for

stroke with sickle cell disease. Materials and methods. Twenty-two children with

sickle cell disease and no history of stroke were evaluated by both TCD and;

TCDI. Examinations were performed on the same day without knowledge of the

other modality results and read independently using manually obtained

measurements. Mean velocities, peak systolic velocities, and end diastolic

velocities obtained by the two techniques were compared. In a subgroup, manual

measurements were compared to electronically obtained measurements. Results.

TCDI values were lower than TCD measurements for all vessels. TCDI

TAMMV values were most similar to the TCD values in the middle cerebral

artery (-9.0 %) and distal internal cerebral artery (-10.8 %), with greater

variability in the anterior cerebral artery (-19.3 %), bifurcation (-16.3 %), and

basilar arteries (-23.1%). Risk group placement based on middle cerebral artery

TAMMV values did not change when comparing the two techniques.

Measurements obtained electronically were lower than those obtained manually.

Conclusion. Velocities obtained by TCDI may be lower than TCD measurements,

and these differences should be taken into consideration when performing

screening for stroke risk and selection for prophylactic transfusion based on the

STOP protocol



Keywords: anemia/ANGIOGRAPHY/arteries/carotid/carotid arteries/cerebral/cerebral

artery/CEREBROVASCULAR-DISEASE/CHILDREN/Doppler/duplex/history/

knowledge/middle cerebral

artery/MRA/NEW-YORK/prevention/RISK/screening/sickle cell anemia/sickle

cell disease/stroke/stroke

prevention/TCD/transcranial/transfusion/ULTRASONOGRAPHY/ultrasound



Jones, A.M., Seibert, J.J., Nichols, F.T., Kinder, D.L., Cox, K., Luden, J., Carl, E.M.,

Brambilla, D., Saccente, S. and Adams, R.J. (2001), Comparison of transcranial

color Doppler imaging (TCDI) and transcranial Doppler (TCD) in children with

sickle-cell anemia. Pediatric Radiology , 31 (7), 461-469.

Abstract: Background. Transcranial Doppler (TCD) has been demonstrated to identify

those at highest risk of stroke among children with sickle-cell disease. Based on

a randomized clinical trial [Stroke Prevention in Sickle-Cell Anemia Trial

(STOP)], which ended in 1997, the National Heart Lung and Blood Division of

NIH has recommended TCD screening and chronic blood transfusion based on

Nicolet TC 2000 dedicated Doppler (TCD). Studies performed using TCD

imaging modalities need to be correlated to that used in the clinical trial to

provide information for treatment decisions when screening with TCDI.

Objective. To correlate transcranial arterial time-averaged mean velocities

obtained from an Acuson Transcranial Doppler Imaging to those obtained using

the TCD as the gold standard for treatment decisions based on STOP. Materials

and Methods. A total of 29 children with sickle-cell disease, age 3-16 years, were

studied at one of two scanning sessions using both techniques and a scanning

protocol based on that used in STOP performed and read independently. The

average difference in the measured velocities for each arterial segment was tested

to determine difference from zero. Differences were compared before and after

modifications to the TCDI technique were made to mimic the STOP protocol

more closely. Results. TCDI velocities were generally lower than TCD velocities

for the same segment, but the difference was reduced (from 15% to 10% for the

middle cerebral artery) by modifications to the TCDI protocol. Conclusions.

Measurements using the Acuson system are modestly lower than those obtained

with dedicated Doppler using the Nicolet TCD



Keywords: age/anemia/arterial/blood transfusion/cerebral/cerebral

artery/children/clinical trial/DISEASE/Doppler/middle cerebral

artery/NEW-YORK/randomized/randomized clinical trial/risk/screening/sickle

cell anemia/sickle cell disease/STROKE/TCD/transcranial/transcranial

Doppler/transfusion/treatment/trial/ULTRASONOGRAPHY



Ferriero, D.M., Sheldon, R.A., Black, S.M. and Chuai, J. (1995), Selective Destruction

of Nitric-Oxide Synthase Neurons with Quisqualate Reduces Damage After

Hypoxia-Ischemia in the Neonatal Rat. Pediatric Research, 38 (6), 912-918.



Abstract: The vulnerability of the developing CNS to hypoxia-ischemia (H- I) differs

from that of the mature brain and is due in part to release of nitric oxide (NO)

from parenchymal neurons. If NO is important in the generation of excitotoxic

injury after H-I in the developing CNS, then selective destruction of the neuronal

nitric oxide synthase (nNOS) cells before H-I should lessen the injury seen after

the insult. Using low dose quisqualic acid (QA) injected into neonatal (postnatal

d 7) parietal cortex, the nNOS neurons were eliminated while sparing other

neuronal and glial populations as ascertained by NADPH diaphorase

histochemistry, nNOS immunocytochemistry, and Nissl counterstain. Animals

subjected to focal ischemia followed by global hypoxia 24 h after the

intracortical injection of QA had more viable cortex remaining than

vehicle-injected animals (83.4 +/- 4.3% versus 62.7 +/- 8.3%) and lower injury

severity represented by less neuronal loss and gliosis. Intracortical injections of

QA without H-I resulted in minimal cell loss at the injection site with elimination

of nNOS neurons throughout the parietal cortex. Microglial and astrocytic

proliferation was seen in areas damaged by H-I 3 wk after injury and clearly

marked infarcted areas. Prevention or elimination of NO production from nNOS

cells can prevent much of the delayed neuronal necrosis seen after H-I in the

developing CNS



Keywords:

BRAIN-DAMAGE/focal/IMMUNOREACTIVITY/INJURY/ischemia/MECHA

NISMS/NADPH-DIAPHORASE/necrosis/neurons/PROTEIN/severity/SPREAD

ING DEPRESSION/STROKE



Abbott, R.D., White, L.R., Ross, G.W., Petrovitch, H., Masaki, K.H., Snowdon, D.A.

and Curb, J.D. (1998), Height as a marker of childhood development and late-life

cognitive function: The Honolulu-Asia Aging Study. Pediatrics, 102 (3),

602-609.



Abstract: Objective. Growing evidence suggests that structural and functional brain

reserves, thought to develop in childhood and adolescence, may be crucial in

determining when cognitive impairment begins. The purpose of this report is to

examine the relationship of height, as a marker of childhood development, to

late-life cognitive function in a sample of elderly Japanese-American men.

Method. Cognitive performance was assessed from 1991 to 1993 in the

Honolulu-Asia Aging Study in 3733 men aged 71 to 93 years and related to

height that was measured 25 years earlier. Results. Among the study sample,

shorter men were older, leaner, and less educated than taller men. Shorter men

also spent more years of their childhood living in Japan and were more likely to

have had fathers in unskilled professions. After adjustment for age, the

prevalence of poor cognitive performance declined consistently with increasing

height from 25% in men shorter than 154 cm (61 in) to 9% in those taller than

174 cm (69 in). Excluding men with stroke or dementia did not alter the

association between height and cognitive performance. Apolipoprotein E4 was

unrelated to height and did not effect the association between height and

cognitive function. The prevalence of Alzheimer's disease was higher in men

who were 154 cm (61 in) or shorter as compared with men who were taller (4.7%

vs 2.9%, respectively). There was no association between height and vascular

dementia. Conclusion. Efforts to improve prenatal and early life conditions to

maximize growth in childhood and adolescence could diminish or delay the

expression of cognitive impairments that occur later in life. prevention of some

late-life cognitive impairments may have pediatric origins



Keywords: ABILITY/ADULT

BRAIN-WEIGHT/AGE/aged/ALZHEIMERS-DISEASE/childhood

development/cognitive

function/DEMENTIA/dementia/development/elderly/HAWAII/HEAD

SIZE/LOW-BIRTH-WEIGHT/MINI-MENTAL

STATE/PREVALENCE/prevention/stroke/vascular

Kimm, S.Y.S., Barton, B.A., Obarzanek, E., McMahon, R.P., Sabry, Z.I., Waclawiw,

M.A., Schreiber, G.B., Morrison, J.A., Similo, S. and Daniels, S.R. (2001),

Racial divergence in adiposity during adolescence: The NHLBI growth and

health study. Pediatrics, 107 (3), U30-U36.



Abstract: Background. Black women are particularly vulnerable to obesity, with a

prevalence rate of >50%. The higher mortality and morbidity from

cardiovascular disease, stroke, and diabetes have been attributed, in part, to their

obesity. In recent years, a particular public health concern is the increasing

secular trend in obesity with an even greater racial disparity, especially in girls

and women. Between the early 1960s and late 1980s, the prevalence of obesity

tripled in young black girls 6 to 11 years of age, while it doubled in white girls.

Similarly, both overweight and obesity in adolescent girls 12 to 17 years of age

also increased, with a greater increase again seen in adolescent black girls. This

secular trend in obesity with a greater increase in black girls signals a potentially

grave future chronic disease burden on black women, which is already higher

than in white women. The increasing occurrence in children and adolescents of

noninsulin-dependent diabetes, traditionally viewed as an adult-onset condition,

may be a consequence of the currently high prevalence of obesity in American

youth. Not surprisingly, this condition is seen more frequently among black

youths. Prepubescent black girls are generally leaner than age-comparable white

girls, but by 20 years of age, black women are considerably heavier than are

white women. Thus, it is assumed that the racial disparity in adiposity evolves

during adolescence. However, the specific age at which this occurs and

underlying factors are yet to be identified because of the current paucity of

longitudinal cohort data. Objectives. In 1985, the National Heart, Lung, and

Blood Institute (NHLBI) initiated a 10-year longitudinal multicenter study (the

NHLBI Growth and Health Study [NGHS]) to investigate the development of

obesity in black and white girls during adolescence and its environmental,

psychosocial, and cardiovascular disease risk factor correlates. The purpose of

this report is to examine the natural history of adiposity and weight accretion

during adolescence in a biracial cohort of girls to investigate the evolution of the

racial divergence in adiposity and to examine the relationships between increases

in adiposity and pubertal maturation, energy intake, and physical activity.

Participants and Setting. A total of 2379 black (51%) and white (49%) girls, 9 to

10 years of age, were recruited from public and parochial schools in Richmond,

California, and Cincinnati, Ohio, and from families enrolled in a large health

maintenance organization in the Washington, DC area. Participant eligibility was

limited to girls and their parents who declared themselves as being either black

or white and who lived in racially concordant households. Design and Statistical

Analysis. The NGHS is a multicenter prospective study of black and white girls

with annual visits from 9 to 10 years of age through 18 to 19 years of age. The

follow-up rate was 89% at the 10th annual visit. Skinfold measurements were

obtained at the triceps, suprailiac, and subscapular sites with Holtain calipers.

Sexual maturation was assessed by trained registered nurses. The onset of

menarche was ascertained annually by questionnaire. All clinical assessments

were conducted using a common protocol by centrally trained staff. Longitudinal

regression (generalized estimating equations) models were used to examine the

relationship between adiposity and race, age, pubertal maturation, daily energy

intake, and physical activity. Main Outcome Measures. The main outcome

measure was the sum of skinfolds (SSF) at the triceps, subscapular, and

suprailiac sites as an index of adiposity for comparison between the 2 racial

groups. Body mass index (BMI; weight in kilograms divided by height in meters,

squared) distributions were examined by age and race. Results. Racial

differences in SSF, unadjusted for maturation, were evident at 10 years of age.

For each chronological age, there was a higher proportion of black girls with

more advanced pubertal maturation than white girls. The 15th percentiles for

SSF were similar and remained thus throughout the study. The median for SSF

for black girls, although similar to the median SSF of white girls at 9 years of age,

became greater for black girls at 12 years of age (36 mm vs 32.5 mm) and at age

19 years the difference was 6 mm (49.5 mm vs 43.5 mm). In contrast, the

difference in the 85th as well as the 95th percentile values for SSF were

substantially higher in black girls at all ages (9 mm and 10 mm, or 18% and 15%,

respectively, at age 9 years) and these racial differences widened with age (20

mm and 26 mm, or 25% and 24%, respectively, by age 19 years). The racial

difference in the median BMI increased from 0.4 to 2.3 kg/m(2) between ages 9

and 19 years. Unlike SSF at the 15th percentile, the BMI for lean 9-year-old

black girls was similar to3% higher than whites. As with SSF, for heavier girls,

BMI at the 85th percentile even at age 9 years was 11% greater in black girls and

became 23% greater by age 19 years. Differences in BMI at the 95th percentile

also increased from 3.6 to 8.1 kg/m(2) between ages 10 and 18 years. After

adjusting for stages of maturation in multivariate longitudinal regression models,

adiposity for black girls became significantly greater at age 12 years compared

with white girls. The largest gain in adiposity for both groups was seen at the

time of pubescence, an approximate increase of 8.0 mm in SSF for white girls

and 10.8 mm for black girls. The next milestone for a gain in adiposity occurred

around menarche with an increase in SSF of 5.0 mm for white girls and 3.4 mm

for black girls. Additionally, there was a significantly greater accrual of adiposity

with earlier achievement of menarche, ie, a gain of 3.7 mm for white girls and

3.0 mm for black girls for each year. Although the effect of puberty on the gain

in adiposity was similar for both races, for each chronological age, there was a

greater accrual of adiposity in black girls because they matured earlier than white

girls. Energy intake was significantly and inversely associated with increasing

adiposity but not with levels of physical activity. Conclusion. The time of the

largest accrual of body fat occurred around the 2 major pubertal milestones, the

onsets of puberty and menarche. Even after adjusting for pubertal maturation,

after age 12 years, black girls were significantly fatter than were white girls.

Earlier menarche conferred an additional risk for greater gain in adiposity for

both racial groups. Primary prevention of obesity, therefore, should commence

with fostering the maintenance of normal growth in young girls before the

initiation of pubertal maturation because increased adiposity is associated with

earlier menarche. Next, and more importantly, pediatricians should be

particularly vigilant with growth monitoring during the critical milestones of

pubertal development, a vulnerable time for a large accrual of adiposity. Greater

emphasis needs to be placed on preventive efforts in black girls to minimize their

risk for developing obesity during adolescence



Keywords: adiposity/adolescence/adolescents/age/body mass index/BODY-MASS

INDEX/cardiovascular/cardiovascular disease/children/chronic

disease/correlates/DEPENDENT

DIABETES-MELLITUS/development/diabetes/disease/disease risk/energy

intake/ENERGY-INTAKE/health/history/monitoring/morbidity/mortality/NATI

ONAL-HEALTH/NUTRITION EXAMINATION

SURVEYS/OBESITY/obesity/outcome/OVERWEIGHT/physical

activity/prevalence/prevention/prospective study/pubertal maturation/public

health/race/racial differences/risk/risk factor/stroke/TRENDS/weight/WHITE

GIRLS/women/YOUNG-ADULTS



Lynch, J.K., Hirtz, D.G., DeVeber, G. and Nelson, K.B. (2002), Report of the National

Institute of Neurological Disorders and Stroke workshop on perinatal and

childhood stroke. Pediatrics, 109 (1), 116-123.



Abstract: The National Institute of Neurological Disorders and Stroke and the Office of

Rare Disorders sponsored a workshop on perinatal and childhood stroke in

Bethesda, Maryland, on September 18 and 19, 2000. This was an international

workshop to bring together experts in the field of perinatal and childhood stroke.

Topics covered included epidemiology, animal models, risk factors, outcome and

prognosis, and areas of future research for perinatal and childhood stroke. Stroke

in infants and children is an important cause of morbidity and mortality and an

emerging area for clinical and translational research. Currently, there is no

consensus on the classification, evaluation, outcome measurement, or treatment

of perinatal and childhood stroke. Pediatric stroke registries are needed to

generate data regarding risk factors, recurrence, and outcome. The impact of

maternal and perinatal factors on risk and outcome of neonatal stroke needs to be

studied. This information is essential to identifying significant areas for future

treatment and prevention



Keywords: animal/ANTIPHOSPHOLIPID ANTIBODIES/ARTERIAL ISCHEMIC

STROKE/ARTERIOVENOUS-

MALFORMATIONS/BRAIN-DAMAGE/cerebrovascular

diseases/CEREBROVASCULAR- DISEASE/child/children/CLINICAL

CHARACTERISTICS/consensus/epidemiology/essential/evaluation/infant/INTR

AARTERIAL THROMBOLYSIS/morbidity/morbidity and

mortality/mortality/NEONATAL CEREBRAL INFARCTION/Neurological

Disorders and Stroke

workshop/outcome/prevention/prognosis/recurrence/research/risk/risk

factors/RISK-FACTORS/SICKLE-CELL DISEASE/stroke/treatment/USA



Deymann, A.J. and Goertz, K.K. (2003), Myocardial infarction and transient ventricular

dysfunction in an adolescent with sickle cell disease. Pediatrics, 111 (2),

art-e183.

Abstract: We report a case of an adolescent who had sickle cell disease and previous

evidence of myocardial damage and presented with abdominal pain and rapid

progression to cardiogenic shock and subsequent development of myocardial

infarction. To our knowledge, this represents only the second report of a case of

acute myocardial ischemia and subsequent infarction resulting transient

ventricular dysfunction reported in a child with sickle cell disease successfully

treated with exchange transfusion. The pathophysiology of this complication

remains unclear, and cardiac complications may remain undetected as lung, bone,

and brain infarcts are more common and the pain associated with sickle cell

crisis may mask the ischemic symptoms. Multiple factors may contribute to

ischemia in addition to the presence of a vaso-occlusive crisis or infection. Acute

or chronic myocardial ischemia are probably more prevalent than currently

known



Keywords: acute/ANEMIA/brain/cardiac/CARDIAC

DYSFUNCTION/child/CHILDHOOD/chronic/complication/complications/deve

lopment/disease/exchange

transfusion/infarction/infection/ischemia/ischemic/knowledge/myocardial/myoca

rdial infarction/pain/pathophysiology/progression/sickle cell disease/STROKE

PREVENTION/symptoms/transfusion/transient/USA



Ernst, E., Szirmai, I. and Bogar, L. (1992), Hemorheological Effects of Pyritinol in

Patients After Ischemic Stroke - A Placebo-Controlled, Double-Blind Trial.

Perfusion, 5 (6), 184-&.



Abstract: Patients who had suffered an ischaemic stroke were randomized to receive

either oral pyritinol or placebo for 4 weeks. Blood and plasma viscosity,

haematocrit and red cell filterability were quantified at baseline as well as 1 and

4 weeks after. No changes were seen in the placebo group. Blood viscosity

decreased significantly in the experimental group. Since this variable can be

viewed as a secondary risk factor for stroke survivors, one should test the

possibility that pyritinol may be useful in the secondary prevention after stroke



Keywords: BLOOD VISCOSITY/HEMATOCRIT/ISCHEMIC STROKE/PYRITINOL



Marshall, M. (1992), Stroke and Sex - Prevalence and Prevention. Perfusion, 5 (11),

338-339



Morl, H. (1993), Stroke Prophylaxis and Prevention of Recurrence - Therapeutic

Strategies and Dosages. Perfusion, 6 (3), 126-128



Michna, S. (1998), FDA approves CSE inhibitor Pravastatin for stroke prevention and

reduction of recurrent events in infarction patients with normal cholesterol levels.

Perfusion, 11 (5), 235



Keywords: cholesterol/infarction/PERFUSION/prevention/stroke/stroke prevention

Yasue, H., Ogawa, H., Tanaka, H., Miyazaki, S., Hattori, R., Saito, M., Ishikawa, K.,

Masuda, Y., Yamaguchi, T., Motomiya, T. and Tamura, Y. (1999), Effects of

aspirin and trapidil on cardiovascular events after acute myocardial infarction.

Perfusion, 12 (8), 342-348.



Abstract: Aspirin therapy confers conclusive net benefits in the acute phase of evolving

myocardial infarction, but no clear evidence of benefit from the long-term use of

aspirin after acute myocardial infarction (AMI) has been shown in any single

study, This multicenter study, the Japanese Antiplatelets Myocardial Infarction

Study, was performed to find out whether aspirin or trapidil would improve

clinical outcome compared with no antiplatelets in postinfarction patients, The

study was a multicenter, open-label, randomized controlled trial of aspirin 81

mg/day, trapidil 300 mg/day, and no antiplatelets in patients with AMI admitted

within 1 month from the onset of symptoms, Seven hundred twenty-three

patients were enrolled at 70 hospitals in 18 prefectures of Japan; 250 were

randomly assigned to treatment with 81 mg aspirin (aspirin-group), 243 to that

with trapidil (trapidil-group), and 230 were not given antiplatelet agents, The

mean follow-up period was 475 days, This study demonstrated that long-term

use of aspirin at the dose of 81 mg/day reduced the incidence of recurrent AMI

compared with the group receiving no antiplatelets after AMI (p = 0.0045) and

that trapidil also reduced the occurrence of reinfarction compared with the group

receiving no antiplatelets, but the difference was not significant (p = 0.0810).

The incidence of cardiovascular events including cardiovascular death,

reinfarction, uncontrolled unstable angina requiring admission to hospital, and

nonfatal ischemic stroke was reduced in the group receiving 300 mg trapidil

daily compared with the group receiving no antiplatelets (p = 0.0039). The use of

aspirin 81 mg/day provided almost no benefit over no antiplatelets therapy in the

incidence of cardiovascular events, In conclusion, low-dose aspirin (81 mg)

effectively prevented recurrent AMI in postinfarction patients after thrombolysis

or coronary angioplasty when used over a long term, Furthermore, the long-term

use of trapidil resulted in a significant reduction in the incidence of

cardiovascular events



Keywords: acetyl salicylic acid/ACID/acute/acute myocardial

infarction/angina/angioplasty/antiplatelet agents/ANTIPLATELET

THERAPY/antiplatelets/aspirin/cardiovascular/cardiovascular events/coronary

angioplasty/GROWTH-FACTOR

ANTAGONIST/HEART-DISEASE/hospital/incidence/infarction/ischemic/ische

mic stroke/MORTALITY/myocardial/myocardial

infarction/PERFUSION/randomized/randomized controlled

trial/RESTENOSIS/SECONDARY

PREVENTION/stroke/therapy/thrombolysis/TRANSLUMINAL CORONARY

ANGIOPLASTY/trapidil/treatment/TRIAL/TRIAZOLOPYRIMIDINE/unstable

angina



Xiao, W., Wang, L., Scott, T., Counsell, R.E. and Liu, H. (1999), Radiolabeled

cholesteryl iopanoate/acetylated low density lipoprotein as a potential probe for

visualization of early atherosclerotic lesions in rabbits. Pharmaceutical Research,

16 (3), 420-426.



Abstract: Purpose. Atherosclerosis is the underlying factor leading to such

cardiovascular diseases (CVD) as stroke, aneurysm, and myocardial infarction.

The early detection of atherosclerotic plaques is considered to be crucial for

successful prevention and/or therapeutic and dietary intervention of CVD.

Current diagnostic practice, on the other hand, can only detect the problem at an

advanced stage. The purpose of this study was to examine the potential of using a

radiolabeled cholesterol ester analog/acetylated low density lipoprotein (AcLDL)

conjugate as a diagnostic agent for the early and non-invasive detection of

atherosclerosis and for the monitoring of the effects of drug therapy. Methods.

Cholesteryl iopanoate (CI), a cholesterylester analog, was synthesized,

radiolabeled, and incorporated into AcLDL. Early atherosclerotic lesions were

induced in New Zealand White rabbits. I-125-Cl/ AcLDL was injected

intravenously at 2 mu Ci/kg. Blood samples were taken at different time intervals

after injection and clearance of the injected drug from blood was studied. The

rabbits were sacrificed after 72 hours and the distribution of radioactivity in

various organs was investigated. Aortae of both atherosclerotic lesion and control

rabbits were removed for Sudan IV staining and autoradiography in order to

confirm the formation of the atherosclerotic lesion and localization of

radioactivity. Results. The injected drug was found to be cleared from blood

following a two compartment model. Radioactivity in the atherosclerotic aorta

was found to be about 8 times higher than that in normal aorta, suggesting that

the proposed diagnostic probe was selectively taken up by the atherosclerotic

lesion. The autoradiography and staining confirmed that the localization of the

proposed probe was superimposed with the atherosclerotic lesion site.

Conclusions, The results suggested that incorporation of CI into AcLDL resulted

in the selective localization of CI at the atherosclerotic plaque areas. Cl/AcLDL

labeled with appropriate radioisotope has the potential to be used as a probe for

visualization of early atherosclerotic lesion using scintigraphy technology



Keywords:

AcLDL/aneurysm/atherosclerosis/autoradiography/BINDING/BIODISTRIBUTI

ON/cardiovascular/cardiovascular diseases/CELLS/cholesterol/cholesteryl

iopanoate/control/DEGRADATION/DEPOSITION/detection/diagnostic

agent/DISEASE/diseases/drug therapy/FAMILIAL

HYPERCHOLESTEROLEMIA/formation/IMAGING AGENTS/infarction/low

density

lipoprotein/MACROPHAGE/METABOLISM/monitoring/myocardial/myocardia

l infarction/NEW-YORK/plaque/prevention/stroke/therapy/visualization



Scott, G. and Scott, H.M. (1997), Application of the findings of the European Stroke

Prevention Study 2 (ESPS-2) to a New Zealand ischaemic stroke cost analysis.

Pharmacoeconomics, 12 (6), 667-674.

Abstract: The aim of this study was to apply the findings of the European Stroke

Prevention Study 2 (ESPS-2) to a paper that quantified and described the annual

cost of ischaemic stroke in New Zealand, and to compare the cost of alternative

drug regimens in the secondary prevention of ischaemic stroke. Comparisons

were made between the costs of low-dosage aspirin (acetylsalicylic acid)

monotherapy and a combination of modified-release dipyridamole and

low-dosage aspirin. Differences in undiscounted costs were calculated over a

2-year period. The New Zealand cost per stroke event was multiplied by the

ESPS-2 incremental reduction in stroke events to derive the cost of strokes

avoided. As the focus of the paper was on direct medical costs, the primary

perspective adopted was that of a healthcare provider or funder, but a societal

perspective was also considered by evaluation of direct nonmedical and indirect

costs. Compared with aspirin monotherapy, combination therapy generated

incremental net direct costs of 18.22 New Zealand dollars ($NZ) per patient or

$NZ18 223 per 1000 patients. However, individually, each treatment regimen

resulted in direct cost savings when compared with placebo: combination therapy

$NZ905.16 per patient; aspirin monotherapy $NZ923.39 per patient (a difference

between the 2 regimens of $NZ18.22 per patient). Total direct and indirect

incremental cost savings were $NZ40.96 per patient, and $NZ40 963 per 1000

patients, for the combination therapy. The analysis demonstrates that changing

patients from low-dosage aspirin to a combination therapy of modified-release

dipyridamole plus low-dosage aspirin would result in a small rise in incremental

direct costs (using our conservative assumptions relating to hospital and

continuing institutional care costs). If less conservative unit cost assumptions

were adopted, a more likely outcome would be a saving in direct incremental

costs of up to $NZ400 per patient treated



Keywords: acetylsalicylic

acid/ASPIRIN/cost/costs/dipyridamole/evaluation/hospital/institutional/ISCHEM

IC STROKE/NEW-ZEALAND/prevention/secondary

prevention/stroke/therapy/treatment



Milne, R.J., VanderHoorn, S. and Jackson, R.T. (1997), A predictive model of the health

benefits and cost effectiveness of celiprolol and atenolol in primary prevention of

cardiovascular disease in hypertensive patients. Pharmacoeconomics, 12 (3),

384-408.



Abstract: This study compares the antihypertensive and lipid modifying effects of

treatment of mild to moderate hypertension with celiprolol or atenolol. It also

models the 5-year cardiovascular risk reduction and the cost effectiveness of

monotherapy from a partial societal perspective. The effects of celiprolol and

atenolol on systolic blood pressure (SBP), total serum cholesterol (TC) and high

density lipoprotein cholesterol (HDL-C) were obtained from a pooled analysis of

published studies. Although celiprolol and atenolol had similar effects on SBP,

celiprolol reduced the ratio of TC to HDL-C by 10.2% [95% confidence intervals

(95% CI) -16.4%, -4.0%] but atenolol increased the ratio by 7.7% (95% CI of

3.4%, 12.0%). The 5-year absolute risks of an initial coronary or cerebrovascular

event or cardiovascular death were computed for cohorts of patients treated with

either agent or remaining untreated, using an accelerated failure time (AFT)

model, based on Framingham Heart Study data. Inputs to the model were age,

gender, smoking: status, SEP, TC and HDL-C. The change in absolute risk was

estimated using the changes in SEP and TC :HDL-C obtained from the pooled

analysis. Average life-months gained by therapy were computed as differences

between the Kaplan-Meier survival curves estimated from the model plus

differences in 5-year cardiovascular death rates multiplied by average life

expectancy obtained from life tables. Direct medical costs included drug

treatment. and the costs of acute care for initial coronary and cerebrovascular

events deferred by therapy over the 5-year treatment period, The model shows

that in the lowest-risk base case (60-year-old men who are nondiabetic and

nonsmokers with SEP of 160mm Hg and a 5-year absolute cardiovascular risk of

12%), celiprolol (271 mg/day) is 2-fold more effective than atenolol (77.4

mg/day) in reducing coronary event risk, and equally effective in reducing

cerebrovascular event risk. The number of individuals that would have to be

treated for 5 years to avoid 1 coronary event is about 30 for celiprolol versus 70

for atenolol. Therapy with celiprolol yields more life-months and at current

prices, the cost per life-year gained by therapy is significantly lower. Both drugs

are cost effective by international standards in the treatment of patients with

5-year absolute cardiovascular risk greater than 10%, and are more cost effective

in those patients at higher levels of absolute cardiovascular risk. The direct

medical costs of treatment for 5 years with celiprolol are the same or slightly less

than treatment with atenolol at the dosages used in the clinical trials, despite a

19% higher tablet price. Both drugs are more cost effective in patients at higher

levels of absolute cardiovascular risk. These findings are sensitive to the drug

dosages, tablet prices and the discount rate. Based on epidemiological and

clinical data, replacing atenolol with celiprolol in patients with mild to moderate

hypertension, but without overt cardiovascular disease, is predicted to have

similar effects on stroke risk, but to be substantially more effective in reducing

the risk of coronary events at no additional direct medical cost over a 5- year

treatment period



Keywords: absolute risk/age/blood pressure/BLOOD- PRESSURE/cardiovascular

disease/cerebrovascular/cholesterol/CHOLESTEROL LEVELS/clinical

trials/CORONARY HEART-DISEASE/cost/cost

effectiveness/cost-effectiveness/costs/drugs/health/high density

lipoprotein/hypertension/ISCHEMIC STROKE/life

expectancy/MYOCARDIAL-INFARCTION/NEW-ZEALAND/prevention/prim

ary prevention/risk/RISK-FACTORS/serum/SERUM-LIPIDS/smoking/societal

perspective/stroke/SYSTEMIC HYPERTENSION/therapy/TO-MODERATE

HYPERTENSION/treatment/trials



Szucs, T.D. (1998), Resource utilisation in the management of dyslipidaemia.

Pharmacoeconomics, 14 11-18.

Abstract: In Western countries, cardiovascular disease accounts for substantial morbidity

and mortality. In the US, where medical costs and intervention rates are the

highest in the world, the direct and indirect costs of cardiovascular disease and

stroke have been estimated at $US274 billion (1998 dollars), with the costs of

hospitalisation ($US 119.9 billion) and lost productivity because of early

mortality ($US77.9 billion) representing the largest proportions of this amount.

Dyslipidaemia is an important risk factor for coronary heart disease (CHD), a

condition which accounts for $US39.3 billion and $US37.9 billion (1998 dollars)

in hospitalisation/nursing home costs and lost productivity, respectively,

annually in the US. Similarly, the UK National Health Service spends more than

500 million pounds sterling annually on the treatment of CHD. Numerous studies

have shown the benefit of lowering cholesterol levels in terms of decreasing

CHD-associated morbidity and mortality; however, drug therapy costs for

dyslipidaemia can be high. US and European treatment guidelines for

dyslipidaemia recommend aggressive treatment for those at highest CHD event

risk. Because of the high prevalence of dyslipidaemia in Western countries, these

recommendations impact on a substantial proportion of the population and have

increased the use of cholesterol-lowering medications. In a limited number of

economic studies using clinical data from large prevention trials, the cost of drug

therapy was nearly offset by the reduction in costs associated with

hospitalisations and revascularisation procedures. Therefore, it appears that the

strategy of identifying and treating individuals at highest risk for CHD, although

expensive in terms of drug costs, would be expected to reduce the substantial

direct and indirect costs associated with this condition



Keywords: ARTERY DISEASE/AUCKLAND/cardiovascular/cardiovascular

disease/cholesterol/cholesterol-lowering/coronary heart disease/CORONARY

HEART-DISEASE/cost/COST-EFFECTIVENESS/costs/drug

therapy/dyslipidaemia/guidelines/heart/HYPERCHOLESTEROLEMIA/INTER

VENTION/LIPOPROTEIN CHOLESTEROL/MIDDLE-AGED

MEN/morbidity/mortality/NEW-ZEALAND/population/prevalence/PREVENTI

ON/risk/risk factor/RISK-FACTORS/SERUM-CHOLESTEROL

CONCENTRATION/stroke/therapy/treatment/treatment guidelines/trials



Chambers, M., Hutton, J. and Gladman, J. (1999), Cost-effectiveness analysis of

antiplatelet therapy in the prevention of recurrent stroke in the UK - Aspirin,

dipyridamole and aspirin-dipyridamole. Pharmacoeconomics, 16 (5), 577-593.



Abstract: Objectives: To evaluate the cost effectiveness from a UK health and social

services perspective of antiplatelet therapies tested in the Second European

Stroke Prevention Study (ESPS-2) in preventing recurrent stroke. To

demonstrate the value of modelling studies in this area. Design and setting: A

decision- analytic model was developed to evaluate health outcomes and

associated costs. Sources of data for efficacy, adverse events, background event

risks, disability and mortality were ESPS-2, the Oxfordshire Community Stroke

Project and UR national statistics. Published national unit costs were applied to

clinician panel estimates of resource use for acute stroke, rehabilitation and long

term care. Outcome measures were strokes or disabled life-years averted, and

disability-free, stroke-free or quality-adjusted life-years gained. Patients and

interventions: 30-day survivors of ischaemic stroke treated with low dose aspirin,

modified-release dipyridamole; the coformulation of low dose aspirin plus

modified-release dipyridamole, or no antiplatelet therapy. Main outcome

measures and results: The model predicted that over 5 years the coformulation

prevented 29 more strokes than aspirin alone per 1000 patients, at an additional

cost of pound 1900 per stroke averted (1996 values). Over 5 years, each

antiplatelet therapy was cost saving compared with no therapy. Results were

sensitive to the cost of acute care, the cost of long term care of disabled stroke

survivors, the effectiveness of therapy and the background risk of recurrent

stroke. In sensitivity analyses, the cost effectiveness did not exceed pound 7000

per stroke averted or pound 11 000 per quality-adjusted life-year (QALY) gained,

except when varying the effectiveness parameter. Conclusions: Application of a

decision-analytic model to the results of ESPS-2 indicated that first-line therapy

with the coformulation of modified-release dipyridamole and low dose aspirin to

patients with a previous ischaemic stroke is likely to generate significant health

benefits at modest extra costs to health and social services. The extra costs of

treatment are balanced by the savings in future costs of acute care and long term

care of the disabled. Future economic evaluations in this area should pay

particular attention to the cost perspective, the duration of analysis, the selection

of trials from which effectiveness data are derived, and the impact of the pooling

of outcome events with potentially different economic consequences



Keywords: acute/adverse events/antiplatelet therapy/aspirin/COMMUNITY/cost/cost

effectiveness/cost-effectiveness/costs/dipyridamole/England/FIRST-EVER

STROKE/health/HIGH-RISK PATIENTS/ischaemic

stroke/MINNESOTA/mortality/NEW-ZEALAND/PERSPECTIVE/prevention/q

uality-adjusted life-years/recurrent

stroke/REHABILITATION/risk/ROCHESTER/SERVICES/stroke/SURVIVAL/t

herapy/TICLOPIDINE/treatment/trials



Marissal, J.P., Selke, B. and Lebrun, T. (2000), Economic assessment of the secondary

prevention of ischaemic events with lysine acetylsalicylate. Pharmacoeconomics,

18 (2), 185-200.



Abstract: Objective: to analyse the economic benefits, in comparison with placebo, of

the secondary prevention of ischaemic stroke and myocardial infarction (MI)

with lysine acetylsalicylate (Kardegic(R)) in patients with a history of ischaemic

stroke, MI or stable and unstable angina pectoris. Design and setting: This was a

modelling study from the perspectives of direct medical costs, the social security

system and society in France. Methods: Efficacy data for the secondary

prevention of ischaemic events were derived from the Antiplatelet Trialists'

Collaboration meta-analysis on antithrombotics. The rates and costs of ischaemic

disease and of serious gastrointestinal adverse affects arising from long term

aspirin treatment, as well as the costs of treatment with lysine acetylsalicylate,

were taken from published sources, using French data where possible. Results:

From the social security perspective, the estimated cost-effectiveness ratios show

that the prevention of MI in patients with a history of unstable angina (with a

1-year follow-up) is a cost-saving strategy, with net benefits ranging from

$US5703 (1996 prices) per avoided MI for lysine acetylsalicylate 300 mg/day to

$US5761 per avoided MI for lysine acetylsalicylate 75 mg/day. The prevention

of MI and stroke is also a cost-saving strategy in patients with prior MI [net

benefits in a 2-year follow-up (5% discount rate) ranging from $US15 to $US494

per avoided MI and from $US37 to $US1170 per avoided stroke]. This was also

true in patients with prior ischaemic stroke (net benefits in a 3-year follow-up

ranging from $US610 to $US2082 per avoided MI and from $US176 to $US599

per avoided stroke). Finally, a 4-year follow-up in patients with a history of

stable angina pectoris shows that prophylactic treatment with lysine

acetylsalicylate is associated with net costs per avoided MI, ranging from

$US4375 to $US3608 per avoided event. Sensitivity analysis confirmed that

prophylaxis with lysine acetylsalicylate in patients at high risk of cardiovascular

and cerebrovascular events results in savings in social security expenditure.

Conclusions: Our results underline the high economic benefit of using lysine

acetylsalicylate to prevent secondary ischaemic stroke and MI in patients at high

risk of cardiovascular and/or cerebrovascular events, leading to savings for the

social security system and society



Keywords: ALZHEIMERS-DISEASE/angina/angina

pectoris/antithrombotics/aspirin/aspirin

treatment/AUCKLAND/cardiovascular/CARE/CEREBRAL-

ISCHEMIA/cerebrovascular/CONTROLLED TRIAL/CORONARY-ARTERY

DISEASE/cost

effectiveness/COST-EFFECTIVENESS/costs/HEART-DISEASE/high

risk/history/infarction/ischaemic stroke/LOW-DOSE ASPIRIN/lysine

acetylsalicylate/meta-analysis/myocardial/myocardial

infarction/MYOCARDIAL-

INFARCTION/NEW-ZEALAND/prevention/prophylaxis/risk/secondary

prevention/STROKE/treatment/unstable angina/unstable angina pectoris



Darba, J., Izquierdo, I., Pontes, C., Navas, C. and Rovira, J. (2002), Economic

evaluation of triflusal and aspirin in the treatment of acute myocardial infarction.

Pharmacoeconomics, 20 (3), 195-201.



Abstract: Objective: To compare the costs to the Spanish healthcare system of 35 days'

treatment with triflusal (600 mg/day) and aspirin (300 mg/day) in patients with

confirmed acute myocardial infarction within 24 hours of onset of symptoms.

Design: A cost minimisation analysis based on the results of the Triflusal in

Acute Myocardial Infarction study (TIM) was conducted. The hypothesis was

that despite a higher acquisition cost of triflusal, savings would result because of

differences in efficacy and safety outcome (non-fatal cerebrovascular event and

haemorrhagic events). Diagnostic Related Groups were used as a proxy for

determining hospital costs in Spain and the values were obtained from different

sources and refer to year 2000 costs. Only direct medical costs were considered

for the economic analysis. Results: Although the acquisition cost of triflusal was

more expensive than that of aspirin, the cost of prevented events - non-fatal

ischaemic cerebrovascular events and cerebral haemorrhages - entirely

compensated for the cost of triflusal. The overall cost of treating patients with

triflusal, compared with aspirin, represented a net saving of 28.4% per patient

treated. Conclusion: Our study showed that triflusal is cost saving compared with

aspirin in the treatment of the acute phase of myocardial infarction



Keywords: acute/acute myocardial

infarction/aspirin/AUCKLAND/cerebral/cerebrovascular/cerebrovascular

event/CLINICAL-TRIALS/cost/costs/DOUBLE-BLIND/evaluation/hospital/infa

rction/ischaemic/medical/myocardial/myocardial

infarction/NEW-ZEALAND/outcome/PLACEBO/PREVENTION/safety/Spain/

STROKE/symptoms/THERAPY/TICLOPIDINE/treatment/triflusal



Buller, N., Gillen, D., Casciano, R., Doyle, J. and Wilson, K. (2003), A

pharmacoeconomic evaluation of the Myocardial Ischaemia Reduction with

Aggressive Cholesterol Lowering (MIRACL) study in the United Kingdom.

Pharmacoeconomics, 21 25-32.



Abstract: Objective: To determine the short-term healthcare costs associated with

intensive lipid lowering with atorvastatin initiated within 24-96 hours of the

occurrence of acute coronary syndrome (ACS) in patients in the UK. Methods:

Patient-level clinical outcome data from the Myocardial Ischaemia Reduction

with Aggressive Cholesterol Lowering (MIRACL) trial and standard cost data

were used to compare the total expected 16-week cost per patient on atorvastatin

80 mg/day versus placebo. Clinical outcomes assessed included the following:

death: cardiac arrest with resuscitation; nonfatal myocardial infarction:

worsening angina pectoris with objective evidence of myocardial ischaemia

requiring rehospitalisation; surgical or percutaneous coronary revascularisation;

nonfatal stroke; hospitalisation for angina without objective evidence of

myocardial ischaemia; and new or worsening congestive heart failure requiring

rehospitalisation. All relevant direct medical costs from the perspective of the

NHS were considered. Results: The total expected cost was 784.05 pounds per

patient in the placebo cohort and 851.59 pounds per patient in the atorvastatin

cohort, resulting in an incremental cost of 67.54 pounds per patient in the

atorvastatin group. The cost per event avoided was 1762.04 pounds. A third of

the cost of atorvastatin treatment was offset within 16 weeks by the cost savings

resulting from the reduction in the number of events in the atorvastatin cohort

compared with the placebo cohort. Conclusion: The clinical benefits of

short-term intensive atorvastatin treatment administered after ACS is attainable

through a marginal increase in 'upfront' costs



Keywords: acute/acute coronary syndrome/angina/angina

pectoris/ATORVASTATIN/AUCKLAND/benefits/cardiac/congestive heart

failure/CORONARY

HEART-DISEASE/cost/COST-EFFECTIVENESS/costs/death/England/evaluati

on/EVENTS/heart/heart failure/infarction/INHIBITORS/ischaemia/lipid

lowering/lipid-lowering/medical/myocardial/myocardial

infarction/NEW-ZEALAND/outcome/outcomes/POPULATION/SECONDARY

PREVENTION/SIMVASTATIN/STATINS/stroke/treatment/trial/United

Kingdom



Simons, W.R. (2003), Comparative cost effectiveness of angiotensin II receptor blockers

in a US managed care setting - Olmesartan medoxomil compared with losartan,

valsartan, and irbesartan. Pharmacoeconomics, 21 (1), 61-74.



Abstract: Objective: To compare the cost effectiveness of the angiotensin II receptor

blockers (ARBs) olmesartan medoxomil, losartan, valsartan and irbesartan for

the treatment of hypertension, from the perspective of a US managed care setting.

Methods: The evaluation was based on a recently completed, prospective,

randomised, double-blind clinical trial comparing the antihypertensive efficacy

of these agents. Differences in diastolic blood pressure reductions among the

comparative agents were used to estimate reductions in the annualised risk of

cardiovascular (CV) and cerebrovascular events using the Framingham model.

These annualised risks were translated into reductions in healthcare expenditures

associated with treating CV events covered by managed care in the US. Data

sources included: the recently published clinical trial of ARB antihypertensive

efficacy, the Framingham Heart Study and a managed care database. Actual

reimbursed amounts were used. Results: Based on antihypertensive efficacy data

versus irbesartan, the use of olmesartan medoxomil is expected to reduce the

number of new cases of CV disease, resulting in a first-year reduction in cost in a

cohort of 100 000 patients of $US906 000. Similarly, a reduction in new cases of

coronary heart disease (CHD) resulted in a cost reduction of $US701 000; a cost

reduction of $US 196 000 for fewer myocardial infarctions (MI); and a cost

reduction of $US28 000 for fewer strokes. Over 5 years, these estimates increase

to $US5 410 000 for fewer cases of CV disease; $US3 975 000 for fewer cases

of CHD; $US 1430 000 for fewer MI; and $US497 000 for fewer strokes.

Compared with valsartan, the use of olmesartan medoxomil is estimated to

reduce by $US3 397 000 the expected cost of treating a cohort of 100 000

patients in the first year for fewer cases of CV disease; by $US2 426 000 for

fewer cases of CHD; by $US565 000 for fewer MI; and by $US 124 000 for

fewer strokes. Over 5 years, these estimates increase to $US 16 231000 for CV

disease; $US 11955 000 for CHD; $US4 505 000 for MI; and $1741000 for

stroke. Compared with losartan, the estimated reduction in first-year cost is $US2

969 000 for CV disease for the cohort of 100 000 patients; $US2 163 000 for

CHD; $US732 000 for MI; and $US 124 000 for stroke. Over 5 years, these

estimates increase to $US 15 149 000 for CV disease; $US 11 107 000 for CHD;

$US4 057 000 for MI; and $1437 000 for stroke. Conclusion: Based on

comparative antihypertensive efficacy data, treatment of hypertensive patients

with olmesartan medoxomil instead of the other leading ARBs has the potential

to reduce overall cost of medical care in a US managed care setting

Keywords: angiotensin/angiotensin II/AUCKLAND/blood

pressure/BLOOD-PRESSURE/cardiovascular/cerebrovascular/CHD/clinical

trial/coronary heart disease/cost/cost effectiveness/cost-effectiveness/diastolic

blood pressure/DISEASE/evaluation/heart/heart

disease/hypertension/irbesartan/losartan/medical/myocardial/NEW-ZEALAND/

PREVENTION/REDUCTIONS/risk/risks/stroke/treatment/trial/US/USA/use/val

sartan



Maitland-van der Zee, A., Stricker, B.H.C., Klungel, O.H., Kastelein, J.J.P., Hofman, A.,

Witteman, J.C.M., Breteler, M.M.B., Leufkens, H.G.M., van Duijn, C.M. and de

Boer, A. (2002), The effectiveness of hydroxy-methylglutaryl coenzyme A

reductase inhibitors (statins) in the elderly is not influenced by apolipoprotein E

genotype. Pharmacogenetics, 12 (8), 647-653.



Abstract: We aimed to assess whether the effectiveness of statins in the prevention of

myocardial infarction, stroke and total mortality is influenced by apolipoprotein

E (apoE) genotype in an elderly population. We used data from the Rotterdam

Study, a prospective population-based cohort study in the Netherlands which

started in 1990 and included 7983 subjects aged 55 years and older. Subjects

who were treated with cholesterol lowering drugs at baseline or with a serum

total cholesterol greater than or equal to 6.5 mmol/l at baseline were included.

We compared the incidence of myocardial infarction, stroke and total mortality

in subjects who received greater than or equal to 2 years of statin treatment with

that in subjects who had been treated for less than 2 years, and in untreated

subjects, using a Cox proportional hazard model with cumulative statin use

defined as time-dependent covariates. The adjusted relative risk of all-cause

mortality was 0.79 [95% confidence interval (CI) 0.51-1.22] and of myocardial

infarction and stroke 0.50 (95% CI 0.28-0.91) for subjects treated with statins for

greater than or equal to 2 years compared to untreated subjects. The adjusted

relative risks for subjects with the epsilon4 allele were 0.91 (95% CI 0.45-1.84)

for allcause mortality and 0.63 (95% CI 0.23-1.78) for myocardial infarction and

stroke. In subjects without the epsilon4 allele, adjusted relative risks were 0.71

(95% CI 0.41-1.24) for all-cause mortality and 0.46 (95% CI 0.22-0.95) for

myocardial infarction and stroke. We found a protective effect of statins on the

risk of myocardial infarction and stroke that was independent of apoE genotype.

The protective effect of statins on total mortality was not statistically significant,

but did not seem to differ between subjects with different apoE genotypes



Keywords: aged/all-cause mortality/apolipoprotein/apolipoprotein E/apolipoprotein E

genotype/CHOLESTEROL/cholesterol-lowering/cohort study/CORONARY

ATHEROSCLEROSIS/drugs/E PHENOTYPE/E

POLYMORPHISM/effectiveness/elderly/HETEROZYGOUS FAMILIAL

HYPERCHOLESTEROLEMIA/hydroxymethylglutaryl coenzyme

A/incidence/infarction/LIPOPROTEIN RESPONSE/LOVASTATIN

TREATMENT/mortality/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/Netherlands/pharmacogenetics/popul

ation/population-based/prevention/relative

risk/risk/risks/serum/SIMVASTATIN/statin/statins/stroke/the

Netherlands/THERAPY/treatment/USA/use



Drago, F., La Manna, C., Emmi, I. and Marino, A. (1998), Effects of sulfinpyrazone on

retinae damage induced by experimental diabetes mellitus in rabbits.

Pharmacological Research, 38 (2), 97-100.



Abstract: The protective activity of the phenylbutazone derivative, sulfinpyrazone on

retinal lesions has been assessed in rabbits with severe streptozotocin-induced

diabetes. Sulfinpyrazone (8 mg kg(-1) per day per os) was administered in

diabetic animals in two different experimental procedures: for 135 days in a

preventive approach (beginning on the day of initial hyperglicaemia); and for 30

days in a therapeutic approach (beginning on the day of appearance of severe

retinal damage). The drug treatment made either with the preventive or the

therapeutic approach reduced the incidence of serious retinal lesions and

increased that of light lesions as assessed by a biomicroscopic method.

Biochemical analyses showed that experimental diabetes was accompanied by

sustained decrease in glucose and pyruvate and an increase of the lactate content

in the retina. A decrease of alpha-ketoglutarate and citrate and an increase of

succinate were also observed along with a decrease of ATP, ADP and an

increase in AMP. Either the preventive or the therapeutic approach was followed

by an increased pyruvate and ATP content and decreased lactate and AMP

content in the retinal tissue. It is possible that this drug acts on the retinal tissue

by inhibiting platelet aggregation and protecting vasal endothelium with the

consequent suppression of the release of vasoactive substances that facilitate

platelet adhesion. (C) 1998 The Italian Pharmacological Society



Keywords: ADP/aggregation/diabetes/diabetes

mellitus/endothelium/ENGLAND/glucose/incidence/ISCHEMIC

STROKE/metabolism/platelet

aggregation/PREVENTION/retina/sulfinpyrazone/THERAPY/treatment



Gurbel, P.A., O'Connor, C.M., Cummings, C.C. and Serebruany, V.L. (1999),

Clopidogrel: The future choice for preventing platelet activation during coronary

stenting? Pharmacological Research, 40 (2), 107-111.



Abstract: Ticlopidine has become an established therapy in patients with stroke, and

during stenting in patients with coronary artery disease. Clopidogrel, another

thienopyridine, is a safe and promising alternative, that irreversibly inhibits

ADP-induced platelet aggregation, and reduces formation of both arterial and

venous thrombi. In a recent, large, well-controlled trial (CAPRIE), clopidogrel

has been shown to be superior to aspirin in terms of prevention of ischaemic

stroke, myocardial infarction and death in patients with atherosclerotic vascular

disease. Clopidogrel provides a safe opportunity to enhance reperfusion when

administered during stent placement, by protecting platelets from excessive

activation. However, the ability of clopidogrel to be superior to ticlopidine in

terms of its antiplatelet properties in the clinical setting of coronary stenting, is

unknown. The effects of clopidogrel versus ticlopidine on platelet and

endothelial function are yet to be determined and may strongly affect the

outcome, benefits, and complications following coronary stent placement.

Further clinical trials, well-designed, and carefully conducted, should elucidate

possible benefits of clopidogrel during coronary interventions, especially in

conjunction with new and aggressive reperfusion techniques. The benefits of

clopidogrel in an expanding array of clinical conditions, including myocardial

infarction, may be directly related to platelet inhibition. Moreover, marginal

clinical benefits, and recently reported severe bleeding events in some patients

after oral platelet glycoprotein IIb/IIIa therapy, may advance clopidogrel as a

safe, and efficient alternative during coronary interventions. This review

summarises the latest, and often confusing data on the effects of thienopyridines

on certain haemostatic characteristics in interventional cardiology. (C) 1999

Academic Press



Keywords: activation/acute coronary syndromes/ACUTE

MYOCARDIAL-INFARCTION/AGGREGATION/antiplatelet/ANTIPLATELE

T THERAPY/ASPIRIN/C7E3 FAB/clinical

trials/clopidogrel/complications/coronary artery

disease/ENGLAND/formation/human/infarction/ischaemic stroke/ISCHEMIC

STROKE/MOLECULAR-WEIGHT HEPARIN/myocardial/myocardial

infarction/platelet activation/platelet

aggregation/platelets/prevention/RECEPTOR

EXPRESSION/reperfusion/review/stenting/stents/stroke/therapy/thienopyridines

/THROMBIN

GENERATION/TICLOPIDINE/ticlopidine/trials/vascular/vascular disease



Horner, R.D. (1998), The high cost of stroke to society, the family, and the patient.

Pharmacotherapy, 18 (3), 87S-93S.



Abstract: Stroke is the third leading cause of mortality in the United States, after heart

disease and cancer, and is a major cause of adult disability. Stroke-related

neurologic deficits affect language, cognition, and motor function. They are often

persistent, exerting a negative effect on the patient's quality of life. Besides

affecting the patient, stroke also places a heavy emotional burden on the

caregivers of patients with stroke. In the United States, the medical and

nonmedical costs of caring for patients with stroke during the first year after their

stroke are $30 billion/year, or approximately $50,000/patient. Many strokes are

preventable, however, through judicious medical or surgical therapies. In

addition, emerging thrombolytic and neuroprotective drugs, administered early

after stroke onset, may minimize or eliminate some of the residual deficits

associated with stroke. A massive educational effort is needed to raise public and

professional awareness about stroke and emerging stroke therapies



Keywords:

BURDEN/costs/DATA-BANK/drugs/ENGLAND/heart/IMPACT/ISCHEMIC

STROKE/MORTALITY/PREVENTION/stroke/THERAPY/TRENDS/TRIALS/

UNIT



Wittkowsky, A.K. (1998), The stroke pharmacopeia: Current medical therapies.

Pharmacotherapy, 18 (3), 94S-100S.



Abstract: Drug therapies that inhibit or reverse thrombus formation are important

components of the management of acute ischemic stroke. The role of antiplatelet

and anticoagulant therapies in stroke prevention has been defined, but further

research is needed to confirm the possible benefits of aspirin, heparin, and

low-molecular-weight heparin products in acute ischemic stroke. Recently,

double-blind, placebo-controlled studies have evaluated the role of the

thrombolytic agents streptokinase and tissue plasminogen activator (t-PA) in

patients with acute ischemic stroke. Intravenous t-PA, administered within 3

hours of symptom onset at a dose of 0.9 mg/kg, is safe and effective in carefully

selected patients



Keywords: ACUTE ISCHEMIC STROKE/anticoagulant/ANTITHROMBOTIC

THERAPY/aspirin/ENGLAND/formation/HEPARIN/ischemic

stroke/plasminogen activator/PREVENTION/stroke/stroke

prevention/t-PA/thrombus/TRIALS



Etminan, M. and Levine, M. (1999), Interpreting meta-analyses of pharmacologic

interventions: The pitfalls and how to identify them. Pharmacotherapy, 19 (6),

741-745.



Abstract: Meta-analyses are key components of evidence-based decision making. The

numbers of meta-analyses published in different areas of health care increased

dramatically during the past 10 years. Many of them covered different

pharmacologic interventions, making them useful resources to clinical

pharmacists. Although a well-conducted meta-analysis may be valuable, a pearly

conducted one may have false conclusions and thus incorrectly alter a clinician's

recommendations. Several key concepts must be considered when appraising

meta-analyses of pharmacologic interventions



Keywords: BLOOD-PRESSURE/decision-making/ENGLAND/health/health

care/HEART-DISEASE/INDOMETHACIN/meta-analysis/METAANALYSIS/

MYOCARDIAL-INFARCTION/NONSTEROIDAL ANTIINFLAMMATORY

DRUGS/pharmacists/PRAVASTATIN/PREVENTION/RANDOMIZED

TRIALS/STROKE



Bungard, T.J., Ackman, M.L., Ho, G. and Tsuyuki, R.T. (2000), Adequacy of

anticoagulation in patients with atrial fibrillation coming to a hospital.

Pharmacotherapy, 20 (9), 1060-1065.



Abstract: Study Objective. To evaluate the adequacy of anticoagulation in patients with

atrial fibrillation (AF) coming to a hospital. Design. Retrospective medical

record review Setting. Tertiary care hospital. Patients. Consecutive patients with

a history of AF who had been prescribed warfarin and who had the international

normalized ratio (INR) measured when they arrived at the hospital. Those who

developed AF as a complication during hospitalization were excluded.

Measurements and Main Results. Of 1085 patients, 375 (mean age 73 yrs, 56.3%

men) were eligible for further evaluation. Most had nonvalvular AF; in 44.5%

the INR was subtherapeutic, in 36.5% it was therapeutic, and in 18.9% it was

supratherapeutic. Patients admitted for any thromboembolic event and for

ischemic stroke were significantly more likely to have subtherapeutic INRs.

Conclusion. It is well documented in the literature that warfarin is

underprescribed, but our results suggest that even in treated patients, about half

are inadequately protected from thromboembolism



Keywords: AF/age/anticoagulation/atrial

fibrillation/CARE/ENGLAND/evaluation/fibrillation/history/hospital/hospitaliza

tion/INR/international normalized ratio/ischemic/ischemic

stroke/MANAGEMENT/men/review/stroke/STROKE

PREVENTION/thromboembolism/TRIALS/WARFARIN



Sharp, R.P. and Havrda, D.E. (2002), Possible effect of refrigeration of warfarin on the

international normalized ratio. Pharmacotherapy, 22 (1), 102-104.



Abstract: A 43-year-old African-American woman taking warfarin for prevention of

ischemic stroke experienced fluctuating international normalized ratio (INR)

values over 8.5 months; no cause could be identified. After reading a pharmacy

information sheet that accompanied a warfarin refill, she reported that she had

been refrigerating her warfarin because her other drugs had been "sticking

together." She then was instructed to store her warfarin at room temperature.

During the 8.5 months she had been refrigerating her warfarin, 80% of her INR

values had been outside her goal range versus 37.5% during 9 months of storage

at room temperature. A MEDLINE search and communication with the drug's

manufacturer provided no information regarding storage of warfarin outside the

temperature range of 59-86 degreesF and resultant changes in potency of the

drug. Because of potential fluctuation in anticoagulation control, patients should

be reminded to store their warfarin at room temperature



Keywords: African

American/anticoagulation/changes/control/drug/drugs/ENGLAND/INR/internati

onal normalized ratio/ischemic/ischemic

stroke/pharmacy/prevention/stroke/USA/warfarin



Keyser, A. (1993), Platelet-Aggregation Inhibitors in Neurology. Pharmacy World &

Science, 15 (6), 243-251.



Abstract: This literature review reports on secondary prevention bf ischaemic stroke.

The aim of secondary prevention is to protect patients who belong to a risk group

from the occurrence of brain infarction. Symptomatic patients with a

demonstrated carotid artery stenosis of 70% and more will most probably benefit

from carotid endarterectomy if performed by a skilled surgeon in the absence of

contraindications. Oral anticoagulant drugs play a minor role in the medical

prevention of brain infarction. Antiplatelet drugs, however, have been in use for

almost two decades and (meta-)analysis of clinical trials points io acetylsalicylic

acid as a drug with a modest but certain contribution of about 15% in the

endpoint reduction, even at lower dosages. The addition of dipyridamole to

classic acetylsalicylic acid dose appears to increase the endpoint reduction to

30%. Neither dipyridamole nor sulfinpyrazone as monotherapy have been

demonstrated to be efficacious in the secondary prevention of ischaemic stroke.

Ticlopidine seems a promising alternative for acetylsalicyclic acid in those

patients who suffer adverse effects from acetylsalicylic acid. Ticlopidine itself,

however, has a number of side-effects that limit its application. New clinical

trials are under way in order to improve the efficacy of drug treatment in the

secondary prevention of brain infarction



Keywords: acetylsalicyclic acid/ACETYLSALICYLIC

ACID/ACETYLSALICYLIC-ACID/ADVERSE EFFECTS/carotid/carotid

endarterectomy/CEREBRAL INFARCTION/CEREBRAL

ISCHEMIA/CEREBRAL-

ISCHEMIA/CEREBROVASCULAR-DISEASE/clinical trials/CONTROLLED

TRIAL/DIPYRIDAMOLE/DOSAGE/endarterectomy/LOW-DOSE

ASPIRIN/prevention/PRIMARY

PREVENTION/PROGNOSIS/risk/SECONDARY

PREVENTION/STROKE/SULFINPYRAZONE/TICLOPIDINE/TRANSIENT/

TRANSIENT ISCHEMIC ATTACKS/treatment/trials



Krest, I. and Keusgen, M. (1999), Stabilization and pharmaceutical use of alliinase.

Pharmazie, 54 (4), 289-293.



Abstract: In recent years, numerous clinical trials were undertaken in order to elucidate

the active principle of garlic (Allium sativum L., Alliaceae). The most prominent

effect of garlic preparations is a contribution to the prevention of stroke and

arteriosclerosis. Allicin [(2-propenyl)-2-propenethiosulfinate] and other sulfur

containing compounds were suggested as active compounds. The extremely

unstable allicin itself is liberated from the more stable alliin

[S-(+)-2-propenyl-L-cysteine sulfoxide] by the enzyme alliinase (EC 4.4.1.4) if

fresh garlic is crunched or garlic powder is moistened. Therefore, an active

enzyme is required in alliin containing remedies like those prepared from garlic

powder. In order to investigate enzyme stability, alliinase was isolated from

garlic powder. The partially purified enzyme could be stabilized over several

months by addition of sodium chloride, sucrose, and pyridoxal- 5'-phosphate.

Alliinase may also be freeze-dried. This allows combinations of synthetic alliin

and purified alliinase as components of an acid resistant tablet or capsule. In the

intestine, the pro-drug alliin would be enzymatically converted to allicin. In

clinical trials, highly dosed preparations of this kind should yield a precise

information about the physiological effects of allicin. In addition, alliin-

homologues substances which bear a modified alkyl side chain and do not occur

in nature may be tested



Keywords: ALLICIN/arteriosclerosis/C-S LYASES/clinical trials/GARLIC

ALLIUM-SATIVUM/HIGHER-PLANTS/OXIDATION/prevention/PURIFICA

TION/sodium/stroke/trials



Khaw, K.T. (1997), Epidemiological aspects of ageing. Philosophical Transactions of

the Royal Society of London Series B-Biological Sciences, 352 (1363),

1829-1835.



Abstract: A major societal challenge is to improve quality of life and prevent or reduce

disability and dependency in an ageing population. Increasing age is associated

with increasing risk of disability and loss of independence, due to functional

impairments such as loss of mobility hearing and vision; a major issue must be

how far disability can be prevented. Ageing is associated with loss of bone tissue,

reduction in muscle mass, reduced respiratory function, decline in cognitive

function, rise in blood pressure and macular degeneration which predispose to

disabling conditions such as osteoporosis, heart disease, dementia and blindness.

However, there are considerable variations in different communities in terms of

the rate of age-related decline. Large geographic and secular variations in the

age-adjusted incidence of major chronic diseases such as stroke, hip fracture,

coronary heart disease, cancer, visual loss from cataract, glaucoma and macular

degeneration suggest strong environmental determinants in diet, physical activity

and smoking habit. The evidence suggests that a substantial proportion of

chronic disabling conditions associated with ageing are preventable, or at least

postponable and not an inevitable accompaniment of growing old. Postponement

or prevention of these conditions may riot only increase longevity, but, more

importantly, reduce the period of illnesses such that the majority of older persons

may live high-quality lives, free of disability, until very shortly before death. We

need to understand better the factors influencing the onset of age-related

disability in the population, so that we have appropriate strategies to maintain

optimal health in an ageing population



Keywords: age/blood pressure/CHOLESTEROL/cognitive function/coronary heart

disease/CORONARY

HEART-DISEASE/dementia/diet/diseases/ENGLAND/HEALTH/heart/incidenc

e/LOWER BLOOD-PRESSURE/MORTALITY/muscle/osteoporosis/physical

activity/PREVENTION/quality of life/risk/SALT

REDUCTION/SMOKING/STROKE/TRIALS



Kammer, C.S., Young, C.C. and Niedfeldt, M.W. (1999), Swimming injuries and

illnesses. Physician and Sportsmedicine, 27 (4), 51-+.



Abstract: Swimming has a distinct profile of injuries and medical conditions. Common

problems seen among swimmers include 'swimmer's shoulder,' an overuse injury

that causes inflammation of the supraspinatus and/or the biceps tendon; overuse

injuries of the elbow, knee, ankle, and back; medical conditions such as asthma,

folliculitis, and otitis externa; and problems associated with overtraining.

Swimmers are more likely to comply with treatment plans that minimize time

spent out of the water. Prevention and treatment of musculoskeletal injuries often

focus on proper stroke mechanics



Keywords: COMPETITIVE

SWIMMERS/elbow/ELITE/inflammation/LAXITY/MUSCLE/overuse

injury/PAIN/PHYSICIAN/SHOULDER/STRENGTH/stroke/treatment



Johnson, J.N., Gauvin, J. and Fredericson, M. (2003), Swimming biomechanics and

injury prevention - New stroke techniques and medical considerations. Physician

and Sportsmedicine, 31 (1), 41-46.



Abstract: Shoulder injuries are common in swimmers of all ages and abilities. Advances

in the understanding of biomechanics help identify and correct stroke flaws to

prevent shoulder injury. Physicians can demonstrate correct pull patterns and

body alignment in an office setting, and proper coaching can help correct

mistakes made in the water. If injury occurs, swimmers can employ rehabilitation

techniques, including preventive scapular stabilization exercises, to prevent

recurrence. The treating physician and physical therapist who understand stroke

technique and prevention concepts may help decrease the incidence of

swimming-related shoulder injuries



Keywords: ATHLETIC

SHOULDER/biomechanics/incidence/injury/medical/MUSCLES/PHYSICIAN/p

revention/recurrence/REHABILITATION/shoulder/stroke/SWIMMERS/USA



Inzitari, D. (1993), Therapeutic Approach to Symptomatic and Asymptomatic Carotid

Stenosis. Platelets, 4 18-19



Keywords: ASPIRIN/BLOOD-PRESSURE/DISEASE/ISCHEMIC

ATTACKS/PREVENTION/STROKE/TICLOPIDINE



Nenci, G.G. (1993), Antithrombotic Therapy of Peripheral Vascular-Disease. Platelets,

4 21-23



Keywords: ASPIRIN/DIPYRIDAMOLE/INDOBUFEN/INTERMITTENT

CLAUDICATION/PREVENTION/RISK/STROKE/TICLOPIDINE/TRIAL



Pathansali, R., Smith, N.M. and Bath, P.M.W. (2001), Prothrombotic megakaryocyte

and platelet changes in hypertension are reversed following treatment: a pilot

study. Platelets, 12 (3), 144-149.



Abstract: Platelets are formed from, and their function determined by, bone marrow

megakaryocytes (MK). Previous studies have found that hypertension is

associated with accentuated platelet function and that some anti-hypertensive

drug classes have antiplatelet activity. We measured MK ploidy (DNA content),

size, granularity, and expression of the adhesion molecule glycoprotein (GP) IIIa,

using flow cytometry and measures of platelet function, in 12 untreated

hypertensive patients and 14 normotensive subjects. Eight hypertensive patients

were then treated with losartan (50 mg daily), an angiotensin receptor antagonist

that lowers blood pressure, and MK and platelet parameters re-measured after 6

weeks. Hypertensive patients had, as compared with matched normotensive

subjects: increased MK ploidy (mean +/- SD) 22.9 +/- 2.2 N versus 20.8 +/- 1.6

N (2P = 0.009); increased platelet size, 10.67 +/- 1.03 fl versus 9.26 +/- 0.72 fl

(2P = 160/95 mm Hg on >= 2 occasions within 3 months or

received antihypertensives, High proportions of cases (82%) and controls (85%)

were on treatment. There was a continuous relationship between the risk of

stroke and levels of BP control. Of 73 cases and 135 controls who were

hypertensive and responded to the postal questionnaire, 56 and 83%, respectively,

were aware of hypertension (P 18 on the

HAM-D-17 and score :9 on the HAM-D-6. Approximately 10% of the

sertraline-treated group developed depression according to either definition,

whereas 30% developed depression in the placebo group. On the HAM-D-6 the

superiority of sertraline to placebo was demonstrated already after 6 weeks of

therapy. Treatment was well tolerated; patients treated with sertraline

experienced significantly fewer adverse events



Keywords: acute/acute ischemic stroke/adverse

events/Denmark/depression/FLUOXETINE/FOLLOW-UP/FUNCTIONAL

RECOVERY/ischemic/ischemic stroke/LABILITY/POSTSTROKE

DEPRESSION/prevention/stroke/stroke

patients/THERAPY/treatment/TRIAL/USA



Helmert, U. and Shea, S. (1994), Social Inequalities and Health-Status in Western

Germany. Public Health, 108 (5), 341-356.

Abstract: Study Objective: To examine social class gradients for seven self-reported

diseases in western Germany. Design: A pooled analysis of three cross-sectional

representative health surveys in western Germany and three health surveys in the

six intervention regions of the German Cardiovascular Prevention Study.

Participants: 44,363 study subjects, of both sexes, with German nationality, aged

25-69 years, were examined in the national and regional health surveys from

1984 to 1991. Measurement and main results: Assessment of disease prevalence

was carried out by a standardized self-administered questionnaire. Social class

was assessed using a composite index combining educational achievement,

occupational status and household income. Cigarette smoking and Pattern A

behaviour were based on self-report. Height and weight were measured by

physical examination and body mass index was calculated. Statistical analysis

were performed using multiple logistical regression. Response rates ranged from

66.0 to 71.4% in the national surveys and from 65.9 to 83.8% in the regional

surveys. For both sexes, the prevalence of previous myocardial infarction and the

prevalence of stroke, diabetes mellitus and chronic bronchitis was significantly

higher in the lower social classes. In males only, the prevalence of intervertebral

disc damage and peptic ulcer was significantly higher in the lower social classes.

In females only, there was a similar gradient for hyperuricaemia and gout. In

both sexes, allergies and hay fever were the only diseases with higher prevalence

in the higher social classes. Adjusting these trends for smoking, obesity and

Pattern A behaviour resulted in only minor changes in the slopes of the

disease-specific social class gradients. Conclusion: In western Germany, despite

a health system with almost free access for the general population, strong social

class inequalities exist for many diseases. These inequalities cannot be explained

by social class differences in smoking, obesity or Pattern A behaviour. More

research is needed to identify underlying causes for these persistent social

inequalities in health status



Keywords: aged/diabetes

mellitus/DISEASE/diseases/EDUCATION/ENGLAND/HEALTH/INEQUITIES

/myocardial infarction/smoking/stroke/SWEDEN



Smith, G.D., Shipley, M.J., Batty, G.D., Morris, J.N. and Marmot, M. (2000), Physical

activity and cause-specific mortality in the Whitehall study. Public Health, 114

(5), 308-315.



Abstract: A prospective cohort study of London civil servants was used to examine the

relation of physical activity to various causes of death. 6.702 men aged 40-64y

who participated in a baseline examination between 1969 and 1970 were

followed up for 25y during which time there were 2859 deaths. The association

of two measures of physical activity (leisure time activity and usual walking pace)

with cause-specific mortality was examined. Walking pace demonstrated inverse

relations with mortality from all-causes, coronary heart disease (CHD), other

cardiovascular disease (CVD), all cancers, respiratory disease, colorectal cancer

and haematopoietic cancer following adjustment fur risk factors which included

age, employment grade, smoking, body mass index, and forced expiratory

volume (P [trend] 7.2 mmol/l) was at lower risk than a man with low

cholesterol (20% in

the EC). Functional recovery on hospital discharge was worse in the group with

systemic complications (IB: 43.05+/--34.1: as compared with IB: 72.8+/--22.7 in

the group without complications). This difference persisted after 3 months.

Conclusions. Systemic complications related to hospitalization have a negative

effect on the functional recovery of patient with ictus and also prolong the time

spent in hospital



Keywords: age/CEREBRAL INFARCTION/cerebrovascular/cerebrovascular

disease/complications/CONTROLLED TRIAL/DEATH/hospital/hospital

morbidity/hospitalization/HYPERGLYCEMIA/ischemic/ISCHEMIC

CEREBROVASCULAR-DISEASE/MANAGEMENT/MORTALITY/NATURA

L-HISTORY/prevention/prospective

study/RISK/SPAIN/stroke/treatment/vascular/vascular disease



Biller, J. (1997), Treatment protocol for stroke. Revista de Neurologia, 25 (137), 114



Keywords: PREVENTION/SPAIN/stroke



AlvarezSabin, J., Calvo, G. and Morros, R. (1997), Secondary prevention of ischaemic

strokes: Effect of dosage of aspirin. Revista de Neurologia, 25 (140), 541-544.



Abstract: Introduction and objective. The value of acetylsalicilic acid (AAS) in the

secondary prevention of ischemic stroke is well established. However, the

optimum dose of AAS for stroke- threatrened patients remains unsettled. This

paper reviews the pattern of adverse reactions to AAS and their relationship to

the dosage of AAS evaluated. Method. All the clinical trials in which AAS was

used as the sole antiaggregant in the secondary prevention of ischemic stroke

were reviewed. The crude odds ratio for the different adverse reactions was

calculated using three sub tests: AAS versus placebo; AAS330 mg/d; and each dosage level versus a placebo. Results. There is an

increased risk associated with the use of AAS as compared to a placebo with

respect to gastrointestinal bleeding (OR 2.3, IC 95% (1.6-4.1)), peptic ulcer (10.1

2.5-85.2)), intracerebral hemorrhage (2.2 (1.3-4)) and other hemorrhagic

phenomena (2.6 (2-3.3)). Conclusions. There seems to be a direct relationship

between the dosage of AAS and the frequency with which adverse reactions

occur, except in the case of intracerebral hemorrhage. In the latter case there was

no relationship with the dose give (0.8 (0.5-1.4))



Keywords: aspirin/ATTACKS/CEREBRAL-ISCHEMIA/clinical trials/dose of

aspirin/hemorrhage/intracerebral hemorrhage/ischemic/ischemic stroke/platelet

antiaggregation/prevention/RANDOMIZED TRIAL/RISK/secondary

prevention/SPAIN/stroke/stroke prevention/trials/WARFARIN



MatiasGuiu, J., AlvarezSabin, J. and Codina, A. (1997), A comparative study of the

effect of low doses of acetylsalicylic acid and triflusal in the prevention of

cardiovascular incidents in young adults with ischemic cerebrovascular disease.

Revista de Neurologia, 25 (147), 1669-1672.



Abstract: Introduction. The effectiveness of the low doses AAS in the prevention of the

cerebral infaction has not been clearly still verified. Objective. To compare the

long term effectiveness of the treatment with low doses AAS in front of triflusal

in the reduction of the stroke, ischemic cardiopathy, and cardiovascular death

risks. Material and methods. Of 386 patients with a first ischemic stroke, 217

were selected (106 triflusal, 111 AAS) that had completed the approaches of

atheromatous infarct (161 males, 72.2% and 58 female, 25.8%). The mean age

was 43 years (standard deviation, SD 6.4, 95% CL 20-50). The patients received

one of theses treatments: a) AAS (Sedergine(R)) 330 mg/day (once a day); b)

triflusal (Disgren(R)), 900 mg/day (300 mg 3 times a day). The mean time of

follow-up for the group triflusal was of 48.3 months (20- 94), while for the group

AAS it was of 46.3 months (2-84). Results. The combined incidence of cerebral

infarcts, ischemic cardiopathy and vascular death was 19.8% in the patients

treated with triflusal, and 28.8% in the patients treated with AAS what supposes

a reduction of the risk of the 39% (OR 0.61, CL 0.30-2.01). In the subgroup of

patients with carotid stenoses of more than 70% demonstrated by angiography,

triflusal produces a significant reduction of risk (OR 0.30, CL 0.10-0.90). Also,

triflusal reduced in 76% the risk of hemorrhagic complications in comparison of

the AAS (OR 0.24; IC 0.06-0.94). Conclusions. The study adds new doubts

about the effectiveness of the low doses of AAS in the secondary prevention of

the cerebral infarct. The triflusal shows effectiveness in subgroup of high risk

and a significant reduction of the hemorrhagic complications that would be

confirmed in controlled clinical trials with a greater number of patients

Keywords: acetylsalicylic acid/adults/age/antiplatelet

drugs/ASPIRIN/aspirin/carotid/cerebral/cerebrovascular/cerebrovascular

disease/clinical trials/complications/incidence/ischemic/ischemic

cardiopathy/ischemic stroke/prevention/risk/secondary

prevention/SPAIN/STROKE/stroke/SUBGROUPS/treatment/trials/triflusal/vasc

ular/young adults



LopezPousa, S., MercadalDalmau, J., MartiCuadros, A.M., VilaltaFranch, J. and

LozanoGallego, M. (1997), Triflusal in the prevention of vascular dementia.

Revista de Neurologia, 25 (146), 1525-1528.



Abstract: Introduction. Vascular dementia is the second commonest cause of dementia

after Alzheimer's disease. The most important risk factor for this is previous

cerebral vascular accident. Objective. To eliminate the risk factors and/or

progression of this illness would be of considerable benefit to these patients.

Triflusal, a platelet anti-aggregant chemically I elated to the salicylates, whose

clinical efficacy has been shown in cardiac and cerebrovascular pathology, has

been used in the treatment of patients with vascular dementia. Material and

methods. Ail open study was done a sample of 73 patients with vascular

dementia randomly distributed into two groups (control and undergoing

treatment with triflusal). Results. To check the efficacy of treatment with triflusal,

the percentage of variation in the scoring of the Cognitive Mini Examination was

used after a clinical course of 12 months (IVP 12), considering the critical point

of no efficacy to be a loss equal ol greater than 10%. In the control group, 33%

(8/24) and in the group treated with triflusal 8% (3/35) had a negative course

which was greater than this critical point. Conclusions. The difference in the IVP

12 between the two groups was statistically significant (p=0.0375), with a

statistical power of 87% (beta=0.13). This gives triflusal a therapeutic activity

which is sufficient to limit cognitive deterioration of patient with vascular

dementia



Keywords: anti-aggregants/ASPIRIN/cerebral/CEREBRAL

BLOOD-FLOW/cerebrovascular/control/dementia/DIAGNOSIS/DISEASE/HOS

PITALIZED COHORT/LESIONS/MULTI-INFARCT

DEMENTIA/prevention/risk/risk

factors/RISK-FACTORS/SPAIN/STROKE/treatment/TRIAL/triflusal/vascular/v

ascular dementia



Vila, N. and Chamorro, A. (1997), The effect of clinical trials on hospital admission for

stroke. Revista de Neurologia, 25 (143), 1129-1131.



Abstract: Objective. To analyze the contribution of clinical trials in the hospital

treatment of acute ischaemic cerebrovascular disease. Development. In recent

studies many trials have been designed for the treatment of the acute phase of

this illness. Based on experimental studies, the drugs used in the trial need to be

given within a 'therapeutic window' of less than six hours from the onset of the

illness. This time factor has led to a radical change in the organization of hospital

services dealing with this illness. In order to run clinical trials the medical staff

have had to be organized into functional stroke units for the swift protocolized

diagnosis of the condition. Also information has to be given to health workers

regarding the need for urgent specialized treatment. Several studies have shown

that early, specialist treatment reduces morbi-mortality, time spent in hospital

and financial cost in these patients. Conclusion. Clinical trials in acute

cerebrovascular pathology have formed the basis for the creation of stroke units,

led to the drawing up of protocols for the diagnosis and guidelines for treatment.

It has also made the medical profession more aware of the importance of early

diagnosis and specialized treatment in acute cerebral ischemia



Keywords: ACUTE ISCHEMIC STROKE/CARE/cerebral/cerebral

ischemia/cerebrovascular/cerebrovascular disease/clinical

trials/cost/diagnosis/drugs/guidelines/health/hospital/ischemia/MANAGEMENT/

PREVENTION/protocols/SPAIN/stroke/stroke units/THERAPY/treatment/trials



Palomeras, E., Roquer, J. and Pou, A. (1998), Oral anticoagulation in the prevention of

secondary cerebral vascular disease. A long-term follow-up of 169 patients.

Revista de Neurologia, 27 (159), 772-776.



Abstract: Introduction. Although the indications for oral anticoagulation (AO) in the

treatment of cerebral vascular disease (CVD) are well established, their potential

side effects continue to give cause for worry. Objectives. To describe the

complications and ischemic relapses inpatients treated with AO for secondary

prevention of CVD of cardiac embolic origin. Patients and methods. We included

169 patients with embologenic cardiopathy who,following an CVD, were treated

with AO and followed-up at our medical centre for at least three months, We

recorded their past clinical history and risk factors, occurrence of vascular

relapses (VR), complications involving hemorrhage (CH), and data regarding

course and follow-up. Results. During an average follow-up of 50.3 months of a

total of 707.9 patient/years, 20 VR (2.8% per year) were recorded; 15 of these

were cerebro- vascular and mainly mild. We recorded 59 CH in 41 patients

(8.3% per year) of which 6 were considered to be major: There was a 30%

drop-out rate from follow-up at our centre, mainly due to death from other causes

or to change referral centre. Conclusions. There is a low incidence of relapse and

of complications (usually mild) following AO for the secondary prevention of

CVD of cardio-embolic origin. Efficacy and security are maintained in the long

term [REV NEUROL 1998; 27:772-6]



Keywords: anticoagulation/cerebral vascular disease/complications/embologenic

cardiopathy/hemorrhage/HEMORRHAGIC

COMPLICATIONS/history/incidence/NONRHEUMATIC

ATRIAL-FIBRILLATION/oral

anticoagulation/OUTPATIENTS/prevention/risk/risk factors/secondary

prevention/SPAIN/STROKE/THERAPY/treatment/vascular/vascular

disease/WARFARIN

Sabin, J.A., Matias-Guiu, J., Galiano, L. and Puiggros, A.C. (1998), The risk of

hemorrhage in long-term treatment with aspirin and triflusal. Revista de

Neurologia, 27 (160), 951-955.



Abstract: Introduction. Different studies have shown that aspirin (AAS), in low doses,

may lend to a considerable frequency of hemorrhagic complications when used

in the long term. Objective. We compare the long-term occurrence of

hemorrhagic complications with low doses of AAS and high doses of triflusal.

Patients and methods. Our series included 106 patients who took 900 mg triflusal

per day (300 mg 3 times per day) and I I I who took AAS (330 mg/day once

daily). The former were followed up for an average period of 48.3 months (20-94)

and the latter for 46.3 months (2-84). The average follow-up period for the study

was 47.3 months. The presence of hemorrhagic complications was evaluated as

was their frequency and follow-up curve. Results. Compared with AAS, triflusal

led to a 76% reduction in risk of hemorrhagic complications (2.8% against

10.8%; OR 0.24; IC 0.06-0.94). There was a slightly increased incidence of

hemorrhages in the women's group. There were more hemorrhages than

gastrointestinal hemorrhages (4.5% against 0.9%) and intracranial hemorrhages

(1.8%-0.9%). The follow-up curve showed significant differences in the form of

an increased risk of hemorrhagic complications with AAS. Conclusions. The risk

of hemorrhage with AAS depended on the period of follow-up, in a similar

manner to with oral anticoagulant agents, in patients with prophylaxis of cerebral

infarct. On the other hand, this did not occur with triflusal, with which the risk

was homogeneous and lower in the long term [REV NEUROL 1998; 27: 951-5]



Keywords: ACETYLSALICYLIC-ACID/anticoagulant/antiplatelet

agents/aspirin/cerebral/complications/DIPYRIDAMOLE/hemorrhage/incidence/I

NHIBITION/intracerebral hemorrhage/ISCHEMIC

STROKE/prophylaxis/risk/SECONDARY

PREVENTION/Spain/stroke/SUBGROUPS/treatment/TRIAL/triflusal/YOUNG-

ADULTS



Davalos, A. and Suner, R. (1999), Monitoring and the management of strokes in the

acute phase. Revista de Neurologia, 29 (7), 622-627.



Abstract: Introduction. Treatment of acute strokes in a Stroke Unit reduces intrahospital

mortality and dependence by 29%. One year later this effect is still present. It is

not known whether the use of intermediate care in the so-called Acute Stroke

Units, with continuous cardiovascular and neurological monitoring, provides

further benefit in addition to that obtained by specialized care units in which

monitoring is carried out at the usual intervals. Development and conclusions. In

this article we analyze the advantages of Acute Stroke Units in the application of

new treatments and their potential benefits in the prevention of medical

complications, we also review the general recommendations for treatment in the

acute phase of strokes [REV NEUROL 1999; 29: 622-7]

Keywords: acute/ACUTE ISCHEMIC STROKE/acute stroke/BLOOD-

PRESSURE/cardiovascular/CEREBRAL-ARTERY

INFARCTION/complications/CONTROLLED

TRIAL/monitoring/mortality/prevention/PROGNOSIS/PROPHYLAXIS/review/

Spain/stroke

unit/TEMPERATURE/THERAPY/THROMBOSIS/treatment/UNITS



Vivancos-Mora, J., Leon-Colombo, T. and Monforte-Dupret, C. (1999), Hypolipemic

treatment in the prevention of atherosclerotic plaque complications. Revista de

Neurologia, 29 (9), 857-863.



Abstract: Introduction and objective. Hypercholesterolemia has been shown to be a

definite risk factor for coronary disease, although its relevance in cerebrovascular

disease is more controversial. This study reviews the part played by different

hypolipemic treatments in primary and secondary prevention of the

complications of atherothrombotic diseases, particularly stroke. Development.

We based our study mainly on the HMG-CoA inhibitors (3-hydroxyl 3 methyl

glutaryl coenzyme A) reductase, or statines. This group of drugs acts by,

inhibiting the synthesis of cholesterol and increasing the expression of LDL-c

receptors, achieving a 25-35% lowering of plasma LDL-c levels. In diverse

clinical trials they have been shown to have a beneficial effect in the prevention

of cardiovascular disease. The results of these studies indicate that in addition to

their purely hypolipemic effect, other antiatherothrombotic mechanisms are

involved. We analyse the main studies on hypolipemic drugs in the primary and

secondary prevention of coronary and cardiovascular disease. Conclusions. The

role of statines is clearly defined in reduction of the risk of overall and

cardiovascular mortality and also in reduction of the incidence of cardiovascular

incidents inpatients with a past history of coronary disease and a cholesterol level

over 155 mg/dl. Reduction of the risk from cerebrovascular disease has only

been observed in primary prevention studies; (patients with a past history of

coronary disease). Therefore, we shall have to await the results of the clinical

trials currently being carried out to determine the true role of statines in the

secondary prevention of cerebrovascular disease



Keywords: acute cerebrovascular disease/arteriosclerosis/AVERAGE CHOLESTEROL

LEVELS/cardiovascular disease/cardiovascular mortality/CAROTID

ATHEROSCLEROSIS/cerebrovascular/cerebrovascular

disease/cholesterol/CLINICAL EVENTS/clinical trials/COA REDUCTASE

INHIBITORS/complications/coronary disease/CORONARY- ARTERY

DISEASE/diseases/drugs/history/HYPERCHOLESTEROLEMIA/hypolipemic

treatment/incidence/MEN/mortality/myocardial

infarct/plaque/PRAVASTATIN/prevention/primary

prevention/PROGRESSION/prophylaxis/receptors/risk/risk factor/secondary

prevention/Spain/statines/stroke/STROKE/treatment/trials



Berciano, J. (1999), From the genetics to the prevention of stroke. Revista de Neurologia,

29 (9), 836-847.

Abstract: Genetic risk factors implicated in stroke are reviewed. There is evidence that

family history of vascular disease is an independent risk factor for stroke. Twin

studies demonstrated that there is a genetic component for stroke. I review the

possible pathogenetic relevance of several vascular risk factors, namely

dyslipoproteinemia, Lp(a), ApoE, homocystein, and prothrombotic states. Finally,

I carry out an overview of genetic monogenic disorders manifesting with embolic

stroke, thrombotic stroke or hemorrhagic stroke. This review corroborates that

there are many genetic risk factors of stroke, though further studies will be

necessary, to establish whether ol not these factors ave pathogenetically

independent from acquired factors



Keywords: CADASIL/embolism/genetic/genetics/hemorrhage/HEREDITARY

HEMORRHAGIC TELANGIECTASIA/history/INTRACRANIAL

ANEURYSMS/ISCHEMIC

CEREBROVASCULAR-DISEASE/MANIFESTATIONS/MOYAMOYA-

DISEASE/prevention/PROTEIN-C RESISTANCE/PROTHROMBOTIC

STATES/risk/risk factor/risk

factors/SNEDDONS-SYNDROME/Spain/stroke/thrombosis/vascular/vascular

disease/YOUNG-ADULTS



Alvarez-Sabin, J. and Montaner-Villalonga, J. (1999), Antiplatelet therapy of secondary

stroke prevention after ESPS- 2 and CAPRIE. Revista de Neurologia, 29 (8),

780-784.



Abstract: Introduction. Antiplatelet therapy is effective for secondary prevention of

atherothrombotic stroke. Aspirin, the more frequently used antiplatelet drug,

prevents 13 to 17% of ischemic events after stroke. New and more effective

antiplatelet therapies are needed. Development. Two large secondary stroke

prevention trials have been recently published (CAPRIE and ESPS-2), including

more than 25,000 patients. As well TACIP trial designed to assess the efficacy of

triflusal, is close to end. The combination of ticlopidine and Aspirin has shown

synergistic effect. Conclusions. Clopidogrel, like ticlopidine, increase 9% the

relative risk reduction of stroke over Aspirin. Clopidogrel has a better safety

profile than ticlopidine. Dipyridamole is an effective antiplatelet drug but in

combination with low doses of Aspirin is more effective. The possible efficacy

of clopidogrel-Aspirin combination should be evaluated [REV NEUROL 1999;

29: 780-4]



Keywords: antithrombotic therapy/ASPIRIN/aspirin/clopidogrel

dipyridamole/DIPYRIDAMOLE/ischemic/prevention/relative

risk/risk/safety/secondary prevention/secondary stroke

prevention/Spain/stroke/stroke

prevention/therapy/TICLOPIDINE/TRIAL/trials/triflusal



Ameriso, S.F. (1999), Treatment of cerebrovascular disease with anticoagulants and

platelet anti-aggregants. Revista de Neurologia, 29 (12), 1285-1290.

Abstract: Introduction. The use of anticoagulants and platelet anti- aggregants is one of

the basic features of the management of patients with cerebrovascular disease.

Development. The indications for the use of these agents have evolved from

initial empirical use based on anecdotic evidence to current recommendations

following multi-centre trials. Aspirin, ticlopidine, clopidogrel and warfarin are

drugs of choice for secondary prevention of ischemic stroke (IS). Anticoagulants

are used more inpatients with IS of cardio-embolic origin. The use of

anti-aggregants/anticoagulation in acute IS has not been shown to be clearly

effective and its use is limited to particular cases in which fibrinolytic treatment

cannot be used. For satisfactory use of these drugs it is essential to correctly

identify the type of IS and its progress over time. This article reviews the criteria

established for the use of such treatment and describes the developing areas of

multi- centre clinical trials [REV NEUROL 1999; 29: 1285-90]



Keywords: ACETYLSALICYLIC-ACID/acute/ACUTE ISCHEMIC

STROKE/AMERICAN-HEART-ASSOCIATION/anti-aggregant/anti-aggregant

s/anticoagulant/anticoagulants/ANTITHROMBOTIC

THERAPY/ATRIAL-FIBRILLATION/cerebral

infarction/CEREBRAL-ISCHEMIA/cerebrovascular/cerebrovascular

disease/clinical trials/clopidogrel/disease/drugs/essential/FACTOR-V

LEIDEN/inpatients/ischemic/ischemic

stroke/MYOCARDIAL-INFARCTION/PREVENTION/secondary

prevention/SPAIN/stroke/ticlopidine/treatment/trials/use/VENOUS

THROMBOEMBOLISM/warfarin



Chamorro, A. (1999), Oral anticoagulation in the secondary prevention of stroke.

Revista de Neurologia, 29 (8), 784-788.



Abstract: This review considers secondary prevention of ictus based on the use of oral

anticoagulant drugs. For this, we analyze separately the secondary preventive

aspects of the two most frequent ischemic aetiologies: cardioembolic and

atherothrombotic infarcts [REV NEUROL 1999: 29: 784-8]



Keywords: anticoagulant/anticoagulation/atherothrombotic

prevention/ATRIAL-FIBRILLATION/cardioembolic prevention/CEREBRAL

INFARCTION/DISEASE/drugs/INHIBITORS/ischemic/LACUNAR/oral

anticoagulation/PLATELET-

AGGREGATION/prevention/RECURRENCE/RISK-FACTORS/secondary

prevention/Spain/stroke/TRANSIENT ISCHEMIC ATTACKS/WARFARIN



Grau, A. and Buggle, F. (1999), Infection, atherosclerosis and ischemic stroke. Revista

de Neurologia, 29 (9), 847-851.



Abstract: The established risk factors for ischemic stroke no nor sufficiently explain all

clinical and epidemiological features of the disease, such as the winter peak of

stroke incidence, the decline of stroke during this century and the time point of

cerebral ischemia. A role of infectious disease as stroke risk factor may partly

explain above features. Several case-control studies with both hospital and

population control groups showed that acute infection within the preceding week

and mainly respiratory infection of both viral and bacterial origin increase the

risk of cerebral ischemia independent from other risk factors (odds ratio

2.9-14.5). Infection as a risk factor appears to be most important in young age

groups. Infection may cause a procoagulant state and thus, trigger thrombosis

and cerebral ischemia. There is increasing evidence for chronic infection as

stroke risk factor. A case-control study indicated chronic and recurrent bronchitis

to increase stroke risk. Two case-control and one cohort study showed that

chronic dental infection, mainly parodontitis, is a risk factor for stroke. There ape

conflicting results on chronic infection with cytomega-lovirus and insufficient

evidence for a role of Helicobacter pylorii infection in pathogenesis of stroke.

Seroepidemiological studies and analyses of carotid plaques indicate a role of

Chlamydia pneumoniae in ischemic stroke. However, causality can not yet be

inferred from present results. Acute and chronic infectious diseases are treatable

and partly preventable conditions. Their recognition as stroke risk factors could

therefore be important for stroke prevention



Keywords: acute/ACUTE

MYOCARDIAL-INFARCTION/age/ASSOCIATION/atherosclerosis/BRAIN

INFARCTION/CARDIOVASCULAR-DISEASE/carotid/case-control

studies/cerebral/cerebral ischemia/CEREBROVASCULAR

ISCHEMIA/CHLAMYDIA/Chlamydia pneumoniae/cohort

study/control/diseases/hospital/incidence/infection/INFLAMMATION/inflamma

tion/ischemia/ischemic/ischemic stroke/MORTALITY/prevention/risk/RISK

FACTOR/risk factor/risk factors/SPAIN/stroke/stroke incidence/stroke

prevention/thrombosis/YOUNG



Lainez, J.M. and Pareja, A. (2000), The medical treatment of intracerebral hemorrhage.

Revista de Neurologia, 31 (2), 174-179.



Abstract: Objective. To review the main aspects of the practical management of

intracerebral hemorrhage. Development. We begin by briefly reviewing the

pathophysiology, clinical features and recommended complementary

investigations which are necessary for satisfactory diagnosis and treatment.

These vary depending on the characteristics of the bleeding on neuroimaging,

age and clinical situation of the patient. We particularly consider the therapeutic

aspects, basically of medical treatment but also some aspects of surgical

treatment, both during the acute phase of bleeding, when the main objective is to

prevent and treat the neurobiological and systemic complications, such as the

specific underlying disorder or lesion causing the intracerebral hemorrhage, so as

to prevent further bleeding. The medical treatment: general measures,

mechanical ventilation control of blood pressure, the prevention and treatment of

raised intracranial pressure and the possibilities of specific medical treatment in

reducing the zone of ischemic penumbra are also reviewed Since surgical

treatment is controversial, we have considered the most generally accepted

indications for this and the different techniques used. Finally we review the risk

factors identified in cerebral hemorrhage which permit primary prevention



Keywords: acute/age/bleeding/blood pressure/CAVERNOUS

MALFORMATIONS/cerebral/cerebral

hemorrhage/complications/control/diagnosis/HEMATOMA/hemorrhage/intracer

ebral/intracerebral hemorrhage/INTRACRANIAL HEMORRHAGE/intracranial

pressure/ischemic/ischemic penumbra/MANAGEMENT/medical

treatment/pathophysiology/penumbra/prevention/primary/primary

prevention/PUTAMINAL HEMORRHAGE/RADIOSURGERY/review/risk/risk

factors/Spain/STROKE/SURGERY/surgical treatment/treatment



Gonzalez-Gonzalez, J.A. and Lozano, R. (2000), A study of the tolerability and

effectiveness of nicardipine retard in cognitive deterioration of vascular origin.

Revista de Neurologia, 30 (8), 719-728.



Abstract: Introduction. Nicardipine is a calcium antagonist which in previous trials has

been shown to be effective in the prevention of stroke and the treatment of its

sequelae, such as cognitive deterioration of vascular origin. We consider a phase

IV study at primary care level to analyze the tolerability and efficacy of a

retarded action formulation of 40 mg nicardipine. Patients and methods. In this

open, prospective, multicentric trial 6,375 patients took part, of whom 5,593

were evaluated (87.7%). All were diagnosed as having vascular-type dementia

(Hachinski >6) and were given treatment with nicardipine retard (40 mg/day/6

months). The patients were assessed on the Montorio (daily activity) and

SPMSQ (cognitive function) scales at the first visit and after one, three and six

months, together with a record of side effects. Results. Only 0.9% of the patients

recruited abandoned the study for problems of tolerability of the drug. The

average improvement seen on Montorio's test was statistically significant from

the first month, and reached 9% after six months. The 65.5% of the patients who

started the study in seriously deteriorated condition showed improvement after

six months. For the SPMSQ test, the average improvement was also statistically

significant from the first visit and over 40% after six months. There was

improvement in 64.4% of the patients who were severely deteriorated at the start

of the study. Conclusion. Nicardipine retard is a drug which is safe and effective

when used for the treatment of mental deterioration of vascular origin



Keywords: ARTERIES/calcium/calcium antagonist/CEREBRAL

BLOOD-FLOW/cognitive function/dementia/MULTI-INFARCT

DEMENTIA/nicardipine/prevention/primary/primary

care/Spain/stroke/treatment/trials/vascular/vascular cognitive impairment



Heros, R.C. (2001), Carotid endarterectomy and angioplasty: A surgical perspective.

Revista de Neurologia, 32 (3), 266-269.



Abstract: Introduction. Carotid endarterectomy (CE) is a well-established operation,

although recently it has been challenged by newer, less invasive procedures such

as carotid angioplasty with or without insertion of a stent. Development. In this

article the author gives his views on the use of CE in patients with carotid

stenosis, both those with and those without symptoms, and also those in whom

no definite indication has yet been established. In symptomatic carotid stenosis it

had been clearly shown that CE is an effective procedure for the prevention of

strokes and death from strokes in patients with carotid stenosis of over 70%,

provided that the patients have reasonable general health and life expectation.

there is only minor benefit from surgery inpatients with asymptomatic disease of

the carotid arteries and much less than in those with symptomatic carotid disease.

Therefore endarterectomy is recommended when there is obvious progression of

the degree of stenosis, especially when the stenosis has reached 70% or the

patient begins to complain of symptoms. One of the most serious complications

of CE is acute myocardial infarction. Conclusion. It is a good time to design

careful randomised studies to compare endarterectomy with angioplasty,

probably with stenting, in a selected group of patients at greater risk than those

accepted for endarterectomy



Keywords: acute/acute myocardial

infarction/angioplasty/arteries/asymptomatic/asymptomatic carotid

stenosis/carotid/carotid angioplasty/carotid arteries/carotid

endarterectomy/carotid

stenosis/complications/death/design/DISEASE/endarterectomy/health/infarction/

inpatients/myocardial/myocardial

infarction/prevention/risk/SPAIN/STENOSIS/stent/stenting/stroke/surgery/symp

tomatic carotid stenosis/symptoms/use



Legido, A. (2002), Prevention of epilepsy. Revista de Neurologia, 34 (2), 186-195.



Abstract: Objective. To review the preventive and prophylactic aspects of epilepsy.

Development. The description of the prevention of the causes of epilepsy

includes the measures to prevent epilepsy and epileptic seizures. The concept of

antiepileptogenesis is discussed according to the available information about the

role that both the classic and new antiepileptic drugs (AEDs) play in this process.

Neuroprotection is discussed in the context of the mechanisms of action of the

AEDs and of the mechanisms of neuronal lesion produced by the causes of

epilepsy or by the seizures themselves. Among the new therapeutic modalities

the current knowledge about the vagus nerve stimulator and the surgical

treatment is summarized. The potential future therapeutic modalities include

alternative medicine, farmacologic treatment of the epileptogenic focus, genetic

treatment and vaccination. Conclusions. The first step in preventing epilepsy is to

avoid the causes or the risk factors. Some classic AEDs have demonstrated to be

effective in the prophylaxis of provoked seizures (acute, symptomatic) but not of

unprovoked seizures (epileptic). The best knowledge of the pathogenesis and the

molecular and biological basis of epileptogenesis secondary to lesional causes,

suggest that antioxidant and neuroprotective agents, including the new AEDs,

may prevent epilepsy. There is a need to design studies with the goal of

demonstrating their antiepileptogenic and/or neuroprotective activity at different

ages in life. New and future therapeutic modalities may offer additional

preventive options



Keywords: acute/anticonvulsivants/antiepileptic drugs/ANTIEPILEPTIC

DRUGS/antiepileptogenesis/antioxidant/causes/CHILDREN/convulsions/design/

drugs/epilepsy/FEBRILE

SEIZURES/GENE-THERAPY/genetic/INTRACTABLE

EPILEPSY/knowledge/mechanisms/METAANALYSIS/NERVE-STIMULATIO

N/neuroprotection/pathogenesis/prevention/prophylaxis/PROPHYLAXIS/review

/risk/risk factors/secondary/SPAIN/STROKE/SURGERY/surgical

treatment/treatment



Casanova-Sotolongo, P., Casanova-Carrillo, P. and Casanova-Carrillo, C. (2002), Aids:

Is it a risk factor in cerebrovascular disease? Revista de Neurologia, 35 (9),

808-811.



Abstract: Introduction. Cerebrovascular disease (CVD) has become an important health

problem throughout the world. It is generally one the main causes of morbidity

and mortality in the world, especially in developed countries. In these countries

the frequency with which it appears is linked with the progress reached in the

organisation of the public health system and the higher economic and social

standards of their populations, which have given rise to prolonged life

expectancy and a greater number of elderly people. In poor countries, however,

in recent times there has also been an increase in the number of cases of this

entity, although there is no correspondence with the arguments mentioned above

concerning rich nations. The risk factors (RF) that are invoked when talking

about its genesis must always be taken into account when dealing with its

prevention. Aims. To draw attention to the increase in the number of CVD in an

under-developed country, apparently due to the high frequency of the acquired

immunodeficiency syndrome suffered by the population. Patients and methods.

A study was conducted involving all the patients admitted to the Hospital Central

de Beira between I January 1988 and 30 June 1999 with a clinical picture

compatible with a CVD. They had all been examined by a neurologist (always

the same one) and had also been submitted to serological tests to detect the

human immunodeficiency virus (HIV). Results. Of the 155 cases with CVD,

56.7% were HIV. Below the age of 50, CVD is generally not associated with any

other RF Conclusion. These findings show that we must expect an increase in the

morbidity and mortality from CVD in poor nations, which will balance out the

difference that existed up to a few years ago with the more developed countries.

The appearance of CVD in young subjects, without any other apparent cause,

will force us to rule out a possible HIV infection in high-risk individuals



Keywords: age/aids/ASSOCIATION/causes/cerebrovascular/cerebrovascular

disease/disease/elderly/health/high

risk/HIV/human/IMMUNODEFICIENCY-VIRUS INFECTION/infection/life

expectancy/morbidity/mortality/neurologist/population/PREVENTION/public

health/risk/risk factor/risk factors/SPAIN/STROKE

Ferrer, O., Plumacher-Rincon, Z., Arteaga-Vizcaino, M., Weir-Medina, J. and

Hernandez-Pernia, A. (2002), Silent cerebral infarct in patients with sickle cell

anemia. Revista de Neurologia, 35 (8), 716-719.



Abstract: Introduction. Stroke is a complication inpatients with sickle cell anemia (SCA),

in these is of importance the precocious diagnosis of silent cerebral infarcts(SCI).

Objective. To determine the incidence of SCI in patients with SCA without

neurological symptoms but with images in cerebral magnetic resonance (CMR).

Patients and methods. A total of 18 patients (13 males, 5 females) with ages

between 5 and 24 years (11.5+/- 4.9), without history of neurological alterations,

taken care at the Instituto Hematologico de Occidente-Banco de Sangre, Estado

Zulia-Venezuela. A clinical history was made to each patient in addition to

detailed physical and neurological examinations that included the state of mind,

conscience, language, sensitivity, cranial pairs, muscular force, reflexes,

cerebella tests, neck and march. Later, CMR studies were carried out. Results. It

was found that 2118 (11.1%) patients without neurological manifestations

showed alterations in the CMR and they were diagnosed as SCI. The findings by

images showed asymmetry of lateral ventricles and one of them showed gliosis

as well. Conclusion. 11.1% of the all the studied cases (2118) showed SCI for

what is suggested to carry out neurological evaluation and images, once a year,

and to offer opportune therapies, for their impact in the function neurocognitive



Keywords:

anemia/cerebral/CEREBROVASCULAR-DISEASE/CHILDREN/diagnosis/eval

uation/history/incidence/inpatients/magnetic resonance imaging/neurological

alterations/PREVENTION/RECURRENT STROKE/RISK/sickle cell

anemia/silent cerebral infarct/SPAIN/stroke/symptoms/TRANSCRANIAL

DOPPLER ULTRASONOGRAPHY/TRANSFUSIONS/ventricles



Gonzalez-Garcia, S., Fernandez-Concepcion, O., Gonzalez-Quevedo, A.,

Fernandez-Carriera, R.A. and Valdes-Reina, M. (2003), The role of blood lipids

in the different aetiologies of cerebral infarction. Revista de Neurologia, 36 (7),

625-628.



Abstract: Introduction. In order to determine the role lipids play in cerebral infarction

(CI), the different aetiological subgroups of this disease should first be separated.

Aims and methods. We conducted case-control studies to identify whether there

is a relation between blood lipid levels and the occurrence of cerebral infarction

caused by atheromatosis (CIA). Our study involved a total of 98 patients with

cerebral infarction of an atherothrombotic or lacunar aetiopathogenesis that were

included in the CIA category. Two control groups were set up: one consisted of

23 patients with non-atheromatous cerebral infarction (NACI), which included

other aetiologies (cardioembolic, unusual and unspecified), and the other was

made up of 101 healthy subjects who had not had a stroke. Results. The group of

patients with CIA presented higher average cholesterol rates than the group of

subjects with NACI (p=0.005). Nevertheless, compared to the control group they

had higher average levels of cholesterol (p=0.003), triglycerides (p=0.011),

VLDL (p=0.028) and LDL (p=0.000), as well as a higher average atherogenic

index (p=0.028). Furthermore, the average levels of LDL (p=0.030) and the

atherogenic index (p=0.008) were seen to be statistically higher in the group of

subjects with NACI than in the control group. Lastly, it must be pointed out that

no differences in the average HDL levels were found between the three groups

studied (p=0.500). The presence of high blood pressure and a history of ischemic

heart disease inpatients with CI did not modify the variations that were observed

in the lipids. Conclusions. Patients with CIA have a more atherogenic lipid

profile than healthy individuals, while subjects with NACI are situated midway

between the two groups



Keywords: atherosclerosis/blood pressure/cardioembolic/case-control

studies/cerebral/cerebral

infarction/CEREBROVASCULAR-DISEASE/cholesterol/control/CORONARY-

HEART-DISEASE/DENSITY-LIPOPROTEIN

CHOLESTEROL/disease/FOLLOW- UP/HDL/heart/heart disease/high blood

pressure/history/infarction/inpatients/ischemic/ischemic heart

disease/ISCHEMIC STROKE/LDL/lipid

profile/lipids/MEN/MORTALITY/PRAVASTATIN/PREVENTION/risk

factors/RISK-FACTORS/SPAIN/stroke/triglycerides



Nogueira-Antunano, F., Nogueira-Bonanata, G.J. and Pla-Gaspari, G.B. (2003), An

exploratory study of the relation between cerebrovascular accidents and

personality structures. Revista de Neurologia, 36 (9), 821-828.



Abstract: Introduction. In recent years the psychological aspects linked with

cerebrovascular accidents (CVA)have often been studied from the consequences

they generate. Aims. To explore the type of relation that exists between CVA and

personality structures as a premorbid risk factor (RF), including their possible

relation to the characteristics of brain injury. Patients and methods. 97 patients

who were admitted to hospital consecutively for a first CVA were evaluated and

a follow-up was carried out on 38 of them. In the acute episode and in the

follow-up we collected data about their medical history, from studies using

neuroimaging and from a semi-structured interview which was administered to

the patient or a relative. Results. A predominance of personality traits similar to

those of 'type A personality' was found. These traits are grouped in the following

structures: moody (depressive), over-adapted, logical (obsessive) and

suspicious-distrustful (paranoid), with a clear predominance of traits of low

tolerance to frustration, irritability, lack of care for or abuse of the body,

exigency, perfectionism, rigidity, magical thought and illness understood as

being weakness or bad luck and health as a 'must be' . Depressive states, with or

without anxiety, were also found with significant frequency. None of these states

or reactions was associated to any kind of brain injury in particular, both in their

type and in their topography. Conclusions. Results show a tendency that is

similar to studies with heart patients and with patients with CVA that have

already been published and can be grouped under the denomination of 'type A

personality'. Therefore, type A personality can be considered as a factor linked to

vascular diseases involving at least two territories (heart and brain). It remains to

be ascertained whether the brain territory is only a RF or a necessary or sufficient

condition. Psychological evaluation of the subjects at risk or already affected by

a CVA is relevant and to be taken into account in both prevention and therapy

and rehabilitation



Keywords: A BEHAVIOR/acute/approach/brain/brain

injury/cerebrovascular/CVA/DEPRESSION/diseases/evaluation/health/heart/hist

ory/hospital/injury/LESIONS/LOCATION/medical/medical history/MOOD

DISORDERS/MORTALITY/personality

structure/prevention/rehabilitation/RISK/risk

factor/SPAIN/STRESS/STROKE/therapy/vascular



Gil-Nunez, A.C. (1998), Primary prevention of ischemic stroke. Revista Ecuatoriana de

Neurologia, 7 (3), 99-100



Keywords: ischemic/ischemic stroke/prevention/Spain/stroke



Guiu, J.M., Alvarez-Sabin, J. and Codina, A. (1998), A comparative study of the effect

of low doses of acetylsalicylic acid and triflusal in the prevention of

cardiovascular incidents in young adults with ischemic cerebrovascular disease.

Revista Ecuatoriana de Neurologia, 7 (1), 28-32.



Abstract: The effectiveness of the low doses AAS in the prevention of the cerebral

infarction has not been clearly still verified. Objective. To compare the long term

effectiveness of the treatment with low doses AAS in front of triflusal in the

reduction of the stroke, ischemic cardiopathy, and cardiovascular death risks.

Material and methods. Of 386 patients with a first ischemic stroke, 217 were,

selected (106 triflusal, 111 AAS) that completed the approaches of atheromatous

infarct (161 males, 72.2% and 58 female, 25.8%). The mean age was 43 years

(standard deviation, SD 6.4, 95% CL 20-50). The patients received one of these

treatments: a) AAS (Sedergine(R)) 330 mg/day (once a day); b) Triflusal

(Disgren(R)), 900 mg/day (300 mg 3 times a day). The mean time of follow-up

for the group triflusal was of 48.3 months (20- 94), while for the group AAS was

of 46.3 months (2-84). Results. The combined incidence of cerebral infarcts,

ischemic cardiopathy and vascular death was 19.8% in the patients treated with

triflusal, and 28.8% in the patients treated with AAS what supposes a reduction

of the risk of the 39% (OR 0.61; CL 0.30-2.01). In the subgroup of patients with

carotid stenoses of more than 70% demonstrated by angiography, triflusal

produces a significant reduction of risk (OR 0.30; CL 0.10-0.90). Also, triflusal

reduced in 76% the risk of hemorrhagic complications in comparison of the AAS

(OR 0.24; IC 0.06-0.94). Conclusions. The study adds new doubts about the

effectiveness of the low doses of AAS in the secondary prevention of the

cerebral infarct. The triflusal shows effectiveness in subgroup of high risk and a

significance reduction of the hemorrhagic complications that would be confirmed

in controlled clinical trials with a greater number of patients

Keywords: acetylsalicylic acid/adults/age/ASPIRIN/carotid/cerebral

infarction/cerebrovascular disease/clinical

trials/complications/incidence/infarction/ischemic

stroke/prevention/risk/secondary

prevention/STROKE/SUBGROUPS/treatment/trials/vascular



Lopez-Pousa, S., Mercadal-Dalmau, J., Marti-Cuadros, A.M., Villalta-Franch, J. and

Lozano-Gallego, M. (1998), Triflusal in the prevention of vascular dementia.

Revista Ecuatoriana de Neurologia, 7 (1), 33-37.



Abstract: Vascular dementia is the second commonest cause of dementia after

Alzheimer's disease. The most important risk factor for this is previous cerebral

vascular accident. Objective. To eliminate the risk factors and/or progression of

this illness would be of considerable benefit to these patients. Triflusal, a platelet

anti-aggregant chemically related to the salicylates, whose clinical efficacy has

been shown in cardiac and cerebrovascular pathology, has been used in the

treatment of patients with vascular dementia. Material and methods. An open

study was done a sample of 73 patients with vascular dementia randomly

distributed into two groups (control and undergoing treatment with triflusal).

Results. To check the efficacy of treatment with triflusal, the percentage of

variation in the scoring of the Cognitive Mini Examination was used after a

clinical course of 12 months (IVP 12), considering the critical point of no

efficacy to be a loss equal or greater than 10%. In the control group, 33% (8/24)

and in the group treated with triflusal 8% (3/35) had a negative course which was

greater than this critical point. Conclusions. The difference in the IVP 12

between the two groups was statistically significant (p=0.0375), with a statistical

power of 87% (beta=0,13). This gives triflusal a therapeutic activity which is

sufficient to limit cognitive deterioration of patient with vascular dementia



Keywords: ASPIRIN/CEREBRAL

BLOOD-FLOW/dementia/DIAGNOSIS/DISEASE/HOSPITALIZED

COHORT/LESIONS/MULTI-INFARCT DEMENTIA/prevention/risk/risk

factors/RISK-FACTORS/STROKE/treatment/TRIAL/vascular



de Castroviejo, E.V.R., Rubio, A.M., Sanfeliu, H.P., Cabezas, C.L., Herrera, M.G.,

Castellani, A.T. and Vilardebo, C.P. (2000), Oral anticoagulation use among

patients with nonrheumatic atrial fibrillation. Revista Espanola de Cardiologia,

53 (2), 200-204.



Abstract: Introduction. The efficacy of anticoagulant treatment in the prevention of

thromboembolic complications among patients with nonrheumatic atrial

fibrillation is established. In our country, data on the use of this therapy in

clinical practice are not available. Objective. To examine anticoagulants use

among patients with nonrheumatic atrial fibrillation and to analyze the influence

of several thromboembolic risk factors in anticoagulant use. Patients and

methods. We have studied, 302 patients retrospectively, with nonrheumatic atrial

fibrillation. We determined the presence of heart failure, hypertension, previous

thromboembolism, diabetes and left atrium dilation. We added age, sex, pattern

of non-permanent arrhymia and hospitalization and we conducted univariate and

multivariate analyses to identify their influence the establishment of the

anticoagulant treatment. Results. 28,8% of patients were treated with oral

anticoagulants. 83,7% were treated with oral anticoagulant or antiplatelet agents.

Only three patients, out of 49, aged 80 years or older were treated with

anticoagulants. Multivariate analysis showed that previous thromboembolism

(odds ratio 4.03 [1.9-8.1]), permanent atrial fibrillation (odds ratio 2.6 [1.3-5.3]),

left atrium dilation (odds ratio 2.3 [1.2-4.1]) and heart failure (odds ratio 1.9

[1.07-3.6]) were factors that predicted higher use of anticoagulant treatment.

Conclusions. a) Anticoagulant treatment is underused among patients with

nonrheumatic atrial fibrillation; b) previous thromboembolism, left atrium

dilation and heart failure have conditioned higher probability of undergoing

anticoagulant treatment, and c) patients aged 80 years and over and non

permanent atrial fibrillation predicted less use of the therapy



Keywords: age/aged/anticoagulant/anticoagulant

treatment/anticoagulants/anticoagulation/antiplatelet/antiplatelet agents/atrial

fibrillation/clinical

practice/complications/diabetes/embolism/fibrillation/heart/heart

failure/hospitalization/HOSPITALS/hypertension/left atrium/NATIONAL

PATTERNS/nonrheumatic/oral

anticoagulants/POPULATION/PREVENTION/PROPHYLAXIS/RISK/risk

factors/sex/Spain/STROKE/THERAPY/THROMBOEMBOLIC

COMPLICATIONS/thromboembolism/treatment/use/WARFARIN USE



Abadal, L.T., Puig, T. and Vintro, I.B. (2000), Incidence, mortality and risk factors for

stroke in the Manresa Study: 28 years of follow-up. Revista Espanola de

Cardiologia, 53 (1), 15-20.



Abstract: Introduction and objectives. The information concerning stroke mortality is

limited in Spain, and the information on morbidity is even scarcer similarly to

other countries. This is true also for the decrease of frequency observed in the

last decades. The objective of this paper is to provide data in the incidence,

mortality and cardiovascular risk factors associated to stroke in our surrounding

through by the prolonged observation of a working population. Material and

methods. In the Manresa Study, which began in 1968, a cohort of 1,059 men,

from 30 to 59 years old, was followed for 28 years. We recorded new ca ses of

fatal and nonfatal stroke and the relationship between stroke incidence and risk

factors of cardiovascular disease found in the initial examination. Results.

Incidence rate for stroke was 183 x 100,000 per year, 6496 of the cases were

registered after they turned 60 years of age. Mortality rate due to stroke was 88 x

100,000 per year, 91.6% of fatal cases were over 60 years old. Factors associated

to the stroke morbimortality incidence were age, high blood pressure and

overweight. In a bivariate regression model, stroke mortality was found

significantly associated to the presence of atrial fibrillation, diabetes,

hypercholesterolemia and tobacco smoking. Conclusions. Stroke frequency rates

in the Manresa cohort are ranged at a medium level compared to data from other

general population studies. The role of atrial ii brillation in the stroke

morbimortality has been confirmed. The associated factors, age, high blood

pressure and overweight, are similar role to that wich was found in other research

studies. The priorities in the cerebrovascular disease prevention in our

surroundings are discussed



Keywords: age/atrial fibrillation/ATRIAL-FIBRILLATION/blood

pressure/cardiovascular/cardiovascular disease/CARDIOVASCULAR

MORTALITY/cardiovascular risk/cardiovascular risk

factors/cerebrovascular/cerebrovascular disease/cerebrovascular

diseases/diabetes/disease/fibrillation/FRAMINGHAM/HEART-DISEASE/high

blood

pressure/hypercholesterolemia/hyperglicaemia/hypertension/incidence/men/morb

idity/mortality/obesity/population/population

studies/PREVENTION/prevention/risk/risk factors/risk factors for

stroke/SEGOVIA/smoking/SPAIN/stroke/stroke incidence/stroke

mortality/tobacco/TRANSIENT ISCHEMIC ATTACKS



Pintor, E., Sanmartin, M., Azcona, L., Hernandez, R., Fernandez-Cruz, A. and Macaya,

C. (2001), Leucocytoclastic vasculitis after ticlopidine. Revista Espanola de

Cardiologia, 54 (1), 114-116.



Abstract: In the last five years the combination of ticlopidine plus aspirin has been the

treatment of choice to avoid thrombi formation after the implantation of

intracoronary stents. The adverse effects observed include the appearance of a

maculopapulous, pruritic, painless, cutaneous rash. We present the case of a

patient who developed leucocytoclastic vasculitis associated with the

administration of ticlopidine



Keywords: administration/adverse effects/aspirin/combination/coronary

angioplasty/EFFICACY/formation/INTRACORONARY STENT

PLACEMENT/platelet aggregation

inhibitors/PREVENTION/Spain/stent/stents/STROKE/THERAPY/ticlopidine/tre

atment



de Castroviejo, E.V.R., Barranco, M.J.M., Rubio, A.M., Pineda, A.F., Cabezas, C.L.,

Herrera, M.G., Castellani, A.T., Vilardebo, C.P., Galiano, E.M. and Munoz, A.A.

(2002), Changes in the clinical profile of patients treated with oral anticoagulants

during the decade of the ninety. Revista Espanola de Cardiologia, 55 (1), 55-60.



Abstract: Introduction. During the last few years the efficacy of oral anticoagulant

treatment in the prevention of thromboembolic complications among patients

with cardiac diseases has been well established. This has determined an increase

in the number of patients undergoing this therapy and a change in the clinical

profile of these patients. Objective. To determine the number and the changes in

the clinical characteristics of patients treated with oral anticoagulants during the

last decade. Patients and method. The charts of 5,771 hospitalized patients

between January 1, 1991 and December 31, 1999, were retrospectively reviewed.

We analyzed the number of patients discharged with anticoagulant treatment, the

clinical profile and the evolution during the decade. Results. 761 (13.1%)

patients were discharged with anticoagulants. The therapy was prescribed to

7.4% of the patients from 1991-1993 and to 15.1% of the patients from

1998-1999. The mean age of the patients was 60.4 from 1991-1993 and 67.1

from 1998-1999 (p 8% year). All the studies have demonstrated the benefit of

a primary or secondary prevention by antivitamin K with an INR between 2 and

3 (reduction of the relative risk of about 68%). Conversely, the efficacy of

aspirin has not been proven in this population of elderly patients. Once stroke has

occurred, it is not recommended to initiate an anticoagulation (unfractioned or

low molecular weight heparin) within the first hours. Prevention of venous

thrombosis remains necessary. Future prospects and projects. - Currently, less

than 30% of the patients older than 75 years are given anticoagulation, the risk of

the treatment being probably overestimated. The risk benefit ratio should be

evaluated more properly for a given patient. (C) 2002 Editions scientifiques et

medicales Elsevier SAS. All rights reserved



Keywords: acute/anticoagulant/anticoagulant

therapy/anticoagulation/ANTITHROMBOTIC THERAPY/antivitamin

K/aspirin/ASSOCIATION/atrial

fibrillation/CARDIOVERSION/COMPLICATIONS/elderly/ELDERLY

PATIENTS/fibrillation/heparin/high risk/INR/ischemic/ischemic

stroke/knowledge/low molecular weight heparin/OLDER PATIENTS/permanent

atrial fibrillation/POPULATION/prevention/primary/primary and secondary

prevention/RANDOMIZED TRIAL/relative risk/risk/secondary/secondary

prevention/stroke/STROKE PREVENTION/therapy/thrombosis/treatment/under

utilisation of oral anticoagulants/venous thrombosis/WARFARIN/weight



Leclerc, J.R. (1999), Strategies for the prevention of pulmonary embolus for patients at

risk during surgical operations and also in the medical environment. Revue des

Maladies Respiratoires, 16 (5BIS), 939-948.



Abstract: Pulmonary embolus is a significant aspect of thromboembolic venous disease

which globally is the third most important cardiovascular disorder. There are

several methods of primary prevention to decrease morbidity and mortality

related to this disease. This article consists of a review of the most current

methods of prophylaxis followed by practical recommendations for surgical,

medical and obstetric patients



Keywords: ACUTE ISCHEMIC STROKE/DEEP-VEIN

THROMBOSIS/DOUBLE-BLIND TRIAL/embolus/INDUCED

THROMBOCYTOPENIA/LOW- DOSE HEPARIN/MOLECULAR-WEIGHT

HEPARIN/morbidity/mortality/prevention/primary

prevention/prophylaxis/review article/risk/SUBCUTANEOUS

HEPARIN/TOTAL HIP- REPLACEMENT/UNFRACTIONATED

HEPARIN/venous thromboembolism/VENOUS THROMBOEMBOLISM



Koudstaal, P.J. (1999), Anticoagulant treatment in stroke prevention. Revue

Neurologique, 155 (9), 694-696.



Abstract: This review aims to summarise the value of long-term oral anticoagulant

treatment in stroke prevention. Oral anticoagulation is the treatment of first

choice in patients with atrial fibrillation (AF) and vascular risk factors and in AF

patients with recent cerebral ischemia. The treatment also substantially reduces

the risk of stroke in patients after myocardial infarction. The optimal target

intensity of anticoagulation in stroke prevention is an international Normalized

Ratio (INR) between 2.0 and 3.0. The treatment has been found to be hazardous

at INR intensities between 3.0 and 4.5 in patients with transient ischemic attack

(RA) or minor stroke of presumed arterial origin. The value of the treatment in

lower intensity in such patients still has to be established



Keywords: AF/anticoagulant/anticoagulant treatment/anticoagulation/atrial

fibrillation/cerebral/cerebral

ischemia/fibrillation/infarction/INR/ischemia/ischemic/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/Netherlands/NONRHEUMATIC

ATRIAL-FIBRILLATION/prevention/review/RISK/risk factors/stroke/stroke

prevention/transient/transient ischemic attack/treatment/vascular



Crassard, I. and Bousser, M.G. (1999), Antiplatelet drugs for stroke prevention. Revue

Neurologique, 155 (8), 531-541.



Abstract: Antiplatelet (AP) drugs play a major role in stroke prevention. Aspirin

(50-1300 mg), ticlopidine (500 mg), clopidogrel (75 mg) and dipyridamole (400

mg) are effective in secondary prevention of atherothrombotic brain infarcts.

Aspirin has been the most extensively studied drug and remains the most

cost-effective one. The optimal dose is still debated; doses between 100 and 300

mg are the most widely used. The preventive efficacy of aspirin is already

present at the acute phase of cerebral infarct. In primary prevention, aspirin

nearly halves the risk of myocardial infarction but does not reduce that of stroke.

Cardiac diseases with a high embolic risk require the use of oral anticoagulation.

In non valvular atrial fibrillation, the choice of antithrombotic drugs depends on

risk stratification: oral anticoagulants are indicated in high risk subjects whereas

aspirin is recommended in low risk subjects and when oral anticoagulants are

contraindicated. Studies with new associations of AP and with new drugs are

required to increase the yield of the antiplatelet approach in high risk subjects,

this should be done in parallel with efforts to detect and to treat the vascular risk

factors associated with the development of a mass approach for stroke primary

prevention



Keywords: acute/anticoagulants/anticoagulation/antithrombotic/aspirin/atrial

fibrillation/brain/cerebral/clopidogrel/development/DIPYRIDAMOLE/DISEAS

E/diseases/drugs/fibrillation/HOMOCYSTEINE/infarction/LOW-DOSE

ASPIRIN/myocardial/myocardial infarction/NONRHEUMATIC

ATRIAL-FIBRILLATION/oral anticoagulants/oral

anticoagulation/prevention/primary prevention/RANDOMIZED

TRIAL/RISK/risk factors/risk stratification/SECONDARY

PREVENTION/stroke/stroke prevention/TICLOPIDINE/vascular/WARFARIN

Dimitrijevic, J., Gavranovic, M., Dzirlo, K., Bratic, M., Hrnjica, M., Bulic, G. and Hebib,

L.J. (1999), Stroke in Sarajevo during the war. Revue Neurologique, 155 (5),

359-364.



Abstract: Purpose: Neurologists in the main hospital in Sarajevo (Bosnia- Herzegovinia),

we worked in the neurological department throughout the war and the siege of

the town, from 1992/4/6 to 1995/12/15 We report on strokes which happened

during that period, comparing stroke incidence and severity in relation to those

two years before. We reviewed 3002 cases of stroke recorded in the neurological

department registry from 01/01/90 to the end of the war. Results: The activity of

the department was reduced by about 40 p. 100, as was the population of the

town. Yet the number of strokes decreased only by 26.5 p. 100. The comparative

incidence of strokes increased by 25 p. 100 during the war. Sex ratio and age

incidence were the same. The relative role of atherosclerosis, cardiac embolic

sources, intracranial and meningeal hemorrhage remained the same. The

incidence of intracranial hemorrhage increased by 20 p. 100. Death, evaluated

after one month, increased by 36 P. 100 Death by intracranial hemorrhage

increased by 30 p. 100 those by cardiac embolic infarction by 26 p. 100 and

those by atherosclerosis by 20 p. 100. At the end of the first year of the war,

mortality was 65p. 100 in comparison with the previous year and death by

meningeal hemorrhage increased by 74 p. 100 for the first two years of the war.

The major changes in life conditions have produced change in medical

conditions. Patients had to stop their treatment because there was no more

medecine in the city, and, among others, no more drugs for anticoagulation,

diabetes mellitus, cardiopathy... In the hospital, medical doctors, nurses, drugs,

food and even heating were missing. So stopping the treatment for vascular

disease together with the high level of stress generated by daily shelling can

explain the increase in stroke incidence and especially, the hemorragic cases. The

poor life conditions which weakened people and the lack of treatment at the

acute stage of the disease and also later, when secondary events occurred, can

explain the high mortality observed Conclusion: we recognize the bias of our

study: the war itself, the condition which we have carried out this work and the

use of a hospital registry. Nevertheless, it seems that morbidity not directly due

to the battle can change during a war like this one. This study also demonstrates,

"a contrario", that preventive treatment and care of stroke at the acute phase, as

they are currently recommended, are useful



Keywords: 1ST STROKE/acute/ACUTE

CEREBROVASCULAR-DISEASE/age/anticoagulation/atherosclerosis/COMM

UNITY/CONSECUTIVE PATIENTS/diabetes/diabetes

mellitus/drugs/EPIDEMIOLOGY/HEART-DISEASE/hemorrhage/hospital/incid

ence/INFARCTION/INTRACEREBRAL HEMORRHAGE/intracranial

hemorrhage/morbidity/mortality/population/PREVENTION/SCORE/severity/str

ess/stroke/stroke incidence/treatment/vascular/vascular disease



Chatellier, G., Colombet, I. and Dreau, H. (1999), Hypertension and stroke: the need for

improved prevention strategies. Revue Neurologique, 155 (9), 670-676.

Abstract: It is well demonstrated that the antihypertensive treatment is effective,

particularly for the primary prevention of stroke. However, benefits of treatment

are rather small in certain groups of patients. The explicit assessment of absolute

cardiovascular risks and likely treatment benefits in patients with hypertension

can usefully guide treatment decisions and provide a more rational basis for

initiating therapy than blood pressure levels alone. This approach highlights the

generally greater cardiovascular risk and potential treatment benefits in older

compared with younger hypertensive patients. Some specific questions remain

still unanswered. Evidence is accumulating concerning protective effect of

antihypertensive treatment against dementia. Trials are in progress to investigate

the effect of treatment on stroke incidence in hypertensive patients over the age

of 80 years. Finally, despite the worldwide use of calcium antagonists and

converting enzyme inhibitors, solid evidence of their safety and efficacy

compared with the references drugs (beta-blockers and diuretics) is still lacking



Keywords: age/ANTIHYPERTENSIVE

TREATMENT/ARTERIAL-HYPERTENSION/beta-blockers/blood

pressure/calcium/calcium

antagonists/calcium-antagonists/cardiovascular/CARDIOVASCULAR-DISEAS

E/CORONARY

HEART-DISEASE/dementia/drugs/GENERAL-PRACTICE/HIGH

BLOOD-PRESSURE/hypertension/incidence/POPULATION/PREVALENCE/p

revention/primary prevention/risk/safety/stroke/stroke incidence/SYSTOLIC

HYPERTENSION/therapy/treatment/TRIAL



Leys, D. (1999), Prevention of cerebral ischaemia: antiplatelet agents. Revue

Neurologique, 155 (9), 688-693.



Abstract: Besides the optimal management of risk factors for stroke and carotid surgery,

antiplatelet agents are the cornerstone for prevention of cerebral ischaemia. The

aim of this overview is to determine their role in the prevention of cerebral

ischaemia, from available literature. in primary prevention, the benefit of aspirin

has been established only for patients with non-valvular atrial fibrillation and a

low risk of cardioembolism, or as an alternative choice of warfarin, and in

subjects at highrisk of atherosclerosis. In secondary prevention, antiplatelet

agents are effective to reduce the risk in patients with ischaemic stroke due to

atherosclerosis: aspirin (50 to 1300 mg), ticlopidine (500 mg), clopidogrel (75

mg) and dipyridamole (400 mg) are effective, but the higher levels of risk

reduction are obtained with clopidogrel, ticlopidine and the association aspirin -

dipyridamole. Aspirin is recommended in most other causes of cerebral

ischaemia, except in high risk cardiopathies when anticoagulation is possible.

Other domains should still be explored: are antiplatelet agents also effective to

reduce the risk of cerebral ischaemia in patients with other causes, especially

lipohyalinosis of the deep perforators leading to lacunar infarcts? In daily

practice, does prescription follow recommendations? Will it be possible to

reproduce the results of the European Stroke Prevention Study (ESPS) 2? Are

antiplatelet agents other than aspirin effective in non- valvular atrial fibrillation?

Are other associations of antiplatelet agents more effective than these agents

alone? Finally, what will be the role of new antiplatelet agents in the future?



Keywords: anticoagulation/antiplatelet agents/ASPIRIN/atherosclerosis/atrial

fibrillation/carotid/cerebral/cerebral

ischaemia/clopidogrel/COST-EFFECTIVENESS/DIPYRIDAMOLE/fibrillation/

FRAMINGHAM/ischaemia/ischaemic stroke/non-valvular atrial

fibrillation/NONRHEUMATIC ATRIAL-FIBRILLATION/prevention/primary

prevention/RANDOMIZED TRIAL/RISK/risk factors/risk factors for

stroke/SECONDARY PREVENTION/stroke/STROKE

PREVENTION/surgery/ticlopidine/WARFARIN



Niclot, P. and Bousser, M.G. (1999), Anti-platelet and anti-coagulant therapy for acute

cerebral events. Revue Neurologique, 155 (9), 656-661.



Abstract: Therapeutical trials in the acute phase of stroke have showed a moderate

benefit of administration of aspirin in prevention of death or recurrent cerebral

events. This benefit was obtained despite a small increase in systemic and

cerebral haemorrhages. Heparin used at high dosage, without any control of

coagulation test, induces an excess of cerebral and systemic haemorhage which

overset its benefit in prevention of recurrent cerebral events. Similar results have

been observed with heparinoid and nadroparine used at high dosage. The only

benefit of anticoagulation is the prevention of total and fatal pulmonary

embolism which has been observed in all recent studies. The anti-thrombotic

treatment which offers the best ratio benefit- risk in the acute phase of stroke is

aspirin at a minimum dosage of 160 mg by day and, if risk factors are present,

heparin at an adequate dosage to prevent-venous thrombo- embolism.

Explicative studies are required to explore the potential benefit of heparin in

patients with a high risk of recurrent cerebral ischemic events



Keywords: acute/ACUTE ISCHEMIC

STROKE/administration/anticoagulant/anticoagulation/antithrombotic/ASPIRIN

/cerebral/coagulation/control/embolism/HEPARIN/ischemic/PREVENTION/pul

monary embolism/RANDOMIZED TRIAL/risk/risk

factors/stroke/therapy/treatment/trials



Gallucci, M. (1997), Perfusional MR in ischemic stroke. Rivista di Neuroradiologia,

10 99-101.



Abstract: The main application of perfusional techniques based on MR concerns the

evaluation of stroke. Our experience, based on 25 cases (15 acute) confirms the

literature data, allowing to affirm its simplicity (2 minutes of acquisition,

obtainable also with low field equipments). In perspective it is possible to foresee

an increasing employment that, in case of stroke, could: 1. facilitate the

differential diagnosis; 2. allow the early recognition of the ischemic area (in the

first minutes after the occlusion); 3. facilitate the prognostic judgment; 4. help in

differentiating the ischemic core from penumbra; 5. replace SPET in the

evaluation of the so-called therapeutic window; 6. allow the correct selection of

pts susceptible of thrombolitic therapy, excluding those with spontaneous

recanalization; 7. appraise the effectiveness of thrombolitic therapy in follow-up

evaluations. To our opinion, however, much more interesting seems the possible

application in prevention, and more particularily, in: 1. evaluation of critical

zones in subjects with stenosis of big vessels; 2. study of the efficiency of

collateral supply; 3. evaluation of the vasodilatory reserve (i.e.: pharmacological

tests); 4. presurgical planning (perfusional MR together with MRA will replace

caterer angiography?)



Keywords: brain ischemia/brain perfusion/diagnosis/evaluation/ischemic/ischemic

stroke/MRI/penumbra/perfusion studies/prevention/recanalization/stroke/therapy



Houdart, E. (2003), Current role of angioplasty of the intracranial arteries. Rivista di

Neuroradiologia, 16 (1), 105-109.



Abstract: This paper presents our indications for angioplasty of intracranial stenoses in

secondary prevention of stroke. This technique was first implemented at our

institution in 1993. Inclusion criteria are very strict: severe stenoses located on

large arteries, symptomatic despite antithrombotic therapy. Thirty patients have

been successfully treated to date. Twenty- seven patients are free of symptoms

with a mean follow-up of four years. Neurological complications occurred in two

patients. One patient developed an early symptomatic restenosis. Intracranial

angioplasty is feasible and efficient for stroke prevention but inclusion criteria

should remain strict



Keywords: angioplasty/antithrombotic/antithrombotic

therapy/arteries/carotid/complications/DISEASE/intracranial/prevention/restenos

is/secondary/secondary prevention/stenosis/stent/stroke/stroke

prevention/symptoms/therapy



Scienza, R. and Pavesi, G. (2003), Surgical treatment of intracranial aneurysms. Rivista

di Neuroradiologia, 16 (1), 149-156.



Abstract: Cerebrovascular disease continues to be a major source of morbidity and

mortality in our aging population. Cerebrovascular disease continues to present

challenges in the diagnostic and therapeutic arena. Prevention and treatment of

stroke represent an unconquered frontier in clinical neuroscience. The ability to

identify and treat cerebrovascular abnormalities before permanent ischemic

deficit occurs is rapidly increasing. Endovascular therapy of vascular

malformations and vasospasm are today a necessary comparison with

microsurgery; cerebral blood flow measurements tool give clinicians the

opportunity to identify patients at risk for ischemic damage and to suggest new

therapeutic paths; minimally invasive diagnostic tools are gradually reducing the

indication for cerebral angiography. Such major advances in technology, that are

actually changing our therapeutic approach to cerebrovascular disease, and to

cerebral aneurysms treatment, will soon result in safer more effective treatments,

minimizing the onset of permanent neurologic deficits. Anyway, it is a fact that

the majority of cerebral aneurysms are still treated by, microsurgery, either

because of the wider diffusion of specialized centers offering this technique, or

because of the longer follow up on the obtained results achieved by

neurosurgeons. The object of the present study is to show how the surgical

treatment of cerebral aneurysms is organized, and which are the main problems

that neurosurgeons are facing in the effort to conjugate microsurgical treatment

with the new ancillary technologies for the study of cerebrovascular

malformations



Keywords: aging/aneurysm/angiography/blood flow/cerebral/cerebral

angiography/cerebral blood flow/cerebrovascular/cerebrovascular

disease/clipping/COMPLICATIONS/diagnostic/disease/intracranial/ischemic/M

ANAGEMENT/microsurgery/morbidity/morbidity and

mortality/mortality/population/results/risk/SAH/stroke/SUBARACHNOID

HEMORRHAGE/SURGERY/surgical

treatment/therapy/treatment/vascular/vasospasm



Inzitari, D. (2003), Carotid artery atherosclerotic disease - Medical therapy and clinical

trials. Rivista di Neuroradiologia, 16 (1), 27-30.



Abstract: Carotid endarterectomy represents one of the main strategies for primary and

secondary prevention of atherothrombotic ischemic stroke. ECST and NASCET

studies on symptomatic carotid stenosis showed a significantly higher benefit of

surgical compared to medical therapy to reduce the risk of ischemic stroke in

case of severe stenosis, (over 70% in NASCET study and over 85% in ECST

study) with a Number Needed to Treat, NNT, at 2 years of 8. For moderate

stenosis (50-69% in the NASCET study) there was a smaller benefit (NNT = 20),

while there was no benefit for stenosis 75% (331; 68.5%), ulceration (41;

8.5%), bilateral stenosis (61; 12.5%) and unilateral stenosis with contralateral

occlusion (51; 10.5%). Intraluminal shunt was used in nearly all patients whereas

special management of cerebral metabolism (intraoperative

electroencephalogram, somatosensory evoked potentials) were used in high-risk

patients only. Overall early mortality was 1.8%. Three patients died from the

sequelae of a neurologic injury, whereas six patients died from myocardial

infarction or intractable arrhythmia. Mortality decreased from 2.4% between

1978 and 1984 to 0.8% between 1985 and 1991. At 6 and 8 years, actuarial

survival rates of 88.1% and 76.1% and stroke-free survival rates of 86% and

81.5% were observed. Late mortality was essentially due to ischemic cardiac

complications (38.5% of the actuarial late mortality at 8 years). Review of the

literature shows that carotid endarterectomy is the treatment of choice for

symptomatic high-grade extracranial carotid stenosis in patients who are not

high-risk candidates. Asymptomatic hemodynamically significant (>70%)

carotid stenosis poses special clinical problems in patients scheduled for major

surgery; in cardiovascular surgery there may be an increased risk of stroke in

patients with tight stenosis (>90%) or occlusion of the carotid artery; in this

special group of patients simultaneous cardiac and carotid surgery should be

considered a valuable alternative. Our results show that carotid endarterectomy

can be performed with acceptable mortality and morbidity even in a teaching

hospital. Early postoperative use of antiplatelets and accurate surgical technique

are important factors in the prevention of postoperative embolism and

thrombosis



Keywords:

ARTERY/CLOSURE/COMPLICATIONS/MANAGEMENT/PROGNOSIS/TIG

HT STENOSIS/VEIN PATCH



Reinhart, W.H. (1993), Stroke. Schweizerische Medizinische Wochenschrift, 123 (16),

775-782.



Abstract: Stroke is an ischemic event in 80% and hemorrhagic in 20%, which can be

distinguished by computed tomography of the brain. Unfortunately, no routinely

applicable therapy is available for stroke. Several thrombolysis studies are

underway and their results will become available in the next few years.

Hemodilution has been abandoned except for hematocrits above 50%. Calcium

antagonists such as nimodipine reduce vascular spasms after subarachnoidal

hemorrhage, but their administration after ischemic stroke is unsuccessful. A

new experimental approach is offered by glutamate receptor antagonists, which

may prevent cell damage induced by the excitatory amino acid glutamate. In the

case of cardio-embolic stroke, heparin should be started after 48 hours.

Hypertension should only be treated above values of 200/120 mm Hg, with

short-acting intravenous drugs. Because of the limited therapeutic options for

completed stroke, primary prevention (treatment of hypertension, anticoagulation

for atrial fibrillation) and secondary prevention after transitory ischemic attacks

(endarterectomy for carotid stenosis >70%, aspirin) should be intensified



Keywords:

ANGIOGRAPHY/ATRIAL-FIBRILLATION/BLOOD-PRESSURE/CAROTID

ENDARTERECTOMY/CEREBRAL- ISCHEMIA/CONTROLLED

TRIAL/CORONARY HEART-DISEASE/EPIDEMIOLOGIC

ASSESSMENT/HEMORRHAGE/PATENT FORAMEN OVALE



Stahelin, H.B., Evison, J. and Seiler, W.O. (1994), Prevention of Cerebrovascular

Infarction. Schweizerische Medizinische Wochenschrift, 124 (45), 1995-2004.



Abstract: Cerebrovascular infarction is the third leading cause of mortality following

coronary heart disease and malignancies. WHO studies show that more than half

of patients admitted for cerebrovascular infarction were not treated for

hypertension. The risk factors for coronary heart disease and cerebrovascular

infarction are not identical. Patients with systolic and diastolic hypertension,

atrial fibrillation, stenosis of the carotid artery, and smoking, have a significantly

elevated risk for cerebrovascular accidents. Hypercholesterolemia and diabetes

are less important risk factors. Risk factors amendable by adequate nutritional

intake are low supply of carotene and vitamin C. Homocysteinemia appears to be

a risk factor that may be influenced by appropriate nutrition. Antihypertensive

therapy is the most important primary and secondary preventive measure. No

smoking and adequate dietary intake are also important. Primary prevention with

low dose salicyclic acid (ASA) is recommended in the presence of additional

cardiovascular risk factors. The benefit of low dose anticoagulant therapy in

atrial fibrillation without symptoms is not fully established. In subjects with

atrial fibrillation with cerebrovascular events anticoagulants are superior to ASA.

Surgical treatment of significant stenosis of the carotid artery is indicated. In

secondary prevention of thromboembolic events, low dose ASA is recommended.

A valuable alternative in case of side effects is available in ticlopidine



Keywords: ALCOHOL-CONSUMPTION/anticoagulants/atrial

fibrillation/ATRIAL-FIBRILLATION/BLOOD-PRESSURE/cardiovascular risk

factors/carotid/coronary heart disease/CORONARY

HEART-DISEASE/fibrillation/heart/hypertension/ISCHEMIC

STROKE/mortality/MYOCARDIAL-

INFARCTION/nutrition/prevention/risk/RISK FACTOR/risk factors/secondary

prevention/SERUM-CHOLESTEROL/smoking/ticlopidine/TICLOPIDINE

ASPIRIN STROKE/treatment/UNITED-STATES/vitamin C

Zimmermann, M. (1994), Anticoagulation in Atrial-Fibrillation - for and Against.

Schweizerische Medizinische Wochenschrift, 124 (35), 1560-1565.



Abstract: Atrial fibrillation is a common arrhythmia, and the risk of embolic stroke in

patients with nonrheumatic atrial fibrillation is increased about fivefold. Until

recently, there has been no consensus on the use of anticoagulants in patients

with nonrheumatic atrial fibrillation, and the role of aspirin has been

controversial. Since 1989, 5 randomized, controlled trials have been published

comparing warfarin or aspirin with placebo for primary prevention of stroke in

patients with nonrheumatic atrial fibrillation. All these trials have shown a clear

benefit of anticoagulant therapy (risk reduction 35 to 86%), whereas the benefit

of aspirin has been less obvious (risk reduction 15 to 42%). In all these studies,

anticoagulation level was moderate (INR 1.5 to 3.0), and the rate of major

bleeding was reported to be low (0.8 to 2.5% per year). Anticoagulant therapy

does not seem to be warranted in patients 75 years old in

whom the risk of major bleeding is high. In these situations, aspirin (325 mg per

day) appears to be a safe and reasonable native



Keywords: anticoagulants/anticoagulation/aspirin/atrial

fibrillation/consensus/fibrillation/PREVENTION/primary

prevention/risk/STROKE/trials/WARFARIN



Lyrer, P. (1994), New Treatment Concepts for Acute Cerebral-Ischemia. Schweizerische

Medizinische Wochenschrift, 124 (45), 2005-2012.



Abstract: Up to the present, treatment strategies for acute cerebral ischemia have not

shown scientifically proven efficacy. Based upon new knowledge on stroke

pathogenesis and experimental data, new concepts of cerebral ischemia treatment

are being clinically tested. The main therapeutic instrument is clot lysis by

systemic or local application of thrombolytic drugs or the use of cytoprotective

agents. For both treatment strategies clinical trials to show efficacy are ongoing

or planned. Early reperfusion can be obtained by fibrinolysis, but its clinical

usefulness has yet to be proven



Keywords: ARTERY/CAROTID TERRITORY/cerebral ischemia/clinical

trials/CONTROLLED TRIAL/EMBOLIC

STROKE/ischemia/knowledge/LOCAL INTRAARTERIAL

FIBRINOLYSIS/OCCLUSION/PREVENTION/stroke/THROMBOLYTIC

THERAPY/TISSUE-PLASMINOGEN-ACTIVATOR/treatment/trials/URGENT

THERAPY



MacMahon, S., Neal, B. and Rodgers, A. (1995), Blood pressure lowering for the

primary and secondary prevention of coronary and cerebrovascular disease.

Schweizerische Medizinische Wochenschrift, 125 (51-52), 2479-2486.



Abstract: An overview of the 17 completed randomised trials of antihypertensive

treatment demonstrates that a 5-6 mm Hg reduction in DBP reduced stroke risk

by 38 % (SD 4) and CHD risk by 16% (SD 4). These results indicate that a few

years' treatment with diuretic- or beta- blocker-based therapy produces most or

all of the long-term stroke avoidance and much of the long-term CHD avoidance

that would be predicted from observational epidemiological studies, given the

blood pressure reductions that were achieved in the trials. The relative risk

reductions were similar in trials of older and younger patients, although the

absolute reduction in events was more than twice as great in the trials in older

patients. From these results it can be estimated that in fully compliant patients at

similar risk of vascular disease to those included in the trials, antihypertensive

treatment for 5 years would prevent one major vascular event among every 20

older patients and one major vascular event among every 60 younger patients.

Obviously the benefits of treatment will be greater among those at higher risk

than the patients included in the previous trials. The greatest benefits are likely to

be achieved in those with a history of vascular disease since their risk of future

events is particularly high. Among such patients it is possible that blood pressure

reduction will confer worthwhile benefits in those without hypertension, as well

as those with hypertension. It is also possible that the benefits of treatment will

be determined by the size of the blood pressure reduction and by the choice of

the antihypertensive agent. However, each of these possibilities requires

confirmation in large scale randomised controlled trials



Keywords: antihypertensive treatment/blood pressure/cerebrovascular

disease/CHOLESTEROL/EPIDEMIOLOGIC

CONTEXT/HEART-DISEASE/history/HYPERTENSION/J-CURVE

PHENOMENON/MORTALITY/MYOCARDIAL-INFARCTION/prevention/rel

ative risk/risk/secondary

prevention/STROKE/treatment/TRIAL/TRIALS/UNSTABLE

ANGINA/vascular/vascular disease



Luscher, T.F. (1995), Hypertension and Vascular-Disease - Molecular and Cellular

Mechanisms. Schweizerische Medizinische Wochenschrift, 125 (7), 270-282.



Abstract: Increased blood pressure can be observed in about 15-20% of the Swiss

population. Hypertension causes few or no symptoms, but is an important risk

factor for myocardial infarction, stroke, renal failure and peripheral vascular

disease. All these clinical complications of hypertension are preceded by

functional changes of blood vessels and the myocardium (left ventricular

hypertrophy). In conduit arteries, hypertension is associated with atherosclerotic

changes, while in resistance arteries only increased medial thickness can be

observed. In atherosclerosis, functional changes of the endothelium, vascular

smooth muscle, platelets and monocytes occur. These changes lead to

hypercontractility, increased interaction of circulating blood cells with the blood

vessel wall, and to proliferation and migration of vascular smooth muscle cells.

These events impair local blood flow and eventually may cause vascular

occlusion. The endothelium plays a particularly important role as a regulator of

these mechanisms. Accordingly, it is likely that an endothelial dysfunction

occurs at the very beginning of the athersclerotic process. In resistance arteries,

remodeling of vascular smooth muscle cells leads to thickening of the media

with encroachment on the lumen due to an increased media lumen ratio. These

hypertension-induced vascular changes are in part reversible by antihypertensive

drugs. Hypertension-induced vascular disease is preceded by numerous

alterations in the expression, secretion and action of mediators and receptors of

endothelial cells, vascular smooth muscle, platelets and monocytes. It is hoped

that increased understanding of the cellular/ molecular mechanisms of

hypertensive vascular disease will allow more effective therapy (and in the future

also gene therapy) as well as better prevention of coronary artery disease in

hypertensive patients



Keywords: atherosclerosis/blood pressure/BLOOD-PRESSURE/CEREBRAL

ARTERIOLES/complications/CORONARY

HEART-DISEASE/endothelium/ENDOTHELIUM-DEPENDENT

CONTRACTIONS/hypertension/hypertrophy/L-ARGININE/MESSENGER-RN

A/muscle/myocardial infarction/NITRIC-OXIDE

SYNTHASE/platelets/prevention/receptors/RELAXING

FACTOR/RESISTANCE ARTERIES/risk/smooth/SMOOTH-MUSCLE

CELLS/stroke/vascular/vascular disease



Mattle, H.P. (1997), Recent advances in treatment and prevention of stroke.

Schweizerische Medizinische Wochenschrift, 127 (40), 1663-1666.



Abstract: In the acute stage of stroke, fibrinolytics are beneficial for up to 3, and in some

patients up to 6, hours. If fibrinolytics are contraindicated, aspirin should be

given. Heparin is dangerous due to the threat of intra-and extracranial

hemorrhage. For secondary prevention, antiplatelet agents and, in selected

patients, anticoagulants are indicated. When hypercholesterolemia is present,

statins should be given



Keywords: ACUTE ISCHEMIC STROKE/anticoagulants/antiplatelet

agents/aspirin/EVENTS/hemorrhage/hypercholesterolemia/PRAVASTATIN/pre

vention/secondary prevention/statins/stroke/treatment



Mattle, H.P., Vella, E.E., Bassetti, C. and Sandercock, P. (1999), International Stroke

Trial Switzerland: some epidemiological data. Schweizerische Medizinische

Wochenschrift, 129 (50), 1964-1969.



Abstract: Randomised trials provide the best evidence on the effects of treatment on a

particular disease. They can also provide valuable data on outcome. In the

present article, data from 1631 Swiss patients randomised in the International

Stroke Trial (IST) are presented. Baseline characteristics and outcome in the

Swiss patients were compared with the 17 804 patients randomised in other

countries. On average, compared with other countries, Swiss patients were: 2.5

years older (CI: 1.9-3.1; p 10 was found in 62.5% of subjects and 12.5% of

controls. Between patients and controls there was a significant difference in AHI

(mean [range]: 28 (0-140) vs 5 (0-24), p 0.8). The

following measures were found to differ with speed (data format: measure at 1.3

m/s+/-SD measure at 2.2 m/s+/-SD): minimum shoulder abduction angle during

propulsion (34.5 degrees+/-6.7, 21.6 degrees+/-7.2), range of motion during the

entire stroke in elbow flexion/extension (54.0 degrees+/-9.9, 58.1 degrees+/-10.4)

and shoulder sagittal flexion/extension (74.8 degrees+/-9.4, 82.6 degrees+/-8.5),

and peak acceleration in shoulder sagittal flexion/extension (4044 degrees/s(2)+/-

946, 7146 degrees/s(2)+/-1705), abduction/adduction (2678 degrees/s(2)+/-767,

4928 degrees/s(2)+/-1311), and elbow flexion/extension (9355

degrees/s(2)+/-4120, 12889 degrees/s(2)+/-5572). This study described the

motion occurring at the shoulder and elbow using a local coordinate system.

Stable parameters that characterize the propulsive stroke and differed with speed

were found. In the future these same parameters may provide insight into the

cause and prevention of shoulder and elbow injuries in manual wheelchair



Keywords: 3-DIMENSIONAL

KINEMATICS/BIOMECHANICS/elbow/ENGLAND/motion/prevention/range

of motion/shoulder/SPINAL CORD/stroke/UPPER

EXTREMITY/wheelchair/wheelchair propulsion



Binkley, H.M. and Williams, L.C. (2003), Emergency procedures for the strength and

conditioning coach. Strength and Conditioning Journal, 25 (1), 7-18



Keywords: ACCLIMATION/asthma/athlete collapse/cold

illness/diabetes/EXERCISE-INDUCED ASTHMA/FIELD/heat illness/HEAT

ILLNESS/management/prevention/recognition/RESPONSES/STRATEGIES/ST

RENGTH/STROKE/USA



Leonberg, S.C. and Elliott, F.A. (1981), Prevention of Recurrent Stroke. Stroke, 12 (6),

731-735



Keywords: HEART/STROKE



Sorensen, P.S., Pedersen, H., Marquardsen, J., Petersson, H., Heltberg, A., Simonsen, N.,

Munck, O. and Andersen, L.A. (1983), Acetylsalicylic-Acid in the Prevention of

Stroke in Patients with Reversible Cerebral Ischemic Attacks - A Danish

Cooperative Study. Stroke, 14 (1), 15-22



Keywords: HEART/STROKE



Taylor, D.W., Sackett, D.L. and Haynes, R.B. (1984), Sample-Size for Randomized

Trials in Stroke Prevention - How Many Patients do We Need. Stroke, 15 (6),

968-971

Keywords: HEART/STROKE



Gent, M., Blakely, J.A., Hachinski, V., Roberts, R.S., Barnett, H.J.M., Bayer, N.H.,

Carruthers, S.G., Collins, S.M., Gawel, M.G., Girouxklimek, M., Hopkins, M.,

Jain, P., Lamy, M., Meloche, J.P., Saerens, E., Sicurella, J. and Turpie, A.G.G.

(1985), A Secondary Prevention, Randomized Trial of Suloctidil in Patients with

A Recent History of Thromboembolic Stroke. Stroke, 16 (3), 416-424



Keywords: HEART/STROKE



Kelley, R.E., Vibulsresth, S., Bell, L. and Duncan, R.C. (1987), Evaluation of Kinetic

Therapy in the Prevention of Complications of Prolonged Bed Rest Secondary to

Stroke. Stroke, 18 (3), 638-642



Keywords: HEART/STROKE



Sze, P.C., Reitman, D., Pincus, M.M., Sacks, H.S. and Chalmers, T.C. (1988),

Antiplatelet Agents in the Secondary Prevention of Stroke - Meta-Analysis of the

Randomized Control Trials. Stroke, 19 (4), 436-442



Keywords: HEART/STROKE/TRIAL/TRIALS



Futrell, N. and Millikan, C. (1989), Frequency, Etiology, and Prevention of Stroke in

Patients with Systemic Lupus-Erythematosus. Stroke, 20 (5), 583-591



Keywords: HEART/STROKE



Hermsmeyer, K., Hatton, D.A., Karanja, N. and Mccarron, D. (1990), Effects of Dietary

Calcium on Nimodipine-Sensitive Calcium- Channel Function in Stroke-Prone

Spontaneously Hypertensive Rats. Stroke, 21 (12), 98-101.



Abstract: We studied the effects of dietary Ca2+ on blood pressure, survival, and

calcium channel function to investigate cardiovascular disease mechanisms in

stroke-prone spontaneously hypertensive rats. Beginning at 3 weeks of age, rats

were fed high sodium chloride diets (8.0%) in combination with either high

(2.0%) or low (0.2%) Ca2+ group diets for 8 weeks. At 12 weeks of age, survival

was 90% in the high Ca2+ group and 30% in the low Ca2+ group. The higher

blood pressure and lower survival in the low Ca2+ group suggest an

intensification of altered vascular muscle cell mechanisms by a dietary Ca2+

deficit. Nimodipine (1-10 nM) effectively blocked L-type Ca2+ currents in

isolated vascular muscle cells from both groups. Contraction of isolated cells that

were not patch clamped to high potassium solutions were also blocked by 1 nM

nimodipine. Disappearance of the L-type Ca2+ channel current was accelerated

by holding at depolarizing potentials (positive to -50 mV) and by depolarizing

steps to 0 mV. Nimodipine block of the L-type Ca2+ currents in vascular muscle

is believed to contribute substantially to antihypertensive properties and stroke

prevention, actions that may develop fully only in stroke-prone spontaneously

hypertensive rats on a diet of at least normal Ca2+

Keywords: CALCIUM/CALCIUM CHANNELS/HEART/HYPERTENSION/STROKE



Anderson, D.C. (1990), Progress Report of the Stroke Prevention in Atrial-Fibrillation

Study. Stroke, 21 (11), 12-17



Keywords: HEART/STROKE



Mcbride, R. (1990), Design of A Multicenter Randomized Trial for the Stroke

Prevention in Atrial-Fibrillation Study. Stroke, 21 (4), 538-545



Keywords: HEART/STROKE



Lowenthal, A. (1990), European Stroke Prevention Study. Stroke, 21 (8), 1122-1130



Keywords: HEART/STROKE



Dunbabin, D.W. and Sandercock, P.A.G. (1990), Preventing Stroke by the Modification

of Risk-Factors. Stroke, 21 (12), 36-39.



Abstract: Epidemiologic research has revealed the major risk factors in cerebrovascular

disease. This review will concentrate on three important risk factors: elevated

blood pressure, the most common and important, since it is responsible for up to

70% of all strokes; raised cholesterol; and smoking. These factors are important

not only because they increase the risk of stroke, but also because they are

amenable to modification by drugs, diet, or other interventions. Strategies to

avoid stroke can either 1) try to produce substantial reductions, usually with

drugs, in the level of the risk factor in the few individuals in the population with

high levels (the "high-risk" approach), or 2) try to produce modest reductions int

he level of the risk factor in every individual in the population, usually not with

drugs but with lifestyle modification (the "mass" approach). The prevention of

stroke could best be achieved through continuing medical efforts to deal with

high- risk individuals and through political strategies to encourage a healthier

lifestyle in the population as a whole



Keywords: BLOOD-PRESSURE/CEREBROVASCULAR

DISORDERS/CEREBROVASCULAR-DISEASE/COMMUNITY/CONTROLL

ED TRIAL/CORONARY

HEART-DISEASE/HEART/HYPERTENSION/MALE CIGARETTE

SMOKERS/MORTALITY/RISK

FACTORS/SERUM-CHOLESTEROL/SMOKING/STROKE



Woo, J., Lau, E., Lam, C.W.K., Kay, R., Teoh, R., Wong, H.Y., Prall, W.Y., Kreel, L.

and Nicholls, M.G. (1991), Hypertension, Lipoprotein(A), and

Apolipoprotein-A-I As Risk- Factors for Stroke in the Chinese. Stroke, 22 (2),

203-208.



Abstract: We analyzed the serum concentrations of lipids and lipoproteins and the

prevalence of other risk factors in a case-control study of 304 consecutive

Chinese patients with acute stroke (classified as cerebral infarction, lacunar

infarction, or intracerebral hemorrhage) and 304 age- and sex-matched controls.

For all strokes we identified the following risk factors: a history of ischemic

heart disease, diabetes mellitus, or hypertension; the presence of atrial fibrillation

or left ventricular hypertrophy; a glycosylated hemoglobin A1 concentration of >

9.1%; a fasting plasma glucose concentration 3 months after stroke of > 6.0

mmol/l; a serum triglyceride concentration 3 months after stroke of > 2.1 mmol/l;

and a serum lipoprotein (a) concentration of > 29.2 mg/dl. We found the

following protective factors: a serum high density lipoprotein-cholesterol

concentration of > 1.59 mmol/l and a serum apolipoprotein A-I concentration of

greater-than-or- equal-to 106 mg/dl. The patterns of risk factors differed among

the three stroke subtypes. When significant risk factors were entered into a

multiple logistic regression model, we found a history of hypertension, a high

serum lipoprotein(a) concentration, and a low apolipoprotein A-I concentration

to be independent risk factors for all strokes. The attributable risk for

hypertension was estimated to be 24% in patients aged greater-than-or-equal-to

60 years. In this population, in which cerebrovascular diseases are the third

commonest cause of mortality, identification of risk factors will allow further

studies in risk factor modification for the prevention of stroke



Keywords: ATHEROSCLEROSIS/CEREBRAL INFARCTION/CORONARY

HEART-DISEASE/HEART/HISTORY/INTRACEREBRAL

HEMORRHAGE/LACUNAR

INFARCTION/LIPIDS/MEN/MORTALITY/PLASMA/RISK

FACTORS/SERUM-CHOLESTEROL/STROKE



Sacco, R.L., Hauser, W.A., Mohr, J.P. and Foulkes, M.A. (1991), One-Year Outcome

After Cerebral Infarction in Whites, Blacks, and Hispanics. Stroke, 22 (3),

305-311.



Abstract: Little is known about outcome after cerebral infarction for different ethnic

groups. Of 590 stroke patients hospitalized from 1983 to 1986 at the

Neurological Institute, cerebral infarction over age 39 years occurred in 135

whites, 177 blacks, and 82 Hispanics. Outcome after cerebral infarction differed

by ethnicity. The 1-month mortality rate was similar in whites and blacks and

least in Hispanics. Whites had a slightly greater risk of recurrent stroke or death

than blacks or Hispanics until 6 months after infarction, when their risk stabilized,

while the risk in blacks and Hispanics continued to rise for the entire year of

follow-up. By 1 year, the rate of recurrent stroke or death was 34.8 +/- 4.2% in

whites, 31.1 +/- 3.6% in blacks, and 21.4 +/- 4.8% in Hispanics (p = 0.04).

Differences were found in the distribution of various stroke risk factors in the

three ethnic groups. A Cox proportional hazards model demonstrated that the

ethnic differences in stroke risk factors and infarct subtype were responsible for

the ethnic differences in outcome. An abnormal first electrocardiogram was a

risk factor for stroke recurrence or death in all three ethnic groups, while a

nonlacunar infarct subtype and a history of diabetes were significant only in

Hispanics. Understanding the associations of stroke determinants with ethnicity

may lead to more focused secondary prevention of recurrent stroke



Keywords: CEREBROVASCULAR DISORDERS/CIRCULATION OCCLUSIVE

DISEASE/EPIDEMIOLOGY/HEART/ISCHEMIC STROKE/LEHIGH-

VALLEY/MEXICAN-AMERICANS/NEW-YORK/NORTH-CAROLINA/POP

ULATION/RACIAL

DIFFERENCES/RACIAL-DIFFERENCES/RISK-FACTORS/STROKE/STRO

KE PROGRAMS



Tuomilehto, J., Bonita, R., Stewart, A., Nissinen, A. and Salonen, J.T. (1991),

Hypertension, Cigarette-Smoking, and the Decline in Stroke Incidence in Eastern

Finland. Stroke, 22 (1), 7-11.



Abstract: Finland has high rates of both cardiovascular disease and cardiovascular

disease risk factors. We studied random samples of the population 30-59 years of

age for risk factors in two provinces of eastern Finland in 1972 and 1977. We

then followed both cohorts until 1985 through linkage with national hospital

discharge and death certificate registers. The prevalence of hypertension and

smoking in both provinces declined between 1972 and 1977, as did the stroke

incidence in the 8-year period of follow-up of each cohort. We observed no

differences in stroke incidence between the two provinces. The relative risk of

stroke in the later period (1977-1985) was 0.71 and 0.58 for men and women,

respectively, when compared with the earlier period (1972-1980). Overall, 28%

of all stroke events could be attributed to hypertension, 17% to smoking, and

43% to these two factors jointly. The decrease in the prevalence of hypertension

and smoking accounted for about 29% of the decline



Keywords: ANTIHYPERTENSIVE

TREATMENT/BLOOD-PRESSURE/CARDIOVASCULAR-DISEASE/CIGAR

ETTE

SMOKING/COMMUNITY/FINLAND/HEART/HYPERTENSION/INTERVEN

TION PROGRAM/MORTALITY/NORTH KARELIA

PROJECT/PREVENTION/RISK FACTOR/STROKE/TRENDS



Sacco, R.L., Hauser, W.A. and Mohr, J.P. (1991), Hospitalized Stroke in Blacks and

Hispanics in Northern Manhattan. Stroke, 22 (12), 1491-1496.



Abstract: Background and Purpose: The growing black and Hispanic populations in the

United States call for studies of the rates and prognosis for cerebral infarction to

help plan more focused prevention programs. Methods: Using the Statewide

Planning and Research Cooperative System, we obtained discharge data for

1,034 patients over age 39, who were hospitalized for stroke from 1983 to 1986,

using four zip code areas of the ethnically mixed community of Northern

Manhattan. Results: Stroke incidence increased with age in both men and women

in all three race/ethnic groups. The age-adjusted stroke incidence per 100,000 per

year for men greater-than-or-equal-to 40 years of age was 567 for blacks, 306 for

Hispanics, and 351 for whites. Incidence in women greater-than-or-equal-to 40

years was 716 in blacks, 361 in Hispanics, and 326 in whites. Hypertension and

diabetes were more prevalent in blacks and Hispanics with stroke, whereas

whites had more ischemic cardiac disease. Crude in-hospital mortality was

greater in younger blacks and Hispanics compared with whites, whereas 2-year

readmission rates, overall and for stroke, were similar in the three groups.

Conclusions: These estimates of hospitalized stroke incidence and mortality

substantiate the greater incidence of stroke in blacks and provide new data

concerning Hispanics for public health planning



Keywords: BLACKS/CEREBROVASCULAR DISORDERS/CIRCULATION

OCCLUSIVE DISEASE/EPIDEMIOLOGY/HEART/HISPANIC

AMERICANS/MEXICAN-

AMERICANS/POPULATION/RACIAL-DIFFERENCES/RISK-FACTORS/ST

ROKE/TEXAS



Noel, P., Gregoire, F., Capon, A. and Lehert, P. (1991), Atrial-Fibrillation As A Risk

Factor for Deep Venous Thrombosis and Pulmonary Emboli in Stroke Patients.

Stroke, 22 (6), 760-762.



Abstract: In 539 consecutive stroke patients admitted to a rehabilitation department, we

studied the possible role of atrial fibrillation as a risk factor for deep venous

thrombosis and pulmonary embolism by analyzing a series of relevant clinical

data in patients with and without atrial fibrillation and in patients with and

without venous thromboembolic complications. Deep venous thrombosis as well

as advanced age and cardiac disease were significantly (p 20

cigarettes/day) was 11.1 (95% confidence interval [CI], 5.0-24.9); for current

light smokers (less-than-or-equal-to 20 cigarettes/day), 4.1 (95% CI, 2.3- 7.3);

and for former smokers, 1.8 (95% CI, 1.0-3.2). The risk associated with smoking

was greatest in the 3 hours after a cigarette (odds ratio [OR] = 7.0; 95% Cl,

3.7-13.1) and then fell, not reaching the risk in those who had never smoked until

more than 10 years had passed since the last cigarette. Heavy alcohol use (>2

drinks/day) was also associated with bleeds (OR = 2.2; 95% CI, 0.9-5.1, after

adjusting for smoking status). These associations were not substantially altered

after adjusting for several possible confounding factors, including a history of

hypertension. Conclusions: Cigarette smoking and heavy alcohol use are

associated with the occurrence of subarachnoid hemorrhage



Keywords: ALCOHOL DRINKING/CAROTID-ARTERY

ATHEROSCLEROSIS/CIGARETTE

SMOKING/CONSUMPTION/DISEASE/ELASTASE

ACTIVITY/EPIDEMIOLOGY/HEART/HYPERTENSION/NONHEMORRHA

GIC STROKE/ORAL-

CONTRACEPTIVES/RISK-FACTORS/STROKE/SUB-ARACHNOID

HEMORRHAGE/SUBARACHNOID HEMORRHAGE/WOMEN



Herderschee, D., Hijdra, A., Algra, A., Koudstaal, P.J., Kappelle, L.J. and Vangijn, J.

(1992), Silent Stroke in Patients with Transient Ischemic Attack Or Minor

Ischemic Stroke. Stroke, 23 (9), 1220-1224.



Abstract: Background and Purpose. We studied silent stroke (i.e., infarcts on computed

tomographic scan not related to later symptoms) in patients after transient

ischemic attack or minor ischemic stroke. Methods: Ours is a cross-sectional

study of 2,329 patients who were randomized in a secondary prevention trial

after transient ischemic attack or minor ischemic stroke and had no residual

deficit after the qualifying event. Results: Silent stroke was observed in 13% of

the 2,329 patients. Lacunes formed 79%, cortical lesions 14%, and border zone

lesions 7% of all silent strokes. Silent lacunes were most often located in the

basal ganglia and symptomatic lacunes most often in the corona radiata. Age,

hypertension, and current cigarette smoking were related to the presence of silent

stroke. Silent stroke was equally common in different types of transient ischemic

attack, including transient monocular blindness. Residual symptoms of any kind

were more common in patients with silent stroke than in those without.

Conclusions: Because only the sites of silent stroke infarcts differed slightly from

those of symptomatic infarcts and the frequency of vascular risk factors was

similar to that of symptomatic infarcts, silent stroke may have the same bearing

on future risk as known prior stroke

Keywords: CAROTID ENDARTERECTOMY/CEREBRAL

INFARCTION/CEREBRAL ISCHEMIA/CHRONIC

ATRIAL-FIBRILLATION/DIAGNOSIS/HANDICAP/HEART/INTEROBSER

VER AGREEMENT/RISK/RISK

FACTORS/STROKE/TOMOGRAPHY/TRANSIENT/X-RAY COMPUTED



Lysko, P.G., Lysko, K.A., Yue, T.L., Webb, C.L., Gu, J.L. and Feuerstein, G. (1992),

Neuroprotective Effects of Carvedilol, A New Antihypertensive Agent, in

Cultured Rat Cerebellar Neurons and in Gerbil Global Brain Ischemia. Stroke, 23

(11), 1630-1636.



Abstract: Background and Purpose: Free radical generation mediates part of the

ischemic neuronal damage caused by the excitatory amino acid glutamate.

Carvedilol, a novel multiple-action antihypertensive agent, has been shown to

scavenge free radicals and inhibit lipid peroxidation in swine heart and rat brain

homogenates. Therefore, we studied the neuroprotective effect of carvedilol on

cultured cerebellar neurons and on CA1 hippocampal neurons of gerbils exposed

to brain ischemia. Methods: Neuroprotective mechanisms were studied using an

in vitro ischemia model of cultured rat cerebellar granule cell neurons exposed to

either glutamate or oxygen free radical- generating systems. Prevention of lipid

peroxidation by carvedilol was studied by measuring the formation of

thiobarbituric acid-reactive substance. Gerbil CA1 neuron survival was examined

by direct neuronal count 7 days after 6 minutes of global ischemia with

reperfusion. Results: Carvedilol protected cultured neurons in a dose-dependent

manner against glutamate-mediated excitotoxicity (inhibitory concentration

[IC50] = 1.1 muM) as well as against a 20-minute oxidative challenge (IC50=5

muM). The IC50 against the oxidative challenge was lowered to 1.3 muM by

growing neurons for 24 hours in the presence of carvedilol. At 10 muM

carvedilol inhibited lipid peroxidation 50% and 73% (n=4, p70 years; 1.9%), those with anterior site of myocardial infarction (1.35%), a

previous history of myocardial infarction (1.8%), hypertension (1.4%), stroke in

the past (4.1%), and chronic atrial fibrillation (9%). Multivariate analysis

identified the following as independent predictors of stroke/transient ischemic

attacks occurring in the year after hospital discharge: chronic atrial fibrillation,

older age, history of previous myocardial infarction, anterior myocardial

infarction site, serum glutamic oxaloacetic transaminase levels more than four

times above upper normal limits, and stroke in the past. The age-adjusted 1-year

and long-term mortality rates (4.5 to 7 years; mean, 5.5 years) were significantly

higher in patients with (31% and 62%) than in those without stroke/transient

ischemic attacks (9% and 31%, respectively; P20 vn). All participants underwent

1.5-T MRI and demanding neuropsychological testing. Semiautomated

measurements of the total white matter hyperintensity area and the size of

ventricles and cortical sulci were conducted. Results There were 180 subjects

(77.3%) with negative, 35 (15.0%) with low positive, and 18 (7.7%) with

moderately high positive aCL titers. The frequency and extent of focal and

diffuse brain abnormalities were not related to the aCL status of those examined.

However, subjects with positive aCL results performed worse than those with

negative findings on almost all tests administered, and this effect was mainly IgG

titer related. When an ANCOVA test and partial correlations to correct for slight

group differences in age and for the presence of major vascular risk factors were

used, values of P3.65 L) was 1.4 (95% confidence interval, 1.0 to 2.0). The

inverse association between FEV1 and stroke was only apparent in older men,

current nonsmokers, hypertensive men, and men with preexisting ischemic heart

disease. Lower FEV(1) was associated with higher rates of stroke in hypertensive

men irrespective of smoking status. Inclusion of FEV(1) in a risk score for stroke

provided only a small increase in the absolute risk or the yield of cases in the top

fifth of the score distribution during the follow-up period. Conclusions Lower

levels of FEV(1) are associated with an increased risk of stroke in those already

at high risk, eg, those with ischemic heart disease or hypertension. However, the

association is not strong enough to warrant the use of FEV(1) in making clinical

decisions regarding the treatment of hypertension as it relates to the prevention

of stroke



Keywords: absolute risk/aged/antihypertensive treatment/atrial fibrillation/blood

pressure/BLOOD-PRESSURE/BRITISH MEN/CARDIOVASCULAR-

DISEASE/ENGLAND/fibrillation/FOLLOW-UP/GENERAL-PRACTICE/HEA

RT/HEART-ATTACKS/hypertension/ischemic heart

disease/LEFT-VENTRICULAR FUNCTION/LUNG/MIDDLE-AGED

MEN/myocardial infarction/POPULATION/prevention/prospective

study/PULMONARY-FUNCTION/RESPIRATORY FUNCTION

TESTS/risk/RISK FACTORS/smoking/STROKE/treatment



Nagao, T., Hamamoto, M., Kanda, A., Tsuganesawa, T., Ueda, M., Kobayashi, K.,

Miyazaki, T. and Terashi, A. (1995), Platelet Activation Is Not Involved in

Acceleration of the Coagulation System in Acute Cardioembolic Stroke with

Nonvalvular Atrial-Fibrillation. Stroke, 26 (8), 1365-1368.



Abstract: Background and Purpose It is generally accepted that the coagulation system is

activated in ischemic stroke and that platelet activation is involved in the

pathogenesis of this disease. However, little is known about how and to what

extent platelet activity participates in coagulation system enhancement. We

evaluated the hemostatic condition, especially with regard to platelet function

and the coagulation system, within 3 days of onset of acute stroke. The study

participants were limited to elderly patients with cardioembolic stroke due to

nonvalvular atrial fibrillation. Methods Seventeen elderly patients with acute

cardioembolic stroke due to nonvalvular atrial fibrillation were investigated,

Within 3 days of stroke onset, beta-thromboglobulin (BTG), platelet factor 4

(PF4), thrombin-antithrombin III complex (TAT), and D-dimer from arterial

blood were carefully evaluated in these patients. Blood samples from 19 healthy

age-and sex-matched control subjects were also examined. Results The two

studied markers of platelet activity did not change in the patients or the control

subjects, and the between-group differences between the stroke and control

groups were not statistically significant (BTG, 43.8 versus 31.9 ng/mL; PF4,

9.06 versus 5.78 ng/mL; respectively). In contrast, the two studied

coagulation-system indicators were markedly elevated in the patients compared

with the control subjects (TAT, 13.8 versus 3.5 ng/mL, P 70%

stenosis (P70% stenosis, a cerebral

angiogram was reported as seldom or never used by 42% of physicians who

viewed the test as readily available versus 67% if cerebral angiography was

perceived as not readily available (P=.005). Multinomial multiple logistic

regression analysis showed that symptom status, the degree of stenosis,

perceived availability of CE, and physician specialty independently contributed

to the explained variance in the reported use of CE (P70% stenosis compared with patients with 50% to 70% stenosis

(P 6 hours) from onset

to first CT and small hematoma ( 6 hours after ictus who has a hematoma

volume 75 years and a history of congestive heart

failure. Conclusions Almost 1 in 5 patients underwent CEA inappropriately,

which was most commonly due to apparent overestimation of stenosis severity,

and half had uncertain indications. Our high complication rate possibly negated

any overall surgical benefit in the large group of asymptomatic patients



Keywords: age/angina/asymptomatic/CARDIAC RISK/carotid/carotid

endarterectomy/CEREBRAL-ISCHEMIA/complications/CORONARY-ARTER

Y DISEASE/endarterectomy/health/health services misuse/HEART/heart

failure/history/infarction/LARGE METROPOLITAN

AREA/MORTALITY/MULTICENTER/myocardial

infarction/PATTERNS/PREVENTION/randomized/randomized controlled

trial/risk/risk factors/risk factors for stroke/severity/STENOSIS/STROKE/trials



Tutuarima, J.A., vanderMeulen, J.H.P., deHaan, R.J., vanStraten, A. and Limburg, M.

(1997), Risk factors for falls of hospitalized stroke patients. Stroke, 28 (2),

297-301.



Abstract: Background and Purpose Patients with stroke are at a high risk for falling. We

assessed the fall incidence and risk factors for patients hospitalized as the result

of an acute stroke. Methods We studied a cohort of 720 stroke patients from 23

hospitals in The Netherlands. The data were abstracted from the medical and

nursing records. Results We studied 346 women and 374 men with a median age

of 75 years; 77% of the patients had had a cerebral infarct, 17% had had a

hemorrhage, and 6% had had an undefined stroke. We recorded 104 patients

(14%) who fell at least once; there were a total of 173 falls. The incidence of

falls was 8.9/1000 patients per day. The daily incidence was 6.2/1000 patients for

first falls and 17.9/1000 patients for second falls. Heart disease (relative risk

[RR], 1.6; 95% confidence interval [CI], 1.0 to 2.4), mental decline (RR, 1.6;

95% CI, 1.0 to 2.4), and urinary incontinence (RR, 2.3;95% CI, 1.3 to 4.1) were

incremental risk factors for first falls, whereas the use of major psychotropic

drugs lowered the fall risk (RR, 0.5; 95% CI, 0.3 to 0.8). The fall RR for patients

with one previous fall was 2.2 (95% CI, 1.5 to 3.2), adjusted for the other risk

factors. Most falls occurred during the day. Approximately 25% of the falls

caused slight-to-severe injury, whereas three falls (2%) led to hip fractures.

Conclusions Stroke patients have a high risk of falling. The identification of

patients at risk may be a first step toward the implementation of fall-prevention

measures for these patients



Keywords: accidental falls/acute/age/cerebral/cerebrovascular

disorders/COMMUNITY/drugs/ELDERLY

PERSONS/fractures/HEART/hemorrhage/incidence/incidences/INJURIES/INTE

RVENTION/men/Netherlands/PREVENTION/relative risk/risk/risk

factors/stroke/women



Yamamoto, Y., Akiguchi, I., Oiwa, K., Hayashi, M. and Kimura, J. (1998), Adverse

effect of nighttime blood pressure on the outcome of lacunar infarct patients.

Stroke, 29 (3), 570-576.



Abstract: Background and Purpose-Antihypertensive therapy has dramatically reduced

the incidence of stroke recurrence; however, recent studies have suggested that

the excessive lowering of blood pressure (BP) could cause ischemic cerebral

lesions. We conducted a prospective study using MRI and ambulatory blood

pressure monitoring to elucidate the appropriate BP control level for the

prevention of silent and symptomatic cerebral infarction. Methods-We studied

105 patients with symptomatic lacunar infarcts who underwent repeated MRI

and 24-hour BP monitoring in the period between the two MRI examinations.

The patients were divided into five groups according to their outcome as follows:

group 1, those who showed neither symptomatic episodes nor the development

of new silent lesions detected by repeated MRI; group 2, those who only showed

the development of silent lacunae; group 3, those who showed development of

diffuse white matter lesions only; group 4, those who showed the development of

both silent lacunae and diffuse white matter lesions; and group 5, those who

showed symptomatic cerebrovascular disease. Groups 2 through 5 were then

compared with group 1 with respect to the ambulatory BP values, Results-The

average follow-up period was 3.2+/-2.6 years (mean+/-SD). In all patients in

group 1 and group 5, nighttime systolic BPs were significantly higher than in

group 1 (both P90 mm Hg and

90 mm Hg may be

regarded as a factor predictive of the recurrence of HBH



Keywords: blood pressure/cerebral

hemorrhage/hemorrhage/hypertension/INTRACEREBRAL

HEMORRHAGE/recurrence/risk/risk factors/STROKE/stroke prevention



Ay, H., Buonanno, F.S., Abraham, S.A., Kistler, J.P. and Koroshetz, W.J. (1998), An

electrocardiographic criterion for diagnosis of patent foramen ovale associated

with ischemic stroke. Stroke, 29 (7), 1393-1397.



Abstract: Background and Purpose-An M-shaped bifid notch on the ascending branch,

or on the zenith, of the R wave in inferior ECG leads (II, III, aVF), so called

"crochetage," is an indicator of ostium secundum atrial septal defects. The

pathophysiology underlying this finding remains unknown. A crochetage pattern

has not been previously reported in patients with patent foramen ovale (PFO);

however, the location of this defect and the secundum atrial septum are similar.

The purpose of this study was to determine the prevalence of crochetage in

cryptogenic stroke patients with or without PFO. Methods-A conservative

selection scheme was used to identify patients likely to have had PFO-associated

strokes tie, cryptogenic) and to exclude any structural, functional, or vascular

heart disease responsible for ECG changes. All patients had a standard 12-lead

EGG. The prevalence of crochetage in each group was determined. Results-Sixty

consecutive patients were studied (28 with echo-documented PFO and 32

echo-negative control subjects). The crochetage pattern was present in at least 1

inferior limb lead in 10 of 28 PFO patients (36%) and 3 of 32 control subjects

(9%) (P84 age group). Concomitantly, there

was a significant decrease in mortality (1.2% versus 0.8%), cardiac complication

rate (ICD-9- CM 997.1, 4.1% versus 3.0%) and percentage of patients discharged

>7 days postoperatively (8.9% versus 4.9%), Mean length of stay declined 28%

(5.8 versus 4.1 days), and mean adjusted charges declined 7% ($19 456 versus

$18 055). Although the average case was less costly, the increased volume

resulted in an estimated $56 million increase in annual hospital payments.

Conclusions-The dramatic increase in the number of CEAs performed in the state

of Florida after release of the ACAS Clinical Advisory suggests a causal

relationship and mandates further cost-effectiveness analyses



Keywords: AD-HOC-COMMITTEE/age/ARTERY

STENOSIS/atherosclerosis/carotid/carotid arteries/carotid

endarterectomy/cerebrovascular disorders/COMPLICATIONS/cost

effectiveness/cost-effectiveness/DISEASE/endarterectomy/epidemiology/EPIDE

MIOLOGY/GUIDELINES/hospital/mortality/PREVENTION/race/RISKS/STR

OKE/stroke prevention/SURGICAL-TREATMENT/trials



Hsia, D.C., Moscoe, L.M. and Krushat, M. (1998), Epidemiology of carotid

endarterectomy among Medicare beneficiaries - 1985-1996 update. Stroke, 29 (2),

346-350.



Abstract: Background and Purpose-This article describes changes in the rate and

outcome of carotid endarterectomies among Medicare beneficiaries.

Methods-We analyzed Interventional Classification of Diseases, 9th Revision,

Clinical Modification (ICD-9-CM) codes as shown on Medicare bills to calculate

carotid endarterectomy frequency, rate, and perioperative mortality by patient

demography and hospital characteristics. Results-After initially peaking at 61273

procedures (20.6 per 10000 beneficiaries) in 1985, the frequency of carotid

endarterectomy among Medicare beneficiaries declined to 46571 (14.3 per 10000)

in 1989 and then rose to 108275 (28.6 per 10000) in 1996. Patients were

predominantly aged 65 to 74 years, male, and white; surgery occurred mainly in

large, urban, nonprofit, and teaching hospitals. Perioperative mortality declined

from 3.0% in 1985 to 1.6% in 1996. Conclusions-The frequency and rate of

carotid endarterectomy showed prompt response to reports from clinical trials.

Perioperative mortality both improved and converged over time but did not attain

the rates reported by the trials. Patients aged 85+ years suffered twice the

average perioperative mortality



Keywords: ACCURACY/aged/carotid/carotid endarterectomy/cerebral

ischemia/CEREBRAL- ISCHEMIA/clinical

trials/elderly/endarterectomy/EXTRACRANIAL

ARTERIES/HEAD/hospital/mortality/PERFORMANCE/PREVENTION/PROS

PECTIVE-PAYMENT SYSTEM/STENOSIS/STROKE/stroke

management/surgery/trials



Sacco, R.L., Gan, R., Boden-Albala, B., Lin, I.F., Kargman, D.E., Hauser, W.A., Shea, S.

and Paik, M.C. (1998), Leisure-time physical activity and ischemic stroke risk -

The Northern Manhattan Stroke Study. Stroke, 29 (2), 380-387.



Abstract: Background and Purpose-Physical activity reduces the risk of premature death

and cardiovascular disease, but the relationship to stroke is less well studied. The

objective of this study was to investigate the association between leisure- time

physical activity and ischemic stroke in an urban, elderly, multiethnic population.

Methods-The Northern Manhattan Stroke Study is a population-based incidence

and case-control study. Case subjects had first ischemic stroke, and control

subjects were derived through random-digit dialing with 1:2 matching for age,

sex, and race/ethnicity. Physical activity was recorded through a standardized

in-person interview regarding the frequency and duration of 14 activities over the

2 prior weeks. Conditional logistic regression was used to calculate odds ratios

(OR) and 95% confidence intervals after adjustment for medical and

socioeconomic confounders. Results- Over 30 months, 369 case subjects and 678

control subjects were enrolled. Mean age was 69.9+/-12 years; 57% were women,

18% whites, 30% blacks, and 52% Hispanics. Leisure-time physical activity was

significantly protective for stroke after adjustment for cardiac disease, peripheral

vascular disease, hypertension, diabetes, smoking, alcohol use, obesity, medical

reasons for limited activity, education, and season of enrollment (OR=0.37; 95%

confidence interval=0.25 to 0.55). The protective effect of physical activity was

detected in both younger and older groups, in men and women, and in whites:

blacks, and Hispanics. A dose-response relationship was shown for both intensity

(light-moderate activity OR=0.39; heavy OR=0.23) and duration (2 days. Data were available for 98% of the cohort at 5 years, by which time 199

patients (58%) had died and 52 (15%) had experienced a recurrent stroke, 12

(23%) of which were fatal within 28 days. The 5-year cumulative risk of first

recurrent stroke was 22.5% (95% confidence limits [CL], 16.8%, 28.1%). The

risk of recurrent stroke was greatest in the first 6 months after stroke, at 8.8%

(95% CL, 5.4%, 12.1%). After adjustment for age and sex, the prognostic factors

for recurrent stroke were advanced, but not extreme, age (75 to 84 years) (hazard

ratio [HR], 2.6; 95% CL, 1.1, 6.2), hemorrhagic index stroke (HR, 2.1; 95% CL,

0.98, 4.4), and diabetes mellitus (HR, 2.1; 95% CL, 0.95, 4.4).

Conclusions-Approximately 1 in 6 survivors (15%) of a first- ever stroke

experience a recurrent stroke over the next 5 years, of which 25% are fatal within

28 days. The pathological subtype of the recurrent stroke is the same as that of

the index stroke in 88% of cases. The predictors of first recurrent stroke in this

study were advanced age, hemorrhagic index stroke, and diabetes mellitus, but

numbers of recurrent events were modest. Because the risk of recurrent stroke is

highest (8.8%) in the first 6 months after stroke, strategies for secondary

prevention should be initiated as soon as possible after the index event



Keywords: Australia/CEREBRAL INFARCTION/diabetes

mellitus/HYPERTENSION/MINNESOTA/MORTALITY/predictors/prevention/

prognosis/recurrence/risk/ROCHESTER/secondary prevention/stroke/stroke

outcome/SUBTYPES/SURVIVAL/transient/transient ischemic attack



Schmidt, H., Schmidt, R., Niederkorn, K., Gradert, A., Schumacher, M., Watzinger, N.,

Hartung, H.P. and Kostner, G.M. (1998), Paraoxonase PON1 polymorphism

Leu-Met54 is associated with carotid atheroselerosis - Results of the Austrian

Stroke Prevention Study. Stroke, 29 (10), 2043-2048.



Abstract: Background and Purpose-Genetic polymorphism at the paraoxonase locus is

associated with serum concentration and activity of paraoxonase and with

increased risk for coronary heart disease. Two frequent polymorphisms present at

the paraoxonase gene are the methionine (M allele) leucine (L allele) interchange

at position 54 and the arginine (B allele) glutamine (A allele) interchange at

position 191. This is the first study to determine the effect of these

polymorphisms on carotid atherosclerosis. Methods-The paraoxonase genotypes

at positions 54 and 191 of 316 randomly selected individuals aged 44 to 75 years

were determined by polymerase chain reaction-based restriction enzyme

digestion. Carotid atherosclerosis was assessed by color-coded Duplex scanning

and was graded on a 5- point scale ranging from 0 (normal) to 5 (complete

luminal obstruction). Results-The LL, LM, and MM genotypes at position 54

were noted in 137 (43.4%), 132 (41.8%), and 47 (14.9%) subjects; the AA, AB,

and BE genotypes at position 191 occurred in 172 (54.4%), 124 (39.2%), and 20

(6.3%) individuals. The LL genotype was significantly associated with the

presence and severity of carotid disease (P=0.022), whereas the 191

polymorphism had no effect. Logistic regression analysis with age and sex

forced into the model demonstrated plasma fibrinogen (odds ratio [OR], 1.005

per mg/dL), LDL cholesterol (OR, 1.01 per mg/dL),cardiac disease (OR, 1.75),

and the paraoxonase LL genotype to be significant predictors of carotid

atherosclerosis. The ORs for the associations with age and sex were 1.09

(P=0.0003) and 1.66 (P=0.052) per year. Conclusions- These data suggest that

the paraoxonase LL genotype may represent a genetic risk factor for carotid

atherosclerosis



Keywords: age/aged/APOLIPOPROTEIN-A-I/atherosclerosis/carotid/carotid

arteries/cholesterol/coronary heart disease/CORONARY

HEART-DISEASE/DIABETES-MELLITUS/fibrinogen/GENE/genetic/genetics/

heart/HUMAN SERUM

PARAOXONASE/LDL/LIPID-PEROXIDATION/LOW-DENSITY-LIPOPROT

EIN/OXIDATIVE

MODIFICATION/paraoxonase/predictors/RISK/severity/sex/STROKE/TRANS

GENIC MICE



Goldstein, L.B., Hey, L.A. and Laney, R. (1998), North Carolina Stroke Prevention and

Treatment Facilities Survey - rtPA therapy for acute stroke. Stroke, 29 (10),

2069-2072.

Abstract: Background and Purpose-North Carolina is situated in the "stroke belt" region

of the United States, an area of the country with a particularly high incidence of

cerebrovascular disease. The North Carolina Stroke Prevention and Treatment

Facilities Survey was carried out to determine the availabilities of a variety of

stroke prevention and treatment services throughout the state. The purpose of the

present study was to determine how widely recombinant tissue-type plasminogen

activator (rtPA) has been adopted for the treatment of patients with acute

ischemic stroke and to determine the characteristics of the medical facilities in

the state offering this therapy. Methods-A single-page survey was mailed to the

medical center directors of each inpatient medical facility in North Carolina.

Data collected included questions related to the availability of selected basic and

advanced diagnostic tests and procedures, stroke prevention and treatment

programs and services (community stroke awareness program, acute stroke

identification program, acute stroke team, stroke rtPA protocol, stroke care map,

neurologist), and facilities (Stroke Acute Care Unit or equivalent).

Results-Responses were obtained from all 125 inpatient medical facilities in

North Carolina, rtPA stroke protocols were adopted in 54 facilities located in 46

of the state's 100 counties. Seventy-four percent of the state's population resides

in counties with hospitals providing rtPA treatment. Compared with facilities not

offering rtPA, those with rtPA protocols more commonly sponsored stroke

community awareness programs (41% versus 17%, P=0.003) and more

frequently had an organized stroke team (31% versus 8%, P=0.001), used stroke

care maps (56% versus 17%, P75 years) who have a higher incidence of bleeding events

while undergoing anticoagulation. Methods-We calculated the incremental costs

per life-year gained for 4 base cases using efficacy data from the Boston Area

Anticoagulation Trial for Atrial Fibrillation, the meta- analysis of the 5

nonrheumatic atrial fibrillation trials, cost data from a district general hospital,

and review of the literature. Results-The cost per life-year gained free from

stroke over 10 years ranged from -pound 400.45 (ie, a resource saving achieved

for each life-year gained free from stroke) to pound 13221.29. The results were

most sensitive to alteration in the frequency of anticoagulation monitoring.

Conclusions-For medical and economic reasons, anticoagulation treatment in the

prevention of ischemic stroke is justified. Although older patients are more at

risk of adverse events, anticoagulation is more cost-effective in this group



Keywords: adverse events/aged/anticoagulation/ASPIRIN/atrial fibrillation/clinical

trials/cost effectiveness/cost-benefit analysis/cost-effectiveness/costs/district

general hospital/elderly/fibrillation/hospital/incidence/ischemic

stroke/prevention/primary prevention/risk/stroke/treatment/trials/WARFARIN



Lee, I.M. and Paffenbarger, R.S. (1998), Physical activity and stroke incidence - The

Harvard Alumni Health Study. Stroke, 29 (10), 2049-2054.



Abstract: Background and Purpose-PhysiologicaIly, it appears plausible for physical

activity to decrease stroke risk; however, epidemiological studies have produced

mixed findings. Furthermore, few studies have examined specific kinds and

intensities of activities. The purpose of this study was to examine the association

between physical activity, including its various components (walking, climbing

stairs, participation in sports and recreational activities), and stroke risk.

Methods-This was a prospective cohort study of 11 130 Harvard University

alumni (mean age, 58 years) without cardiovascular disease and cancer at

baseline. Men reported their walking, stair climbing, and participation in sports

or recreation on baseline questionnaires in 1977. Stroke occurrence was assessed

with another questionnaire in 1988. Death certificates were obtained for

decedents through 1990 to determine strokes not previously reported (total

strokes = 378). We used Cox proportional hazards regression to estimate the

relative risks and 95% CIs for stroke occurrence associated with physical activity.

Results-After adjustment for age, smoking, alcohol intake, and early parental

death, the relative risks of stroke associated with 90% responded to

the survey. Nearly all respondents reported prescribing aspirin in patients at risk

of atherothrombotic stroke, but significant differences between NA and WE are

shown by the recommended doses (P500 mg daily are

given exclusively by American participants (36%), whereas doses 95% stenosis (89% versus 53%; P8% between 1992 and 1996. Conclusions-Increased research on stroke in blacks

is needed to develop more effective strategies for primary and secondary

prevention of stroke to reduce the high burden of premature mortality and

morbidity. Renewed efforts to prevent and control stroke risk factors tin

particular elevated blood pressure, diabetes, and smoking) are needed among US

blacks



Keywords: AFRICAN-AMERICANS/blacks/blood pressure/carotid/carotid

artery/cerebral/cerebral infarction/cerebrovascular

disorders/control/DECLINE/diabetes/DISEASE/EPIDEMIOLOGY/ETHNIC-DI

FFERENCES/EXPERIENCE/HYPERTENSION/infarction/men/morbidity/mort

ality/population-based/prevention/primary/review/risk/risk factors/secondary

prevention/smoking/STROKE/United States/UNITED-STATES/WHITE

DIFFERENCES/WOMEN



Leppala, J.M., Virtamo, J., Fogelholm, R., Albanes, D. and Heinonen, O.P. (1999),

Different risk factors for different stroke subtypes - Association of blood

pressure, cholesterol, and antioxidants. Stroke, 30 (12), 2535-2540.



Abstract: Background and Purpose-Blood pressure is an important risk factor for stroke,

but the roles of serum total and HDL cholesterol, alpha-tocopherol, and

beta-carotene are poorly established. We studied these factors in relation to

stroke subtypes, Methods-Male smokers (n=28 519) aged 50 to 69 years without

a history of stroke participated in the Alpha- Tocopherol, Beta-Carotene Cancer

Prevention (ATBC) Study, a controlled trial to test the effect of alpha-tocopherol

and beta-carotene supplementation on cancer. From 1985 to 1993, a total of 1057

men suffered from primary stroke: 85 had subarachnoid hemorrhage; 112,

intracerebral hemorrhage; 807, cerebral infarction; and 53, unspecified stroke.

Results- Systolic blood pressure greater than or equal to 160 mm Hg increased

the risk of all stroke subtypes 2.5 to 4-fold. Serum total cholesterol was inversely

associated with the risk of intracerebral hemorrhage, whereas the risk of cerebral

infarction was raised at concentrations greater than or equal to 7.0 mmol/L, The

risks of subarachnoid hemorrhage and cerebral infarction were lowered with

serum HDL cholesterol levels greater than or equal to 0.85 mmol/L. Pretrial high

serum alpha-tocopherol decreased the risk of intracerebral hemorrhage by half

and cerebral infarction by one third, whereas high serum beta-carotene doubled

the risk of subarachnoid hemorrhage and decreased that of cerebral infarction by

one fifth. Conclusions-The risk factor profiles of stroke subtypes differ,

reflecting different etiopathology, Because reducing atherosclerotic diseases,

including ischemic stroke, by lowering high serum cholesterol is one of the main

targets in public health care, further studies are needed to distinguish subjects

with risk of hemorrhagic stroke. The performance of antioxidants needs

confirmation from clinical trials



Keywords: aged/antioxidants/beta carotene/BETA-CAROTENE/blood pressure/BRAIN

INFARCTION/CARDIOVASCULAR-DISEASE/cerebral/cerebral

infarction/cholesterol/CIGARETTE-SMOKING/clinical

trials/DIETARY/diseases/Finland/HDL/HDL cholesterol/health/health

care/hemorrhage/history/infarction/intracerebral

hemorrhage/INTRACEREBRAL HEMORRHAGE/ischemic/ischemic

stroke/men/PLATELET-FUNCTION/public health/risk/risk factor/risk

factors/serum/SERUM-CHOLESTEROL/stroke/subarachnoid

hemorrhage/SUBARACHNOID HEMORRHAGE/trials/VITAMIN-E



Evenson, K.R., Rosamond, W.D., Cai, J.W., Toole, J.F., Hutchinson, R.G., Shahar, E.

and Folsom, A.R. (1999), Physical activity and ischemic stroke risk - The

Atherosclerosis Risk in Communities Study. Stroke, 30 (7), 1333-1339.



Abstract: Background and Purpose-The relationship between physical activity and stroke

is inconclusive according to the 1996 US Surgeon General's Report on Physical

Activity and Health. Therefore, this study examined the relationship between

physical activity and ischemic stroke risk among 14 575 Atherosclerosis Risk in

Communities Study participants aged 45 to 64 years free of self-reported stroke

and coronary heart disease at baseline. Methods-Eligible potential stroke

hospitalizations were identified from ongoing hospital surveillance and from

hospitalizations reported by the cohort study participants. All strokes were

validated by hospitalization records. Physical activity was measured as sport,

leisure (nonsport), and work with the use of the Baecke questionnaire.

Multivariable Poisson and Cox proportional hazards models were used to

determine the association of differing levels of physical activity with ischemic

stroke incidence. Results-During an average of 7.2 years of follow-up, 189

incident ischemic strokes occurred. Ischemic stroke incidence rates were highest

in the lowest quartile of sport, leisure, and work scores. The hazard rate ratios

with 95% Cls for ischemic stroke for the highest quartile compared with the

lowest quartile of activity adjusted for age, sex, race-center, education, and

smoking, were sport 0.83 (0.52, 1.32), leisure 0.89 (0.57, 1.37), and work 0.69

(0.47, 1.00). Further adjustment for factors that likely were intermediate

variables (hypertension, diabetes, fibrinogen, and body mass index) between

physical activity and stroke attenuated the associations. Conclusions-Our

findings suggest that physical activity was weakly associated with a reduced risk

of ischemic stroke among middle-aged adults. The association may be due to

links between physical activity and other risk factors or due to chance



Keywords: adults/age/aged/ARTERY WALL THICKNESS/body mass

index/CEREBRAL INFARCTION/CEREBROVASCULAR-DISEASE/cohort

study/coronary heart disease/CORONARY HEART-

DISEASE/diabetes/DIABETES-MELLITUS/DOSE-RESPONSE/education/epid

emiology/fibrinogen/FOLLOW-UP/heart/hospital/hospitalization/hypertension/i

ncidence/ischemic/ischemic stroke/leisure activities/LIFE-STYLE

FACTORS/MIDDLE-AGED MEN/NORTHERN MANHATTAN

STROKE/physical activity/risk/risk factors/sex/smoking/stroke/stroke

incidence/stroke prevention



Di Carlo, A., Lamassa, M., Pracucci, G., Basile, A.M., Trefoloni, G., Vanni, P., Wolfe,

C.D.A., Tilling, K., Ebrahim, S. and Inzitari, D. (1999), Stroke in the very old -

Clinical presentation and determinants of 3-month functional outcome: A

European perspective. Stroke, 30 (11), 2313-2319.



Abstract: Background and Purpose-The oldest old represent the fastest- growing

segment of the elderly population in developed countries. Knowledge of

age-specific aspects of stroke is essential to establish diagnostic and therapeutic

pathways and to set up prevention and rehabilitation programs. We sought to

evaluate stroke features and functional outcome in patients aged greater than or

equal to 80 years compared with the younger age groups. Methods-In a European

Union Concerted Action involving 7 countries, 4499 patients hospitalized for

first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical

presentation, resource use, and 3-month disability (Barthel Index) and handicap

(Rankin Scale). Results-Overall, 3141 patients (69.8%) were aged 160 mm Hg (RR=2.3, P2 million person-years were analyzed. Age-adjusted

rates for first-ever stroke and for all stroke events were calculated and temporal

trends estimated by means of Poisson regression, Results-The overall annual

stroke attack rate per 100 000 person-years in the age range greater than or equal

to 25 years was 272 in men and 226 in women. Age-adjusted stroke attack rates

decreased among men by 3.9% per year and by 4.1% among women.

Age-adjusted stroke incidence rates declined by 2.9% in men and by 3.1% in

women. The trends were statistically significant in both sexes, However, the

proportion of elderly people in the study population increased during the time

period of the study, Hence the numbers of stroke victims in the population

remained largely unaltered. Conclusions-Decreasing age-adjusted stroke

incidence rates point to a reduction of stroke risk during the time period of the

study. Cardiovascular prevention, in particular improved hypertension control, is

believed to have contributed to the incidence reduction, However, the burden of

stroke on the healthcare system did not substantially diminish. The gain likely

achieved from reduction of preventable risk factors was almost counterbalanced

by population aging



Keywords: age/aging/attack rate/BLOOD- PRESSURE/CASE-FATALITY

RATES/cerebrovascular

disorders/control/DENMARK/elderly/epidemiology/FINLAND/HYPERTENSI

ON/incidence/men/MINNESOTA/MORTALITY-RATES/prevention/PROJECT

/risk/risk factors/RISK-FACTORS/SECULAR TRENDS/stroke/stroke

incidence/women



Gorelick, P.B., Born, G.V.R., D'Agostino, R.B., Hanley, D.F., Moye, L. and Pepine, C.J.

(1999), Therapeutic benefit - Aspirin revisited in light of the introduction of

clopidogrel. Stroke, 30 (8), 1716-1721.

Abstract: Background-Antiplatelet agents are widely recognized for their efficacy in

reducing the occurrence of vascular events in patients with atherothrombotic

disease. Aspirin is currently considered to be the "reference standard" antiplatelet

agent and is recommended by the American Heart Association for use in patients

with a wide range of manifestations of cardiovascular disease on the basis of its

high benefit-to-risk and benefit- to-cost ratios. Recently, clopidogrel (Plavix,

Bristol-Myers Squibb Co), another antiplatelet agent, was approved by the Food

and Drug Administration for many of the same indications as aspirin. Summary

of Review-Because physicians will be faced with deciding whether to switch sam

the well-established practice of recommending aspirin for use in patients with

atherothrombotic disease, both aspirin and clopidogrel are compared with respect

to the primary factors that influence such decisions tie, their relative efficacy,

safety, cost, and convenience of use). Conclusions-Based on the available

evidence, aspirin is preferred for the majority of stroke or myocardial infarction

patients at risk of recurrent atherothrombotic events. Clopidogrel may, however,

provide valuable therapeutic benefit over aspirin in patients with peripheral

arterial disease and in stroke or myocardial infarction patients for whom aspirin

treatment is contraindicated or for whom aspirin fails to achieve the desired

therapeutic effect



Keywords: ACETYLSALICYLIC- ACID/ANTIPLATELET/aspirin/aspirin

treatment/cardiovascular/cardiovascular disease/clopidogrel/cost/decision

analysis/DRUG/infarction/MORTALITY/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/peripheral arterial

disease/prevention/primary/risk/safety/SECONDARY

PREVENTION/STROKE/STROKE

PREVENTION/TICLOPIDINE/treatment/TRIAL/UNSTABLE

ANGINA/vascular



Stern, E.B., Berman, M.E., Thomas, J.J. and Klassen, A.C. (1999), Community

education for stroke awareness - An efficacy study. Stroke, 30 (4), 720-723.



Abstract: Background and Purpose-This study examined the effectiveness of a

slide/audio community education program aimed at increasing knowledge of

stroke risk factors, stroke warning signs, and action needed when stroke warning

signs occur. The program targets audiences at higher risk for stroke, especially

individuals who are black or >50 years of age. Methods-Subjects were 657 adults

living in the community or in senior independent-living settings. The study

examined the effectiveness of the program when presented alone and when

accompanied by discussion (facilitation) led by a trained individual. Knowledge

of stroke risk factors and warning signs was assessed using parallel pretests and

posttests developed and validated specifically for the study. Results-ANCOVA

indicated that neither pretesting nor facilitation had a significant effect on

posttest measures of knowledge. Paired t tests of groups receiving both the

pretest and posttest demonstrated significant increase in knowledge (mean

increase, 10.87%; P50% (P75 years compared with 99 of 154 patients (64%) less than or equal to 75

years (P75 years of age, and was associated with

clinical risk factors in all patients. Eligibility for anticoagulation was seen in 72

of 154 (47%) to 105 of 154 (68%) patients aged less than or equal to 75 years,

depending on the criteria used, and in 66 of 80 patients (83%) >75 years,

regardless of criteria used (P75

years (P4.9 ng/mL) of tPA antigen compared with the lowest quartile. The

dose-response relationship between tPA antigen and stroke was equally present

in white and nonwhite women, and further adjustment for total and HDL

cholesterol levels only modestly attenuated this association. Conclusions-This

population-based case-control study shows that elevated plasma tPA antigen

level is independently associated with an increased risk for ischemic stroke in

nondiabetic females 15 to 44 years of age. These findings support the hypothesis

that impaired endogenous fibrinolysis is an important risk factor for stroke in

young women



Keywords: ADULTS/age/ANGINA-PECTORIS/body mass index/cerebral/cerebral

infarction/cerebrovascular/cerebrovascular disease/cholesterol/cigarette

smoking/control/disease

risk/FIBRINOGEN/fibrinolysis/FIBRINOLYTIC-ACTIVITY/HDL/HDL

cholesterol/heart/history/hypertension/infarction/INHIBITOR-1/ischemic/ISCHE

MIC CEREBROVASCULAR-DISEASE/ischemic heart disease/ischemic

stroke/men/MYOCARDIAL-INFARCTION/PAI-1

COMPLEX/PLASMA/plasminogen

activator/population-based/prevention/risk/risk factor/risk

factors/smoking/stroke/stroke prevention/T-PA/women/young adults

Baumgartner, R.W., Mattle, H.P. and Schroth, G. (1999), Assessment of >= 50% and 160/100 mmHg) were history of

hypertension, education less than college, and higher cognitive functioning.

Conclusions-Blood pressure values in excess of national guidelines are common

after stroke and TIA, especially among diabetic patients. Efforts to lower blood

pressure control may enhance secondary prevention



Keywords: ACUTE MYOCARDIAL-INFARCTION/adherence/age/blood

pressure/blood pressure control/cerebrovascular

disorders/control/CT/education/estrogen/EVENTS/guidelines/HEALTH/health

services research/HEART-

DISEASE/history/hypertension/HYPERTENSION/ischemic/PREVENTION/pro

gnosis/randomized/randomized clinical trials/randomized

trial/RECURRENCE/RISK/secondary prevention/secondary stroke

prevention/stroke/stroke prevention/TIA/transient/transient ischemic

attack/TRANSIENT ISCHEMIC ATTACKS/treatment/trial/TRIALS/women



Holroyd-Leduc, J.M., Kapral, M.K., Austin, P.C. and Tu, J.V. (2000), Sex differences

and similarities in the management and outcome of stroke patients. Stroke, 31 (8),

1833-1837.



Abstract: Background and Purpose-Previous studies have documented sex differences in

the management and outcome of patients with cardiovascular disease. However,

little data exist on whether similar sex differences exist in stroke patients. We

conducted a study to determine whether sex differences exist in patients with

acute stroke admitted to Ontario hospitals. Methods-Using linked administrative

databases, we performed a population- based cohort study. The databases

contained information on all 44 832 patients discharged from acute-care

hospitals in Ontario between April 1993 and March 1996 with a most responsible

diagnosis of acute stroke. The main outcomes measured consisted of sex

differences in comorbidities, the use of rehabilitative services, the use of

antiplatelet therapy and anticoagulants tin elderly stroke survivors aged greater

than or equal to 65 years only), discharge destination, and mortality.

Results-Male stroke patients were more likely than female stroke patients to have

a history of ischemic heart disease (18.1% versus 15.3%, respectively; P80 years, poor command of Hebrew, and being hospitalized in a given

medical department emerged as independent variables negatively influencing

warfarin use: P=0.0001, OR 0.30 (95% CI0.17 to 0.55);P=0.02, OR 0.59 (95%

CI 0.36 to 0.94); and P=0.0002, OR 0.26 (95% CI 0.12 to 0.52), respectively. In

contrast, past history of stroke and availability of echocardiographic information,

regardless of the findings, each increased warfarin use (P=0.03, OR 1.95 [95%

CI 1.04 to 3.68], and P=0.0001, OR 3.52 [95% CI 2.16 to 5.72], respectively).

Conclusions-Old age, language difficulties, insufficient doctor alertness to

warfarin benefit, and patient disability produced reluctance to treat. Warfarin use

still lags behind requirements



Keywords: age/ANTICOAGULATION/anticoagulation/ANTITHROMBOTIC

THERAPY/aspirin/atrial fibrillation/bleeding/cardiac/chronic atrial

fibrillation/COMMUNITY/COMPLICATIONS/disability/ELDERLY

PATIENTS/fibrillation/history/Israel/NATIONAL

PATTERNS/population/PREVALENCE/prevention/stroke/stroke

prevention/thromboembolism/treatment/UNIVERSITY

HOSPITALS/use/valves/warfarin



Ellekjaer, H., Holmen, J., Ellekjaer, E. and Vatten, L. (2000), Physical activity and

stroke mortality in women - Ten-year follow-up of the Nord-Trondelag Health

Survey, 1984-1986. Stroke, 31 (1), 14-18.

Abstract: Background and Purpose-Few studies have reported a protective effect of

physical activity on stroke in women, particularly among elderly women. This

study was conducted to examine the association between different levels of

leisure-time physical activity and stroke mortality in a large prospective study of

middle-aged and elderly women. Methods-We conducted a 10-year mortality

follow-up of women aged greater than or equal to 50 years, free from stroke at

baseline (n=14101), who participated in the Nord-Trondelag Health-Survey in

Norway during 1984-1986. Main outcome measures were relative risk of stroke

mortality according to increasing levels of physical activity, with the least active

group used as reference. Results-In groups aged 50 to 69, 70 to 79, and 80 to 101

years, the relative risk: of dying decreased with increasing physical activity, after

adjustment for potentially confounding factors. In groups aged 50 to 69 and 70 to

79 years, the most active women had an adjusted relative risk of 0.42 (95% CI;

0.24 to 0.75) and 0.56(95% CI, 0.36 to 0.88), respectively. In the group aged 80

to 101 years, there was a consistent negative association with physical activity;

the adjusted relative risk for the most active was 0.57 (95% CI, 0.30 to 1.09).

Conclusions-Physical activity was associated with reduced risk of death from

stroke in middle-aged and elderly women. This association persisted after we

excluded individuals with prevalent cardiovascular and cerebrovascular disease

at baseline and women who died during the first 2 years of follow-up. These

observations strengthen the evidence that physical activity should be part of a

primary prevention strategy against stroke in women



Keywords: aged/cardiovascular/cerebrovascular/cerebrovascular disease/CORONARY

HEART-DISEASE/DEATH/disease/elderly/epidemiology/exercise/EXERCISE/

FITNESS/INFARCTION/LIFE-STYLE

FACTORS/MEN/mortality/outcome/physical

activity/POPULATION/prevention/primary/primary prevention/prospective

study/relative risk/risk/risk factors/RISK-FACTORS/stroke/stroke

mortality/stroke prevention/women



Martin, J.B., Pache, J.C., Treggiari-Venzi, M., Murphy, K.J., Gailloud, P., Puget, E.,

Pizzolato, G., Sugiu, K., Guimaraens, L., Theron, J. and Rufenacht, D.A. (2001),

Role of the distal balloon protection technique in the prevention of cerebral

embolic events during carotid stent placement. Stroke, 32 (2), 479-484.



Abstract: Background and Purpose-We sought to quantitatively and qualitatively

evaluate the release of atheromatous plaque debris induced by carotid stenting

procedures. Methods-Eight patients with severe carotid atheromatous stenoses

were treated by stent implantation under distal balloon protection, Blood

samplings were obtained after stent deployment in the blood pooled below the

inflated protection balloon. The samples were centrifuged and evaluated for

plaque debris with the use of light microscopy. The debris release was

quantitatively estimated by dividing the total volume of debris obtained by the

mean debris size. Five patients without endovascular procedure were used as a

control group. Results-The 2 main debris types found were nonrefringent

cholesterol crystals (4 to 389 mum; 115 to 8697 in number) and lipoid masses (7

to 600 mum; 341 to 34 000 in number). There was a statistically significant

difference compared with the samples obtained in the control group (P = 0,017).

Conclusions-Blood samples collected during stent implantation procedures

contain a large quantity of atheromatous plaque debris. This emphasizes the role

of distal protection techniques in avoiding migration of this plaque material into

the cerebral circulation



Keywords:

ANGIOGRAMS/ANGIOPLASTY/ARTERY/ATHEROSCLEROSIS/atheroscler

osis/carotid/carotid stenosis/carotid stent/carotid

stenting/cerebral/cholesterol/control/distal

protection/EMBOLIZATION/plaque/prevention/protection/protection

device/STENOSIS/stent/stenting/stents/STROKE/SURGERY/Switzerland/SYST

EM/TRANSCRANIAL DOPPLER/use



Handschu, R., Garling, A., Heuschmann, P.U., Kolominsky-Rabas, P.L., Erbguth, F. and

Neundorfer, B. (2001), Acute stroke management in the local general hospital.

Stroke, 32 (4), 866-870.



Abstract: Background and Purpose-The majority of stroke patients are treated in local

general hospitals. Despite this fact, little is known about stroke carl in these

institutions. We sought to investigate the status quo of acute stroke management

in nonspecialized facilities with limited equipment and resources. Methods-Four

general hospitals located in smaller cities of a rural area in Germany participated

in this study. The 4 hospitals were similar in structure and technical equipment;

none had a CT scanner in-house. We reviewed the medical records of every

stroke patient hospitalized in I of the 4 hospitals within a period of 8 weeks

within 1 year. Results-We collected data of a total of 95 patients at all 4 hospitals.

The frequency of diagnostic tests was low: at least 1 CT scan was obtained in

only 36.8% of all cases, whereas diagnostic methods available in-house were

used more frequently, such as Doppler ultrasound (49.0%), echocardiography

(42.3%), and 24-hour ECG registration (48.4%). Each hospital had a different

therapeutic approach. Main therapeutic options were the use of pentoxyfilline

(0% to 90.5%), osmodiuretics (0% to 90%), piracetam (0% to 93.3%), and

hydroxyethylstarch (4.8% to 30%). Medication for long-term secondary

prevention was given to 69.8% of all patients. Conclusions-This study provides

one of the few data samples reflecting stroke care in smaller general hospitals.

The findings demonstrate a partially suboptimal level of care in these institutions.

To achieve future improvements, extended human and technical resources as

well as research for stroke care should not be restricted to academic stroke

centers



Keywords: acute/ACUTE ISCHEMIC STROKE/acute stroke/acute stroke

management/ADMISSION/AUDIT/CARE/CT/diagnosis/Doppler/Doppler

ultrasound/echocardiography/Europe/Germany/hospital/hospitals/human/manage

ment/medical/prevention/QUALITY/quality of health

care/research/secondary/secondary prevention/status/stroke/stroke

management/TRIAL/ultrasound/use



Zotz, R.J., Muller, M., Genth-Zotz, S. and Darius, H. (2001), Spontaneous echo contrast

caused by platelet and leukocyte aggregates? Stroke, 32 (5), 1127-1133.



Abstract: Background and Purpose-Spontaneous echocardiographic contrast (SEC) is

correlated to clinical thromboembolic events, We sought to determine the origin

of SEC by utilizing direct analysis of left atrial blood. Methods-We examined the

blood of 13 patients with and 19 without SEC. Blood samples were taken from

the femoral vein and artery and from the right. and left atria after transseptal

puncture. Samples were incubated with fluorescence labeled antibodies directed

against. the platelet (CD41a-PE, CD42b-PE, and CD62p-FITC) and leukocyte

membrane epitopes (CD45-APC and CD14-FITC). The expressed epitopes were

analyzed by dual laser flow cytometry immediately after blood withdrawal.

Results-In the peripheral blood of both groups, more activation and aggregation

were found in the venous blood than in the arterial blood (CD41a, P=0.007;

CD14neutro, P=0.017; and leukocyte-platelet aggregates [LTAg], P=0.002). In

patients without SEC, the degree of activation and aggregation of the cardiac

samples closely resembled the results of the peripheral samples. The degree of

activation and aggregation was significantly higher in the right atrium than in the

left atrium (LTAg, P 24 g/d: OR 0.95, 95% CI 0.43 to 2.10) in

comparison to never drinking. Analyses of beverage type (beer, wine, liquor)

indicated a protective effect for wine consumption in the previous year (19.7 mm Hg per minute of exercise duration had a 2.3-fold increased

risk of any stroke and a 2.3-fold increased risk of ischemic stroke compared with

men whose SBP rise was 70% had a recombinant tissue

plasminogen activator (r-TPA) protocol. We found that 93.2% of residents in

Illinois lived in a county with at least I acute care facility with an r-TPA

treatment protocol. However, many of the non-GCMA receiving hospitals did

not have a neurologist or a neurosurgeon available. Furthermore, specialized

stroke diagnostic technology (eg, transcranial Doppler, diffusion-weighted MRI,

MR angiography) was generally lacking in both the GCMA and non-GCMA, as

were stroke community awareness programs and acute care stroke teams.

Conclusions- Stroke is a preventable and treatable disease. However, there are

barriers to stroke care that are based on the availability of personnel, diagnostic

technology, and programs. A systematic approach to the organization,

implementation, and maintenance of services could improve outcome for stroke

patients and reduce the public health burden of this deadly disease



Keywords: acute/acute stroke/acute stroke

care/angiography/awareness/CENTERS/community/CT/diagnosis/diagnostic/dis

ease/Doppler/health/hospitals/MR/MRI/neurologist/outcome/plasminogen

activator/PREVENTION/public health/recombinant tissue plasminogen

activator/stroke/stroke patients/survey/transcranial/transcranial

Doppler/treatment/treatment outcome



Coull, B.M., Williams, L.S., Goldstein, L.B., Meschia, J.F., Heitzman, D., Chaturvedi,

S., Johnston, K.C., Starkman, S., Morgenstern, L.B., Wilterdink, J.L., Levine,

S.R. and Saver, J.L. (2002), Anticoagulants and antiplatelet agents in acute

ischemic stroke - Report of the Joint Stroke Guideline Development Committee

of the American Academy of Neurology and the American Stroke Association (a

division of the American Heart Association). Stroke, 33 (7), 1934-1942

Keywords: acute/acute ischemic stroke/antiplatelet/antiplatelet

agents/ASPIRIN/CONTROLLED TRIAL/ischemic/ischemic

stroke/MOLECULAR-WEIGHT HEPARIN/PREVENTION/stroke



Bazzano, L.A., He, J., Ogden, L.G., Loria, C., Vupputuri, S., Myers, L. and Whelton,

P.K. (2002), Dietary intake of folate and risk of stroke in US men and women -

NHANES I Epidemiologic Follow-up Study. Stroke, 33 (5), 1183-1188.



Abstract: Background and Purpose-Few population-based studies have examined the

relationship between dietary intake of folate and risk of stroke and cardiovascular

disease (CVD). This study examines the association between dietary intake of

folate and the subsequent risk of stroke and CVD. Methods-Study participants

included 9764 US men and women aged 25 to 74 years who participated in the

National Health and Nutrition Examination Survey I Epidemiologic Follow-up

Study (NHEFS) and were free of CVD at baseline. Dietary intake of folate was

assessed at baseline using a 24-hour dietary recall and calculated using ESHA

software. Incidence data for stroke and CVD were obtained from medical records

and death certificates. Results-Over an average of 19 years of follow-up, 926

incident stroke events and 3758 incident CVD events were documented. The

relative risk (RR) was 0.79 (95% confidence interval [CI], 0.63 to 0.99, P=0.03

for trend) for incident stroke events and 0.86 (95% CI: 0.78 to 0.95, P75th

percentile), after adjustment for demographic and potential medical confounding

factors. Results-The mean age of the 279 subjects was 67.6 +/- 8.5 years; 49%

were men; 63% were Hispanic, 17% black, and 17% white. Mean values for

TNF-alpha and its receptors were as follows: TNF-alpha, 1.88 +/- 3.97 ng/mL;

TNF receptor 1, 2.21 +/- 0.99 ng/mL; and TNF receptor 2, 4.85 +/- 2.23 ng/mL.

Mean MCPT was elevated in those in the highest quartiles compared with lowest

quartiles of TNF receptor 1 and 2 (1.24 versus 0.79 mm and 1.23 versus 0.80 nun,

respectively). Among those aged 70%

(OR, 2.55; 95% CI, 1.07 to 6.07; P=0.033). No significant differences were

observed in MMP-1 distribution. Patients who were homozygous for both the 6A

and 2G alleles had an elevated relative risk of ICA stenosis (OR, 2.66; 95% CI,

1.23 to 5.72; P=0.016). Multiple logistic regression analysis using the common

risk factors and the 6A and 2G allele variants revealed that the 6A allele was an

independent risk factor for ICA stenosis (P=0.049). When 6A/6A and 2G/2G

were combined, the risk factor for ICA stenosis was 3-fold higher (OR, 3.3 1;

95% CI, 1.48 to 7.42; P=0.004). Conclusions-Homozygosity for the 6A allele of

the MMP-3 promoter is associated with carotid stenosis and, in association with

MMP-1 2G homozygosity, predicts an increased risk of ICA stenosis. Even if

obtained from a relatively limited patient series, these results might have relevant

implications for treatment of ICA stenosis and possibly prevention of

carotid-related stroke



Keywords: atherogenesis/atherosclerosis/carotid/carotid artery/carotid artery

stenosis/carotid endarterectomy/carotid stenosis/COLLAGENASE/CORONARY

ATHEROSCLEROSIS/DISEASE/endarterectomy/EXPRESSION/gene/gene

expression/GUIDELINES/HUMAN STROMELYSIN GENE/internal carotid

artery/metalloproteinases/MORPHOMETRIC

ANALYSIS/PLAQUES/polymorphism/prevention/PROGRESSION/relative

risk/risk/risk factor/risk factors/stenosis/STROKE/TRANSCRIPTION/treatment



Worrall, B.B., Johnston, K.C., Kongable, G., Hung, E., Richardson, D.J. and Gorelick,

P.B. (2002), Stroke risk factor profiles in African American women - An interim

report from the African-American Antiplatelet Stroke Prevention Study. Stroke,

33 (4), 913-919.



Abstract: Background and Purpose-If sex differences in stroke risk factor profiles exist

among African Americans in the United States, prevention strategies will need to

reflect those differences. African Americans and women have been

underrepresented in stroke prevention studies. The purpose of this study was to

determine whether medical and lifestyle factors differ among women and men

who have enrolled in the African-American Antiplatelet Stroke Prevention Study

(AAASPS). Methods-We performed a planned exploratory analysis of

differences in baseline characteristics and risk factors between women and men

enrolled in AAASPS, a double-blind, randomized, multicenter, controlled trial.

Frequencies of vascular risk factors and related conditions, medical therapies,

stroke subtypes, and vascular territories were compared between women and

men by 1- way ANOVA and Fisher's exact test where appropriate. Results-A

total of 1087 African American patients (574 women, 513 men) enrolled

between December 1995 and June 1999. Women had higher rates of

hypertension, diabetes, family history of stroke, and no reported leisure exercise.

Men had higher rates of smoking and heavy alcohol use. Few differences were

noted in proportions of stroke subtype or proportions receiving preventive

therapy. Conclusions-AAASPS represents the largest enrollment of African

American women in a recurrent stroke prevention study. Our data suggest that

African American women in a clinical trial differ from men in the frequency of

key vascular risk factors. Although limited, these data provide an important first

characterization of sex differences in African Americans with stroke



Keywords: AAASPS/African American/African Americans/alcohol/baseline

characteristics/BLOOD-PRESSURE/cerebrovascular disorders/clinical

trial/diabetes/DIABETES-MELLITUS/ETHNIC-DIFFERENCES/exercise/GEN

DER DIFFERENCES/HEALTH/history/hypertension/ischemia/ISCHEMIC

STROKE/lifestyle/medical/men/NON-HISPANIC WHITES/NORTHERN

MANHATTAN STROKE/PHYSICAL-ACTIVITY/prevention/racial

differences/randomized/recurrent stroke/risk/risk factor/risk

factors/sex/smoking/STROKE/stroke prevention/stroke subtype/stroke

subtypes/therapy/trial/United States/UNITED-STATES/use/vascular/vascular

risk/vascular risk factors/women



Anderson, D.C., Kappelle, L.J., Eliasziw, M., Babikian, V.L., Pearce, L.A. and Barnett,

H.J.M. (2002), Occurrence of hemispheric and retinal ischemia in atrial

fibrillation compared with carotid stenosis. Stroke, 33 (8), 1963-1967.

Abstract: Background and Purpose-The goal of this study was to examine the

hypotheses that retinal ischemia is caused more often by carotid atherosclerosis

than by atrial fibrillation and that the odds of retinal events compared with

hemispheric events increase with worsening carotid stenosis. Methods-We used

data from the Stroke Prevention in Atrial Fibrillation (SPAF) I through III trials

and North American Symptomatic Carotid Endarterectomy Trial (NASCET),

calculating hemispheric:retinal (H:R) odds for the territory of ischemic events

during follow- up in patients with atrial fibrillation and medically treated 50% to

99% carotid stenosis or occlusion in the respective trials. Results-The H:R odds

were 25:1 in the SPAF aspirin- assigned patients and 2:1 for NASCET vessels.

In NASCET patients, the H:R odds of recurrent ischemic events were 1:4 for

vessels randomized initially for retinal symptoms compared with 6:1 for those

randomized for hemispheric events (significant difference; P24 hours (prolonged), more focused prevention strategies are possible in the

future. Methods-All patients with ischemic stroke, cerebral TIA, RAO, and

amaurosis fugax presenting to our hospital from 1994 to 1999 were examined by

a stroke physician. Risk factors were documented, and patients underwent

carotid Doppler ultrasound. Results-We registered 1491 patients with ischemic

stroke, 580 with cerebral TIA, 79 with RAO, and 138 with amaurosis fugax.

Atrial fibrillation was more common in brain than eye events, whether prolonged

[ischemic stroke versus RAO: odds ratio (OR), 3.6; 95% confidence interval (CI),

1.1 to 12] or transient (cerebral TIA versus amaurosis fugax: OR, 2.9; 95% CI,

0.7 to 13), and more common in prolonged than transient events, whether brain

(stroke versus cerebral TIA: OR, 3.3; 95% CI, 2.1 to 5.1) or eye (RAO versus

amaurosis fugax: OR, 2.7; 95% CI, 0.4 to 16). Severe ipsilateral carotid disease

was less common in brain than eye events, whether prolonged (ischemic stroke

versus RAO: OR, 0.6; 95% CI, 0.3 to 1.0) or transient (cerebral TIA versus

amaurosis fugax: OR, 0.4; 95% CI, 0.2 to 0.6). Conclusions- These data suggest

that there are pathogenetic differences between transient and permanent eye and

brain ischemic syndromes. Improved understanding of these mechanisms could

lead to more effective stroke prevention



Keywords: amaurosis fugax/AMAUROSIS FUGAX/ATTACKS/brain/carotid/carotid

stenosis/cerebral/cerebral infarction/cerebral ischemia/disease/Doppler/Doppler

ultrasound/embolism/fibrillation/hospital/ischemic/ischemic

stroke/mechanisms/MORTALITY/prevention/PROGNOSIS/retinal

artery/risk/risk factors/stroke/STROKE/stroke

prevention/symptoms/TIA/transient/transient ischemic

attacks/ultrasound/vascular/vascular disease



Spence, J.D., Eliasziw, M., DiCicco, M., Hackam, D.G., Galil, R. and Lohmann, T.

(2002), Carotid plaque area - A tool for targeting and evaluating vascular

preventive therapy. Stroke, 33 (12), 2916-2922.



Abstract: Background and Purpose-Carotid plaque area measured by ultrasound

(cross-sectional area of longitudinal views of all plaques seen) was studied as a

way of identifying patients at increased risk of stroke, myocardial infarction, and

vascular death. Methods-Patients from an atherosclerosis prevention clinic were

followed up annually for up to 5 years (mean, 2.5+/-1.3 years) with baseline and

follow-up measurements recorded. Plaque area progression (or regression) was

defined as an increase (or decrease) of greater than or equal to0.05 cm(2) from

baseline. Results-Carotid plaque areas from 1686 patients were categorized into

4 quartile ranges: 0.00 to 0.11 cm(2) (n=422), 0.12 to 0.45 cm(2) (n=424), 0.46

to 1.18 cm(2) (n=421), and 1.19 to 6.73 cm(2) (n=419). The combined 5-year

risk of stroke, myocardial infarction, and vascular death increased by quartile of

plaque area: 5.6%, 10.7%, 13.9%, and 19.5%, respectively (P 194 ng/mL) was associated with

significantly higher relative odds of ischemic stroke compared with the lower

concentrations after adjustment for potential confounding variables (relative odds

2 1 95% CI 1 1 to 4 3) After fibrinogen and total white blood cell count were

added to the multivariable model the relative odds were 2 1 (95% CI 1 1 to 4 2)

and 2 2 (95% CI 1 1 to 4 8) respectively The risk associated with raised

concentrations of sICAM I seemed to be highest for large disabling strokes of

cardioembolic origin Conclusions- Elevated concentrations of sICAM 1 a marker

of inflammation are associated with increased risk of ischemic stroke

independent of other traditional cerebrovascular risk factors and of plasma

fibrinogen among patients at increased risk because of manifest coronary heart

disease



Keywords: age/APPARENTLY HEALTHY-MEN/bezafibrate/C-REACTIVE

PROTEIN/cardioembolic/cardiovascular/cardiovascular

events/CARDIOVASCULAR-DISEASE/CAROTID

ATHEROSCLEROSIS/case-control study/cell adhesion

molecules/cerebrovascular/cerebrovascular risk factors/chronic/confounding

variables/control/coronary heart

disease/design/disease/E-SELECTIN/ENDOTHELIAL

EXPRESSION/FIBRINOGEN/heart/heart

disease/inflammation/ischemic/ischemic stroke/Israel/LEUKOCYTE

ADHESION/MYOCARDIAL-

INFARCTION/pathogenesis/PLASMA-CONCENTRATION/prevention/risk/ris

k factors/secondary/secondary prevention/serum/sex/stroke/stroke ischemic/trial

Vickrey, B.G., Rector, T.S., Wickstrom, S.L., Guzy, P.M., Sloss, E.M., Gorelick, P.B.,

Garber, S., McCaffrey, D.F., Dake, M.D. and Levin, R.A. (2002), Occurrence of

secondary ischemic events among persons with atherosclerotic vascular disease.

Stroke, 33 (4), 901-906.



Abstract: Background and Purpose-Few data exist for large managed care populations

on the occurrence of subsequent acute ischemic events in persons with

established atherosclerotic vascular disease. We estimated the occurrence of

secondary stroke, acute myocardial infarction (AMI), and vascular deaths among

2 large, managed care samples. Methods-With the use of International

Classification of Diseases, Ninth Revision, Clinical Modification codes, patients

aged :2:40 years and with stroke, AMI, or peripheral arterial disease (PAD) were

identified from administrative data of UnitedHealthcare plans during 1995-1998.

Stroke, AMI, and PAD cohorts were identified within a commercial insurance

sample and a Medicare sample. Cumulative occurrences of subsequent stroke,

AMI, or vascular death were estimated by survival analysis. Results-In the stroke

commercial cohort (n= 1631; mean age, 62.1 years), cumulative occurrence of

subsequent events was 4.2%, 6.5%, 9.8%, and 11.8% at 0.5, 1, 2, and 3 years,

respectively; cumulative secondary event occurrence in the AMI commercial

cohort (n=6458; mean age, 56.0 years) was 3.5%, 4.8%, 7.3%, and 8.5% and in

the PAD commercial cohort (n=5813; mean age, 59.2 years) was 1.5%, 2.8%,

4.8%, and 6.5%, respectively. Cumulative secondary event occurrences were

even higher in stroke (n=1518; mean age, 79.5 years), AMI (n=2197; mean age,

76.2 years), and PAD (n=5033; mean age, 76.6 years) cohorts of the Medicare

sample: 18.1%, 17.0%, and 8.7%, respectively, at 3 years. More than 75% of

each stroke cohort's secondary events were strokes; more than 75% of each AMI

cohort's secondary events were AMIs. Of the PAD cohorts' secondary events,

27% to 39% were strokes, 48% to 57% were AMIs, and 13% to 16% were

vascular deaths. Conclusions- Among these managed care enrollees with existing

atherosclerotic vascular disease, subsequent ischemic events represent a

significant symptomatic disease burden. Given these findings, it is very

important to determine whether secondary prevention strategies are being

effectively used to manage patients with diagnosed atherosclerosis



Keywords: ACCURACY/acute/acute myocardial infarction/ACUTE

MYOCARDIAL-INFARCTION/age/aged/arterial/atherosclerosis/CARE/CERE

BROVASCULAR-DISEASE/data

interpretation/death/disease/epidemiology/ICD-9-CM/infarction/ischemic/myoca

rdial/myocardial infarction/peripheral arterial

disease/prevention/RISK/secondary/secondary

prevention/statistical/stroke/STROKE

INCIDENCE/SURVIVAL/use/vascular/vascular disease



Tanne, D., Shotan, A., Goldbourt, U., Haim, M., Boyko, V., Adler, Y., Mandelzweig, L.

and Behar, S. (2002), Severity of angina pectoris and risk of ischemic stroke.

Stroke, 33 (1), 245-250.

Abstract: Background and Purpose-Ischemic stroke and coronary heart disease (CHD)

share risk factors and pathogenic process, ie, atherosclerosis and thrombosis. We

examined the relationship between severity of angina pectoris and its

accompanying characteristics and the risk of incident ischemic stroke.

Methods-We traced 3122 patients with stable CHD, included in a secondary

prevention trial of lipid modification, the Bezafibrate Infarction Prevention trial.

CHD was documented by a history of myocardial infarction greater than or equal

to6 months and 200 mg/dL were discharged without a

statin. Conclusions-The determination of serum lipid profiles varies widely

between different centers. Statins are highly underused in patients with recent

ischemic stroke or TIA, particularly in those in whom statins are indicated

according to existing recommendations (eg, patients with additional coronary

artery disease and hypercholesterolemia). Currently, international guidelines

concerning the use of statins are not adequately implemented in clinical practice

in patients with stroke or TIA



Keywords: acute/acute ischemic stroke/ACUTE

MYOCARDIAL-INFARCTION/atherosclerosis/Austria/cerebrovascular/CHOL

ESTEROL/clinical practice/cohort study/coronary artery

disease/CORONARY-ARTERY-DISEASE/disease/elderly/elderly

patients/guidelines/HEART-DISEASE/hospital/hypercholesterolemia/HYPERLI

PIDEMIA/infarction/ischemic/ischemic stroke/lipids/low density

lipoprotein/low-density lipoprotein cholesterol/LOWERING

THERAPY/myocardial/myocardial infarction/peripheral artery

disease/prevention/PROJECT/prospective cohort study/RISK/SECONDARY

PREVENTION/serum/statin/statins/stroke/TIA/transient/transient ischemic

attack/treatment/TRIALS/USA/use/vascular/vascular disease

Algra, A. (2003), Oral anticoagulation in patients after cerebral ischemia of arterial

origin and risk of intracranial hemorrhage. Stroke, 34 (6), E45-E46.



Abstract: Background and Purpose-In the recently published Warfarin Aspirin Recurrent

Stroke Study (WARSS), a low-intensity anticoagulation regimen was used

because of safety concerns. Such concerns are corroborated by the results of the

Stroke Prevention in Reversible Ischemia Trial (SPIRIT), which was stopped

early because of a high incidence of intracranial hemorrhage with a target

international normalized ratio (INR) of 3.0 to 4.5. In the ongoing

European/Australasian Stroke Prevention in Reversible Ischaemia Trial

(ESPRIT), an intermediate anticoagulation regimen (INR 2.0 to 3.0) is used.

Methods-We performed an interim analysis of the incidence of intracranial

hemorrhage in ESPRIT. Results-Thus far the overall rate of intracranial

hemorrhage is 0.31% (95% CI, 0.18% to 0.52%) per year and 1.21% if all of

these were in the anticoagulation group. Conclusions-We conclude that

anticoagulation with achieved INR of 2.0 to 3.0 is reasonably safe in patients

with cerebral ischemia of arterial origin



Keywords: anticoagulants/anticoagulation/arterial/aspirin/cerebral/cerebral

ischemia/ESPRIT/hemorrhage/incidence/INR/international normalized

ratio/intracerebral hemorrhage/intracranial/intracranial

hemorrhage/ischemia/Netherlands/PREVENTION/results/risk/safety/STROKE/

USA/Warfarin



Kernan, W.N., Inzucchi, S.E., Viscoli, C.M., Brass, L.M., Bravata, D.M., Shulman, G.I.,

McVeety, J.C. and Horwitz, R.I. (2003), Pioglitazone improves insulin

sensitivity among nondiabetic patients with a recent transient ischemic attack or

ischemic stroke. Stroke, 34 (6), 1431-1436.



Abstract: Background and Purpose - The aim of this study was to determine the

effectiveness of pioglitazone compared with placebo for improving insulin

sensitivity among nondiabetic patients with a recent transient ischemic attack

(TIA) or nondisabling ischemic stroke and impaired insulin sensitivity. Methods

- Eligible subjects were men and women >45 years of age who had no history of

diabetes, fasting glucose 3-fold

increase in relative odds of incident ischemic stroke (3.3; 95% Cl, 1.2 to 10.2).

Homocysteine concentrations at the highest quartile (> 17.4 mumol/L) were

associated with significantly higher odds of ischemic stroke compared with the

lowest quartile in matched- pair analysis (3.1; 95% Cl, 1.1 to 9.8) and after

multivariable adjustments (4.6; 95% Cl, 1.3 to 18.9). Adding fibrinogen or

soluble intercellular adhesion molecule-1 concentrations, markers of

inflammation, to the model did not attenuate this association. The linear trends

across the quartiles were significant for all models (P 0.25 for each variable).

Among the patients undergoing Dacron patch angioplasty three strokes (two

temporary and one permanent), seven episodes of bleeding requiring reoperation,

and two neck wound infections requiring rehospitalization occurred. The final 32

patients with Dacron patch closures had their anticoagulation reversed and had

no bleeding complications. Complications in patients undergoing vein patch

closure included one fatal perioperative stroke, two episodes of bleeding

requiring reoperation including one patch rupture, and three groin infections

requiring hospitalization. No significant difference was seen between the two

groups in the rate of perioperative stroke (p = 0.62), episodes of bleeding (p =

0.17), or infection (p => 0.67). Conclusions. Carotid patch angioplasty can be

performed with an acceptably low complication rate with either Dacron or vein,

and the choice of patch material does not clinically affect patient morbidity.

However, reversal of anticoagulation is recommended to minimize bleeding

complications in patients undergoing Dacron patch angioplasty



Keywords: anticoagulation/carotid/carotid

endarterectomy/CLOSURE/ENDARTERECTOMY/hospitalization/LARGE

METROPOLITAN AREA/morbidity/OPERATIONS/PREVENTION/risk/risk

factors/RUPTURE/SAPHENOUS-VEIN PATCH/STENOSIS/stroke/SURGERY



Koudsi, B., Yu, C.D., Ferguson, E.W., Miller, G.A., Merkel, K.D., Wun, T.C. and

Kraemer, B.A. (1996), Prevention of spinal cord injury after transient aortic

clamping with tissue factor pathway inhibitor. Surgery, 119 (3), 269-274.



Abstract: Background. Lower limb paralysis that occurs in 11% of patients after

treatment of thoracic and thoracoabdominal aortic aneurysms is unpredictable

and at present not preventable. The proposed cause for the neurologic changes is

believed to be spinal cord ischemia combined with ischemia/reperfusion injury.

Recombinant tissue factor pathway inhibitor (rTFPI), a multivalent Kunitz-type

inhibitor that binds to tissue factor- VIIa complex, was evaluated. Methods. The

effectiveness of rTFPI as an agent to limit spinal cord ischemia/reperfusion

injury teas studied in a rabbit spinal cord made ischemic for 20 minutes. rTFPI or

phosphate-buffered saline solution (control) was given in randomized blinded

fashion at the onset and conclusion of ischemia. Animals underwent neurologic

evaluation at 24 hours in a blinded fashion with a modified Tarlov Scale to rate

the lower limb paralysis (score of 4 = normal function, score of 0 = complete

paralysis). Results. Seventy-five percent of the TFPI-treated animals had Tarlov

scores of 3 to 4, whereas only 29% of the animals treated with

phosphate-buffered saline solution had such scores (p 50%) carotid

stenosis poses special clinical questions in patients scheduled to undergo general

surgical or major cardiovascular operations. With general surgical procedures,

there is no increased risk of stroke. With cardiovascular operations, however,

there may be an increased risk of stroke in patients with critical (> 90%) carotid

stenosis or occlusion. When perioperative stroke occurs, the most common cause

is embolism rather than focal hemodynamic change. For symptomatic high-

grade (> 70%) extracranial carotid stenosis, carotid endarterectomy is the

treatment of choice in patients who are not high-risk surgical candidates.

Alternatively, for high- risk patients, new drugs such as ticlopidine appear quite

promising, and percutaneous angioplasty may also prove effective. Prevention of

stroke must continue to be a major goal of national medical policy. Because

cigarette smoking is the most important risk factor for extracranial carotid

disease, more strenuous efforts must be directed toward eliminating this health

risk



Keywords: ANGIOPLASTY/ARTERIAL OCCLUSIVE

DISEASES/ATHEROSCLEROSIS/CAROTID/CAROTID ARTERY

DISEASES/CEREBROVASCULAR

DISORDERS/EMBOLISM/ENDARTERECTOMY/HEART/STROKE/TEXAS/

TRANSIENT ISCHEMIC ATTACK/TRANSLUMINAL



Takach, T.J., Ott, D.A., Reul, G.J. and Cooley, D.A. (1996), Critical decision analysis

for extracranial cerebrovascular disease. Texas Heart Institute Journal, 23 (1),

45-50.



Abstract: Results from 6 major prospective studies that have recently been either

completed or terminated prematurely provide compelling evidence of the benefit

of carotid endarterectomy in treating certain groups of patients who have carotid

stenosis. Results of these studies show that symptomatic patients (Those

experiencing transient ischemic attack amaurosis, or completed mild stroke) with

a 70% ipsilateral carotid stenosis have an absolute risk reduction of 39% to 65%

for stroke or death when treated with carotid endarterectomy as opposed to

medical therapy alone. Asymptomatic patients with a 60% ipsilateral carotid

stenosis have a 53% absolute risk reduction for stroke or death when treated with

carotid endarterectomy, rather than medical therapy alone. Combined neurologic

morbidity and perioperative mortality rates for treating carotid stenosis should

not exceed 3% in the asymptomatic patient or 5% to 7% in the symptomatic

patient, on the basis of criteria established by the American Heart Association.

These studies show that prophylactic carotid endarterectomy can effectively

reduce The risk of stroke in both asymptomatic and symptomatic patients.

Centers specializing in vascular surgery can benefit patients by minimizing the

operative risk to levels well below those established by the American Heart

Association



Keywords: absolute risk/arterial occlusive diseases/ARTERY STENOSIS/aspirin

therapeutic use/ASYMPTOMATIC CAROTID STENOSIS/CARDIAC

RISK/carotid/carotid arteries surgery/carotid endarterectomy/carotid

stenosis/carotid stenosis surgery/cerebrovascular disease/cerebrovascular

ischemia/cerebrovascular ischemia prevention and

control/CORONARY-BYPASS/ENDARTERECTOMY/endarterectomy/HEAR

T/MINNESOTA HEART SURVEY/morbidity/MORTALITY/PERIPHERAL

VASCULAR-DISEASE/prospective

studies/risk/STROKE/surgery/SURGICAL-PROCEDURES/TEXAS/transient/tr

ansient ischemic attack



Hernandez-Vila, E., Strickman, N.E., Skolkin, M., Toombs, B.D. and Krajcer, Z. (2000),

Carotid stenting for post-endarterectomy restenosis and radiation-induced

occlusive disease. Texas Heart Institute Journal, 27 (2), 159-165.



Abstract: Surgical treatment of carotid restenosis and radiation-induced occlusive

disease is challenging because of the high morbidity and mortality associated

with this procedure. Carotid stenting has been proposed as an alternative

approach. We report a series of 8 patients who were treated via the percutaneous

approach for either carotid restenosis (n = 4) or radiation- induced occlusive

disease (n = 4). Technical success was achieved in all of the cases. There have

been no deaths or strokes during the periprocedural or follow-up period. After

dilation of the extracranial vessel, 1 patient experienced severe intracranial

internal carotid arterial spasm that required stent placement. Wallstents(R) were

used in 6 patients and S.M.A.R.T(TM) stents were used in the remaining 2.

Restenosis occurred in 2 patients and was treated successfully with redilation or

restenting. Carotid stenting appears to be a feasible and safe alternative to

surgery for restenosis after carotid endarterectomy and for radiation-induced

occlusive disease



Keywords: ANGIOPLASTY/ARTERIAL-DISEASE/blood vessel

prosthesis/carotid/carotid arteries/surgery/carotid endarterectomy/carotid

stenosis/surgery/cerebrovascular disorders/prevention &

control/COMPLICATIONS/endarterectomy/EXPERIENCE/HEART/morbidity/

mortality/NECK/radiotherapy/adverse

effects/RECURRENT/RISK/STENOSIS/stenting/stents/STROKE/surgery/SUR

GICAL-MANAGEMENT/TEXAS/treatment



Grooters, R.K., Thieman, K.C., Schneider, R.F. and Nelson, M.G. (2000), Assessment

of perfusion toward the aortic valve - Using the new dispersion aortic cannula

during coronary artery bypass surgery. Texas Heart Institute Journal, 27 (4),

361-365.



Abstract: When there is an echocardiographic diagnosis of severe mobile atherosclerotic

plaque in the aortic arch or descending aorta, perfusion toward the aortic arch

during cardiopulmonary bypass may create a high risk of embolic neurologic

injury. Other perfusion methods, such as cannulation of the femoral or axillary

arteries, are not always possible, due to atherosclerosis. The ascending aorta may

be an alternative site for perfusion, since it is less frequently diseased. We

assessed a new technique of perfusion toward the aortic valve using a new

cannula designed for this purpose (Dispersion aortic cannula). Our study

included 100 consecutive patients, 72 men and 28 women, with an average age

of 68 +/- 7.0 years (range, 39-89 years). There were no complications related to

insertion of The cannula or perfusion. The ascending aorta could be

cross-clamped and side-clamped without perfusion problems. Three deaths

occurred; none was related to the cannulation technique. No intra-operative

stroke occurred. Two patients suffered neurologic events, one on day 1 and the

other on day 6, both had been fully alert after surgery. Perfusion toward the

aortic valve appears to be sale and hemodynamically effective. This cannulation

technique appears to be an acceptable alternative to present methods,

Comparative studies will be needed to determine whether this alternative

technique is effective in patients with severe aortic arch disease



Keywords: age/aorta/arteries/ASCENDING

AORTA/atherosclerosis/BRAIN-DAMAGE/bypass/bypass surgery/cardiac

surgical procedures/CARDIOPULMONARY BYPASS/cardiopulmonary

bypass/methods/cerebrovascular accident/prevention and

control/cholesterol/prevention and

control/complications/diagnosis/DISEASE/embolism/HEART/high

risk/INJURY/men/MYOCARDIAL REVASCULARIZATION/OPEN-HEART

SURGERY/plaque/PREVENTION/risk/STROKE/surgery/surgical

instruments/TEXAS/thoracic/surgery/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/women



Tan, W.A., Jarmolowski, C.R., Wechsler, L.R. and Wholey, M.H. (2000), New

developments in endovascular interventions for extracranial carotid stenosis.

Texas Heart Institute Journal, 27 (3), 273-280.



Abstract: We provide an overview of recent developments in carotid interventional

technique and equipment including new stents and emboli protection devices.

The newer self-expanding stents lessen the problem of external stent

compression associated with balloon expandable stents, but precise deployment

and the matching (by length) of stents to lesions remain problematic. We also

discuss emerging pharmacologic strategies for cerebral protection in stroke.

Multiple randomized clinical trials and multicenter registries are under way to

compare percutaneous with surgical strategies for the treatment of carotid

stenosis. These include the evaluation, of emboli protection devices, and, to a

lesser degree, intravenous glycoprotein IIb/IIIa antagonists. Other clinical trials

are aimed towards refining the ability to stratify patients by risk, in order to

identify the subsets that would benefit most from these complex and expensive

procedures



Keywords: ACUTE ISCHEMIC STROKE/angioplasty/BALLOON

ANGIOPLASTY/balloon/adverse effects/blood vessel prosthesis

implantation/brain ischemia/drug therapy/prevention & control/carotid/carotid

artery diseases/therapy/carotid stenosis/cerebral/cerebrovascular

disorders/prevention & control/clinical trials/COATED

STENTS/emboli/endarterectomy/ENDOTHELIAL-CELLS/evaluation/GENE-T

HERAPY/HEART/MUSCLE CELL-PROLIFERATION/NEOINTIMA

FORMATION/PORCINE CORONARY-ARTERIES/prosthesis

design/randomized/risk/SHAPE-MEMORY

METAL/stenosis/stents/stents/utilization/stroke/TEXAS/treatment/TRIAL/trials



Kumral, E., Yuksel, M., Buket, S., Yagdi, T., Atay, Y. and Guzelant, A. (2001),

Neurologic complications after deep hypothermic circulatory arrest - Types,

predictors, and timing. Texas Heart Institute Journal, 28 (2), 83-88.



Abstract: To determine the nature of neurologic dysfunction after deep hypothermic

circulatory arrest during aortic arch surgery, we reconsidered the cases of 154

patients who had undergone aortic arch surgery (either of the ascending or

transverse aorta, or both) between November 1993 and July 1999. Temporary

postoperative neurologic dysfunction was seen in 9 patients (5.8%), and another

3 patients (1.9%) experienced stroke. Patients with temporary neurologic

dysfunction had no new infarct and were discharged home with no residual

symptoms. Computed tomographic scans revealed hat 2 patients with stroke had

multiple infarcts in the brainstem, and the 3rd had bilateral border-zone infarcts.

The patients with brainstem infarcts died on postoperative days 7 and 15, and he

patient with border-zone infarct was discharged home with no symptoms 3

months after surgery. Univariate analysis revealed that patients with neurologic

deficits had significantly higher rates of history of hypertension, concomitant

coronary artery bypass grafting, cardiac ischemia times longer than 90 minutes,

and chronic renal failure. A multivariale logistic regression analysis revealed that

the significant preoperative variables associated with neurologic deficits were a

history of hypertension and a cardiac ischemia time longer than 90 minutes.

Deep hypothermic circulatory arrest is a safe and useful technique for protection

of he brain during surgery for complex aortic problems. in future, some patients

at extreme risk for perioperative neurologic complications might be offered

novel neuroprotective agents, in combination with deep hypothermia



Keywords: aneurysm/aorta/body temperature/BRAIN/brain

injuries/diagnosis/prevention & control/brain ischemia/brain/metabolism/bypass

grafting/cardiac/combination/complications/DETERMINANTS/dissecting/surger

y/EXCITATORY

AMINO-ACIDS/HEART/history/HUMANS/hypertension/hypothermia/ISCHE

MIA/neurologic dysfunction/NITRIC-

OXIDE/postoperative/predictors/protection/renal/renal

failure/residual/RETROGRADE CEREBRAL

PERFUSION/risk/STROKE/SURGERY/symptoms/TEMPERATURE/TEXAS/ti

ming



Keyser, A. (1991), Antiplatelet Agents and Secondary Stroke Prevention.

Tgo-Tijdschrift Voor Therapie Geneesmiddel en Onderzoek Jdr- Journal for

Drugtherapy and Research, 16 (4), 105-114.



Abstract: This review of the literature reports on secondary prevention of ischemic

stroke. The aim of secondary prevention is to protect patients who belong to a

risk-group from the occurrence of brain infarction. Symptomatic patients with a

demonstrated carotid artery stenosis of 70 percent and above, most probably will

benefit from carotid endarterectomy if performed by a skilled surgeon in the

absence of contraindications. Oral anticoagulant drugs do play a minor role in

medical prevention of brain infarction. Antiplatelet drugs, however, are in use for

almost two decades and (meta-) analysis of clinical trials points to acetylsalicylic

acid (ASA) as a drug with a modest but certain contribution of about 15% in the

endpoint reduction, even in lower dosages. The addition of dipyridamole (DP) to

the classic ASA dose appears to increase the end-point reduction to 30%. Neither

DP nor sulfinpyrazone (SP) as monotherapy have been demonstrated to be

efficaceous in the secondary prevention of ischemic stroke. Ticlopidine (TC)

seems a promising alternative for ASA in those patients that suffer adverse

effects from ASA. TC, however, itself has a number of different side effects that

limit its application. New clinical trials are under way in order to improve the

efficacy of drug treatment in the secondary prevention of brain infarction

Bambauer, R., Schiel, R. and Latza, R. (2001), Current topics on low-density lipoprotein

apheresis. Therapeutic Apheresis, 5 (4), 293-300.



Abstract: The prognosis of patients suffering from severe hyperlipidemia, sometimes

combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease

(CHD) refractory to diet and lipid-lowering drug is poor. For such patients,

regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic

option. today, there are four different LDL- apheresis systems available:

immunoadsorption. heparin-induced extracorporeal LDL/fibrinogen precipitation,

dextran sulfate LDL-adsorption. and LDL-hemoperfusion. Despite substantial

progress in diagnostics. drug therapy. and cardiosurgical procedures,

atherosclerosis with myocardial infarction. stroke, and peripheral cellular disease

still maintains its position at the top of morbidity and mortality statistics in

industrialized nations. Established risk factors widely accepted are smoking,

arterial hypertension. diabetes mellitus, and central obesity. Furthermore, there is

a strong correlation between hyperlipidemia and atherosclerosis. Besides the

elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic

strategies should focus on a drastic reduction of serum lipoproteins. Despite

maximum conventional therapy with a combination of different kinds of

lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached.

Mostly, the prognosis of patients suffering from severe HLP, sometimes

combined with elevated Lp(a) levels and CHD refractory to diet and

lipid-lowering drugs is poor. Hence. in such patients. treatment with

LDL-apheresis can be useful. Regarding the different LDL-apheresis systems

used, there were no significant differences with respect to the clinical outcome or

concerning total cholesterol. LDL, high-density lipoprotein, or triglyceride

concentrations. With respect to elevated Lp(a) levels, however. the

immunoadsorption method seems to be the most effective. The published data

clearly demonstrate that treatment with LDL-apheresis in patients suffering from

severe hyperlipidemia refractory to maximum conservative therapy is effective

and safe in long-term application



Keywords: ACE INHIBITORS/ANAPHYLACTOID

REACTIONS/ANGIOGRAPHICALLY ASSESSED TRIAL/arterial/arterial

hypertension/atherosclerosis/CARDIOVASCULAR-DISEASE/CHD/cholesterol

/combination/coronary heart disease/CORONARY

HEART-DISEASE/DEXTRAN SULFATE/dextran sulfate low-density

lipoprotein-adsorption/diabetes/diabetes

mellitus/diagnostics/diet/disease/drug/drug therapy/drugs/FAMILIAL

HYPERCHOLESTEROLEMIA/Germany/heart/heart

disease/HELP-LDL-APHERESIS/heparin-induced extracorporeal low-density

lipoprotein/fibrinogen precipitation/high density lipoprotein/HUMAN

WHOLE-BLOOD/hyperlipidemia/hypertension/immunoadsorption/infarction/L

DL/lipid lowering/lipid-lowering/lipoproteins/low density

lipoprotein/low-density lipoprotein apheresis/low-density

lipoprotein-apheresis/low-density

lipoprotein-hemoperfusion/morbidity/morbidity and

mortality/mortality/myocardial/myocardial

infarction/obesity/outcome/prognosis/risk/risk factors/SECONDARY

PREVENTION/serum/smoking/statistics/stroke/therapy/treatment



Jaeger, B.R., Kreuzer, E., Knez, A., Leber, A., Uberfuhr, P., Borner, M., Milz, P.,

Reichart, B. and Seidel, D. (2002), Case reports on emergency treatment of

cardiovascular syndromes through heparin-mediated low-density

lipoprotein/fibrinogen precipitation: A new approach to augment cerebral and

myocardial salvage. Therapeutic Apheresis, 6 (5), 394-398.



Abstract: We report the first experiences with HELP apheresis as an emergency

treatment for acute cardiovascular syndromes two patients who were not eligible

for lysis therapy and catheter intervention were treated with HELP apheresis

instead. Both patients had a most severe, generalized atherosclerosis and reached

the hospital too late for conventional measures. In both cases, the use of the

apheresis dramatically improved the clinical situation to such an extent that the

possibilities of this apheresis system urge further investigation



Keywords: acute/ANGIOGRAPHICALLY ASSESSED

TRIAL/atherosclerosis/cardiovascular/cerebral/CHOLESTEROL/CORONARY

HEART-DISEASE/FIBRINOGEN/fibrinolytic drugs/Germany/GIIb/IIIa

inhibitors/HELP/hospital/LDL- APHERESIS MULTICENTER/low-density

lipoprotein apheresis/myocardial/myocardial infarction/plasma

treatment/REDUCTION/SECONDARY

PREVENTION/stroke/therapy/treatment/unstable angina/use



Vanderlinde, F. (1981), Risk-Factors for Stroke and Implications for Prevention.

Therapeutische Umschau, 38 (8), 709-716



Chalon, S., Brudi, P. and Lechat, P. (1996), Treatment of essential hypertension:

Ongoing randomized controlled trials. Therapie, 51 (6), 631-638.



Abstract: In this review, the design and objectives of ongoing clinical trials in essential

hypertension are discussed along with the main results obtained from previously

published therapeutic trials. In a meta-analysis of 14 of the major primary

prevention trials in hyper tension, the difference in diastolic blood pressure

between the intervention groups and the control groups was only 5-6 mmHg.

This difference was associated with significant reductions in all stroke events (42

per cent), all coronary heart disease events (14 per cent) and in cardiovascular

mortality (21 per cent). In elderly hypertensive patients, available studies have

shown that antihypertensive treatment reduces the incidence of non-fatal

cardiovascular events without significantly modifying cardiovascular mortality.

Most of these results were obtained with beta- blockers or diuretics. Despite

official recommendation as first line monotherapy, none of the three new

antihypertensive classes has been shown to have beneficial effects on hard

primary endpoints such as cardiovascular morbidity and mortality. several

ongoing large scale randomized controlled trials vs. P-blockers or diuretics are

addressing this important issue. Moreover, other effects of antihypertensive

treatment such as the 'J-curve phenomenon', the rare of change in the carotid wall

thickness or the exact beneficial effects in elderly patients are being investigated

in some of these studies



Keywords: antihypertensive agents/antihypertensive

treatment/atheroma/ATHEROSCLEROSIS/blood

pressure/BLOOD-PRESSURE/cardiovascular events/cardiovascular

morbidity/cardiovascular mortality/carotid/clinical trials/control/coronary heart

disease/CORONARY-ARTERY

DISEASE/design/elderly/ENGLAND/FOLLOW-

UP/heart/HEART-DISEASE/hypertension/incidence/meta-analysis/morbidity/M

ORTALITY/prevention/primary

prevention/PROGRESSION/randomized/REGRESSION/stroke/treatment/trials



Barry, S. and Mercier, S. (1997), Antiplatelet agents and cardiovascular prevention.

Therapie, 52 (1), 53-58.



Abstract: The main contributions of meta-analysis methodology to antiplatelet therapy in

the field of cardiovascular prevention are presented with regard to the different

sectors of the health system: help with therapeutic information, help in the

planning of clinical trials for the pharmaceutical industry and help in

decision-making for Health Authorities. The results of meta-analysis of available

data concerning aspirin in cardio- vascular prevention are discussed, in an

attempt to define optimal daily dose and duration of aspirin treatment



Keywords: antiplatelet agents/antiplatelet therapy/ARTICLE/ASPIRIN/aspirin/aspirin

treatment/cardiovascular prevention/clinical

trials/CLINICAL-TRIALS/decision-making/DRUGS/ENGLAND/health/MEDI

CAL

LITERATURE/meta-analysis/METAANALYSES/methodology/prevention/RA

NDOMIZED CONTROL

TRIALS/STROKE/THERAPY/treatment/trials/USERS GUIDES/vascular



Bergmann, J.F., Kevorkian, J.P. and Chassany, O. (1998), Synthesis: certainties

uncertainties in the prevention of deep vein thrombosis in medical patients.

Therapie, 53 (6), 571-574.



Abstract: In medical patients there are numerous and variable risk factors for deep vein

thrombosis. Placebo-controlled clinical trials are rare. The efficacy of standard

heparin or low molecular weight heparin for the prevention of deep vein

thrombosis is clearly demonstrated for patients with recent myocardial infarction,

ischaemic stroke with hemiplegia or severe pulmonary sepsis with lung failure.

Pharmacological prophylaxis is probably also efficient in patients with a severe

actue disease and a certain history of deep vein thrombosis. For all other medical

and especially for bedridden elderly patients, use of low molecular weight

heparin might decrease the incidence of deep vein thrombosis but might not

modify the overall mortality. In these situations, placebo- controlled clinical

trials are needed for best evaluation of the benefit-risk ratio



Keywords: clinical trials/deep vein

thrombosis/elderly/ENGLAND/evaluation/hemiplegia/heparin/HEPARIN-PROP

HYLAXIS/history/incidence/infarction/ischaemic stroke/low molecular weight

heparin/medical patient/medical patients/mortality/myocardial/myocardial

infarction/prevention/prophylaxis/risk/risk factors/stroke/thrombosis/trials



McGregor, J., Berdeaux, A., Bonnet, J., Cambien, F., Fitzgerald, D., Lacolley, P., Lu, H.,

Narjoz, A.L., Miossec, P., Netter, P., Poston, R. and Laurent, S. (1998), Cell

adhesion molecules as pharmacological targets. Therapie, 53 (4), 371-379.



Abstract: This workshop intended to perform a "state-of-the art" of current research on

adhesion molecules in various pathophysiologies, and to determine

pharmacological targets. Indeed, recent important progress concerning the

cellular and molecular physiology of adhesion molecules led to the development

of various integrin antagonists in several domains, like cardiovascular disease,

inflammation and cancer. Integrins play a major role in numerous process like

embryonic development, tumor growth and metastasis, apoptosis, hemostasis,

leucocyte recruitment and activation, and bone resorption. The development of

integrin antagonists is well advanced in the cardiovascular domain, since the first

marketed drug (abciximas, Reopro(R)) is an antibody directed against the

GPIIb/IIIa complex (integrin alpha IIb/beta 3) involved in the final pathway of

platelet aggregation. Another active domain of research in pharmacology is

'cardioprotection', i.e. the prevention of cardiac damages induced by the

reperfusion of the coronary bed after an ischemia secondary to thrombolysis,

angioplasty, of coronary bypass. The pharmacological targets of these

antagonists are integrins involved in various process like leucocyte and platelet

adhesion and endothelial function. Other potential indications in the

cardiovascular field are restenosis after angioplasty, and atherosclerosis



Keywords: adhesion

molecules/aggregation/angioplasty/apoptosis/ARTERY/atherosclerosis/BLOOD-

VESSELS/bone disease/cardiovascular

disease/development/ENGLAND/EXTRACELLULAR-MATRIX/integrins/INT

EGRINS/ischemia/MYOCARDIAL-INFARCTION/pharmacology/platelet

aggregation/PLATELET GLYCOPROTEIN

IIIA/POLYMORPHISM/prevention/SIGNAL-

TRANSDUCTION/STROKE/thrombolysis/THROMBOSIS



Mismetti, P., Juillard-Delsart, D., Tardy, B., Laporte-Simitsidis, S. and Decousus, H.

(1998), Evaluation of the venous thromboembolic risk in medical patients.

Therapie, 53 (6), 565-570.



Abstract: The venous thromboembolic risk seems to be demonstrated in medical patients

since the incidence of symptomatic and symptomatic deep vein thrombosis

(DVT) without any prophylactic methods is respectively about 50 per cent in

stroke, 25 per cent in acute myocardial infarction (AMI) and 15 per cent in

internal medicine. A synthesis of clinical trials performed in medical patients

shows that prophylactic doses of heparins (unfractionated heparin or low

molecular weight heparins) reduce the incidence of DVT by 40 to GO per cent

compared with the lack of ano antithrombotic agents but without any significant

effect on total;mortality. Other antithrombotic agents such as antiplatelet agents

seem to reduce the incidence of DVT by about 40 per cent associated,vith a

significant decrease in total mortality of stroke or AMI. But the

recommendations made on the basis of these results have to be extremely

cautious since the number of medical patients included in clinical trials is quite

limited compared with the surgical area. Moreover, each of these

recommendations is not sufficiently proven. Thus more clinical trials have to be

carried out with a placebo control group in internal medicine and an aspirin

control group for stroke and AMI



Keywords: acute/acute myocardial infarction/antiplatelet/antiplatelet

agents/antithrombotic/aspirin/clinical trials/control/deep vein

thrombosis/DEEP-VEIN

THROMBOSIS/DVT/ENGLAND/heparin/heparins/incidence/infarction/medical

patients/mortality/myocardial/myocardial

infarction/PREVENTION/prophylaxis/risk/stroke/thrombosis/TRIAL/trials/unfra

ctionated heparin/WARFARIN



Aouizerate, P., Mabiala, H., Perrot, F. and Guizard, M. (1998), Preventive treatment of

thrombosis: Audit on heparin prescription. Therapie, 53 (2), 101-106.



Abstract: An audit has been carried out, in a French general hospital, studying the use of

heparins in preventive indications, to assess concordance between prescriptions

and thrombotic risk, before and one year after the diffusion of national guidelines.

Platelet monitoring frequency has also been studied. On a defined day, 550

patients were admitted, and 113 treated with preventive heparinotherapy (low

molecular-weight heparin: 98 per cent). 52.2 per cent of patients received a

correct regimen, while 4.4 per cent of underprescriptions and 43.4 per cent of

overprescriptions were observed. Platelet monitoring protocol was respected in

44 per cent of cases, while it was insufficient for 41 per cent and not carried out

in 15 per cent. The results of this study have been communicated to all the

prescriptors. Another audit done one year later showed that 81 per cent of doses

were adapted to the thrombotic risk, 2 per cent were too low, and 17 per cent too

high. The efficiency of this kind of process shows that it should be generalized to

all the sensitive therapeutic classes



Keywords: ACUTE STROKE/audit/CLINICAL-TRIALS/DEEP-VEIN

THROMBOSIS/ENGLAND/guidelines/heparin/hospital/LOW-DOSE

HEPARIN/MEDICAL INPATIENTS/MOLECULAR-WEIGHT

HEPARIN/prevention/risk/SPINAL-CORD INJURY/STANDARD

HEPARIN/thrombosis/TOTAL HIP-REPLACEMENT/treatment/VENOUS

THROMBOEMBOLISM



Plu-Bureau. (1999), Hormone replacement therapy and cardiovascular risk. Therapie, 54

(3), 375-380.



Abstract: Cardiovascular risk associated with hormone replacement therapy (HRT) has

been analysed by large epidemiological studies. This treatment has different

effects depending on the type of vessel (venous or arterial) or site (heart or brain).

The several meta-analyses which have been published conclude that there is a

significant decrease of about 30 to 50 per cent in ischaemic heart disease

associated with HRT. In addition, oestrogen replacement therapy is associated

with a 25 per cent decrease in cardiovascular mortality. A recent meta-analysis

has analysed the effect of HRT on cerebrovascular risk. A significant 20 per cent

increase in ischaemic stroke associated with the use of HRT has been shown.

However, a protective association of about 30 per cent has been observed in

haemorrhagic stroke with HRT use. Recent epidemiological studies have

suggested an increased risk of thromboembolic disease associated with HRT.

The results of a randomized blind placebo-controlled secondary prevention trial

have recently been published. In this clinical trial, women who receive oestrogen

(0.625 mg conjugated equine oestrogen daily) plus progestin (2.5 mg

medroxyprogesterone acetate daily) therapy did not experience a reduction in

overall risk of non-fatal myocardial infarction and cardiovascular heart disease

death. This treatment also significantly increases the rate of thromboembolic

events. Other randomized trials of HRT for primary prevention are scheduled to

yield results by 2000 or 2005. All these studies have been conducted essentially

in Anglo-Saxon countries and have analysed the effects of conjugated equine

oestrogens alone or combined with medroxyprogesterone acetate. This treatment

is not currently used in France. But no randomized trials are under way with the

HRT common in France (transdermic oestrogen combined with natural

progesterone). The effects of this treatment on cardiovascular disease remain

unknown



Keywords: brain/BREAST-CANCER/cardiovascular/cardiovascular

disease/cardiovascular mortality/cardiovascular

risk/cerebrovascular/CORONARY

HEART-DISEASE/ENGLAND/epidemiology/heart/hormone replacement

therapy/HRT/infarction/ischaemic heart disease/ischaemic

stroke/menopause/meta-analysis/mortality/myocardial/myocardial

infarction/POSTMENOPAUSAL WOMEN/PREVENTION/primary

prevention/randomized/RANDOMIZED TRIAL/randomized

trials/risk/secondary prevention/stroke/TAMOXIFEN/therapy/thromboembolic

events/thromboembolism/treatment/trials/USERS/VENOUS

THROMBOEMBOLISM/women



Lechat, P., Lardoux, H., Mallet, A., Sanchez, P., Derumeaux, G., Lecompte, T., Maillard,

L., Mas, J.L., Mentre, F., Pousset, F., Lacomblez, L., Pisica, G.,

Solbes-Latourette, S., Raynaud, P. and Chaumet-Riffaud, P. (2000),

Anticoagulant (fluindione)-aspirin combination in patients with high-risk atrial

fibrillation. A randomized trial (FFAACS). Therapie, 55 (6), 681-689.



Abstract: Background: A combination of low-dose aspirin (A) and anticoagulation (AC)

may provide better protection against thromboembolic events compared with AC

alone in high-risk patients with atrial fibrillation (AF). Methods: We performed a

multicentric placebo-controlled double blind-trial to test the preventive efficacy

against thromboembolic events of the addition of aspirin (A) (100 mg) or

placebo (P) to anticoagulant treatment in patients with high-risk atrial fibrillation.

A total of 157 patients were included, with atrial fibrillation and previous

thromboembolic event ol older than 65 years with either a history of

hypertension, a recent episode of heart failure or a left ventricular dysfunction.

All patients received fluindione (F) and P or F and A, with an INR target

between 2 and 2.6. The primary endpoint was a combined endpoint of stroke

(ischaemic or haemorrhagic), myocardial infarction, systemic arterial emboli or

vascular death. Results: The study had to be stopped prematurely owing to a too

low recruitment rate. During follow-up (0.84 years) 3 non-fatal thromboembolic

events were recorded (1P, 2A) and 6 patients died (3P, 3A), none of them from a

thromboembolic complication. However, 3 deaths were secondary to severe

haemorrhagic complications (1P, 2A). Non-fatal haemorrhagic complications

occurred more often in group A (n = 10, 13.1 pour cent) compared with group P

(n = 1, 1.2 pour cent), p = 0.003. Conclusion: The FFAACS study was not able

to show any of aspirin to anticoagulant therapeutic benefit from the addition in

patients with high-risk AF. Such a combination increased the incidence rate of

bleeding complications, which therefore greatly reduces its potential overall

benefit



Keywords: AF/anticoagulant/anticoagulant

treatment/anticoagulants/anticoagulation/ANTITHROMBOTIC

THERAPY/arterial/ASPIRIN/aspirin/atrial fibrillation/bleeding/bleeding

complications/combination/complications/death/emboli/ENGLAND/fibrillation/f

luindione/FLUINDIONE/heart/heart failure/HEART-VALVE

REPLACEMENT/high

risk/history/hypertension/incidence/infarction/INR/ischaemic/left ventricular/left

ventricular dysfunction/LONDON/myocardial/myocardial

infarction/PLACEBO/PREVENTION/primary/protection/randomized/randomize

d trial/recruitment/secondary/STROKE/thromboembolic

complications/thromboembolic

events/THROMBOEMBOLISM/treatment/trial/vascular/WARFARIN



Tzourio, C. (2002), Epidemiology and risk factors for stroke. Therapie, 57 (6), 569-576



Keywords:

AUCKLAND/DISEASE/HEALTH/HYPERTENSION/MORTALITY/NEW-ZE

ALAND/PREVENTION/risk/risk factors/risk factors for stroke/stroke

Bordet, R. (2002), Preventive neuroprotection: from experimental data to therapeutic

strategies. Therapie, 57 (6), 540-547.



Abstract: The concept of preventive neuroprotection is based on experimental concept of

brain ischemic tolerance in which a cerebral resistance against ischemia

consequences is induced prior to its occurence. Pharmacological agents

mimicking the biological mechanisms observed in brain ischemic tolerance

might increase the resistance of patients with high stroke risk to the deleterious

effects of brain ischemia. Activation of cytoprotective proteins or regulation of

deleterious molecular pathways could constitute the main pharmacological

targets to induce preventive neuroprotection. Several pharmacological agents

such as statins or fibrates have been demonstrated experimentally to induce a

preventive neuroprotection related to their pleiotropic anti-inflammatory and

antioxidant properties. In future, the prevention treatment of stroke occurrence

may be completed by preventive neuroprotective treatment. Moreover, some

drugs could have potentially both preventive and neuroprotective properties,

which are likely linked



Keywords: ACTIVATION/antioxidant/AUCKLAND/brain/brain

ischemia/cerebral/cerebral ischemia/drugs/experimental/fibrates/FOCAL

CEREBRAL-ISCHEMIA/inflammation/ischemia/ischemic/ischemic

tolerance/mechanisms/NEONATAL

RAT/neuroprotection/NEW-ZEALAND/NITRIC-OXIDE

SYNTHASE/POTENTIAL

MECHANISM/prevention/RAT-BRAIN/REDUCTASE

INHIBITORS/risk/statins/STROKE/SUPEROXIDE-DISMUTASE/TOLERANC

E/treatment



Leys, D. and Deplanque, D. (2003), Statins and stroke. Therapie, 58 (1), 49-58.



Abstract: An important issue for stroke prevention is the identification and treatment of

risk factors such as hypercholesterolaemia. The 4 reasons to test if the statins

have a role in stroke prevention are: (i) a statistical link between elevated low

density lipoprotein-cholesterol or decreased high density lipoprotein-cholesterol

and ischaemic stroke; (ii) a reduction in vascular risk with statins in randomised

trials in patients with coronary heart disease; (iii) evidence of a decreased plaque

progression under statins; and (iv) pooled analyses of primary and secondary

prevention trials showing that reduction of total serum cholesterol reduces the

incidence of stroke, especially with the highest rate of cholesterol reduction, and

in patients with the highest risk of stroke (i.e. with statins in secondary

prevention trials). The question of whether statins also have a neuroprotective

effect in humans and reduce the risk of post-stroke dementia remains unsettled



Keywords: AUCKLAND/AVERAGE CHOLESTEROL LEVELS/BRAIN ISCHEMIC

TOLERANCE/CAROTID ATHEROSCLEROSIS/cholesterol/COA

REDUCTASE INHIBITORS/COENZYME-A REDUCTASE/coronary heart

disease/CORONARY HEART-DISEASE/dementia/DENSITY-LIPOPROTEIN

CHOLESTEROL/disease/heart/heart

disease/humans/hypercholesterolaemia/incidence/ischaemic/ischaemic

stroke/NEW-ZEALAND/NITRIC-OXIDE

SYNTHASE/plaque/prevention/primary/primary and secondary

prevention/progression/risk/risk factors/RISK-FACTORS/secondary/secondary

prevention/serum/SERUM- CHOLESTEROL/statins/statistical/stroke/stroke

prevention/treatment/trials/vascular/vascular risk



Bordet, R., Gele, P., Deplanque, D. and Duriez, P. (2003), Lipid-lowering drugs: From

prevention to protection. Therapie, 58 (1), 69-76.



Abstract: Statins and fibrates have been demonstrated to prevent both cardiovascular

events and stroke. While this preventive effect was initially thought to be related

to their lipid-lowering effects, in particular hypocholesterolaemic effect, analysis

of primary and secondary prevention trials suggest that these preventive effects

could be partly independent of their effects on lipid disorders. The pleiotropic

effects, such as vascular, anti-inflammatory or anti-oxidants effects, were

described for both the statins and fibrates. In addition to the preventive effects,

these pleiotropic effects could partially explain the decrease in myocardial or

cerebral ischemia consequences in experimental models. These cellular

protective effects may have a therapeutic interest to decrease severity of stroke or

coronary acute syndrome. They could also explain the drugs' lipid-lowering

preventive effects independent of the treatment of lipid disorders. Beyond

vascular pathologies, the pleiotropic effects of lipid-lowering drugs could explain

their potentially beneficial effect in different diseases, such as dementia or cancer



Keywords: acute/antioxidants/AUCKLAND/AVERAGE CHOLESTEROL

LEVELS/cancer/cardioprotection/cardiovascular/cardiovascular

events/cerebral/cerebral ischemia/CEREBRAL-ISCHEMIA/COA REDUCTASE

INHIBITOR/coronary acute disorders/CORONARY

HEART-DISEASE/dementia/diseases/drugs/experimental/fibrates/ischemia/KA

PPA-B/lipid lowering/lipid-lowering/lipid-lowering

drugs/myocardial/neuroprotection/NEW-ZEALAND/NITRIC-OXIDE

SYNTHASE/PPAR-ALPHA/prevention/primary/primary and secondary

prevention/protection/secondary/secondary

prevention/severity/SMOOTH-MUSCLE

CELLS/STATINS/STROKE/stroke/treatment/trials/vascular



Corvol, J.C., Bouzamondo, A., Sirol, M., Hulot, J.S., Sanchez, P. and Lechat, P. (2003),

Differential effects of lipid-lowering therapies on stroke prevention: A

meta-analysis of randomised trials. Therapie, 58 (1), 37-48.



Abstract: Background: Previous overviews have suggested that the FIMG-CoA

reductase inhibitors (statins), but not other lipid lowering therapies (LLTs), may

reduce stroke incidence in coronary patients. Our objective was to investigate the

amplitude and sources of heterogeneity of LLT effects on stroke prevention.

Methods: A literature search was performed from 1966-2001 to identify all

English-language published trials testing LLT. We then conducted a

meta-analysis including randomised primary and secondary coronary heart

disease prevention trials, which tested statins, nonstatins, diet or other

interventions, and providing data on stroke incidence. Results: The overall meta-

analysis (38 individual trials, 83 161 patients, mean follow-up of 4.7 years)

showed a significant relative risk reduction (RRR) of strokes by LLTs of 17% (p

0) and no effect (RRR 15 min, 30 min after

clopidogrel and remained prolonged even after 24 h). ADP-induced platelet

aggregation was inhibited (more than 78%). Comparatively, aspirin had a

moderate and no dose- dependent effect. Aspirin 2.5 mg kg-1 (n = 6) abolished

cyclic flow reductions in 2 animals, CFR reoccurred spontaneously in one animal

and epinephrine restored it in a second animal. Aspirin 5 mg kg-1 (n = 6)

abolished cyclic flow reductions in only 3 animals and epinephrine always

restored it. Aspirin 100 mg kg-1 (n = 3) was unable to abolish cyclic flow

reductions. On the right femoral artery, aspirin did not significantly prevent

cyclic flow reductions which occurred in all animals after one (n = 14) or two

injuries (n = 1), except for one animal. Basal bleeding time was lengthened but it

shortened rapidly, reaching its basal value after 24 h. ADP-induced aggregation

was not significantly inhibited, whereas arachidonic acid induced aggregation

was always inhibited. Clopidogrel appears as a more potent antithrombotic drug

than aspirin in this model, in treating and preventing spontaneous or

epinephrine-induced cyclic flow reductions and lengthening bleeding time



Keywords: AGGREGATION/ASPIRIN/BLOOD/CANINE

CORONARY-ARTERIES/INHIBITION/PLATELET THROMBUS

FORMATION/PREVENTION/RATS/STROKE/TICLOPIDINE



Heptinstall, S., May, J.A., Glenn, J.R., Sanderson, H.M., Dickinson, J.P. and Wilcox,

R.G. (1995), Effects of Ticlopidine Administered to Healthy-Volunteers on

Platelet-Function in Whole-Blood. Thrombosis and Haemostasis, 74 (5),

1310-1315.



Abstract: Ticlopidine is thought to be a selective inhibitor of ADP- induced platelet

function. Here we have investigated the effects of ticlopidine on platelet function

in whole blood induced by ADP and by other platelet agonists. Whole blood was

used because it was considered that ADP derived from led cells might act

synergistically with other platelet agonists to enhance platelet responses, and that

ticlopidine might interfere with this process. Measurements were performed

using blood from 16 healthy volunteers before ticlopidine administration, after

taking ticlopidine 250 mg daily for 10 days, after taking ticlopidine 250 mg twice

daily for a further 10 days, and after 14 days off treatment. Ticlopidine proved to

be a very effective inhibitor of the platelet aggregation induced by ADP; it was

most effective in enhancing the reversibility of the aggregation response. The

drug modestly but significantly reduced streptokinase, adrenaline, collagen,

sodium arachidonate, PAF and U46619 - induced platelet aggregation. The drug

significantly reduced the extent of the release reaction (C-14-5HT release)

induced by ADP, streptokinase, PAF, ristocetin and sodium arachidonate, and

also reduced the extent of the synergistic C-14-5HT release induced by

combinations of ADP and PAF, ADP and adrenaline and PAF and adrenaline.

The various inhibitory effects of ticlopidine were evident after treatment with

250 mg daily but were more pronounced after 250 mg tn ice daily. AU values

had returned to normal after 14 days off treatment. Ticlopidine had no effect on

serum thromboxane B-2 production nor an several parameters of coagulation and

fibrinolysis. We conclude that ticlopidine is an effective inhibitor of

ADP-induced platelet aggregation and also the platelet aggregation and

C-14-5HT release induced in whole blood by a number of platelet agonists and

combinations of agonists. These latter effects are probably mainly via a selective

effect on ADP. The inhibitory effects of the drug are dose-related



Keywords:

ADENYLATE-CYCLASE/ADP/AGGREGATION/CLOPIDOGREL/coagulatio

n/platelet aggregation/PREVENTION/STROKE/ticlopidine/treatment



Bergmann, J.F. and Neuhart, E. (1996), A multicenter randomized double-blind study of

enoxaparin compared with unfractionated heparin in the prevention of venous

thromboembolic disease in elderly in-patients bedridden for an acute medical

illness. Thrombosis and Haemostasis, 76 (4), 529-534.



Abstract: A multicenter, randomized double-blind study compared in two parallel groups

the efficacy and safety of a low molecular weight heparin (LMWH) enoxaparin

20 mg once daily, with unfractionated heparin (UFH) 5000 IU twice daily,

administered subcutaneously for 10 days, in the prevention of venous thrombosis

disease in 442 hospitalized elderly patients bedridden for an acute medical illness.

The main efficacy endpoint was defined as the occurrence of venous thrombosis,

diagnosed by a daily fibrinogen uptake test, and/or documented clinical

pulmonary embolism. Intention-to-treat analysis of efficacy showed that the

incidence of venous thromboembolic events was low: 4.8% (10/207) in the

LMWH group (9 episodes of isotopic venous thrombosis and one of

scintigraphic pulmonary embolism), and 4.6% (10/216) in the UFH group (10

episodes of isotopic venous thrombosis). The two treatments were equivalent,

where equivalence was defined as a maximum difference of 7% between the two

groups (p = 0.0005). There were no significant differences in terms of safety

between the 216 patients in the LMWH group and the 223 patients in the UFH

group who received at least one injection of the randomized treatment. During

the study period, 15 patients (3.4%) died (7 in the LMWH group and 8 in the

UFH group): 2 sudden deaths, one in each group, including one case in which

pulmonary embolism could not be excluded since no autopsy was performed,

and 13 others deaths unrelated to the study treatments. Six patients (1.4%)

presented a bleeding complication: 2 (0.9%) in the enoxaparin group (one major

and one minor hemorrhage), and 4 (1.8%) in the UFH group (2 major and 2

minor hemorrhages). These results indicate that subcutaneous enoxaparin 20 mg

once daily for 10 days is as effective and well tolerated as subcutaneous UFH

5000 IU twice daily in the prevention of venous thromboembolic disease in

bedridden elderly in-patients presenting an acute medical illness



Keywords:

DEEP-VEIN-THROMBOSIS/DIAGNOSIS/DVT/elderly/EPIDEMIOLOGY/IN

PATIENTS/MOLECULAR-WEIGHT

HEPARIN/PROPHYLAXIS/RISK-FACTORS/STROKE/thrombosis/treatment/

TRIAL



Herbert, J.M., Bernat, A., Samama, M. and Maffrand, J.P. (1996), The antiaggregating

and antithrombotic activity of ticlopidine is potentiated by aspirin in the rat.

Thrombosis and Haemostasis, 76 (1), 94-98.



Abstract: Since ticlopidine specifically inhibits ADP-induced platelet aggregation

without affecting prostaglandin metabolism, it seemed interesting to evaluate the

effect of aspirin with regard to the antithrombotic efficacy of ticlopidine,

Ticlopidine was administered orally to rats alone or in combination with aspirin

and the efficacy of the association was determined in several experimental

models. A synergistic effect of the ticlopidine/aspirin association was

demonstrated with regard to ADP- and collagen-induced platelet aggregation

measured ex vivo but also in several experimental thrombosis models including

silk thread-induced thrombosis in an arteriovenous shunt, Mire coil-induced

thrombosis and In-111- labelled platelet deposition an the subendothelium

following air drying injury of the rat carotid artery. Similar results were obtained

with regard to myointimal proliferation following air-induced injury of the rat

carotid artery which occurred as a consequence of vascular injury, The

ticlopidine/aspirin combination showed only additive-type effects on bleeding

time prolongation induced by tail transection in the rat



Keywords:

ADP/aggregation/aspirin/BLEEDING-TIME/CLOPIDOGREL/INHIBITION/IN

VIVO/platelet

aggregation/PLATELETS/PREVENTION/RABBITS/rat/rats/STROKE/THRO

MBOSIS/ticlopidine



Koefoed, B.G., Gullov, A.L. and Petersen, P. (1997), Prevention of thromboembolic

events in atrial fibrillation. Thrombosis and Haemostasis, 78 (1), 377-381



Keywords: atrial fibrillation/CEREBRAL

BLOOD-FLOW/COAGULATION/COPENHAGEN/fibrillation/FIXED

MINIDOSE WARFARIN/PROPHYLAXIS/RISK/SPONTANEOUS ECHO

CONTRAST/STROKE/SURGERY/thromboembolic events/THROMBOSIS



Koefoed, B.G., Feddersen, C., Gullov, A.L. and Petersen, P. (1997), Effect of fixed

minidose warfarin, conventional dose warfarin and aspirin on INR and

prothrombin fragment 1+2 in patients with atrial fibrillation. Thrombosis and

Haemostasis, 77 (5), 845-848.

Abstract: The efficacy of conventional dose adjusted oral anticoagulation for stroke

prevention in patients with non-valvular atrial fibrillation is well-documented but

not considered ideal as primary antithrombotic treatment in elderly patients. The

antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in

combination with aspirin 300 mg/day, of conventional dose adjusted warfarin

(INR 2.0-3.0), and of aspirin 300 mg/day have been investigated in outpatients

with chronic nonvalvular atrial fibrillation in the second Copenhagen Atrial

Fibrillation, Aspirin and Anticoagulant Therapy Study (AFASAK 2). In order to

investigate the effect on the coagulation system of the treatments, the

International Normalized Ratio of the prothrombin time (WR) and prothrombin

fragment 1+2(F1+2) were monitored at baseline and after three months of

treatment in 100 patients consecutively included in the trial. At baseline no

differences in INR and F1+2 between the four treatment groups were present.

After three months of therapy the level of INR increased significantly from

baseline in patients receiving warfarin in any dose and the level of F1+2

decreased significantly by combined minidose warfarin- aspirin and by dose

adjusted warfarin. When comparing the changes over time in F1+2 (three-month

value minus baseline value) during therapy with fixed minidose warfarin,

combined minidose warfarin-aspirin and aspirin alone no significant difference

between the groups was found. In conclusion, INR was changed by all three

warfarin regimens but only dose adjusted warfarin (INR 2.0-3.0) had a marked

effect on F1+2



Keywords: ANTICOAGULATION/antithrombotic/aspirin/atrial

fibrillation/COAGULATION/COPENHAGEN/elderly/fibrillation/INR/Internati

onal Normalized Ratio/oral

anticoagulation/prevention/PROPHYLAXIS/prothrombin time/STROKE/stroke

prevention/SURGERY/therapy/THROMBOSIS/treatment/warfarin



Herbert, J.M., Dol, F., Bernat, A., Falotico, R., Lale, A. and Savi, P. (1998), The

antiaggregating and antithrombotic activity of clopidogrel is potentiated by

aspirin in several experimental models in the rabbit. Thrombosis and

Haemostasis, 80 (3), 512-518.



Abstract: It is unknown whether the addition of aspirin might increase both the efficacy

and the potency of clopidogrel, a potent and selective ADP blocker. For that

purpose, the efficacy of clopidogrel (1-20 mg/kg, p.o.) administered orally to

rabbits alone or: in combination with aspirin (0.1-10 mg/kg, p.o.) was determined

in several experimental models. A potent synergistic effect of the

clopidogrel/aspirin association was demonstrated with regard to

collagen-induced platelet aggregation measured ex vivo. Similarly, aspirin

potentiated the antithrombotic activity of clopidogrel measured with regard to

experimental thrombosis induced by a silk thread or an stents placed in an

arteriovenous shunt, thrombus formation following electrical stimulation of the

rabbit carotid artery and with regard to In- 111-labeled platelet deposition on a

stent implanted in an arteriovenous shunt or on the subendothelium following air

drying injury of the rabbit carotid artery. A similar potentiating effect of aspirin

was obtained with regard io myointimal proliferation (restenosis) in the femoral

arteries of atherosclerotic rabbits which occurred as a consequence of stent

placement. The clopidogrel/aspirin combination showed only additive-h pe

effects on bleeding rime prolongation induced by ear transection in the rabbit,

therefore showing that combined inhibition of cyclooxygenase and ADP's effects

provide a marked enhanced antithrombotic efficacy, Such a combination may

provide substantial protection against platelet aggregation leading to thrombotic

occlusion at sites of endothelial injuries and coronary artery stenosis in humans



Keywords: ADP/aggregation/ANTIPLATELET/ARTERY/aspirin/BALLOON

ANGIOPLASTY/carotid/clopidogrel/formation/MULTICENTER/platelet

aggregation/PREVENTION/RAT/STENT

IMPLANTATION/stents/STROKE/thrombosis/thrombus/TICLOPIDINE/TRAN

S-LUMINAL ANGIOPLASTY



Feinberg, W.M., Macy, E., Cornell, E.S., Nightingale, S.D., Pearce, L.A., Tracy, R.P.

and Bovill, E.G. (1999), Plasmin-alpha(2)-antiplasmin complex in patients with

atrial fibrillation. Thrombosis and Haemostasis, 82 (1), 100-103.



Abstract: Plasmin-alpha(2)-antiplasmin complex (PAP) is an index of recent fibrinolytic

activity. We examined PAP levels in patients with atrial fibrillation (AF) to

determine whether these levels are correlated with clinical characteristics

associated with stroke risk. We obtained blood for measurement of PAP in a

non-random sample of 586 patients with AF on entering the Stroke Prevention in

Atrial Fibrillation ill Study. PAP levers were measured with an ELISA assay.

PAP Values were transformed with a natural logarithm (PAP(ln)) prior to all

analyses. Older age, female gender, recent congestive heart failure, decreasing

fractional shortening, recent onset of AF, and coronary artery disease were each

univariately associated with higher levels of PAP (all p 160 mm Hg, prior

thromboembolism, recent congestive heart failure, poor left ventricular function,

and women over age 75) had higher PAP levels than low-risk patients (antilog

mean PAP(ln) 5.6 vs 4.9, p 75 years of age (6 events, 5.1% per year) than in younger

patients (5 events, 1.0% per year). The cumulative incidence of major bleeding in

patients over 75 years of age (10.8%; 95% CI, 1.8-19.8) was significantly higher

than in younger patients (2.8%; 95% CI, 0.3-5.3, p = 0.006). Major primary

bleeding unrelated to organic lesions (7 patients, 1 male and 6 females) occurred

in 5 elderly patients (>75 years old) with a cumulative incidence (9.6%; 95% CI

0.8-18.4) significantly higher than in younger patients (1.2%; 95% CI, 0-3.0, p =

0.0003). Univariate analysis revealed a higher frequency of major primary

bleeding in females, in diabetic patients and in in those who had suffered a

previous thromboembolic event. Multivariate analysis revealed that only age

grater than 75 years was independently related to major primary bleedings (RR

6.6; 95% CI 1.2-37, p = 0.032). Minor bleedings (n = 27) were not more frequent

in elderly patients (6% vs 4% per year, p = ns). Patients were kept at optimal

intensity of treatment for 63% of the time. These data confirm the efficacy of OA

but identify elderly patients as a high risk group of major bleeding



Keywords: age/anticoagulant/anticoagulant

therapy/anticoagulants/anticoagulation/ASPIRIN/atrial

fibrillation/bleeding/clinical trials/cohort

study/COMPLICATIONS/death/elderly/elderly patients/fibrillation/FIXED

MINIDOSE WARFARIN/high

risk/HOSPITALS/incidence/INTENSITY/ischemic/ischemic

stroke/non-rheumatic atrial fibrillation/nonrheumatic/oral

anticoagulants/PREVENTION/primary/QUALITY/randomized/randomized

clinical trials/risk/safety/STROKE/stroke

prevention/therapy/THROMBOEMBOLISM/thrombosis/treatment/TRIAL/trials

/vascular



Bousser, M.G. (2001), Antithrombotic strategy in stroke. Thrombosis and Haemostasis,

86 (1), 1-7.



Abstract: Numerous randomised controlled trials have been devoted to antithrombotic

strategy in stroke, thus making evidence-based recommendations possible. The

use of antithrombotic drugs is crucial in the treatment of ischemic stroke though

often limited by the inherent risk of intra-cerebral bleeding. In the prevention of

stroke, the strategy depends on the underlying etiology: (i) antiplatelet drugs

(with aspirin as first choice) in atherothrombotic stroke, and (ii) oral

anticoagulants in cardioembolic stroke. In the acute treatment, the strategy

depends on whether IV rt-PA can be performed; if rt-PA is available and

approved, its use is recommended within 3 h of the onset of symptoms provided

there is strict adherence to the inclusion and exclusion criteria. In all other cases,

aspirin is the treatment of choice, associated with low dose LMWH in the event

of restricted mobility. There is no evidence for efficacy of high dose heparin (or

LMWH) in stroke, except in cerebral venous thrombosis



Keywords: ACETYLSALICYLIC-ACID/acute/ACUTE ISCHEMIC STROKE/acute

treatment/adherence/anticoagulants/antiplatelet/antiplatelet

drugs/antithrombotic/ASPIRIN/ATRIAL-FIBRILLATION/bleeding/cardioembo

lic/cardioembolic stroke/cerebral/cerebral

infarction/CEREBRAL-ISCHEMIA/drugs/etiology/FIRST-LINE

TREATMENT/HEPARIN/intracerebral/ischemic/ischemic stroke/mobility/oral

anticoagulants/prevention/RANDOMIZED CONTROLLED

TRIALS/risk/rtPA/SECONDARY

PREVENTION/stroke/symptoms/thrombolysis/THROMBOLYTIC

THERAPY/thrombosis/treatment/trials/use/venous thrombosis



Vanschoonbeek, K., Feijge, M.A.H., Keuren, J.F.W., Hemker, H.C., Lodder, J.J.,

Hamulyak, K., van Pampus, E.C.M. and Heemskerk, J.W.M. (2002),

Thrombin-induced hyperactivity of platelets of young stroke patients -

Involvement of thrombin receptors in the subject- dependent variability in Ca2+

signal generation. Thrombosis and Haemostasis, 88 (6), 931-937.



Abstract: Activated platelets are implicated in the development of premature arterial

vascular diseases, in particular ischemic stroke. Since elevated cytosolic [Ca2+](i)

is an integrative marker of platelet activation, we determined the generation of

Ca2+ signal in stimulated platelets from 26 young patients recuperating from

stroke, 20 patients with symptomatic peripheral arterial disease, and 56 healthy

volunteers. Even in the presence of aspirin, the platelets from various individuals

showed highly different thrombin-induced Ca2+ responses. On average, the

thrombin-induced Ca2+ responsemas increased for platelets from either patient

group in comparison to the controls (P 1.25) (= secondary ASA-nonresponder (SNR)). Single ASA

dosages of 500 mg or 200 mg were of identical effectiveness. Additional

administration of metoclopramide in combination with 100 mg ASA was more

effective as compared to a single dosage of 1000 mg ASA. Those who were SNR

at onset of ASA therapy remained SNR as well 28 days later. The change from a

normal, ASA corrected PR, to pathological PR values before a period of 12 hours

ended seemed a sudden and irreversible event that could only be corrected by the

next ASA application



Keywords: ACETYLSALICYLIC ACID DOSAGE/ASPIRIN/PLATELET

REACTIVITY/PREVENTION/STROKE/TRIAL



Dembinskakiec, A., Virgolini, I., Rauscha, F. and Sizinger, H. (1992), Ticlopidine and

Platelet-Function in Healthy-Volunteers. Thrombosis Research, 65 (4-5),

559-570.



Abstract: The influence of a 4-weeks therapy with 500 mg ticlopidine daily on platelet

function parameters was examined in 10 male healthy volunteers aged 20-33

years in order to extend the knowledge on the antiplatelet activity of this

substance. Ticlopidine significantly (p < 0.01) affected ex-vivo platelet

aggregation induced by ADP and increased platelet sensitivity to the

antiaggregatory action of PGI2. Generation of TXB2 from endogenous substrate

during spontaneous clotting of blood (serum-TXB2), conversion of exogenous

radio-labelled labelled arachidonic acid into TXB2 and MDA-formation in

isolated platelets were unaffected by the treatment. The TXB2- level in plasma of

volunteers, however, was decreased, after administration of the drug. The

diminished alpha-granule content liberation (beta-thromboglobulin: p < 0,01;

PDGF: p < 0.01; PF4 not significant) indicates that ticlopidine induces a

decrease in platelet activity. The beneficial effect on release reaction is not

associated with a decrease in TXA2-formation. Our results demonstrate that

ticlopidine inhibits platelet activity, especially the PDGF-release. These results

confirm the value of this drug in the prevention of atherosclerosis and its

thromboembolic complications

Keywords:

ACTIVATION/ASPIRIN/ATHEROSCLEROSIS/DOSE-LEVELS/DOUBLE-B

LIND/ISCHEMIC

HEART-DISEASE/MYOCARDIAL-INFARCTION/PLATELET DERIVED

GROWTH FACTOR/PLATELET

FUNCTION/PREVENTION/STROKE/THROMBOXANE-B2/TICLOPIDINE/

TRIAL



Grotemeyer, K.H., Scharafinski, H.W. and Husstedt, I.W. (1993), 2-Year Follow-Up of

Aspirin Responder and Aspirin Nonresponder - A Pilot-Study Including 180

Poststroke Patients. Thrombosis Research, 71 (5), 397-403.



Abstract: Aspirin is proposed to be effective in stroke-prophylaxis because it completely

inhibits the platelet prostanoid-pathway. In about 90% of stroke victims,

increased platelet reactivity (PR) can be reduced to the normal range by aspirin.

Twelve hours later, about one third of them show an enhanced PR again. These

patients are called secondary aspirin non responders (SANR). In this study the

potential pathogenetic and prognostic impact of this biological feature on stroke

recurrence was evaluated. Before discharge from the hospital, PR was

determined 12 hours after an oral administration of 500 mg aspirin in 180

patients aged 58 +/- 15 years; 74 were female and 106 male. All had suffered a

stroke in the internal carotid artery territory. Patients were treated with 3 x 500

mg aspirin/d and were followed up over a 24-month period. Major endpoints of

this study were stroke, myocardial infarction or vascular death. On discharge

from the hospital, 120 of the 180 patients showed a normal PR under aspirin

treatment. High test values were found in 60 patients (SANR). Six patients were

lost for follow-up. Because of side effects 36 (20%) of the 180 patients enrolled

discontinued medication. Major endpoints occurred in 4 of these 36 patients

(11%) and in 25 of the 138 remaining patients (18.1%); 19 patients died in

consequence of a vascular event during the observation period. Major endpoints

were seen in only 5 of 114 (4.4%) of the aspirin responders, but in 24 out of 60

SANR (40%, p < 0.0001). It may be assumed that early identification of SANR's

is a clinically useful tool to classify patients at high risk for recurrence of

vascular events. This may be an important step to a more effective prevention in

post-stroke patients



Keywords: ACETYLSALICYLIC ACID NONRESPONDER/ACID/PLATELET

REACTIVITY/PREVENTION/RANDOMIZED

TRIAL/STROKE/TICLOPIDINE



Fisher, T.C. and Meiselmann, H.J. (1994), Polymorphonuclear Leukocytes in Ischemic

Vascular-Disease. Thrombosis Research, 74 S21-S34.



Abstract: Over the last decade, an extensive amount of evidence has accumulated which

implicates PMN in the etiology and pathophysiology of ischemic/thrombotic

diseases. Tt has become apparent that PMN infiltration is not, as once thought,

an innocent secondary phenomenon following ischemia. Rather, PMN are active

participants in the pathophysiology of infarction, exacerbating the tissue damage.

Since the development of means to achieve reperfusion after thrombosis, this

phenomenon has become of critical importance. Many different approaches,

targeted at prevention of PMN trapping in the capillaries of the ischemic, area,

have been shown to effectively reduce the final infarct size, and will likely prove

valuable adjuncts to reperfusion. However, perhaps the most significant aspect of

the realization that PMN play a significant role in thrombotic disease may prove

to be the potential for early intervention: Elevated PMN counts are predictive of

ischemic events, and there is preliminary evidence that the elevated PMN count

may be also associated with increased PMN activation, suggesting that research

directed at the prophylactic use of anti-PMN agents might someday prove

effective in reducing the incidence of MI and stroke



Keywords: ACTIVATING- FACTOR PAF/ACUTE

MYOCARDIAL-INFARCTION/ANTIINFLAMMATORY

DRUGS/CULTURED ENDOTHELIAL-CELLS/DEPENDENT

DIABETES-MELLITUS/development/diseases/early

intervention/ENGLAND/etiology/incidence/ischemia/NEUTROPHIL

ELASTASE ACTIVITY/NO-REFLOW

PHENOMENON/PLATELETS/POLYMORPHONUCLEAR

LEUKOCYTES/prevention/SICKLE-CELL DISEASE/SKELETAL- MUSCLE

CAPILLARIES/stroke/thrombosis/TUMOR-NECROSIS-FACTOR/VASCULA

R DISEASE



Riess, H. and Riewald, M. (1994), The Clinical Impact of Platelet-Function Testing.

Thrombosis Research, 74 S69-S78



Keywords:

ACTIVATION/AGGREGATION/ATHEROSCLEROSIS/BLEEDING-TIME/C

OMPLICATIONS/ENGLAND/HEALTHY-SUBJECTS/LOW-DOSE

ASPIRIN/MYOCARDIAL-INFARCTION/PLATELET

AGGREGATION/PLATELET FUNCTION/PREVENTION/STROKE



Umemura, K., Ishihara, H. and Nakashima, M. (1995), Antiplatetlet Effects of

Clopidogrel in Rat Middle Cerebral- Artery Thrombosis Model. Thrombosis

Research, 80 (3), 209-216.



Abstract: We have developed a model whereby the middle cerebral artery (MCA) in an

experimental animal can be occluded by photochemical reaction between rose

bengal and green light which causes endothelial injury followed by platelet

adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the

site of photochemical reaction. Using this model, we investigated the effect of

clopidogrel, an analogue of ticlopidine which is a potent inhibitor of adenosine

5'- diphosphate (ADP)-induced platelet aggregation. Oral clopidogrel

(3-10mg/kg) inhibited ex-vivo platelet aggregation induced by ADP, thrombin or

the thromboxane A(2) mimetic, and U46619, when platelets had been primed

with low concentration of phorbol myristate acetate. At these doses, clopidogrel

significantly (P<0.001) prolonged the time to produce thrombotic occlusion of

the MCA and induced a significant (P<0.001) reduction in the size of ischaemic

cerebral damage examined 24 hours after photochemical reaction. The results

suggest that ADP has a key role in the thrombotic occlusion of the MCA in this

model. Clopidogrel may be beneficial in the prevention of arterial thrombosis



Keywords: ADP/AGGREGATION/animal/arterial

thrombosis/CLOPIDOGREL/ENGLAND/formation/MIDDLE CEREBRAL

ARTERY/platelet aggregation/PLATELET- AND FIBRIN-RICH

THROMBOSIS/platelets/PREVENTION/STROKE/thrombosis/thrombus/TICL

OPIDINE



Mieszczak, C. and Winther, K. (1996), Does Warfarin enhance platelet activity?

Thrombosis Research, 84 (4), 285-287.



Abstract: It has been shown in stroke patients with atrial fibrillation as well as those in

regular cardiacrhythm - that platelet aggregation is enhanced (1,2) Whether this

is a result of the disease itself or possibly a result of warfarin therapy, is not clear.

If the enhancement of platelet activation is indeed caused by Warfarin, this could

blunt the beneficial effect that warfarin exerts on stroke patients, and would

favour the addition of a platelet inhibitor. (3) To the best of our knowledge, the

impact of warfarin on platelet function has never been examined in healthy

human volunteers. The aim of the present study therefore was to test if warfarin

affects platelet aggregation induced by ADP, adrenaline and collagen



Keywords:

ADP/aggregation/anticoagulation/ASPIRIN/ATRIAL-FIBRILLATION/coagulat

ion/platelets/PREVENTION/stroke/THROMBOEMBOLIC

COMPLICATIONS/Warfarin



Lee, T.K., Chan, K.W.A., Huang, Z.S., Ng, S.K., Lin, R.T., Po, H.L., Yuan, R.Y., Lai,

M.L., Chang, T.W., Yan, S.H., Deng, J.C., Liu, L.H., Lee, K.Y., Lie, S.K., Sung,

S.M. and Hu, H.H. (1997), Effectiveness of low-dose ASA in prevention of

secondary ischemic stroke, the ASA Study Group in Taiwan. Thrombosis

Research, 87 (2), 215-224.



Abstract: This randomized double-blind controlled study was carried out to investigate

the effect of 100 mg acetylsalicylic acid(ASA) per day on the secondary

prevention of ischemic stroke. Patients who suffered a first ischemic stroke from

13 participating hospitals were enrolled. They were independent or only partially

dependent in activities of daily living and all had received brain CT for diagnosis.

Eligible patients were randomly allocated to the 100 mg ASA or the nicametate

citrate(a vasodilator) groups, and trial medications were started within three to

six weeks after the onset of stroke. The primary end point was cerebral

reinfarction, and intracranial hemorrhage was classified as an adverse event.

Four hundred and sixty-six patients participated in this study; and 222 cases (136

males and 86 females) were allocated to the ASA group while 244 cases (150

males and 94 females) were assigned to the nicametate group. No significant

difference in baseline characteristics between the two groups was observed.

Cerebral reinfarction developed 6.3% (14/222) in the ASA group and 11.9%

(29/244) in the nicametate group. According to the Cox's proportional hazards

model, the estimated risk ratio (ASA group vs. nicametate group) was 0.538,

with a 95% confidence interval of 0.284-1.019. The result was of borderline

statistical significance. The risk for cerebral reinfarction was reduced by almost

50% among those who took 100 mg ASA versus those who took nicametate. (C)

1997 Elsevier Science Ltd



Keywords:

ACETYLSALICYLIC-ACID/ACTIVATION/AGGREGATION/aspirin/ASPIRI

N/brain/cerebral/CEREBRAL ISCHEMIA/Chinese/clinical

trials/CT/diagnosis/ENGLAND/hemorrhage/ischemic/ischemic

stroke/PLATELET-FUNCTION/prevention/randomized/risk/secondary

prevention/stroke/stroke prevention/TRIAL



Yang, L.H., Hoppensteadt, D. and Fareed, J. (1998), Modulation of vasoconstriction by

clopidogrel and ticlopidine. Thrombosis Research, 92 (2), 83-89.



Abstract: Clopidogrel is an antiplatelet drug which has undergone extensive clinical

trials in the management of stroke and other arterial disorders related to platelet

activation. This agent is believed to produce the inhibition of ADP mediated

direct and indirect actions leading to platelet adhesion/aggregation and other

activation processes. Several other observed pharmacologic actions suggest that

this drug may have additional sites of action. Ticlopidine also belongs to the

same class of ADP receptor inhibitors and is extensively used for stroke

prevention. To study the vasomodulatory action of clopidogrel and ticlopidine,

the drugs were administered intravenously into canines at a dose of 10 mg/kg.

Thirty minutes later femoral and pulmonary arteries were removed and taken for

isolated tissue preparations. The intravenous injection of clopidogrel and

ticlopidine caused significant vasomodulatory actions in both femoral and

pulmonary ring preparations showing a marked desensitization to serotonin,

endothelin-1, serum, and platelet rich plasma/arachidonic acid mixtures. In

contrast, when the drugs were added directly to the organ bath containing

femoral or pulmonary ring preparations from untreated animals, both clopidogrel

and ticlopidine did not produce any effect on contractile response induced by

serotonin, endothelin-1, serum, and platelet rich plasma/arachidonic acid

mixtures. These data suggest that endogenous transformation of clopidogrel and

ticlopidine plays an important role in producing their vasomodulatory actions.

Furthermore, these observations indicate that both clopidogrel and ticlopidine

also modulate the vascular sites which may be contributory to the observed

clinical effects. (C) 1998 Elsevier Science Ltd



Keywords: activation/ADP/ADP receptor/ADP receptor

antagonist/ANTIAGGREGATING ACTIVITY/ANTIPLATELET

THERAPY/ASPIRIN/BINDING/canine smooth muscle

preparation/CEREBROVASCULAR-DISEASE/clinical

trials/clopidogrel/ENGLAND/prevention/RAT PLATELETS/stroke/stroke

prevention/THROMBOSIS/ticlopidine/trials/vascular



Patrono, C. (1998), Prevention of myocardial infarction and stroke by aspirin: Different

mechanisms? Different dosage? Thrombosis Research, 92 (1), S7-S12.



Abstract: More than 50 randomized trials have documented the efficacy and safety of

aspirin as an antiplatelet agent and a cardiovascular drug. However, the optimal

dose for preventing coronary and cerebral thrombosis has long been a cause of

debate, For patients with ischaemic heart disease the range recommended for the

prevention of a secondary event, based on strong clinical evidence, is 75-160 mg

aspirin/day. For patients with cerebrovascular disease, recommendations range

from 30-1300 mg/day, If these patients require a higher dose of aspirin it

suggests that a different mechanism of action is involved. This paper considers

hypotheses and reports the findings of recent clinical trials. The SALT study

compared aspirin with placebo in 1360 patients with TIA or minor ischaemic

stroke. It showed an 18% reduction in the risk of stroke or death in patients

receiving 75 mg aspirin/day, Five other trials of 55,000 patients with ischaemic

cerebrovascular disease compared the protective effect of aspirin (range 30-300

mg/day) with placebo, clopidogrel, or oral anticoagulants, Aspirin was better

than placebo, safer than oral anticoagulants, and no different from clopidogrel,

The implications of these findings are discussed. Mechanistic studies and

randomized clinical trials strongly suggest that the mechanism of action and dose

requirement of the antithrombotic effect of aspirin in patients with

cerebrovascular dis ease is the same as that for ischaemic heart disease, (C) 1998

Elsevier Science Ltd



Keywords: ACUTE ISCHEMIC STROKE/anticoagulants/aspirin/cerebrovascular

disease/clinical

trials/clopidogrel/dipyridamole/DISEASE/ENGLAND/HEALTHY-

SUBJECTS/heart/INHIBITION/LOW-DOSE ASPIRIN/myocardial

infarction/PLATELET ACTIVATION/prevention/PROSTAGLANDIN

SYNTHESIS/randomized trials/risk/safety/SALT/SECONDARY

PREVENTION/stroke/THERAPY/thrombosis/TIA/ticlopidine/trials/UNSTABL

E ANGINA



Dippel, D.W.J. (1998), The Results of Caprie, Ist and Cast. Thrombosis Research, 92 (1),

S13-S16.



Abstract: The role of aspirin in the secondary prevention of ischaemic events is being

challenged. CAPRIE, a blinded multicenter randomized trial of over 19000

patients followed for 1-3 years, assessed the effect of clopidogrel in the

secondary prevention of major vascular events. Patients with a recent myocardial

infarction, stroke or peripheral arterial disease were randomized to treatment

with clopidogrel or aspirin. Clopidogrel was associated with a statistically

significant, overall 8.7%, relative reduction in the risk of ischaemic events, but

the direction and size of the effect was not homogeneous with respect to three

predefined clinical subgroups. Clopidogrel may be slightly better in preventing

major ischaemic events in high-risk patients, but the results of CAPRIE suggest

that there is room for doubt. It remains to be seen whether treatment with

clopidogrel is cost-effective compared with aspirin. However, aspirin may still

be of value in the early treatment of acute stroke. IST was a 20,000 patient,

randomized, open-label study of aspirin plus heparin or neither in patients with

acute ischaemic stroke that should be treated in 48 hours. There was a small but

statistically nonsignificant reduction in mortality and disability at 6 months for

patients allocated to early treatment with aspirin compared with those who were

scheduled to avoid aspirin in the first 2 weeks after the stroke. Similar results

were seen in CAST, a double-blind trial of aspirin vs, placebo in patients with

suspected ischaemic stroke treated within 48 hours. A meta-analysis of the

results of IST, CAST and MAST-I showed a statistically significant effect of

early aspirin treatment. The role of aspirin in the treatment of acute stroke within

48 hours appears to be established. (C) 1998 Elsevier Science Ltd



Keywords: ACUTE ISCHEMIC

STROKE/ASPIRIN/aspirin/clopidogrel/ENGLAND/heparin/ischaemia/mortality

/myocardial infarction/Netherlands/PLATELET

ACTIVATION/prevention/risk/secondary

prevention/stroke/TICLOPIDINE/treatment/vascular



Morishita, K. and Iwamoto, M. (1998), Synergistic antithrombotic effects of argatroban

and ticlopidine in the rat venous thrombosis model. Thrombosis Research, 92 (6),

261-266.



Abstract: Argatroban, a synthetic thrombin inhibitor, and ticlopidine, an anti-platelet

agent, are major antithrombotic agents. We investigated the antithrombotic

effects of a combination of argatroban and ticlopidine in the rat venous

thrombosis model. Argatroban or ticlopidine inhibited thrombus formation in a

dose-dependent manner; 50% inhibition (ED,) is obtained with 1.0 mg/kg/h

(infusion) argatroban or 30 mg/kg (p.o.) ticlopidine. The combination of

argatroban and ticlopidine inhibited thrombus formation in a dose-dependent

manner; ED50 is obtained with 0.25 mg/kg/h argatroban plus 10 mg/kg

ticlopidine and 0.5 mg/kg/h argatroban plus 3 mg/kg ticlopidine, whereas 0.5

mg/kg/h argatroban alone or 10 mg/kg ticlopidine alone had negligible effect

(<20% inhibition). Isobole analysis showed that the antithrombotic effects of the

combination of argatroban and ticlopidine involved synergism with potentiation.

In contrast, the combination of argatroban and ticlopidine did not prolong the

bleeding time synergistically. These data showed that the combination therapy of

argatroban and ticlopidine should be clinically beneficial, but the different

administration route may restrict the clinical usage. (C) 1998 Elsevier Science

Ltd



Keywords: anticoagulant/argatroban/bleeding

time/BRAIN-DAMAGE/ENGLAND/experimental venous

thrombosis/formation/INHIBITOR/NO-805/PREVENTION/rat/STROKE/throm

bin inhibitor/thrombosis/thrombus/ticlopidine/VEIN/venous thrombosis



Forbes, C.D. (1998), Secondary stroke prevention with low-dose aspirin, sustained

release dipyridamole alone and in combination. Thrombosis Research, 92 (1),

S1-S6.



Abstract: Patients who had survived a stroke or transient ischaemic attacks (TIA) were

admitted to a trial of low-dose aspirin (50 mg) alone, sustained release

dipyridamole (400 mg/day) alone, or a combination of the two agents, and results

compared with a placebo over 24 months. This low-dose aspirin regimen

produced in pairwise comparisons a significant risk reduction of 18% for stroke,

13% for stroke and/or death but no reduction in all cause mortality. The

sustained release dipyridamole produced a significant risk reduction of 16% for

stroke, 15% for stroke and/or death but no significant reduction of mortality. In

combination, aspirin and dipyridamole produced a risk reduction of 37 % in

stroke, 24% in stroke and/or death, and no reduction in mortality. Similar

findings were found in TIA, which was a secondary endpoint. These results are

highly significant in comparison with placebo. As expected, there were enhanced

reports of alimentary side-effects in the aspirin groups and also enhanced

bleeding. Dipyridamole was associated with a slight increase in headache, which

resolved in most patients if therapy was continued. The conclusions are that 50

mg/day of aspirin alone or 400 mg/day of sustained release dipyridamole alone

are equally effective in stroke and TIA prevention. When used in combination

the effects were additive and were significantly more effective than the single

agents. (C) 1998 Elsevier Science Ltd



Keywords: ACETYLSALICYLIC-ACID/aspirin/dipyridamole/drug

combination/ENGLAND/ischaemia/mortality/prevention/risk/stroke/stroke

prevention/TIA/transient



Wade, W.E. (1998), Cost-effectiveness of venous thrombosis prophylaxis following

ischemic stroke: An assessment of currently available literature. Thrombosis

Research, 89 (4), 199-202



Keywords: cost/DEEP-VEIN THROMBOSIS/DOUBLE-BLIND/ENGLAND/ischemic

stroke/LOW-DOSE

HEPARIN/ORG-10172/PREVENTION/prophylaxis/stroke/thrombosis/thrombos

is prophylaxis/venous thrombosis



Kohda, N., Tani, T., Nakayama, S., Adachi, T., Marukawa, K., Ito, R., Ishida, K.,

Matsumoto, Y. and Kimura, Y. (1999), Effect of cilostazol, a phosphodiesterase

III inhibitor, on experimental thrombosis in the porcine carotid artery.

Thrombosis Research, 96 (4), 261-268.



Abstract: Thrombus formation in the carotid artery is one of the common causes of

transient ischemic attacks and stroke. Platelet aggregation seems to be an

essential component in these processes. The present study was conducted to

determine the ability of cilostazol, a phosphodiesterase III inhibitor, to prevent

formation of totally occlusive thrombus in a porcine carotid artery, in

comparison with ticlopidine. Castrated male Yorkshire pigs were allocated to

control(n = 8), cilostazol (30 mg/kg, twice a day [b.i.d] for 2 days, n = 8), and

ticlopidine (50 mg/kg, b.i.d. for 3 days, n = 7) groups. The endothelium of the

right common carotid artery was injured with electrical stimulation (150 mu A)

without constriction and blood flow in this region was monitored by Doppler

flow probe. Arterial blood was sampled during electrical stimulation for the

measurement of platelet aggregation. Total occlusion rates within 240 minutes

were 87.5% (7.8), 37.5% (3:8), and 85.7% (6:7) in the control, cilostazol, and

ticlopidine groups, respectively. Compared with the control group, the time to

total occlusion was significantly prolonged in the cilostazol group, but not in the

ticlopidine group. Consistently, platelet aggregation was significantly inhibited

only in the cilostazol group. Because ticlopidine increases blood flow in the

intact carotid artery before injury to a greater extent than cilostazol, direct

antiplatelet action is thought to be responsible for cilostazol's beneficial effect in

preventing thrombotic occlusion. These results suggest that cilostazol may be

useful for the inhibition of the thrombus formation in the carotid artery and for

the prevention of cerebral ischemic events. (C) 1999 Elsevier Science Ltd. All

rights reserved



Keywords: aggregation/ANTAGONIST/carotid/carotid

artery/cerebral/cilostazol/control/Doppler/endothelium/ENGLAND/formation/IN

TERMITTENT CLAUDICATION/ischemic/platelet

aggregation/PREVENTION/RETHROMBOSIS/STROKE/thrombosis/thrombus/

TICLOPIDINE/transient/transient ischemic attacks/TRIAL



Agnelli, G. and Sonaglia, F. (2000), Prevention of venous thromboembolism.

Thrombosis Research, 97 (1), V49-V62.



Abstract: Venous thromboembolism is the most common cause of preventable death

among hospitalised patients. Systematic prophylaxis with antithrombotic agents

in patients at risk for venous thromboembolism is the most effective approach to

reduce morbidity and mortality. Despite this evidence, antithrombotic

prophylaxis is still underused, due to the underestimation of incidence of venous

thromboembolism and to the unjustified fear of bleeding complications. Both the

characteristics of the individual patient and the clinical setting contribute to the

definition of the risk for venous thromboembolism. Patient- related risk factors

include clinical and molecular abnormalities. The grade of risk for venous

thromboembolism is defined better by the clinical setting than by the patient

characteristics. Prophylactic studies have been extensively carried out in surgical

patients and, only more recently, in medical patients. Prophylactic methods

include pharmacological agents, such as heparin, low molecular weight heparins,

warfarin, and hirudin, as well as mechanical methods such as compression

stockings and intermittent pneumatic compression. (C) 2000 Elsevier Science

Ltd. All rights reserved

Keywords: ACUTE ISCHEMIC STROKE/antithrombotic/bleeding/BLIND

RANDOMIZED TRIAL/complications/death/deep vein

thrombosis/DEEP-VEIN-THROMBOSIS/ENGLAND/FATAL

PULMONARY-EMBOLISM/GRADUATED COMPRESSION

STOCKINGS/heparin/heparins/hirudin/incidence/low molecular weight

heparin/LOW-DOSE HEPARIN/LOW-MOLECULAR-WEIGHT/MAJOR

ABDOMINAL- SURGERY/medical

patients/morbidity/mortality/prophylaxis/pulmonary embolism/risk/risk

factors/thromboembolism/TOTAL

HIP-REPLACEMENT/UNFRACTIONATED HEPARIN/venous

thromboembolism/warfarin



Ringelstein, E.B. and Nabavi, D. (2000), Long-term prevention of ischaemic stroke and

stroke recurrence. Thrombosis Research , 98 (3), V83-V96.



Abstract: Stroke is the third most important cause of mortality, but the leading cause of

severe handicap, dependency, and loss of social competence, Because of the high

recurrence rate, active secondary prevention is mandatory once a stroke has

occurred. Secondary prevention of stroke implies the primary prevention of

cardiovascular disorders as well. Among the modifiable risk factors hypertension

is worst and should be normalized according to recent WHO criteria, also in the

elderly. Smoking is another major risk factor and hard to delete. Diabetes

mellitus and hyperlipidaemia are also important risk factors and should be treated

consequently by diet and medication. Moderate alcohol intake, normalization of

body weight and regular physical activity also contribute considerably to

prevention of stroke. Whether hyperhomocysteinaemia should be normalized has

not yet been clarified. Cardiovascular disorders are an important source of

ischemic strokes, particularly atrial fibrillation. Low dose anticoagulation can

dramatically reduce stroke risk. Carotid endarterectomy in symptomatic stenoses

is the most expensive means of stroke prevention. In less severe stenoses, or ICA

occlusions, antiplatelet agents are the treatment of choice. Composite drugs with

ASS and other antiplatelet agents seem to be superior to either compound alone,

Dissections of the cervical arteries should not be operated on but may be treated

by anticoagulation or antiplatelet agents in the acute and subacute phase. The

potency of a consequent and comprehensive stroke prevention in preventing

disability and death is much greater than any sophisticated acute stroke treatment.

(C) 2000 Elsevier Science Ltd. All rights reserved



Keywords: acute/acute stroke/acute stroke

treatment/alcohol/anticoagulation/antiplatelet/antiplatelet

agents/arteries/ASS/atrial fibrillation/ATRIAL SEPTAL

ANEURYSM/cardiovascular/CAROTID-ARTERY

STENOSIS/death/diet/disability/drugs/elderly/endarterectomy/ENGLAND/FAC

TOR-V-LEIDEN/fibrillation/Germany/HONOLULU-HEART-PROGRAM/hype

rlipidaemia/hypertension/ischaemic stroke/ischemic/ISOLATED SYSTOLIC

HYPERTENSION/MIDDLE-AGED MEN/MODERATE

ALCOHOL-CONSUMPTION/mortality/PATENT FORAMEN

OVALE/physical activity/prevention/primary/primary

prevention/recurrence/risk/risk factor/risk factors/RISK-FACTORS/secondary

prevention/stroke/stroke prevention/stroke recurrence/stroke

treatment/treatment/US MALE PHYSICIANS



Wu, T.H., Chen, T.H.H. and Lee, T.K. (2000), Factors affecting the first recurrence of

noncardioembolic ischemic stroke. Thrombosis Research, 97 (3), 95-103.



Abstract: Studies of the factors affecting the first recurrence of ischemic stroke have

reported inconsistent findings. Types of initial stroke and the racial differences in

study samples are among the explanations that may account for this

inconsistency. The aims of this study were to estimate the cumulative recurrence

rates of noncardioembolic ischemic stroke and identify the factors that influence

the first recurrence of noncardioembolic ischemic: stroke in the Taiwanese

Chinese population. Four hundred and sixty-six patients with noncardioembolic

ischemic stroke from thirteen hospitals in Taiwan were, followed up in this study

to ascertain first recurrence of noncardioembolic ischemic stroke between

October 1992 and April 1995. The Kaplan-Meier method was used to estimate

the cumulative recurrence rate. The Cox regression model was used to ascertain

the significant factors affecting the first recurrence of noncardioembolic ischemic

stroke. The overall cumulative recurrence rate was 10.5% (49/466) from the

fellow-up period of 30 months. After adjustment for age, sex, treatment modes,

and variables pertinent to blood pressure, the site of brain lesion remained a

significant factor. The relative risk of first recurrence for the basal ganglion vs.

the region of middle cerebral artery was 3.06 (95% CI: 1.29- 7.26). The brain

lesion site was demonstrated to be an independent predictor of risk for the first

recurrence of noncardioembolic ischemic stroke among the Taiwanese Chinese

population. Whether this finding was also seen in other populations should be

corroborated in future research. (C) 2000 Elsevier Science Ltd. All rights

reserved



Keywords: age/blood pressure/brain/cerebral/cerebral artery/CEREBRAL

INFARCTION/Chinese/COMMUNITY/DISEASE/ENGLAND/hospitals/ischem

ic/ischemic stroke/middle cerebral artery/MORTALITY/noncardioembolic

stroke/population/PREDICTORS/PREVENTION/PROGNOSIS/PROJECT/racia

l differences/recurrence/relative risk/risk/risk

factors/RISK-FACTORS/sex/stroke/SURVIVAL/treatment



Horisawa, S., Kaneko, M. and Sakurama, T. (2001), Protective effects of SM-20302, an

orally active GPIIb/IIIa antagonist, in an ADP/epinephrine-induced guinea pig

model of transient cerebral ischemia. Thrombosis Research, 101 (3), 119-126.



Abstract: The potential benefits of SM-20302, (2S)-3-(3-(4-

amidinobenzoylamino)propanoylamino)-2-(4-

ethyl)benzensulfonylaminopropionic acid hydrochloride, a nonpeptide GPIIb/IIIa

receptor antagonist, were compared with those of aspirin and ticlopidine in a

transient cerebral ischemia model in guinea pigs. Transient cerebral ischemia

was induced in guinea pigs by an infusion of ADP/epinephrine into the left

internal carotid artery. Each compound was orally administered 1 h (SM-20302

and aspirin) or 3 h (ticlopidine) before the ADP/epinephrine infusion. The

ischemic area in coronal brain slices was assessed 1 min after the cessation of

ADP/epinephrine infusion by a carbon black perfusion method, in a separate

experiment, neurological deficits and lactate contents of ipsilateral hemispheres

were evaluated 60 min after the cessation of ADP/epinephrine infusion by

neurological scores and the standard enzymatic method, respectively. SM- 20302

(0.3 and 1 mg/kg po) significantly reduced the ischemic area, neurological

deficits and lactate contents in comparison with the vehicle control. Aspirin (100

mg/ kg po) had no significant effect on either parameter. Ticlopidine (300 mg/kg

po) reduced the lactate content. Although a combination of aspirin (100 mg/kg

po) and ticlopidine (300 mg/kg po) also reduced the lactate content, no additive

effect was observed. These results suggest that SM-20302 is of potential clinical

benefit in the treatment of thromboembolic diseases. (C) 2001 Elsevier Science

Ltd. All rights reserved



Keywords: ASPIRIN/brain/carotid/carotid artery/carotid artery

thrombosis/cerebral/cerebral

ischemia/combination/control/diseases/ENGLAND/GLYCOPROTEIN

IIB/IIIA/GPIIb/IIIa/GPIIb/IIIa receptor antagonist/INHIBITION/internal carotid

artery/ischemia/ischemic/Japan/OCCLUSION/platelet

aggregation/PLATELETS/PREVENTION/RECEPTOR

ANTAGONIST/SM-20302/STROKE/THROMBOSIS/TICLOPIDINE/transient/

treatment



Ginsberg, J.S., Bates, S.M., Oczkowski, W., Booker, N., Magier, D., MacKinnon, B.,

Weitz, J., Kearon, C., Cruickshank, M., Julian, J.A. and Gent, M. (2002),

Low-dose warfarin in rehabilitating stroke survivors. Thrombosis Research, 107

(6), 287-290.



Abstract: Background: Patients undergoing rehabilitation after thromboembolic stroke

have a relatively high incidence of venous thromboembolism (VTE). Warfarin,

with a target international normalized ratio (INR) of 2.0-3.0 is effective for the

prevention of VTE. However, because stroke is a major risk factor for bleeding

with warfarin, a less intense regimen (target INR < 2.0), might safely prevent

VTE in stroke rehabilitation patients. Methods: This study was a randomized,

double-blind, placebo-controlled trial of 2 mg of warfarin in patients undergoing

rehabilitation following completed stroke. The major efficacy endpoint. was

symptomatic, objectively proven VTE or asymptomatic VTE detected by

monthly duplex ultrasonography (DU) of the proximal leg veins or mandatory

bilateral contrast venography performed at the end of the study. The major safety

endpoint was bleeding. Results: There were 475 patients screened for enrollment,

355 had one or more exclusion criterion, and 17 had previously undetected

proximal DVT on admission. Of the 103 eligible and consenting patients, 56

received warfarin and 47 received placebo. Of the randomized patients, 88 had

successful venography (47 warfarin and 41 placebo). In the warfarin group, three

(8%) patients had DVT and one (2%) had proximal DVT whereas in the placebo

group, seven (20%) had DVT and five (13%) had proximal DVT. The risk ratio

for any DVT in warfarin-treated patients relative to placebo-treated patients was

0.39 (95% confidence interval (CI), 0.13-1.37). For proximal DVT, the risk ratio

was 0.17 (95% CI, 0.01-1.4). No patients suffered major bleeding. Conclusions:

A fixed dose of 2 mg of warfarin per day in patients undergoing stroke

rehabilitation is safe and associated with a relative risk reduction of about 80% in

the incidence of proximal DVT and 60% in overall DVT. (C) 2002 Elsevier

Science Ltd. All rights reserved



Keywords: asymptomatic/bleeding/BLIND RANDOMIZED TRIAL/DEEP VENOUS

THROMBOSIS/DIAGNOSIS/duplex/DVT/ENGLAND/incidence/INR/internati

onal normalized ratio/PREVENTION/randomized/rehabilitation/relative

risk/risk/risk

factor/safety/stroke/SURGERY/thromboembolic/THROMBOEMBOLISM/trial/

ultrasonography/VEIN THROMBOSIS/venous thromboembolism/warfarin



Yasaka, M., Sakata, T., Minematsu, K. and Naritomi, H. (2002), Correction of INR by

prothrombin complex concentrate and vitamin K in patients with warfarin related

hemorrhagic complication. Thrombosis Research, 108 (1), 25-30.



Abstract: We investigated the effect of prothrombin complex concentrate (PCC, median

500 IU) and vitamin K (10-20 mg) or either on blood coagulation and clinical

findings in 17 patients with major hemorrhagic complication during warfarin

treatment. Their international normalized ratio (INR) at admission was median

2.7 (2.0-above 10.0). In 11 patients treated with PCC and vitamin K, INR

decreased to median 1.13 (0.91-1.36) 10 min after the administration with

elevation of plasma levels of coagulant factors II, VII, IX, X and protein C. INR

decreased abruptly after the administration of PCC without vitamin K in two

patients but it increased again 12-24 h after, with decrease of coagulant factors

levels. In one of them, a hematoma of the brain enlarged with INR re-increase

12-24 h after the administration. In four patients treated with vitamin K alone,

INR decreased slowly from 2.69 (1.03-3.35) to 1.28 (1.25-1.44) 12-24 h after the

administration in parallel with gradual increase of the coagulant factors. PCC

administration with or without vitamin K seems to be more effective in rapidly

correcting increased INR levels than vitamin K treatment without PCC. PCC

without vitamin K may result in re-increase of INR and clinical deterioration. (C)

2002 Elsevier Science Ltd. All rights reserved



Keywords: administration/brain/clinical

findings/coagulation/complication/EFFICACY/ENGLAND/hematoma/HEMAT

OMAS/hemorrhagic/hemorrhagic complication/INR/international normalized

ratio/INTRACEREBRAL HEMORRHAGE/INTRACRANIAL

HEMORRHAGE/intracranial

hemorrhage/Japan/MANAGEMENT/NONVALVULAR

ATRIAL-FIBRILLATION/ORAL ANTICOAGULANT

REVERSAL/PREVENTION/prothrombin complex

concentrate/STROKE/THERAPY/treatment/vitamin/warfarin



Haas, S. (2003), Medical indications and considerations for future clinical decision

making. Thrombosis Research, 109 S31-S37.



Abstract: There are many well-known drawbacks associated with the currently used

antithrombotic agents, warfarin, heparin, and low-molecular-weight heparins

(LMWHs). Because heparins can be administered only parenterally, their

application is limited. Though warfarin can be administered orally, its

unpredictable anticoagulant effect means that it must be regularly monitored.

Ximelagatran (Exanta(TM), AstraZeneca) is a novel, oral direct thrombin

inhibitor (oral DTI) that is rapidly converted to its active form, melagatran, upon

administration. The antithrombotic effects of melagatran have been demonstrated.

Following the oral administration of ximelagatran, melagatran has stable and

reproducible pharmacokinetic and pharmacodynamic properties that enable

ximelagatran to be administered orally, twice daily, according to a fixed-dose

regimen, with no need for routine coagulation monitoring. In view of its

favourable profile, a clinical trial programme has been designed to evaluate the

efficacy and tolerability of ximelagatran compared with standard therapies, for

the prophylaxis and treatment of venous thromboembolism (VTE), the

prevention of stroke in patients with atrial fibrillation (AF), and the prevention of

cardiovascular events in patients with previous acute coronary syndromes. These

studies show that oral ximelagatran is well tolerated at doses of up to 60 mg,

twice daily (bid), and that it is as effective as standard therapy for the prevention

of thromboembolic events in patients undergoing hip or knee replacement

surgery, for the treatment of clinically verified acute deep vein thrombosis

(DVT), and in patients with nonvalvular AF who have a moderate to high risk of

stroke. The protocols and results of some of these studies-and a study that

investigates the use of ximelagatran in combination with aspirin for the

management of acute coronary artery disease-are described in this paper. (C)

2003 Elsevier Science Ltd. All rights reserved



Keywords: ACTIVE FORM/acute/acute coronary

syndromes/administration/AF/anticoagulant/antithrombotic/antithrombotic

agents/ANTITHROMBOTIC THERAPY/aspirin/atrial/atrial

fibrillation/ATRIAL- FIBRILLATION/cardiovascular/cardiovascular

events/clinical trial/coagulation/combination/coronary artery

disease/CORONARY-ARTERY/decision making/decision-making/deep vein

thrombosis/DIRECT THROMBIN

INHIBITOR/DVT/ENGLAND/fibrillation/Germany/heparin/heparins/high

risk/management/MELAGATRAN/MOLECULAR-WEIGHT

HEPARIN/monitoring/oral

administration/prevention/prophylaxis/protocols/results/risk/stroke/surgery/thera

py/thrombin/thrombin inhibitor/thromboembolic

events/thromboembolism/thrombosis/treatment/trial/use/VEIN-THROMBOSIS/

VENOUS THROMBOEMBOLISM/VTE

treatment/warfarin/XIMELAGATRAN/ximelagatran



Sato, Y., Nakatsuka, H., Watanabe, T., Hisamichi, S., Shimizu, H., Fujisaku, S.,

Ichinowatari, Y., Ida, Y., Suda, S., Kato, K. and Ikeda, M. (1989), Possible

Contribution of Green Tea Drinking Habits to the Prevention of Stroke. Tohoku

Journal of Experimental Medicine, 157 (4), 337-343



Keywords: JAPAN



Tomatis, L. (1995), How Much of the Human-Disease Burden Is Attributable to

Environmental Chemicals. Toxicology Letters, 77 (1-3), 1-8.



Abstract: According to the evaluations made by IARC, 66 agents or exposures have

been recognised as human carcinogens. About 60% of all cancer cases occur in

people over 65 years of age, which is indeed the most important risk factor for

cancer, including both the duration of exposure to the variety of carcinogenic

agents and allowing expression of genetically determined disorders. Diet as a

source of mutagens as well as other environmental mutagens may affect blood

pressure either directly or by favouring the development of arteriosclerosis:

mutagens have been shown to accelerate arteriosclerotic plaque development.

Some concern has also been expressed on the possible adverse effect that

environmental chemicals may have on reproductive ability, on the basis of the

decline in semen quality reported over the past decades. Better defining the role

of aetiological agents would result in a more precise definition of attributable

risks. Of particular interest to the latter goal are the studies of inter-individual

variability in the susceptibility to carcinogens, which will hopefully contribute to

define the role of low-level exposure to carcinogens



Keywords: blood

pressure/CANCER/CARCINOGENESIS/carcinogens/CHEMICALS/DEGENER

ATIVE

DISEASES/development/EPIDEMIOLOGY/ETIOLOGY/MUTATIONS/P53/P

REVENTION/risk/STROKE



Nifong, T.P., Bongiovanni, M.B. and Gerhard, G.S. (2001), Mathematical modeling and

computer simulation of erythrocytapheresis for SCD. Transfusion, 41 (2),

256-263.



Abstract: BACKGROUND: Erythrocytapheresis is used to prevent acute chest syndrome

and stroke in patients with sickle cell disease (SCD). However, such regimens

are associated with significant risks, such as iron overload and potential exposure

to transfusion- transmitted infectious diseases. Computer modeling of

erythrocytapheresis procedures may help optimize treatments and minimize risks.

STUDY DESIGN AND METHODS: Mathematical models based upon material

balance equations and patient-specific statistical analyses were developed to

estimate HbS levels immediately after erythrocytapheresis and immediately

before the next treatment. The equations were incorporated into a software

application that was used to model the effects of various treatment values on four

patients treated with 90 erythrocytapheresis procedures. RESULTS: Immediate

postprocedure HbS values were accurately estimated with correlations between

measured and calculated values ranging from R-2 = 0.83 to 0.96. Estimates of

HbS just before the next treatment correlated well in three patients (R-2 = 0.71 to

0.83) but poorly in one (R-2 = 0.28 to 0.46). Varying the treatment values by

computer simulation led to a wide variation in the number of RBC units and the

net RBC volume transfused. CONCLUSION: Computer modeling of

erythrocytapheresis can be used to optimize chronic treatment regimens for SCD

patients and potentially to minimize the risks of overtransfusion



Keywords:

acute/ANEMIA/BLOOD/chest/CHILDREN/DESIGN/disease/diseases/erythrocy

tapheresis/HEMOGLOBIN-S/IRON

OVERLOAD/POLYMERIZATION/PREVENTION/sickle cell

disease/SICKLE-CELL DISEASE/simulation/statistical/stroke/TERM

TRANSFUSION REGIMEN/THERAPY/TRANSFUSION/treatment



Vichinsky, E.P., Luban, N.L.C., Wright, E., Olivieri, N., Driscoll, C., Pegelow, C.H. and

Adams, R.J. (2001), Prospective RBC phenotype matching in a stroke-prevention

trial in sickle cell anemia: a multicenter transfusion trial. Transfusion, 41 (9),

1086-1092.



Abstract: BACKGROUND: Most sickle cell anemia patients undergo transfusion

therapy to prevent complications. The Stroke Prevention Trial in Sickle Cell

Anemia showed that transfusion therapy is effective in the primary prevention of

stroke. Despite its efficacy, transfusion therapy is limited by alloimmunization.

The purpose of this study was to determine if a multicenter trial could implement

a transfusion program utilizing phenotypically matched blood to reduce

alloimmunization. STUDY DESIGN AND METHODS: One hundred thirty

children underwent RBC phenotyping and antibody screening with review of

blood bank records. The protocol required use of WBC- reduced RBCs, which

were matched for E, C, and Kell. Monthly alloantibody testing and review of

transfusion forms were performed to determine compliance and the occurrence

of any adverse events. RESULTS: Patient RBCs expressed a low frequency of

Kell (2%), E (20%), and C (25%) antigens. Sixty-one patients received 1830

units. Ninety-seven percent of all units were WBC reduced. Only 29 units were

inadvertently not matched for E, C, and Kell. Five patients (8%) developed a

clinically significant alloantibody. Four developed a single antibody to E or Kell.

Three patients (5%) developed a warm autoantibody. There were 11 transfusion

reactions and 8 transfusion-associated events. Transfusion reactions included 6

febrile reactions (0.33%/unit), 3 allergic (0.16%/unit), and 2 hemolytic

(0.11%/unit). Associated events included 4 episodes of hypertension

(0.22%/unit), 3 crises (0.16%/unit), and 1 transient ischemic attack (0.05%/unit).

CONCLUSION: This is the first multicenter study to show that extended RBC

phenotyping can be implemented nationwide. Compared to studies, the

alloimmunization rate dropped from 3 percent to 0.5 percent per unit, and

hemolytic transfusion reactions dropped by 90 percent. It is recommended that

all transfused sickle cell anemia patients be antigen matched for E, C, and Kell.

Patients should be closely monitored during transfusions to avoid preventable

risks



Keywords: adverse

events/ALLOIMMUNIZATION/anemia/antibody/ASSOCIATION/autoantibody

/BLOOD/children/complications/DESIGN/DISEASE/EXCHANGE-TRANSFU

SION/HEMOGLOBIN/hypertension/ischemic/low

frequency/MANAGEMENT/MORBIDITY/prevention/primary/primary

prevention/RECIPIENTS/review/screening/sickle cell anemia/stroke/stroke

prevention/THERAPY/transfusion/transient/transient ischemic attack/trial/use



Hartwig, D., Schlager, F., Bucsky, P., Kirchner, H. and Schlenke, P. (2002), Successful

long-term erythrocytapheresis therapy in a patient with symptomatic sickle-cell

disease using an arterio-venous fistula. Transfusion Medicine, 12 (1), 75-77.



Abstract: The use of long-term automated erythrocytapheresis via an arterio-venous

fistula for the prevention of recurrent ischaemic stroke in a child with sickle-cell

disease (SCD) has not been described previously. We report the successful use of

this technique in a 13-year-old boy. A procedure was performed every 36 +/- 6

days, transfusing six units of donor packed red blood cells (RBCs) and

discarding 1318 +/- 174 mL of exchanged erythrocytes (Hct 60%). After

transfusion of 85 units over 17 months, there is no evidence for iron-overload,

red cell alloimmunization, transfusion-transmitted infections, or other

complications. Until now, no cerebrovascular ischaemia has been observed



Keywords: alloimmunization/arterio-venous fistula/arteriovenous fistula/blood

cells/cerebrovascular/complications/disease/ENGLAND/erythrocytapheresis/Ger

many/iron overload/ischaemia/ischaemic/ischaemic stroke/prevention/REDUCE

IRON OVERLOAD/sickle cell disease/sickle-cell

disease/STROKE/therapy/TRANSFUSION/use



Suckfull, M.M., Pieske, O., Mudsam, M., Babic, R. and Hammer, C. (1994), The

Contribution of Endothelial-Cells to Hyperacute Rejection in Xenogeneic

Perfused Working Hearts. Transplantation, 57 (2), 262-267.



Abstract: The mechanisms leading to the hyperacute rejection of a vascularized

xenograft are still incompletely understood. The first stage of the rejection

process is when blood of the recipient comes into contact with the endothelium

of the xenograft. A working heart model was used to examine

endothelium-related processes and their impact on organ function. Pig hearts

were perfused with porcine (autologous) or human (xenogeneic) blood. Cardiac

function was evaluated by calculating the stroke work index, arteriovenous

oxygen, coronary flow, and resistance. PgF1a as a marker of endothelial

activation, its antagonist TXB(2), and myoglobin reflecting myocardial damage

were measured in the hemoperfusate. H&E and PAS staining and

immunohistological demonstration of factor VIII-related antigen was performed.

Xenogeneic perfused porcine hearts showed significantly less stroke work, a

higher arteriovenous oxygen difference, and an increased coronary resistance.

Factor VIII-related antigen could not be demonstrated immunohistologically on

the endothelium after xenogeneic perfusion. PgF1a levels were significantly

higher in the xenogeneic hemoperfusate, indicating endothelial cell activation.

The concentration of myoglobin in the hemoperfusate remained within normal

values and was similar during autologous and xenogeneic perfusion. Therefore

endothelium-related processes are likely to affect the coronary circulation-thus

being one mechanism leading to diminished cardiac performance during

hyperacute rejection



Keywords: endothelium/FACTOR-VIII/heart/INJURY/NATURAL

ANTIBODIES/PLATELETS/PREVENTION/PROSTACYCLIN/RABBIT/REL

EASE/stroke/TRANSPLANTATION/XENOGRAFT REJECTION



Schmoeckel, M., Nollert, G., Shahmohammadi, M., Young, V.K., Chavez, G.,

KasperKonig, W., White, D.J.G., MullerHocker, J., Arendt, R.M.,

WilbertLampen, U., Hammer, C. and Reichart, B. (1996), Prevention of

hyperacute rejection by human decay accelerating: Factor in xenogeneic perfused

working hearts. Transplantation, 62 (6), 729-734.



Abstract: As a potential source of organs for xenotransplantation, pigs that are transgenic

for human decay accelerating factor (DAF) have been bred in order to overcome

hyperacute rejection. We investigated the protective effect of human DAF in a

porcine working heart model perfused by human blood. Hearts of normal

landrace pigs served as controls, The following parameters were measured:

stroke work index, coronary flow and arteriovenous oxygen consumption, 6-keto

prostaglandin F-1 alpha and prostaglandin E(2) as markers of endothelial cell

activation; creatine phosphokinase and lactate dehydrogenase for evaluation of

the extent of myocardial damage; TNF alpha and IL-6 as markers of

mononuclear cell activation, Histological and ultrastructural investigations from

myocardial tissue sections were done at the end of perfusion, Human (h) DAF

appeared to inhibit complement-mediated endothelial cell activation of

transgenic pig hearts successfully. This was in contrast to landrace pig hearts,

which had a sixfold increase of prostaglandin levels during perfusion with human

blood, The cardiac weight increase during perfusion time due to interstitial

edema tended to be less in the hDAF group. Myocardial damage was minimal in

transgenic hearts, whereas normal pig hearts produced a threefold increase of

creatine phosphokinase and lactate dehydrogenase levels. In these hearts,

electron microscopy revealed single cell necrosis of myocytes and vacuolization

of mitochondria with cristae rupture. According to the results obtained in the

working heart model, the breeding of pigs that are transgenic for hDAF

represents a promising step to making heart xenotransplantation a clinical reality

in the future

Keywords: CARDIOPULMONARY

BYPASS/ENDOTHELIAL-CELLS/EXPRESSION/INHIBITION/stroke/TRAN

SPLANTATION/VIVO



Howard, R.J., Patton, P.R., Reed, A.I., Hemming, A.W., Van Der Werf, W.J., Pfaff,

W.W., Srinivas, T.R. and Scornik, J.C. (2002), The changing causes of graft loss

and death after kidney transplantation. Transplantation, 73 (12), 1923-1928.



Abstract: Background. The results of kidney transplantation have improved markedly

over the last three decades. Despite this, patients still lose grafts and die. We

sought to determine whether the causes of graft loss and death have changed over

the last 30 years. Methods. We reviewed patients who underwent transplantation

or who died between January 1, 1970 and December 31, 1999. We compared the

causes of graft loss or death for three decades: 1970 to 1979, 1980 to 1989, and

1990 to 1999. Results. From January 1, 1970 to December 31, 1999, we

performed 2501 kidney transplantations in 2225 patients. For the three periods,

210, 588, and 383 patients lost their grafts, respectively. Graft survival increased

substantially. Graft loss occurred later after transplantation, with 36.0% losing

grafts in the first year during 1970 to 1970, 22.8% during 1980 to 1989, and

11.4% during 1990 to 1999. Death with a functioning graft increased from 23.8%

for 1970 to 1979 to 37.5% for 1990 to 1999. Concomitantly, rejection as a cause

of graft loss fell from 65.7% for 1970 to 1979 to 44.6% for 1990 to 1999.

Approximately two thirds of the patients who died after transplantation died with

a functioning graft and one third died after returning to dialysis. Cardiac disease

as a cause of death increased from 9.6% for 1970 to 1979 to 30.3% for 1990 to

1999. Deaths from cancer and stroke also increased significantly over the three

decades from 1.2% and 2.4%, respectively, for 1970 to 1979, to 13.2% and 8.0%,

respectively, for 1990 to 1999. Conclusions. The causes of graft loss and death

have changed over the last three decades. By better addressing the main causes

of death, cardiac disease, and stroke with better prevention, graft loss due to

death with a functioning graft will be reduced



Keywords: cancer/cardiac/cause of

death/causes/death/disease/POPULATION/prevention/PROGRESS/RECIPIENT

S/REJECTION/RENAL-TRANSPLANTATION/SINGLE-CENTER/stroke/SU

RVIVAL/TRANSPLANTATION/UNITED-STATES



Kelly, J.S. and Sharkey, J. (2001), Immunosuppressants-ligands as neuroprotectants.

Transplantation Proceedings, 33 (3), 2217-2219



Keywords: ALLOGRAFT- REJECTION/CALCINEURIN

INHIBITORS/COMPARING TACROLIMUS

FK506/CYCLOSPORINE-A/ISCHEMIC

STROKE/MANAGEMENT/NEW-YORK/PREVENTION/TRANSPLANTATI

ON/TRIAL

Ridker, P.M. (1995), An epidemiologic reassessment of lipoprotein(a) and

atherothrombotic risk. Trends in Cardiovascular Medicine, 5 (6), 225-229.



Abstract: Lipoprotein(a) [Lp(a)] is a unique lipoprotein particle, which appears to play a

critical role in both atherogenesis and fibrinolysis. On the basis of extensive

laboratory research, as well as several retrospective case-control studies that

demonstrate a positive association between Lp(cr) and vascular risk, Lp(a) has

often been considered an important atherothrombotic risk factor. However, a

controversial series of nine prospective studies evaluating plasma Lp (a) and risk

of future myocardial infarction, coronary heart disease, and stroke has provided

inconsistent evidence of association. Although some of these studies have been

criticized for potential methodologic limitations, the results of four well-

designed, large-scale prospective analyses deriving from the Physicians' Health

Study, the Lipid Research Clinics Coronary Primary Prevention Trial, the British

United Provident Association Study, and the Gottingen Risk Incidence and

Prevalence Study still provide apparently conflicting data. What emerges from an

epidemiologic overview of these studies is that routine clinical assessment of

Lp(a) is likely to have low positive predictive value in terms of screnning for

atherothrombotic disease, and that any true increase in risk associated with

plasma Lp(a) concentration probably is of small absolute magnitude. At the same

time, the available epidemiologic data must not be construed to exclude a critical

role for Lp(a) in either atherogenesis or fibrinolysis, particularly given the

strength of basic science data regarding this unique lipoprotein. Future studies

evaluating isoforms and genetic determinants of Lp(a) will therefore be required

to address the Lp(a) hypothesis fully



Keywords: ARTERY DISEASE/ASSOCIATION/ATHEROSCLEROSIS/case-control

studies/coronary heart disease/CORONARY HEART-DISEASE/EXPRESSING

HUMAN APOLIPOPROTEIN(A)/genetic/heart/LIPIDS/LP(A)/myocardial

infarction/MYOCARDIAL-INFARCTION/PLASMA

LIPOPROTEIN(A)/prospective studies/risk/SERUM

LIPOPROTEIN(A)/stroke/vascular/WOMEN



Picano, E. and Abbracchio, M.P. (1998), European Stroke Prevention Study-2 results:

serendipitous demonstration of neuroprotection induced by endogenous

adenosine accumulation? Trends in Pharmacological Sciences, 19 (1), 14-16.



Abstract: In patients with prior stroke or transient ischaemic attack, anti-platelet

treatment with dipyridamole substantially reduced stroke recurrence, with a

beneficial effect comparable to and additive with that induced by aspirin (the

European Stroke Prevention Study-2). Eugenio Picano end Maria Abbracchio

present here a platelet-independent hypothesis, according to which

cardiovascular and neuroprotective actions achieved by dipyridamole through

chronic elevation of endogenous adenosine levels may have contributed to the

therapeutic success of this study

Keywords: antiplatelet

treatment/aspirin/BRAIN/CELLS/DIPYRIDAMOLE/ENGLAND/neuroprotectio

n/PERMEABILITY/recurrence/stroke/transient/TRANSPORT/treatment/TREN

DS



Denicourt, C. and Dowdy, S.F. (2003), Protein transduction technology offers novel

therapeutic approach for brain ischemia. Trends in Pharmacological Sciences, 24

(5), 216-218.



Abstract: Transient or permanent reduction in cerebral blood flow following ischemia

can lead to severe and irreversible tissue damage to the brain. Emerging

biochemical evidence suggests a role for apoptosis in neuronal death following

cerebral ischemia. Despite the abundance of studies on the subject, therapeutic

interventions for ischemia-related cell injury have so far proved disappointing in

clinical trials. Recently, four new, exciting studies reported the use of protein

transduction technology to deliver anti-apoptotic molecules to protect neuronal

cells following ischemic stroke in vivo. These studies offer new avenues for the

treatment and prevention of cell death following brain injuries



Keywords: apoptosis/BCL-XL/blood flow/brain/brain ischemia/cerebral/cerebral blood

flow/cerebral ischemia/clinical

trials/death/DELIVERY/ENGLAND/ischemia/ischemic/ischemic

stroke/LONDON/NEURONAL

APOPTOSIS/prevention/stroke/treatment/TRENDS/trials/USA/use



Andersen, H.E., Jurgensen, K.S.L. and Boysen, G. (2001), Stroke rehabilitation: effect

of psychosocial intervention following primary rehabilitation in hospital.

Ugeskrift for Laeger, 163 (9), 1250-1254.



Abstract: Psychosocial support has been suggested as a way of easing stroke survivors'

and their carers' adjustment to a life with disability. The literature on

psychosocial support services following primary rehabilitation in hospital was

reviewed. Eleven controlled studies evaluating the effect of psychosocial support

interventions after discharge from hospital were identified. The studies differed

widely with respect to design, intervention and evaluation methods. The results

suggest that psychosocial support after discharge can improve psychological well

being and quality of life for stroke survivors and their families and improve the

social activity of patients. The effect was achieved by using different types of

intervention such as providing information, counselling and support from stroke

clubs. Psychosocial support for carers was effective as well. Future research

should elucidate this area, including evaluation of psychosocial support as a

tertiary prevention strategy



Keywords:

CARERS/CONSEQUENCES/COPENHAGEN/Denmark/design/disability/evalu

ation/hospital/INFORMATION/LEISURE/NEUROPSYCHOLOGICAL

REHABILITATION/prevention/primary/quality of life/RANDOMIZED

CONTROLLED TRIAL/rehabilitation/research/stroke/SUPPORT



Mullins, C.D., Blak, B.T. and Akhras, K.S. (2002), Comparing cost-effectiveness

analyses of anti-hypertensive drug therapy for decision making: Mission

impossible? Value in Health, 5 (4), 359-371.



Abstract: The purpose of this literature review was to compare the methodology used in

the most recently published cost- effectiveness studies of antihypertensive

treatments, and to identify methodological strengths and weaknesses that indicate

the Study's potential as a useful, decision-making tool. Based on the results of a

search of several databases, spanning the years 1995 to 2000, 10

cost-effectiveness studies were identified. Although the majority of the studies

reported their cost-effectiveness ratio in "costs per year of life gained," the

Studies also considered a varying range of components including additional end

points. The methodology used to measure effectiveness, the cost variables

included, and the characteristics of the patient population varied significantly

across studies. Due to this lack of conformity, it would be difficult, if not

impossible, to compare the results and draw conclusions about the relative

cost-effectiveness of different types of antihypertensive drug therapies. This lack

of uniform comparison across studies is likely to draw criticism from both the

clinical and health-care decision-making communities. Future studies within this

field should be thorough and useful for decision making. It is suggested that

short-term outcomes should include systolic and diastolic blood pressure

measurements and long-term outcomes should include end points such as

myocardial infarction, stroke, congestive heart failure and renal events. Other

positive outcomes such as a more favorable side-effect profile, should be used to

enhance the primary outcomes. Additionally, when subpopulations are

considered in submodels, studies should address the issue of generalizability.

Cost calculations should be transparent and related to the perspective of the study.

Modeling the cost- effectiveness of a drug may be an acceptable method

provided that data sources and assumptions are valid and transparent



Keywords: blood pressure/congestive heart failure/cost/cost

effectiveness/cost-effectiveness/decision making/decision-making/diastolic

blood pressure/DISEASE/drug/drug therapy/ENALAPRIL/end

points/guidelines/HEALTH/health care/heart/heart

failure/hypertension/infarction/literature

review/methodology/myocardial/myocardial

infarction/population/PREVENTION/primary/renal/review/stroke/therapy



Chambers, M.G., Koch, P. and Hutton, J. (2002), Development of a decision-analytic

model of stroke care in the United States and Europe. Value in Health, 5 (2),

82-97.



Abstract: Objective: Stroke places a huge burden on society in terms of premature death,

disability, and costs of care. Increasingly, the cost-effectiveness of new

interventions needs to be demonstrated before their widespread implementation.

Clinical trials are unable to measure the long-term impact of such new

interventions in stroke care, and a modeling approach is necessary. The Stroke

Outcome Model has been developed in four Countries: France, Germany, the

United Kingdom, and the United States as a flexible toot for this purpose.

Method: The decision-analytic model represents the management of acute stroke

and long-term care and prevention of recurrence for stroke survivors. The latter

consists of semi-Markov state- transition processes, with health states defined by

therapy, disability, and occurrence of Further stroke. Source S Of Clinical data

include trials, meta-analyses, and prospective cohort studies such as the

Oxfordshire Community Stroke Project and the Northern Manhattan Stroke

Study. Resource use data were obtained from published sources and expert

clinician panels. Outcome measures used were strokes averted, life years, and

quality-adjusted life-years gained. Results: The model has been used to

undertake economic analyses of antiplatelet therapy for the prevention of

recurrent strokes, and of stroke unit care and thrombolytic therapy in acute stroke.

From a health- and social-care perspective, new interventions were found to be

cost saving or to provide health benefits at modest additional cost. Result, were

sensitive to the cost perspective, mile horizon, baseline risk of stroke recurrence,

and choice of effectiveness measure. Conclusion: The development of this model

highlights the need for improved information on prognosis and resources used by

stroke survivors and the importance of differentiating between economically

distinct end points Such as death, disabled survival and nondisabled survival,

which may tic combined as outcomes in clinical trials



Keywords: ACETYLSALICYLIC-ACID/acute/ACUTE ISCHEMIC STROKE/acute

stroke/antiplatelet/antiplatelet therapy/CEREBRAL INFARCTION/cerebral

ischemia/cerebrovascular disease/clinical trials/cohort studies/cost/cost

effectiveness/COST-EFFECTIVENESS/cost-effectiveness analysis/costs/costs

and cost analysis/death/decision analysis/decision analytic

model/development/disability/ECONOMIC-EVALUATION/end

points/England/Europe/FIRST-EVER

STROKE/Germany/HEALTH/HIGH-RISK

PATIENTS/management/modeling/platelet aggregation

inhibitors/PREVENTION/prevention of recurrence/prognosis/prospective cohort

studies/quality-adjusted

life-years/QUALITY-OF-LIFE/recurrence/risk/stroke/stroke recurrence/stroke

unit/stroke units/survival/therapy/thrombolytic/thrombolytic

therapy/TRIAL/trials/United Kingdom/United States/use



Becker, E.I., Jung, A., Voller, H., Wegscheider, K., Vogel, H.P. and Landgraf, H. (2001),

Cardiogenic embolism as the main cause of ischemic stroke in a city hospital: An

interdisciplinary study. Vasa-Journal of Vascular Diseases, 30 (1), 43-52.



Abstract: Background: It is essential to understand the pathogenesis of ischemic stroke

to ensure rational acute therapy and secondary prevention. We wanted to know

the distribution of pathogenesis in patients of a city hospital and the differences

in risk factors, neurologic deficits, disability and delay in clinical admittance.

Patients and methods: During a period of one year 222 patients (mean age 76,6

years; 59% women) with complete acute ischemic stroke were admitted and

underwent complete clinical and diagnostic procedures. CCT/MRI; Doppler- and

color-coded duplex and transcranial sonography; echocardiography; use of the

NINCDS stroke scale and the Oxford disability scaler study of risk factors, and

exploration of delay in admittance. Results: The following percentages of

etiologies were evident: 31% cardiogenic embolism (60% with atrial fibrillation),

13% microangiopathy, 9% macroangiopathy, 11% cerebellar or brain stem

infarction, 18% more than one cause and 18% no cause found. The patients with

cardiogenic embolism showed significantly the highest scores on the stroke scale

and the disability scale and had the shortest delay in admittance (57% were

admitted within 3 hours). Conclusions: In a city hospital, cardiogenic embolism

is the main cause of ischemic stroke. These patients suffer significantly the most

severe neurologic deficits, dependence, and requirement of daily nursing care.

These patients have the shortest delay in clinical admittance and the best chance

of benefiting from acute therapy and early secondary prevention



Keywords: acute/acute ischemic

stroke/age/AMERICAN-HEART-ASSOCIATION/atrial

fibrillation/ATRIAL-FIBRILLATION/ATTACKS/brain/cardioembolic

stroke/CAROTID- ARTERY/CEREBRAL

INFARCTION/CEREBROVASCULAR- DISEASE/DATA-

BANK/DESIGN/diagnostic/disability/Doppler/duplex/echocardiography/embolis

m/essential/fibrillation/Germany/hospital/infarction/ischemic/ischemic

stroke/nursing/pathogenesis of stroke/prevention/risk/risk

factors/secondary/secondary prevention/SPONTANEOUS

ECHO-CONTRAST/stroke/therapy/transcranial/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/use/women



Mohler, E.R., Delanty, N., Rader, D.J. and Raps, E.C. (1999), Statins and

cerebrovascular disease: plaque attack to prevent brain attack. Vascular Medicine,

4 (4), 269-272.



Abstract: Stroke is the third leading cause of death in the USA and in the developed

world. The beneficial role of cholesterol reduction in decreasing stroke has been

uncertain. However, recent data indicate that statin treatment in patients with a

history of myocardial infarction not only reduces the risk of a second myocardial

infarction, coronary heart disease, revascularization procedures and death, but

also significantly reduces the risk of stroke. However, the mechanism(s) by

which statins reduce stroke remain uncertain. Thus, the therapeutic

armamentarium for the reduction of stroke in secondary prevention now includes

cholesterol reduction with statins



Keywords: brain/CAROTID ATHEROSCLEROSIS/CEREBRAL

INFARCTION/cerebrovascular/cerebrovascular

disease/cholesterol/CHOLESTEROL LEVELS/coronary heart

disease/CORONARY

HEART-DISEASE/ENGLAND/heart/history/infarction/LIPIDS/myocardial/myo

cardial infarction/plaque/PRAVASTATIN/prevention/REDUCTASE

INHIBITOR/risk/RISK-FACTORS/secondary prevention/SERUM-

CHOLESTEROL/statins/stroke/STROKE/treatment



Smith, N.M., Pathansali, R. and Bath, P.M.W. (1999), Platelets and stroke. Vascular

Medicine, 4 (3), 165-172.



Abstract: Platelets are anucleate cells with little or no capacity for de novo protein

synthesis. Their potential haemostatic reactivity is established at or before

thrombopoiesis by their precursor cell, the bone marrow megakaryocyte. In some

pathologic conditions, the megakaryocyte-platelet-haemostatic axis (MPHA)

becomes perturbed, resulting in the formation of hyperfunctional platelets which

may contribute to the development of vascular disease or an acute thrombotic

event such as ischaemic stroke or myocardial infarction. Laboratory

measurements of platelet function have established that platelet reactivity is

accentuated in acute ischaemic stroke, particularly following cortical rather than

lacunar infarction. Whether accentuated platelet function is a cause or a

consequence of stroke is not yet clear, but it is likely that patients with certain

risk factor profiles have some degree of platelet activation preceding the stroke.

Further work into the MPHA is required to establish whether enhanced

post-stroke platelet reactivity can be referred to the megakaryocyte. The

antiplatelet agents tested to date are effective in secondary but not primary

prevention of stroke. This probably reflects the diverse pathophysiology of stroke:

accentuated platelet function is only likely to be a significant factor in cortical

stroke



Keywords: ACTIVATION/acute/ACUTE ISCHEMIC STROKE/antiplatelet

agents/CEREBRAL-ISCHEMIA/development/England/formation/HYPERTENS

ION/infarction/ischaemic stroke/lacunar infarction/MEGAKARYOCYTE

PLOIDY/megakaryocytes/myocardial/myocardial

infarction/MYOCARDIAL-INFARCTION/P- SELECTIN/platelet

activation/platelets/prevention/primary prevention/RANDOMIZED

TRIAL/risk/risk factor/stroke/vascular/vascular

disease/VASCULAR-DISEASE/VOLUME



Nenci, G.G. and Minciotti, A. (2000), Low molecular weight heparins for arterial

thrombosis. Vascular Medicine, 5 (4), 251-258.



Abstract: The use of low molecular weight heparin (LMWH) for the prevention and

treatment of venous thromboembolism has been validated by numerous clinical

trials and meta-analyses over the past 25 years. More recently, the possibility of

extending treatment with LMWH to the arterial disease where thrombosis is a

prominent feature has led to the planning of many clinical trials, several of which

have been already published. LMWH has been tested in settings such as acute

coronary syndromes, including myocardial infarction, surgery or percutaneous

revascularization for coronary and peripheral arteries, and stroke. In most

indications, LMWH has proved to be superior to or at least as effective as

unfractionated heparin and it is also easier to administer



Keywords: acute/acute coronary syndromes/ACUTE

MYOCARDIAL-INFARCTION/ANGIOGRAPHIC

RESTENOSIS/arterial/arterial thrombosis/arteries/cardiovascular disease/clinical

trials/CORONARY ANGIOPLASTY/disease/DOUBLE-

BLIND/ENGLAND/ENOXAPARIN/heparin/heparins/infarction/LONDON/low

molecular weight heparin/MANAGEMENT/myocardial/myocardial

infarction/PREVENTION/RANDOMIZED

TRIAL/revascularization/stroke/surgery/thromboembolism/THROMBOLYSIS/t

hrombosis/treatment/trials/UNFRACTIONATED HEPARIN/use/venous

thromboembolism/weight



Leys, D. (2001), Atherothrombosis - the neurologist's point of view. Vascular Medicine,

6 (3), 17-19.



Abstract: Patients with peripheral arterial disease (PAD) have an increased risk of

cerebral ischaemia, but many transient ischaemic attacks are not recognized by

patients, or by physicians who are not neurologists. Similarly, PAD is common

in stroke patients, but often remains unrecognized by neurologists. Major

long-term risks in patients with cerebral ischaemia due to atherosclerosis are

myocardial infarction and recurrence of stroke. Neurologists should consider

concomitant PAD when choosing a treatment strategy. Patients with PAD need

to be educated about their risk for cerebral ischaemic events, and physicians

caring for PAD patients need to identify those individuals who may require

carotid surgery. The appropriate strategy for prevention of stroke in PAD

patients consists of optimal management of risk factors for stroke (smoking,

arterial hypertension, hypercholesterolaemia), antiplatelet therapy with

clopidogrel as first-choice treatment, and carotid surgery in patients with

high-grade stenosis of the internal carotid artery who are at low risk for surgery



Keywords: antiplatelet/ANTIPLATELET THERAPY/arterial/arterial disease/arterial

hypertension/ASPIRIN/atherosclerosis/atherothrombosis/carotid/carotid

artery/carotid surgery/cerebral/cerebral

ischaemia/CLOPIDOGREL/COMMUNITY STROKE PROJECT/coronary heart

disease/DISEASE/ENGLAND/hypercholesterolaemia/hypertension/infarction/in

ternal carotid artery/ischaemia/ischaemic/ISCHEMIC

STROKE/LONDON/management/myocardial/myocardial infarction/peripheral

arterial disease/prevention/recurrence/risk/risk factors/risk factors for

stroke/risks/smoking/stenosis/stroke/stroke

patients/surgery/therapy/transient/transient ischaemic

attacks/treatment/VASCULAR EVENTS



Agnelli, G. (2001), Rationale for the use of platelet aggregation inhibitors in PAD

patients. Vascular Medicine, 6 (3), 13-15.

Abstract: Peripheral arterial disease (PAD) is a major risk marker for systemic ischaemic

events. The understanding of PAD has moved from PAD as an organ-specific

disease to PAD as the lower-limb localization of a multifocal disease, i.e.

atherothrombosis. Blood platelet activation and aggregation is a common

denominator in atherothrombotic events, and use of antiplatelet agents in patients

with PAD can inhibit thrombus formation and reduce the occurrence of

myocardial infarction (MI), ischaemic stroke (IS) and vascular death. Many

studies have investigated various antiplatelet regimens for preventing acute

cardiovascular events in patients with a prior ischaemic event, although many of

these studies had a number of limitations. The Antiplatelet Trialists'

Collaboration performed a meta-analysis of 23 stroke trials and found an average

odds risk reduction of 25% for a combined endpoint of stroke, MI or vascular

death. The concept of atherothrombosis as a multifocal disease was challenged

by the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events

(CAPRIE) trial. This study showed an 8.7 lo decrease in the relative risk

reduction for further atherothrombotic events with clopidogrel over aspirin

(p=0.043) for the overall population, in terms of the combined endpoint of IS, MI

or vascular death



Keywords: activation/acute/aggregation/antiplatelet/antiplatelet agents/arterial/arterial

disease/ASPIRIN/atherothrombosis/cardiovascular/cardiovascular

events/CLOPIDOGREL/death/DIPYRIDAMOLE/disease/DRUGS/ENGLAND/

formation/INFARCTION/ischaemic/ischaemic

stroke/LONDON/meta-analysis/multifocal/myocardial/myocardial

infarction/peripheral arterial disease/platelet/platelet activation/platelet

aggregation/platelet aggregation inhibitors/population/RECEPTOR/relative

risk/risk/SECONDARY

PREVENTION/stroke/thrombus/TRIAL/trials/use/vascular



Samson, R.H., Bandyk, D.F., Showalter, D.P. and Yunis, J.P. (2000), Carotid

endarterectomy based on duplex ultrasonography: A safe approach associated

with long-term stroke prevention. Vascular Surgery, 34 (2), 125-136.



Abstract: To evaluate the short-term and long-term safety of carotid endarterectomy

(CEA) based on duplex ultrasound without confirmatory diagnostic

arteriography. A 4-year retrospective review off CEA based on duplex

ultrasound alone (n = 653) or with confirmatory arteriography (n = 118) was

performed in 244 women and 458 men whose ages ranged from 39 to 92 years

(mean, 70 years). Practice patterns, perioperative morbidity, and stroke rate

(life-table analysis) of a community-based and university-based vascular surgical

practice were analyzed and compared. Surgical intervention based on duplex

ultrasound was judged possible in 85% of the patients (community, 93%;

university, 55%). Indications for arteriography included: testing completed prior

to surgical consultation (44%), nonfocal extracranial carotid stenosis (23%),

nonhemispheric symptoms (13%), and prior stroke (9%). This approach was safe

(with a combined operative mortality and neurologic morbidity of 1.8%),

associated with long-term stroke prevention (a 95% stroke-free survival at 4

years), and yielded results similar to CEA with arteriography (operative

morbidity, 2.6%; 91% stroke-free survival). The incidence and nature of late

neurologic deficits were similar after CEA with and without arteriography.

Twenty-three (4%) of the patients who underwent CEA based on duplex

ultrasound developed late neurologic symptoms including 9 contralateral and 4

ipsilateral strokes; and 4 ipsilateral and 4 contralateral transient ischemic attacks

(TIAs). Cardiac embolism from atrial fibrillation accounted for 6 strokes, lacunar

infarct associated with hypertension (3 strokes), intracranial atherosclerosis (3

strokes), and contralateral internal carotid artery (ICA) occlusion (1 stroke).

Forty patients (6.8%) died predominantly from cardiac events. After CEA with

arteriography 6 (5%) of the patients died. Six late strokes (4 contralateral, and 2

ipsilateral hemisphere) occurred as a result of progressive, untreated ICA

stenosis (n = 3), and lacunar infarct (n = 3). Overall, 11% of the patients

underwent contralateral CEA for progressive ICA stenosis. CEA, based on

duplex scanning, is safe and applicable for the majority of patients undergoing

surgical evaluation. Short-term and long-term outcomes were similar to

outcomes in patients having CEA based on diagnostic arteriography



Keywords: 70-PERCENT/ANGIOGRAPHY/AORTIC-ARCH/ARTERY

STENOSIS/atherosclerosis/atrial fibrillation/cardiac/carotid/carotid

artery/carotid endarterectomy/carotid

stenosis/community/CRITERIA/duplex/duplex

scanning/embolism/endarterectomy/evaluation/fibrillation/HEAD/hypertension/i

ncidence/internal carotid artery/ischemic/life

table/men/morbidity/mortality/PREOPERATIVE

ASSESSMENT/prevention/RELIABILITY/review/safety/SCANNING

SUFFICIENT/SIPHON STENOSIS/stenosis/stroke/stroke

prevention/transient/transient ischemic

attacks/ultrasonography/ULTRASOUND/vascular/women



Gorbacheva, F.Y., Gerasimova, O.B., Latveyeva, L.A., Natyazhkina, G.M., Parfenov,

V.A. and Chuchin, M.Y. (1994), Hemodynamic and Rheological Aspects of

Pathogenesis and Prevention of Cerebrovascular Diseases. Vestnik Rossiiskoi

Akademii Meditsinskikh Nauk, (8), 45-49.



Abstract: Ultrasonography was used to study carotid and central hemodynamics in

patients with cerebrovascular diseases and to analyze the factors responsible for

reduction of cerebral blood supply. Comparative studies of the regulatory system

for blood aggregation in patients elucidated the contribution of the system to the

pathogenesis of cerebral hemorrhage and ischemia, defined the modes of

preventing hemorrhagic and ischemic events in cerebrovascular disease. The

authors also discussed pathogenetic and prophylactic aspects of the diseases in

childhood



Keywords: aggregation/carotid/cerebrovascular disease/cerebrovascular

diseases/diseases/DOPPLER/FLOW/hemorrhage/ischemia/STROKE

Grol, M.E.C., Halabi, Y.T., Gerstenbluth, I., Alberts, J.F. and Oniel, J. (1997), Lifestyle

in Curacao - Smoking, alcohol consumption, eating habits and exercise. West

Indian Medical Journal, 46 (1), 8-14.



Abstract: The Curacao Health Study was carried out among a randomized sample (n =

2248, response rate = 85%) of the adult non- institutionalized population in order

to assess aspects of lifestyle that may pose health risks. Factors examined were

tobacco and alcohol use, eating habits and exercise behaviour. Outcome

variables were cross-tabulated by gender, age and socioeconomic status. 17.1%

of the participants were smokers and 20.5% were regular drinkers, including

6.3% of the men who consumed alcohol excessively (4 or more glasses of

alcohol a day). 75% of the participants did not exercise regularly, 37% did not

eat vegetables daily, and half did not eat fruit daily. Other poor eating habits

were the addition of extra sugar and salt to prepared food by 33% and 20% of the

participants, respectively. On the whole, men had less healthy lifestyles than

women, with the exception of exercise behaviour. People of high socioeconomic

status (SES) drank less alcohol, and exercised more open than those of low SES.

Considering the high prevalence of diabetes mellitus and hypertension in the

Caribbean, research on lifestyle factors in other Caribbean countries is required

to facilitate the development of regional prevention and intervention programmes



Keywords: age/alcohol/CARE/development/diabetes/diabetes

mellitus/DIET/DISEASE/exercise/fruit/HEALTH/hypertension/lifestyle/MORT

ALITY/PHYSICAL-ACTIVITY/prevention/randomized/RISK FACTOR

LEVELS/salt/socioeconomic

status/STROKE/SYSTEM/tobacco/TRENDS/WOMEN



Goodnight, S.H., Coull, B.M., Mcanulty, J.H. and Taylor, L.M. (1993), Antiplatelet

Therapy .1. Western Journal of Medicine, 158 (4), 385-392.



Abstract: We summarize current information about aspirin and other antiplatelet drugs in

patients with cardiac and vascular disease. For each indication, we briefly

summarize the rationale for the use of antiplatelet therapy and describe the

findings of relevant clinical trials. We propose recommendations for the use of

these agents in clinical practice. Part I covers the use of antiplatelet therapy for

the primary and secondary prevention of myocardial infarction, coronary

thrombolysis, unstable and chronic stable angina, and coronary artery-saphenous

vein bypass grafts. In part II we review the use of antiplatelet agents in coronary

angioplasty, atrial fibrillation, artificial cardiac valves, stroke. and peripheral

vascular disease



Keywords: ACUTE MYOCARDIAL- INFARCTION/ARTERY

BYPASS-SURGERY/CARDIOVASCULAR-DISEASE/CLINICAL-TRIALS/L

OW-DOSE ASPIRIN/MORNING INCREASE/PRIMARY

PREVENTION/TISSUE PLASMINOGEN-ACTIVATOR/UNSTABLE

ANGINA/VEIN-GRAFT PATENCY

Moore, W.S. (1993), Carotid Endarterectomy for Prevention of Stroke. Western Journal

of Medicine, 159 (1), 37-43.



Abstract: Carotid endarterectomy, a frequently performed operation, has been used as a

strategy for preventing stroke in patients with carotid bifurcation disease. The

safety and efficacy of the operation were recently challenged by a number of

sources. Three major responses to this challenge were to retrospectively review

the natural history of carotid bifurcation disease compared with the immediate

and long-term results of carotid endarterectomy, to initiate 6 prospective

randomized trials to determine the efficacy of carotid endarterectomy for a

variety of indications, and to develop appropriateness initiatives and guidelines

for using this surgical procedure by organizations concerned with health care

policy. I review the current status of these 3 areas of endeavor. In those areas

where studies are complete, carotid endarterectomy has been shown to be highly

effective in reducing stroke risk. Risk reduction has ranged from 66% to 80%

compared with medical management. Based on these sources and findings, I

present a list of indications for the operation for surgeons who are able to do the

operation safely and within the guidelines established by the Stroke Council of

the American Heart Association



Keywords: AD HOC

COMMITTEE/COMMUNITY/FOR-CARDIOVASCULAR-SURGERY/GUID

ELINES/HOSPITAL

PRIVILEGES/OPERATIONS/PROGNOSIS/STENOSIS/TRANSIENT

ISCHEMIC ATTACKS/VASCULAR-SURGERY



Rothrock, J.F. and Hart, R.G. (1994), Ticlopidine Hydrochloride Use and Threatened

Stroke. Western Journal of Medicine, 160 (1), 43-47.



Abstract: Ticlopidine hydrochloride is an antiplatelet agent of proven antithrombotic

efficacy that in December 1991 became available for general clinical use in the

United States. The relative value of ticlopidine compared with aspirin, also an

effective antiplatelet agent, has become a key clinical issue. Whereas ticlopidine

is somewhat more effective than aspirin for preventing stroke in certain

populations, it is also more expensive and potentially toxic. We recommend its

use for patients with threatened stroke who are intolerant of aspirin and for

patients who have cerebral ischemic symptoms despite aspirin therapy. Patients

surviving major ischemic stroke make up a third group for whom ticlopidine use

may be recommended in preference to aspirin. The use of ticlopidine rather than

aspirin in patients with other cerebrovascular conditions is not strongly supported

by existing data. The risk-benefit-cost equation involving ticlopidine versus other

antithrombotic therapies is complex, rendering a wide range of acceptable

management practices. If reliable laboratory monitoring for neutropenia during

the first 3 months of therapy is not feasible, ticlopidine should not be used



Keywords: ANTIPLATELET

AGENT/ASPIRIN/CALIFORNIA/CEREBROVASCULAR-DISEASE/DRUG/I

NTERMITTENT CLAUDICATION/ischemic

stroke/PREVENTION/RATES/SEVERE

APLASTIC-ANEMIA/stroke/THERAPY/ticlopidine/TRIAL



Gress, D.R. (1994), Stroke - Revolution in Therapy. Western Journal of Medicine, 161

(3), 288-291.



Abstract: Stroke remains the third leading cause of death in this country, although recent

advances in both clinical and basic science research have revolutionized the

concept of stroke. Studies of primary and secondary stroke prevention have now

documented the means to prevent thousands of cases of stroke each year. Three

distinct strategies are evolving for intervention in the acute stroke process.

Evidence is clear that ischemia leads to a toxic accumulation of intracellular

calcium, in part mediated by excitatory neurotransmitters such as glutamate.

Glutamate antagonists have shown clear benefit in experimental stroke models,

and early clinical trials are underway Acute revascularization to restore perfusion

is also feasible and may minimize the extent of infarction. Studies of fibrinolytic

agents are promising, with randomized clinical studies being done. While

reperfusion is desired, it may be associated with additional neuronal injury. The

development of anaerobic metabolism followed by reperfusion and aerobic

conditions favors oxidation and free-radical formation. This mechanism of injury

can be decreased by agents known to scavenge free radicals, and clinical trials

are also testing this. This revolution in the understanding of ischemia, as well as

the outpouring of new pharmacologic agents, is making stroke a true neurologic

emergency requiring immediate intervention



Keywords: CALIFORNIA/clinical

trials/DAMAGE/development/DISEASE/formation/free

radicals/FREE-RADICALS/GERBILS/glutamate/ISCHEMIA/MINUTES/preve

ntion/stroke/stroke prevention/TISSUE

PLASMINOGEN-ACTIVATOR/trials/URGENT THERAPY



Stettin, G.D. (1995), Treatment of Nonvalvular Atrial-Fibrillation. Western Journal of

Medicine, 162 (4), 331-339.



Abstract: Nonvalvular atrial fibrillation is an increasingly common condition. It may

cause disabling symptoms and is an important risk factor for stroke. The goals of

treatment include the relief and prevention of rate- and rhythm-related symptoms

and the prevention of stroke and systemic emboli. Three principal treatments

should be considered: pharmacologic rate control, cardioversion and

antiarrhythmic therapy to restore and maintain sinus rhythm, and prophylactic

anticoagulation or antiplatelet therapy to reduce the risk of stroke. The risks and

benefits of each of these therapies have been reviewed. Symptoms, if present,

can often be managed safely with rate- directed therapy alone. Until issues

regarding safety and long-term efficacy are resolved, cardioversion and

antiarrhythmic therapy should be limited to those patients whose symptoms

cannot otherwise be controlled. The benefits of warfarin anticoagulation for the

primary and secondary prevention of stroke in nonvalvular atrial fibrillation have

been demonstrated convincingly by several randomized clinical trials. These

benefits must be weighed against the real risk of major hemorrhage. For patients

at low risk of stroke, the use of aspirin may be an acceptable alternative to

warfarin sodium therapy



Keywords: anticoagulation/antiplatelet therapy/aspirin/atrial

fibrillation/cardioversion/clinical trials/CURRENT ELECTRICAL

CARDIOVERSION/DIGOXIN/emboli/fibrillation/FLUTTER/FOLLOW-UP/FR

AMINGHAM/hemorrhage/MAINTENANCE/prevention/RANDOMIZED

TRIAL/RECENT-ONSET/risk/safety/secondary prevention/SINUS

RHYTHM/stroke/STROKE-REGISTRY/treatment/trials/warfarin



Albers, G.W. (1997), Management of acute ischemic stroke - An update for primary care

physicians. Western Journal of Medicine, 166 (4), 253-262.



Abstract: Few areas of medicine have had as many major advances in recent years as the

treatment and prevention of ischemic stroke. During the 1990s- ''the decade of

the brain'' -carotid endarterectomy was demonstrated to be effective for

preventing stroke in patients with significant carotid stenosis. Large clinical

studies have documented the effectiveness of new antiplatelet agents and oral

anticoagulant therapy for stroke prevention in specific patient groups, and

recently tissue plasminogen activator was approved for the treatment of acute

ischemic stroke. Because the use of these new therapies is restricted to specific

patient subgroups, the accurate determination of the cause of stroke is now

mandatory. Fortunately, advances in diagnostic methods, including cardiac and

vascular ultrasonographic techniques and brain imaging, facilitate the

determination of the stroke subtype in most patients. Additional advances in

stroke treatment and prevention are on the immediate horizon. New therapeutic

agents, including neuroprotective medications, and new treatment modalities

such as cerebral angioplasty are promising investigational therapies



Keywords: acute ischemic

stroke/AMERICAN-HEART-ASSOCIATION/angioplasty/anticoagulant/antiplat

elet agents/ASPIRIN/brain/carotid/carotid endarterectomy/carotid

stenosis/cerebral/COUNCIL/endarterectomy/GLUTAMATE/GUIDELINES/HE

PARIN/ischemic/ischemic stroke/oral anticoagulant therapy/plasminogen

activator/PREVENTION/primary care/STENOSIS/stroke/stroke

prevention/stroke treatment/therapy/treatment/TRIAL/vascular



LaCroix, A.Z., Newton, K.M., Leveille, S.G. and Wallace, J. (1997), Healthy aging - A

women's issue. Western Journal of Medicine, 167 (4), 220-232.



Abstract: The life expectancy of women currently exceeds that of men by almost seven

years, yet women spend approximately twice as many years disabled prior to

death as their male counterparts. The diseases that account for death and health

care utilization in older women (heart disease, cancer, stroke, fracture,

pneumonia, osteoarthritis, cataracts) are also major contributors to disability.

This paper reviews the scientific evidence that supports specific

recommendations for older women that may prevent or delay these conditions for

as long as possible. Risk factors for falls and fractures should be assessed and,

where possible, modified. Adequate intakes of calcium, vitamin D, fruits, and

vegetables should be encouraged. Weight should be monitored and weight loss

discouraged for most women. Screening for B12 deficiency is recommended.

Engaging women in a shared decision-making process about the use of hormone

replacement therapy for longterm prevention of heart disease and fractures is

important, as is regular screening for breast and cole-rectal cancer. Women

should be encouraged to engage in enjoyable physical activities, including

walking, for 30 minutes daily. These interventions have the potential to delay the

onset and improve the course of many chronic conditions that prevail in later life



Keywords: aging/BONE-MINERAL DENSITY/CORONARY

HEART-DISEASE/decision-making/diseases/ESTROGEN

REPLACEMENT/fractures/health/health care/heart/HIP FRACTURE/hormone

replacement therapy/life expectancy/MAINTAINING MOBILITY/OLDER

ADULTS/OSTEOPOROTIC FRACTURES/PHYSICAL-

ACTIVITY/POSTMENOPAUSAL WOMEN/prevention/RANDOMIZED

TRIAL/stroke/therapy/women



Ragland, D.R., Buffler, P.A., Reingold, A.L., Syme, S.L. and Buffler, M.L. (1998),

Disease and injury in California with projections to the year 2007 - Implications

for medical education. Western Journal of Medicine, 168 (5), 378-399.



Abstract: In this article, as part of an evaluation of the future of medical education in

California, we characterize the distribution of disease and injury in California;

identify major factors that affect the epidemiology of disease and injury in

California, and project the burden of disease and injury for California's

population to the year 2007. Our goal is to elucidate the major causes of illness

and disability at present and in the near future in order to focus state resources on

the interventions likely to have the greatest impact. Data from various

governmental agencies were utilized; the base year, 1993, is the most recent year

with sufficient information available when this report was prepared. Several

major risk factors have decreased, including smoking (30% decline from 1984 to

1993) and drinking and driving. However, hypertension prevalence has not

changed, and overweight has increased dramatically. Poverty continues to burden

about 15% of Californians, with poverty highest among children. During 1993,

220,271 Californians died, with 3 major causes accounting for 61% of these

deaths: coronary heart disease (31%), cancer (23%), and stroke (7%). In terms of

potential years of life lost (years lost before age 65), the most important causes of

death in 1993 were unintentional injury (756 years lost/100,000 population),

cancer (632 years), and the acquired immunodeficiency syndrome (AIDS; 491

years). Mortality rates were highest among blacks and lowest among Asians.

Overall mortality in California has been declining for decades; ire just 1 decade,

from 1980 to 1991, mortality declined from 780 to 680 deaths per 100,000

population. Several major causes of death have declined, including coronary

heart disease, stroke, unintentional injury, cirrhosis, and suicide, while others

have increased, for example, chronic obstructive lung disease and diabetes

mellitus. Death from AIDS increased dramatically in the past decade, but is

leveling off, and death from cancer is beginning to decline. Rates for overall

mortality and morbidity, and for most specific conditions, should continue to

decline. A projected 28% population increase by 2007 will yield a corresponding

increase in the absolute level of disease cages and death; a disproportionate

increase in younger and older groups will yield increased conditions affecting

young (unintentional injury, AIDS) and older (heart disease, cancer, stroke,

diabetes mellitus) people. Californians should experience overall improved

health in coming years, reaping benefits of reduced environmental and

behavioral risk factors as well as improved medical treatment and rehabilitation.

Coordinated strategies for health promotion, disease prevention, delivery of

medical treatment, and rehabilitation are needed to maintain and improve present

levels of health across the life span



Keywords: age/coronary heart disease/diabetes/diabetes

mellitus/education/epidemiology/evaluation/HEALTH/health

promotion/heart/hypertension/medical

treatment/morbidity/mortality/prevention/rehabilitation/risk/risk

factors/smoking/SOCIOECONOMIC-STATUS/stroke/treatment



Lees, K.R., Bath, P.M.W. and Naylor, A.R. (2000), Secondary prevention of transient

ischemic attack and stroke. Western Journal of Medicine, 173 (4), 254-258



Keywords: ischemic/prevention/stroke/transient/transient ischemic attack



Lechner, H., Schmidt, R., Reinhart, B., Grieshofer, P., Eber, B., Fazekas, F.,

Schumacher, M., Horner, S., Freidl, W., Niederkorn, K. and Koch, M. (1993),

Cerebrovascular Risk-Factors in An Elderly Austrian Population - 1St Year

Results of the Austrian-Stroke-Prevention-Study (Asps). Wiener Klinische

Wochenschrift, 105 (14), 398-403.



Abstract: During the first year the Austrian Stroke Prevention Study enrolled 599

volunteers without clinical signs or symptoms of cerebrovascular disease aged 50

to 70 years. Study participants were randomly selected, from the official register

of the city of Graz. The rate of positive response was 26.9 per cent. All subjects

underwent an extensive risk factor screening with Duplex scanning of the carotid

arteries obtained from a subset of 176 individuals. The prevalence of

well-documented cerebrovascular risk factors was 40.6% for arterial

hypertension, 35.4% for cardiac disease, 8.5% for diabetes mellitus und 3% for

elevated haematocrit. The less well- documented cerebrovascular risk factors

dyslipidemia, overweight, physical inactivity, hyperfibrinogenemia and smoking

were noted in 75%, 33.7%, 27.2%, 14.9% and 12.2% of subjects, respectively.

Multiple well-documented risk factors were noted in 23.7% of the examined

volunteers. Multiple linear regression analysis revealed body mass index (p <

0.0001) and age (p < 0.0001) as independent predictors of the frequency of

well-documented risk factors observed in any individual. Atherosclerotic carotid

disease occurred in 61.9% of study participants investigated by Doppler

sonography and was significantly associated with age (p < 0.00001), life-time

tobacco consumption (p < 0.0001) and the concentration of apolipoprotein B (p <

0.05). This study demonstrates high prevalence rates of vascular risk factors in

an elderly Austrian community. Implications for stroke prevention result from

the conjunction of overweight and frequency of risk factors noted in any study

participant, as well as from the relationship of carotid atherosclerosis to smoking

and dyslipidemia



Keywords:

ATHEROSCLEROSIS/BLOOD-PRESSURE/CEREBRAL-HEMORRHAGE/C

EREBROVASCULAR RISK FACTORS/DISEASE/DOPPLER

SONOGRAPHY/INFARCTION/LIPIDS/PREVALENCE



Deecke, L. and Zeiler, K. (1993), Low-Dose Acetylsalicylic-Acid (Asa) As Secondary

Prophylaxis After Ischemic Cerebrovascular Events. Wiener Klinische

Wochenschrift, 105 (17), 485-487.



Abstract: Acetylsalicylic acid (ASA) as secondary prophylaxis after ischaemic

cerebrovascular events is well established and its efficacy unquestioned since

over 15 years. According to the results of two European studies a dose of 100mg

per day is sufficient to reduce the incidence of further stroke, myocardial

infarction, and death due to cardiovascular causes. This satisfactory response to

low-dose ASA applies to patients with transient ischaemic attacks, reversible

ischaemic events, and minor strokes. In cases with severe cardiac disease,

however, a high dosage of ASA or anticoagulation therapy may be necessary to

prevent further vascular events



Keywords: ACETYLSALICYLIC

ACID/ASPIRIN/CEREBRAL-ISCHEMIA/CONTROLLED

TRIAL/PREVENTION/PROPHYLAXIS/STROKE



Polzl, G. and Kuhn, P. (1997), Cerebrovascular event: A rational algorithm for

cardiologic evaluation and treatment. Wiener Klinische Wochenschrift, 109 (10),

366-372.



Abstract: Stroke continues to be a serious socioeconomic problem in the industrialized

countries, The three disease processes responsible for most ischemic

cerebrovascular events (CVE) are large-vessel and small-vessel atherothrombotic

disease and, in up to 20-30% of cases. cardiac embolism. Data from the literature

show that life expectancy after CVE is mainly dependent on the coexistence of

cardiac disease. It is the responsibility of the cardiologist to exclude or identify

the source of cardiac embolism and to initiate adequate treatment for the

prevention of recurrences, as well as to diagnose, and treat any concomitant

cardiac disease which may be present. We propose a cost-effective algorithmic

approach to help the cardiologist in the diagnosis and treatment of patients with

transient ischemic attacks and ischemic stroke



Keywords: ARTERY/CARDIAC SOURCE/cerebrovascular/cerebrovascular

event/diagnosis/diagnostic

algorithm/DISEASE/EMBOLISM/evaluation/improvement of

prognosis/ischemic/ischemic stroke/LACUNAR INFARCTION/life

expectancy/prevention/prevention of recurrence/RISK/stroke/STROKE

PATIENTS/SUBTYPES/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/transient/TRANSIENT ISCHEMIC

ATTACKS/treatment



Sinzinger, H. and Kritz, H. (1997), Acetylsalicylic acid after myocardial infarction.

Wiener Klinische Wochenschrift, 109 25-28.



Abstract: There is no doubt about the positive influence of acetylsalicylic acid on

vascular disease. The antithrombotic therapy with acetylsalicylic acid is a

fundamental of secondary prevention of vascular events, especially in nonfatal

myocardial infarction, instable angina pectoris, stroke and in patients with

amaurosis fugax. Clinical studies done since 1990 about the effect of a low-dose

therapy confirmed the experimental results, which showed that 25-50 mg

acetylsalicylic acid per day are enough, to suppress platelet function as far as

necessary, without influencing the protective function of prostacyclin synthesis.

Side-effects can be reduced to a minimum with a reduced dosage. The

wide-spread use of a low-dose acetylsalicylic acid therapy in primary prevention

especially in patients at high risk has to be reevaluated in further studies



Keywords: acetylsalicylic acid/ACUTE CORONARY

SYNDROMES/angina/antithrombotic therapy/ARTERY

DISEASE/ASPIRIN/infarction/MECHANISMS/MORTALITY/myocardial

infarction/PATHOGENESIS/PLATELETS/PREVENTION/primary

prevention/risk/secondary prevention/stroke/therapy/TRIAL/UNSTABLE

ANGINA/vascular/vascular disease



Esterbauer, E., Anders, I., Ladurner, G., Huemer, M. and Wranek, U. (2001), Stress

coping strategies and heart diseases, obesity, nicotine and alcohol consumption.

Wiener Klinische Wochenschrift, 113 (23-24), 947-953.



Abstract: Introduction: Heart diseases, obesity, nicotine and alcohol abuse are all

relevant stroke risk factors. Some studies refer to stress stimuli and coping

strategies as modulators for stroke risk factors. Aim: This study investigated

differences between stroke prevention patients with heart complaints, obesity,

nicotine or alcohol abuse and stroke prevention patients without these risk factors.

Method: 5993 stroke prevention patients participated in a medical-psychological

stroke risk investigation at the Christian Doppler Clinic in Salzburg. The

differences in coping strategies between groups of patients with risk factors and

groups without were investigated by means of multivariate analysis of

covariance. Results: Significant differences in stress coping were found for every

risk factor (split by sex). Men suffering from heart diseases showed higher values

in the coping strategy tendency to flee. Women with heart complaints

demonstrated significantly lower values in minimising by comparison.

Obese/adipose patients performed significantly higher values in the coping

strategies vicarious satisfaction and aggression (men). Nicotine abusing

prevention patients showed significantly higher values in drug intake and lower

scores in continued thoughts. Non-smoking men furthermore reached higher

values in vicarious satisfaction and non-smoking women in minimising. Persons

not consuming alcohol demonstrated higher drug intake and aggression (men).

Wine drinkers showed lower scores of self-pity and increased situation control

attempts (women). Conclusion: Prevention patients with risk factors

demonstrated significant differences in coping strategies in comparison to those

without risk factors. Persons with heart diseases demonstrate a more defensive

behaviour. The risk factors obesity, nicotine and alcohol consumption are

associated with a risk factor supporting stress coping behaviour. The

modification of the coping strategies drug intake and vicarious satisfaction

towards a more active confrontation could probably influence various risk factors

(nicotine, alcohol consumption, obesity) simultaneously



Keywords: ADOLESCENTS/alcohol/alcohol

consumption/Austria/BLOOD-PRESSURE/CIGARETTE-SMOKING/control/di

seases/Doppler/drug/heart/heart disease/heart

diseases/LIFE-STYLE/men/MIDDLE-AGED MEN/multivariate

analysis/nicotine/obesity/PREVENTION/risk/risk factor/risk

factors/RISK-FACTORS/sex/stress/stress coping/STROKE/stroke/stroke

prevention/WOMEN/YOUNG- ADULTS



Anders, I., Esterbauer, E., Ladurner, G. and Wranek, U. (2001), Stress coping styles and

blood viscosity in stroke prevention patients. Wiener Klinische Wochenschrift,

113 (10), 378-383.



Abstract: Introduction: Hematocrit, fibrinogen and blood viscosity influence blood

fluidity and are well known stroke risk factors. Studies have shown relationships

between these factors and psychological stress. Aim: The aim of this study was

to investigate how stroke risk patients with increased hematocrit, increased

fibrinogen, or increased plasma viscosity differ from patients free of these risk

factors in their ways of stress coping. Method: 6503 persons participated in the

following stroke risk investigations: biographical and risk factor orientated

anamnesis, neurological status investigation, laboratory investigation,

sonographic investigation and psychological investigation. After assessment of

several risk factors, differences in stress coping between risk factor and non-risk

factor groups were investigated by means of the t-test and the Wilcoxon-test.

Results: Men with pathological hematocrit showed significantly higher scores in

the coping strategy resignation and a tendency to less positive self instruction

and response control attempts. Women with higher values of hematocrit

demonstrated higher values in resignation and drug intake. Men with higher

fibrinogen showed significantly higher scores in distraction, vicarious

satisfaction, minimising by comparison and tendency to flee as well as a

tendency towards drug intake. Women with increased fibrinogen showed no

differences. Men with normal plasma viscosity had significantly higher values in

tendency to flee and tendencially in desire for social support and lower values in

minimising by comparison. Women with increased plasma viscosity

demonstrated higher scores in resignation and aggression. Conclusions: The

presence of elevated values in parameters of blood viscosity coincides with

increased passive and defensive coping mechanisms, whereas non-risk factor

persons show raised values in active coping styles



Keywords: ACUTE PSYCHOLOGICAL STRESS/Austria/blood

viscosity/COAGULATION/control/FIBRINOGEN/fibrinogen/FIBRINOLYSIS/

hematocrit/HEMOCONCENTRATION/mechanisms/prevention/risk/RISK

FACTOR/risk factors/social support/status/stress/stress coping/stroke/stroke

prevention/viscosity/WOMEN



Hirschl, M., Palkovits, J., Katzenschlager, R., Bialek, C. and Kundi, M. (2002), Duplex

sonographic predictors of restenosis, vascular and neurological events after

carotid endarterectomy. Wiener Klinische Wochenschrift, 114 (8-9), 327-333.



Abstract: Background: Although excellent short- and long-term results have been

achieved with surgery in extracranial internal carotid artery stenosis, recurrent

stenosis continues to play an important role in post-endarterectomy. Therefore, a

close follow-up of patients is warranted. The value of postoperative duplex

sonographic evaluations in postoperative follow-up is highly disputed. The study

evaluates duplex sonographic parameters as predictors of carotid restenosis,

general vascular events and ipsilateral neurological symptoms, in order to assess

the role of duplex sonography in follow-up after carotid endarterectomy.

Methods: A retrospective cohort study with a follow-up period ranging from 7

months to 7.5 years was performed in 150 patients who underwent carotid

endarterectomy. Pre- and postoperative duplex sonographic and clinical data

were analyzed by life-table analysis and multivariate Cox regression with respect

to carotid restenosis, vascular and ipsilateral neurological events. Main findings:

Duplex sonographic predictors of carotid restenosis include the postoperative

degree of stenosis (residual stenosis greater than or equal to 30% or more:

relative risk (RR) = 1.56; 1.05- 2.32), pre- to postoperative reduction of stenosis

(higher than 50%: RR = 0.61; 0.45-0.83), and residual plaques in the operated

carotid artery (RR = 1.96; 1.31-2.93). Some of these morphological parameters

such as reduction of stenosis are also predictive of vascular events (RR = 1.25;

1.01-1.56) and ipsilateral neurological events (RR = 1.52; 1.05-2.19). In 12 cases

restenosis was discovered by duplex sonography and in 3 cases by evaluation of

clinical symptoms. In 5 cases restenosis was treated by repeat surgery.

Contralaterally, progressive or newly developed carotid stenoses were observed

in 17 cases, and only 5 were discovered on the basis of clinical symptoms.

Fourteen contralateral stenoses required surgery. Overall, 12 patients underwent

treatment for stroke prevention on the basis of duplex follow-up findings (8% of

the study population). Conclusions: Postoperative duplex sonography allows for

the identification of patients at risk for carotid restenosis as well as those at risk

for other vascular events, As expected, regular examinations permit early

detection of restenosis requiring surgical treatment. However, a large number of

contralateral stenoses requiring surgical treatment were detected by routine

duplex sonographic examinations. The timing of follow-up intervals may be

oriented towards the perioperative outcome of duplex sonography



Keywords: ACCURACY/ANGIOGRAPHY/ARTERY

STENOSIS/Austria/carotid/carotid artery/carotid artery stenosis/carotid

endarterectomy/cohort study/detection/DISEASE/duplex/duplex

sonography/endarterectomy/evaluation/FOLLOW-UP/internal carotid artery/life

table/MANAGEMENT/outcome/population/postoperative/predictors/prevention/

RECURRENT/relative risk/residual/restenosis/risk/stenosis/STROKE/stroke

prevention/SURGERY/surgical

treatment/SURVEILLANCE/symptoms/timing/treatment/vascular/vascular

events



Knudsen, J.B., Bastain, W., Sefton, C.M., Allen, J.G. and Dickinson, J.P. (1992),

Pharmacokinetics of Ticlopidine During Chronic Oral- Administration to

Healthy-Volunteers and Its Effects on Antipyrine Pharmacokinetics. Xenobiotica,

22 (5), 579-589.



Abstract: 1. The pharmacokinetics of ticlopidine, a novel antithrombotic agent, have

been investigated in 10 healthy volunteers dosed orally with the drug (250 mg 12

hourly for 21 days), to determine the basic pharmacokinetic parameters in

humans, to investigate its accumulation during repeated administration, and to

assess its effects on hepatic drug-metabolizing enzymes. 2. After the first dose,

peak plasma concentrations (median 0.31, range 0.08-0.80mg/l) were generally

found at 2 h. The levels decreased rapidly to a median concentration of 0.087

mg/l by 4 h then declined to 0.022 (range<0.005-0.128) mg/l at 12 h after

administration, with apparent half-lives of approx. 4 h. The median AUC value

for this first dosage interval (AUC(tau)) was 0.97 (range 0.41-3.49) mg h l-1. 3.

Pre-dose plasma concentrations indicated that steady state was reached after 5-10

days, and then remained essentially unchanged through to the end of the study.

From 30 h after the final dose, drug levels declined exponentially with a median

half- life of 28.8 (range less-than-or-equal-to 20-50) h. 4. Following the final

dose, the median peak concentration and AUC(tau) were 0.99(range

0.22-2.12)mg/l and 4.06 (range 0.90- 15.2) mg h l-1 respectively. Based on AUC

values, the mean accumulation factor+/-SD was 3.73+/-1.14. 5. The metabolic

status of subjects was assessed by administration of single doses of antipyrine

(700 mg orally) 7 days before the first dose of ticlopidine and 2 days after the

final dose. Treatment with ticlopidine decreased antipyrine clearance,

demonstrating that it inhibited drug-metabolizing enzymes. Significant

correlations (r2=0.84, p<0.01) were found between the AUC values for

ticlopidine and antipyrine, indicating that the interindividual variation in the

pharmacokinetics of ticlopidine are explained by differences in metabolic

clearance



Keywords: PLATELET-AGGREGATION/PREVENTION/STROKE



Park, D.C., Nam, H.S., Lim, S.R., Lee, P.H., Heo, J.H., Lee, B.I. and Kim, D.I. (2000),

MRI features of infarcts with potential cardiac source of embolism in the Yonsei

Stroke Registry (YSR), Korea. Yonsei Medical Journal, 41 (4), 431-435.



Abstract: The determination of the embolic source is crucial to understanding the

pathogenesis of ischemic stroke, the initiation of appropriate therapy, and the

prevention of recurrent infarctions. In this study we undertook to identify the

characteristic features on magnetic resonance images of patients who had

suffered from stroke due co cardiac embolism (CE), as classified by TOAST

(possible and probable). We retrospectively studied magnetic resonance imaging

(MRI) findings of patients with ischemic stroke from the Yonsei Stroke Registry

(YSR). On the basis of the TOAST classification, 92 patients were identified to

have a potential cardiac source of embolism (PCSE), in which 69 patients were

found to have high-risk PCSE and 23 patients medium-risk PCSE. To compare

their imaging characteristics, another group of 49 patients who were found to

have had a stroke due to large artery-to-artery (ATA) embolism-common or

internal carotid artery (CCA, ICA)-were identified. Involvement of the

simultaneous superficial and deep territories (58.7%; 6.1%, p<0.001), and

combined new anterior and old posterior circulation (15.2%; 2.0%, p=0.016)

were more frequent in PCSE than ATA embolism. Bilateral anterior hemispheric

involvement was also more frequent in the PCSE group, but it did nor reach

statistical significance (13.0%; 4.1%, p=0.090). ATA embolism tended to

involve only superficial territories compared to PCSE (71.4%; 28.3%, p<0.001).

There were no topographic differences between the high-risk and medium-risk

groups. With respect to the etiology of PCSE in our population, atrial fibrillation

was the most common. Characteristic MRI features of patients with PCSE, which

were not documented previously by computed tomography (CT) included: old

and new, involvement of multiple different vascular territories, bilateral anterior

hemisphere, as well as anterior and posterior circulation. These MRI features,

together with simultaneous superficial and deep territorial involvement, help to

differentiate the underlying embolic sources, whether they are cardiac or ATA in

origin



Keywords: atrial fibrillation/BRAIN INFARCTIONS/carotid/carotid artery/cerebral

infarction/computed

tomography/CT/DATA-BANK/embolism/etiology/fibrillation/high

risk/ischemic/ischemic stroke/magnetic resonance

imaging/MEDICINE/MIDDLE

CEREBRAL-ARTERY/MRI/PATHOGENESIS/population/potential cardiac

source of embolism/prevention/stroke/therapy/TOAST/vascular

Pitsavos, C., Stefanadis, C. and Toutouzas, P. (2000), Contraception in women at high

risk or with established cardiovascular disease. Young Woman at the Rise of the

21St Century: Gynecological and Reproductive Issues in Health and Disease,

900 215-227.



Abstract: Oral contraceptives are one of the most effective and widely used reversible

contraceptive methods, Over 90 million women worldwide, including over 44

million in developing countries, are now using oral contraceptives. Despite their

advantages, there is concern about the links between combined oral

contraceptives and the risk of cardiovascular disease. The risk attributable to oral

contraceptive use in women <35 years of age is small, even if they smoke, but

there are substantially increased risks in older women who both smoke and use

oral contraceptives. Differences between oral contraceptive types ih the relative

risk of venous thromboembolism contribute little to the total cardiovascular

mortality associated with oral contraceptive use, even though the total number of

cardiovascular events is increased. It is important to consider the user's age and

smoking status when determining oral contraceptive-attributable risks. Hormonal

oral contraceptives have changed and now contain lower doses of estrogen and

progestagen



Keywords: age/cardiovascular/cardiovascular disease/cardiovascular

events/cardiovascular mortality/disease/DISORDERS/estrogen/high

risk/HORMONAL CONTRACEPTION/mortality/NEW-YORK/oral

contraceptives/ORAL-CONTRACEPTIVES/PREVENTION/relative

risk/risk/smoking/status/STROKE/thromboembolism/use/venous

thromboembolism/women



Hrastnik, F. (1988), Prevention of Stroke. Zdravstveni Vestnik, 57 (4), 127-129



Feurle, G.E., Bartz, K.O. and Schmitt-Graff, A. (1999), Lymphocytic colitis, induced by

ticlopidine. Zeitschrift fur Gastroenterologie, 37 (11), 1105-1108.



Abstract: Lymphocytic colitis is a chronic inflammatory colonic disease characterized

by watery diarrhea and a dense infiltration of the colonic mucosa with

lymphocytes. The etiology is unknown but an immune reaction to various

immunostimulatory agents including pathogenic or commensal bacteria, products

of bacterial metabolism of dietary degradation, or antigens derived directly from

the diet, and autoimmune phenomena are discussed. We observed a patient with

all features of lymphocytic colitis characterized by a prominent intraepithelial

T-cell component. The colitis resolved completely when therapy with ticlopidine

- an agent inhibiting platelet aggregation - was stopped. This observation

suggests that medical history concerning drug ingestion may reveal the etiology

of lymphocytic colitis and allows cure of this otherwise difficult to treat disorder



Keywords: aggregation/case report/CHRONIC DIARRHEA/COLLAGENOUS

COLITIS/diet/drug-induced/EFFICACY/etiology/FORMS/Germany/history/intr

aepithelial lymphocytes/lymphocytic colitis/metabolism/MICROSCOPIC

COLITIS/microscopic colitis/PHARMACOLOGY/platelet

aggregation/PREVENTION/STROKE/T-lymphocytes/therapy/ticlopidine



Berent, R., Hinterholzer, G., Hobling, W., Auer, J., Haidenthaler, A. and Knoflach, P.

(2000), Cholestatic hepatitis due to a therapy with ticlopidine. Zeitschrift fur

Gastroenterologie, 38 (7), 587-591.



Abstract: A 71-year-old man with chronic atrial fibrillation was treated with aspirin

because of a right cerebral infarction. Oral anticoagulation was not initiated

because of a secondary hemorrhagic transformation. Six years later after a left

cerebral transient ischemic attack aspirin was replaced by ticlopidine. Two weeks

after starting ticlopidine he experienced abdominal cramps and diarrhea. Also

dark urine and gray-colored stools were noticed, so that the patient stopped

taking ticlopidine. 40 days after starting ticlopidine he was admitted to our

hospital because of cholestatic jaundice. Serum alkaline phosphatase (305 U/I)

and gamma GT (143 U/I) were elevated, the total bilirubin was 18,6 mg/dl at

peak. COT and GPT were 2,7 fold increased. After exclusion of a viral infection

and autoimmune disease liver biopsy was performed, which showed a

centroacinar cholestasis compatible with a drug- induced liver damage. 79 days

after discontinuation of the drug laboratory signs of cholestasis had disappeared.

In patients in whom long-term therapy with ticlopidine is indicated regularly

laboratory tests and clinical examinations should be done to recognize infrequent

side effects such as the cholestatic hepatitis in time



Keywords: anticoagulation/ANTIPLATELET/aspirin/atrial

fibrillation/Austria/cerebral/cerebral infarction/cholestasis/cholestatic/cholestatic

hepatitis/fibrillation/hepatitis/hospital/INDUCED PROLONGED

CHOLESTASIS/infarction/infection/ischemic/JAUNDICE/LIVER/PREVENTI

ON/STROKE/therapy/ticlopidine/transient/transient ischemic attack/TRIAL



Luttje, D., Krause, D. and Lucke, C. (1993), Secondary Prevention in Clinical Geriatrics.

Zeitschrift fur Gerontologie, 26 (6), 453-458.



Abstract: Secondary prevention is of importance when the patient is already suffering

from a serious disease, e. g., from arterial obstruction causing a stroke or an

amputation, from a hip fracture or other diseases that might threaten his

independence. Secondary prevention covers a wide field of topics. First of all,

the patient must recover from his acute disease. It is important to avoid

complications which are not specific for the disease, but are typical for a

bedridden old person (decubital ulcer, dehydration and others). Prevention also

means to avoid recurrence of the same disease as well as complications that

frequently occur during the clinical course and may influence the outcome

(spasticity in stroke patients, muscular calcification following hip replacement).

Frequently, old persons do not completely recover following serious disease,

they are limited in their daily activities and their capability to leave home.

Secondary prevention tries to fight isolation; the patient should live a meaningful

life

Keywords:

AMPUTATION/complications/diseases/ELDERLY/OSTEOPOROSIS/preventio

n/REHABILITATION/SECONDARY PREVENTION/SOCIAL

ISOLATION/STROKE



Gosch, M. (2000), The role of ACE inhibitors in the treatment of hypertensive elderly

patients. Zeitschrift fur Gerontologie und Geriatrie, 33 (6), 433-437.



Abstract: Hypertension has a high prevalence among elderly patients. Randomised trials

have already demonstrated that treating healthy older persons with hypertension

is highly efficacious. Nevertheless some questions have arisen. On the one hand

the generalisability of these trial results, particulary for older persons with

serious medical comorbidities and poor functional status, is not clear. On the

other hand different antihypertensive drugs have shown to be effective. Which

drug for which patient? Even data from randomised intervention trials showing

that the treatment affects cardiovascular morbidity and mortality, were missing,

ACE inhibitors have been used for more than a decade to treat high blood

pressure. For a younger population the captopril prevention project showed no

differences between ACE inhibitors and conventional antihypertensive treatment

(diuretics, beta-blocker) concerning the primary endpoints (myocardial infarction,

stroke and other cardiovascular death). The STOP-2 study also confirmed these

results for elderly patients. When treating elderly patients one must be aware of

physiological changes with age and the comorbidities. Of significance among

this patient group is declining renal function. Admissions for uraemia that are

related to the use of ACE inhibitors are still commonplace, although many cases

are preventable by monitoring renal function, but guidelines are still missing.

Concerning the comorbidities ACE inhibitors have benefits compared to other

antihypertensive drugs, especially in cases of heart failure, diabetes and coronary

heart disease



Keywords: ACE inhibitors/age/angiotensin-converting-enzyme inhibitor

hypertension/antihypertensive drugs/antihypertensive treatment/Austria/blood

pressure/captopril/cardiovascular/cardiovascular

morbidity/comorbidities/CONVERTING-ENZYME-INHIBITORS/coronary

heart disease/death/diabetes/disease/diuretics/drugs/elderly/elderly

patients/functional status/guidelines/heart/heart disease/heart

failure/HEART-FAILURE/high blood

pressure/hypertension/infarction/LIFE/medical/monitoring/MORBIDITY/MORT

ALITY/myocardial/myocardial

infarction/population/prevalence/prevention/primary/PROJECT/QUALITY/RA

NDOMIZED TRIAL/renal/renal

function/status/stroke/THERAPY/treatment/trial/trials/use



Renteln-Kruse, W., Nogaschewski, K. and Meier-Baumgartner, H.P. (2002), Knowledge

of disease, expectations in and judgements about therapy in elderly stroke

patients and their proxies - a prospective study during in-hospital treatment.

Zeitschrift fur Gerontologie und Geriatrie, 35 (3), 241-249.

Abstract: Fourty-five stroke patients and their 45 proxies were interviewed after the

patients' hospital admission and before discharge. The topics of the interviews

were disease knowledge, expectations in and judgement about therapy,

estimation of functional health status (CCOP/WONCA Charts), and prognosis.

The patients and proxies were also asked to name the patient's actual three most

important health problems. The depressive symptomatology in the patients

(geriatric depression scale) and their ADL status (Barthel Index) were evaluated

on admission and before hospital discharge. The proxies' general knowledge of

disease was superior compared to that of the patients. There were knowledge

deficits regarding individual risk factors and secondary prevention, in particular.

Information was predominantly obtained from physicians. However, an

additional need for information on prognosis and prevention, in particular, was

expressed by patients and proxies before hospital discharge. There was a high

agreement between the patients and their proxies in mentioning the patients'

actual three most important health problems, apart from psychological problems.

These were mentioned only by the proxies but not by the patients themselves.

Depressive symptomatology in the patients increased significantly. There were

associations of depression with the level of the Barthel Index score and the

patients' self-estimation of functional health status before and after the stroke.

Full recovery was expected by one half of the patients, on admission. The

patients' primary therapeutic goal was the ability to walk again. Their ADL status

improved significantly, as measured by a mean increase in the Barthel Index

score by 22 points. The patients and their proxies, as well, judged the result of

treatment equally high. The proxies' total satisfaction with patient care was

significantly related to their ratings of separate parts of patient care regarding

nurses, therapists, and physicians, to their expectations in therapy, and the

satisfaction of their own personal needs. The results of the study revealed a

particular need for information on prognosis and secondary prevention of stroke.

Furthermore, depression and coping with consequences of the disease should be

important issues in counselling of stroke patients and their proxies. The results

regarding patient and proxy satisfaction with care were of importance for internal

discussion in the clinic



Keywords: ADL/BURDEN/CARERS/depression/disease/elderly/expectations in and

judgement about therapy patient and proxy

satisfaction/Germany/health/hospital/IMPACT/knowledge/knowledge of

disease/prevention/primary/prognosis/prospective study/proxies/risk/risk

factors/SATISFACTION/SCALE/secondary/secondary

prevention/status/stroke/stroke patients/therapy/treatment



Kottkamp, H., Willems, S., Hindricks, G., Chen, X., Haverkamp, W., Hasfeld, M.,

Borggrefe, M. and Breithardt, G. (1993), Oral Anticoagulation for Prevention of

Thromboembolism in Nonrheumatic Atrial-Fibrillation - Indications, Efficacy,

and Risk. Zeitschrift fur Kardiologie, 82 (11), 667-673.



Abstract: Oral anticoagulation in patients with rheumatic heart disease tor prevention of

systemic thromboembolism is accepted clinical practice. The incidence of stroke

in patients with nonrheumatic atrial fibrillation is about five times the rate of

patients in sinus rhythm. However, contradictory findings in several small

retrospective studies have precluded determination of a gold standard for patients

with nonrheumatic atrial fibrillation so far. Recently, the results of five

prospective, placebo- controlled studies in patients with nonrheumatic atrial

fibrillation treated with anticoagulation have been published. A consistent risk

reduction of thromboembolism ranging from 37 to 87% in patients treated with

warfarin was reported. This risk reduction occurred in excess of a relatively low

incidence of intracerebral and/or fatal bleeding complications. The efficacy of

prevention of thromboembolism was comparable for high intensity

anticoagulation (International Normalized Ratio (INR) 2.8-4.2) and low dose

anticoagulation (INR 1.5-2.7). However, fatal and/or intracerebral bleedings only

occurred with INR greater-than-or-equal-to 2.6. In subgroup analysis, recent

congestive heart failure, arterial hypertension, and previous apoplex or arterial

thromboembolism were independent clinical predictors of increased risk for

thromboembolism, whereas results in patients with chronic and intermittent atrial

fibrillation were comparable. In 69 patients with lone atrial fibrillation, no single

event occurred in the follow-up period. Thus, lone atrial fibrillation does not

seem to carry an increased risk for stroke when strict criteria for diagnosis of

lone atrial fibrillation are applied. In two of the five studies, aspirin was

additionally randomized. Since contradictory findings resulted, the role of aspirin

for prophylaxis of stroke still needs to be determined. However, at present, all

patients with nonrheumatic chronic or intermittent atrial fibrillation should be

considered as candidates for oral anticoagulation for prevention of

thromboembolism, except in young patients with lone atrial fibrillation, which

seems to carry no increased risk of thromboembolism



Keywords:

ASPIRIN/COMPLICATIONS/FRAMINGHAM/INTENSITIES/NONRHEUMA

TIC ATRIAL FIBRILLATION/ORAL

ANTICOAGULATION/POPULATION/PREVENTION OF

THROMBOEMBOLISM/STROKE/SYSTEMIC

EMBOLISM/THERAPY/WARFARIN



Kienast, J. (1994), Prevention of Thromboembolism in Atrial-Fibrillation - Antiplatelet

and Anticoagulant-Therapy. Zeitschrift fur Kardiologie, 83 49-58.



Abstract: Over the past five years, the results of six prospective randomized trials have

set new standards in the primary and secondary prevention of thromboembolism

in nonvalvular (''nonrheumatic'') atrial fibrillation. On the one hand, they have

confirmed the increased risk of stroke in these patients amounting to about 5%

per year and an annual recurrence rate after a recent transient ischaemic attack or

minor stroke of 12%. On the other hand, the results of these trials have

unanimously demonstrated a greater than or equal to 60% risk reduction with

oral anticoagulation at an acceptable risk of major bleeding complications. A

reduced intensity of anticoagulant therapy with a target INR of 2,0 - 3,0 is

effective in most of these patients. Both clinical and echocardiographic features

allow the identification of subgroups at low or high risk of thromboembolic

complications and provide the basis for the individual benefit-to-risk assessment

of anticoagulant therapy. Aspirin is currently recommended as a second choice

therapy for patients who are poor candidates for oral anticoagulants or who are

considered to be at low risk for thromboembolism



Keywords: anticoagulants/anticoagulation/ARTERIAL

EMBOLISM/ASPIRIN/ATRIAL FIBRILLATION/CEREBRAL

INFARCTION/COMPLICATIONS/fibrillation/FRAMINGHAM/HYPERCOAG

ULABLE STATE/MITRAL VALVE DISEASE/ORAL

ANTICOAGULANTS/oral anticoagulation/prevention/randomized

trials/risk/RISK-FACTORS/secondary prevention/STROKE/SYSTEMIC

EMBOLIZATION/THROMBOEMBOLISM/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/transient/trials



Piper, C. and Horstkotte, D. (1998), Intracardiac thrombosis and cardiogenic embolism

in patients with heart valve disease: Predisposition and prevention strategies.

Zeitschrift fur Kardiologie, 87 1-6.



Abstract: For patients with acquired heart valve lesions with increased risk for

intracardiac thrombosis and consequent cardiogenic embolism there is consensus

that oral anticoagulation therapy improves the overall prognosis. In mitral valve

lesions anticoagulation is necessary after manifestation of atrial fibrillation or in

cases of unstable sinus rhythm. The risk for thrombembolic events is increasing

parallel to the enlargement of the left ventricular enddiastolic diameter, the left

atrial size and dropping cardiac index. Spontaneous echo contrast (so called

smoke like echos) indicate a prethrombotic state. In these cases an intensive

anticoagulation is indicated. Aortic valve lesions require anticoagulation after

manifestation of atrial fibrillation, the first manifestation of a thrombembolism or

of spontaneous echo contrast. The risk for thrombembolism is increasing parallel

to the reduction of left ventricular pump function. Life long oral anticoagulation

therapy should be managed by use of the International Normalized Ratio (INR),

and should be individualized taking into account patient related cardiac

morphology and physiology, which may predispose to cardiogenic embolism.

The target INR can range between 2.0 and 4.0



Keywords: ADULTS/anticoagulation/ANTITHROMBOTIC THERAPY/aortic valve

lesions/atrial

fibrillation/ATRIAL-FIBRILLATION/consensus/fibrillation/heart/heart valve

lesions/International Normalized Ratio/mitral valve lesions/oral

anticoagulation/prevention/prognosis/risk/STROKE/thrombosis



Fetsch, T., Burschel, G., Breithardt, G., Engberding, R., Koch, H.P., Lukl, J., Trappe,

H.J. and Treese, N. (1999), Antiarrhythmic drug therapy after DC cardioversion

of chronic atrial fibrillation - rationale and design of the PAFAC trial. Zeitschrift

fur Kardiologie, 88 (3), 195-+.

Abstract: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. However,

despite manifold publications reflecting numerous clinical trials about treatment

of AF, the management of this arrhythmia is still under controversial. discussion,

in daily clinical work as well as in research. The present study concentrates on

three major questions: 1. How frequent are recurrences of AF in long-term

follow-up? Most of the previous studies used the occurrence of symptoms as a

surrogate parameter for recurrences of AF, despite the expected high rate of

asymptomatic relapses. In the present study a daily transtelephonic ECG

transmission enables a rhythm monitoring independent of symptoms. 2. Is the

frequency of AF recurrences significantly reduced by antiarrhythmic medication?

A direct comparison of class I and III antiarrhythmic drugs, which still are most

frequently used for this indication,and of placebo will answer this question. 3.

How safe is the long-term treatment for the prevention of AF recurrences with

special respect to proarrhythmic effects? The daily transtelephonic ECG

transmission enables a quantitative and qualitative monitoring of tachy- and

bradyarrhythmias independent of symptoms. Additionally, the daily analysis of

ECG measures may detect parameters predicting subsequent life threatening

arrhythmias. The study design provides a prospective, randomised, double- blind,

placebo controlled, multicenter parallel group comparison. In Germany and in

the Czech Republic about 90 hospitals will include 900 patients with documented

chronic AF, age 18 to 80 years, if they are eligible for electrical cardioversion

without concomitant antiarrhythmic drug therapy and if they are anticoagulated

for at least three weeks prior to inclusion. Neither the size of the left atrium nor

the duration of chronic AF are exclusion criteria. A few hours after successful

electrical cardioversion the patients are randomised either to sotalol (2x 160 mg)

or quinidine + verapamil (3x 160 mg 3x 80 mg) or placebo. Starting at the day

after cardioversion, the patient is asked to record and transmit electrocardiograms

of one minute duration at least once a day using his personal transtelephonic

ECG recording unit (Tele-ECG recorder, credit card size), in case of symptoms

as often as necessary. The ECGs can be transmitted at any time by any regular

phone without additional equipment using a toll free number. A custom made,

computer based, fully automated receiving centre is handling the patient calls

interactively with voice control, including a voice recording of the patient's

symptoms. The ECG tracings and the patient's voice messages are subsequently

computer based analysed by experienced technicians. All ECG measures are

stored in a database. In case of AF recurrence, any other relevant arrhythmia or

additional abnormalities (e.g. QT prolongation) the correspondent hospital is

immediately informed by fax. In case of AF recurrence, a subsequent Holter

recording discriminates in paroxysmal and permanent AE Study medication is

ended if either permanent AF or the third episode of paroxysmal AF are detected

or after 12 months of follow-up. Regular follow-up visits are performed monthly.

Major endpoints are the time to first recurrence of AF or the time to death,

secondary parameters are the number of AF recurrences, the time to end of

medication and AF related symptoms. The recruitment started in the last days of

1996. Until the end of June 1998, 424 patients have been randomised. It is

expected to end recruitment in spring 1999 and to close the study in spring 2000.

Final results will be available in summer 2000

Keywords: AF/age/antiarrhythmic drugs/arrhythmia/arrhythmias/asymptomatic/atrial

fibrillation/cardiac arrhythmia/cardioversion/clinical

trials/control/CONVERSION/design/drug

therapy/drugs/fibrillation/FLUTTER/FOLLOW-UP/FRAMINGHAM/hospital/h

ospitals/left

atrium/MAINTENANCE/monitoring/prevention/quinidine/QUINIDINE/recruit

ment/recurrence/SINUS RHYTHM/sotalol/SOTALOL/STROKE/Tele-EGG

recording/therapy/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/treatment/trials



Ochsenfahrt, C., Hemmer, W., Oertel, F. and Hannekum, A. (1999), The surgical

treatment of atrial septal aneurysm with patent foramen ovale in patients with

cerebral ischemia as an alternative to life-long anticoagulant therapy: operative

strategy and results in 5 cases. Zeitschrift fur Kardiologie, 88 (11), 941-947.



Abstract: There is a significantly higher incidence of cerebral ischemia among patients

with an atrial septal aneurysm and/or a patent foramen ovale. According to the

information provided by modern diagnostic procedures - and in particular by

transesophageal echocardiography - two pathogenic mechanisms should be

considered as possible causes of the cerebral ischemia. Thrombi may develop

locally in the left atrium or atrial septal aneurysm and lead to embolization or,

alternatively, thrombi from the inflow region of the inferior vena cava may

become trapped in the atrial septal aneurysm and pass through the patent

foramen ovale to bring about embolization in the arterial bloodstream. Current

treatment consists of life-long anticoagulation with cumarin derivatives in order

to prevent further neurological complications. With this treatment, however, the

risk of producing hemorrhages cannot be regarded as trivial, especially in old

people. Surgical intervention with the insertion of a button device has so far only

been attempted in a few isolated cases, and it is in any case no use if there is only

an atrial septal aneurysm without a patent foramen ovale. As an alternative to

administering anticoagulants for the rest of the patient's life, we operated on five,

cases of atrial septal aneurysm with patent foramen ovale followed by the

appearance of cerebral ischemia. As with the surgical treatment of atrial septal

defects in general, the risk of the operation (or of subsequent complications) is

very slight indeed. No such problems arose in any of our patients, no blood

transfusions were necessary, and after short postoperative treatment they could

all be discharged. For younger patients with little risk from the treatment itself,

we regard surgical intervention in cases of atrial septal aneurysm with a patent

foramen ovale and cerebral ischemia as an important therapeutic alternative



Keywords: aneurysm/anticoagulant/anticoagulant

therapy/anticoagulants/anticoagulation/atrial septal aneurysm/atrial septal

defect/BLEEDING COMPLICATIONS/cerebral/cerebral

ischemia/CEREBROVASCULAR

EVENTS/CLOSURE/complications/echocardiography/ELDERLY

PATIENTS/EMBOLISM/embolization/epidemiology of cerebral

ischemia/foramen ovale/Germany/incidence/ischemia/left atrium/ORAL

ANTICOAGULATION/patent/patent foramen ovale/postoperative/POTENTIAL

CARDIOEMBOLIC SOURCES/PREVENT STROKE/prevention of cerebral

ischemia/risk/side effects of anticoagulants/STROKE RECURRENCE/surgical

treatment/therapy/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/treatment/use



Jung, W. and Luderitz, B. (2000), Implantable atrial defibrillator. Zeitschrift fur

Kardiologie, 89 206-214.



Abstract: Atrial fibrillation (AF) is a frequent and costly health care problem

representing the most common arrythmia resulting in hospital admission. Total

mortality and cardiovascular mortality are significantly increased in patients with

AF compared to controls. In addition to symptoms of palpitations, patients with

AF have an increased risk of stroke and may also develop decreased exercise

tolerance and left ventricular dysfunction. All of the-se problems may be

reversed with restoration and maintenance of sinus rhythm. External electrical

cardioversion has been a remarkably effective and safe method for termination of

this arrhythmia. Originally described by Lown et al. in 1963, it has been a well

accepted mode of acute therapy. However, this technique requires general

anesthesia or heavy sedation. Internal atrial defibrillation has been evaluated as

an alternative approach to the external technique for over 2 decades. Recent

studies have shown that low-energy internal atrial defibrillation using biphasic

shocks is an effective and safe means in restoring sinus rhythm in patients with

AF and should be considered especially in patients in whom external

cardioversion attempts have failed. Implantable Atrial Defribrillator: Recently, a

stand alone IAD, the Metrix(TM) System (models 3000 and 3820), has entered

clinical investigation. Atrial defibrillation is accomplished by a shock delivered

between electrodes in the right atrium and the coronary sinus. The right atrium

lead has an active fixation in the right atrium. The coronary sinus lead has a

natural spiral configuration for retention in the coronary sinus, and can be

straightened with a stylet. Both leads are 7 French in diameter and the

defibrillation coils are each 6 cm in length. The electrodes may be placed using

separate leads, or very soon by using a single bipolar lead. A separate bipolar

right ventricular lead is used for R wave synchronization and post shock pacing.

The Metrix(TM) defibrillator can be used to induce AF by using R wave

synchronous shocks and can store intracardiac electrograms (EGMs) for up to 2

minutes from the most recent 6 AF episodes. The device can be programmed into

one of the following operating modes: fully automatic, patient activated, monitor

mode, bradycardia pacing only, and off. As AF is not life-threatening, in the

automatic mode the device is only intermittently active in detecting and treating

AE and this "sleep wake-up" cycle interval is programmable. The device

employs extensive processing both for detection and R wave synchronization. In

April 1996, the phase I Metrix(TM) multicenter clinical trial was started. As of

May 1997, a total of 51 Metrix(TM) systems had been implanted as part of the

phase I multicenter clinical trial. Preliminary data suggest that both defibrillation

thresholds and electrograms are stable over time (implant to 3 months).

Detection accuracy has been excellent (100 % specificity, 92.3 % sensitivity) and

there have been no errors of R wave selection for synchronization. No

proarrhythmias have resulted from over 3700 shocks delivered. The device is

effective in electrically converting 96 % of the spontaneous episodes of AF. In

27 % of episodes several shocks were required because of early recurrence of AF.

In 5 patients, the atrial defibrillator was removed: 2 infections, 1 cardiac

tamponade, 1 permanent loss of telemetry, 1 patient required His-Bundle

ablation because of frequent episodes of drug refractory AF with rapid

ventricular response. Initial clinical experience under controlled conditions with

the Metrix(TM) system suggests that the implantable atrial defibrillator may

offer a therapeutic alternative for a subgroup of patients with drug refractory,

symptomatic, long lasting, and infrequent episodes of AE Further efforts must be

undertaken to reduce the patient discomfort associated with internal atrial

defibrillation in an attempt to make this new therapy acceptable to a larger

patient population with AF. Combined Atrioventricular Defibrillator: Recently, a

new dual-chamber defibrillator, the 7250 Jewel(R) AF AMD, has entered clinical

evaluation. Concern has been raised whether or not a stand alone implantable

atrial defibrillator is safe enough or should provide ventricular backup

defibrillation in the rare case of shock induced ventricular proarrhythmia. The

availability of a dual-chamber defibrillator has reactivated the discussion about

the safety of a stand alone implantable atrial defibrillator. The most important

new features of the 7250 Jewel(R) AF AMD system include dual-chamber

pacing, a new dual-chamber detection criterion for rejection of supraventricular

tachycardias, detection and treatment modalities of atrial arrhythmias, prevention

strategies for atrial arrhythmias. Initial clinical experience with the 7250 Jewel(R)

AF AMD device that combines both detection and treatment in the atrium as well

as in the ventricle indicates a significant improvement in the management of

patients with both supraventricular and ventricular tachyarrhythmias



Keywords: acute/AF/arrhythmia/arrhythmias/atrial arrhythmias/atrial

fibrillation/cardiac/cardiovascular/cardiovascular

mortality/cardioversion/combined atrioventricular

defibrillator/CONVENTIONAL EXTERNAL

CARDIOVERSION/detection/ENERGY INTRACARDIAC

CARDIOVERSION/evaluation/exercise/FIBRILLATION/Germany/health/healt

h care/hospital/implantable atrial defibrillator/internal cardioversion/left

ventricular

dysfunction/mortality/pacing/population/prevention/recurrence/risk/safety/sinus

rhythm/stroke/SYSTEM/therapy/treatment



Budoff, M.J. (2000), Electron beam computed tomography: calcification and lipid

lowering interventions. Zeitschrift fur Kardiologie, 89 130-134.



Abstract: Over 50 % of myocardial infarctions lead to sudden death without any prior

warning signs or previously known coronary disease (1). Thus, persons with

preclinical atherosclerosis must be identified prior to the onset of angina, MI,

stroke or death. It has been estimated that primary prevention can avert more

than 100,000 premature deaths each year in the United States alone and 10 times

that worldwide (2). New modalities are being investigated to look for

atherosclerotic plaque burden, plaque morphology, and endothelial function.

Multiple trials on cholesterol reduction have reproducibly demonstrated a

positive mortality benefit in primary (3, 4) and secondary (5-6) prevention

combining diet with statins. Newer therapies, including antibiotics, antioxidants,

and angiogenesis medications ale being introduced for the possible prevention or

treatment of coronary artery disease. The ability to track the progression or

regression of atherosclerosis non-invasively would allow better evaluation of

these therapies



Keywords:

angina/angiogenesis/ANGIOGRAPHY/antibiotics/antioxidants/atherosclerosis/A

VERAGE CHOLESTEROL

LEVELS/calcification/CALCIUM/cholesterol/computed tomography/coronary

artery disease/coronary calcification/coronary disease/CORONARY-ARTERY

DISEASE/death/diet/disease/EBCT/endothelial

function/evaluation/EVENTS/FOLLOW-UP/HUMAN ATHEROSCLEROTIC

LESIONS/lipid

lowering/MEN/mortality/myocardial/plaque/PRAVASTATIN/prevention/primar

y/primary

prevention/REPRODUCIBILITY/statins/stroke/sudden/treatment/trials/United

States



Carlsson, J., Miketic, S., Flicker, E., Erdogan, A., Haun, S., Cuneo, A. and Tebbe, U.

(2000), Neurologic events in patients with atrial fibrillation: outcome and

prevention practices. Zeitschrift fur Kardiologie, 89 (12), 1090-1097.



Abstract: Background: Atrial fibrillation (AF) is associated with neurologic events

(transient ischemic attack (TIA) and stroke). The objective of the present study

was to determine the outcome of patients with neurological events and atrial

fibrillation (AF) in comparison with patients in sinus rhythm (SR), and to

investigate the primary and secondary prevention practices in patients with

neurological events and AF. Patients and methods: In a prospective,

observational, single center study in a large public, university-affiliated hospital

all patients admitted between 1/97 and 1/98 with acute neurologic events were

registered (n = 369). The association between outcome of neurologic events as

assessed by survival status, functional status (Rankin scale) and severity of event

(European Stroke Scale) and heart rhythm was investigated by use of logistic

regression. Antithrombotic medication on admission and at discharge was

recorded. Results: The mean age of the 369 patients was 75.1+/-10.9 years;

56.1% were female. A TIA was present in 26.2% and stroke in 73.8%. 287

patients (77.8%) were in SR and 82 in AF on admission (22.2%). In-hospital

mortality was 12.7% in all patients. In patients with AE mortality was 23.2% and

9.8% in patients with SR (p = 0.0013). Patients with AF were significantly older

than patients with SR (80.4+/-7.5 versus 73.5+/-11.2 years; p<0.001).

Multivariate analysis identified heart rhythm as an independent predictor of

survival (p<0.01). Patients with AF did suffer from a more severe neurological

deficit on admission and at discharge than patients with SR. In 46.3% of patients

with AF severe dependency was present (Rankin 4/5), while this was the case in

28.5% of patients with SR (p<0.01). The ESS score of patients with AF was

77.4+/-30.6 at discharge compared to 88.1+/-20.3 in patients with SR (p<0.01).

In 50 of 82 patients (61%) AF was previously known. Of these 50 patients 36%

did not receive any kind of antithrombotic treatment and only 12% were

receiving oral anticoagulants before the event. Of 63 surviving patients with AF

32 did not have any contraindications against anticoagulation treatment. At

discharge, 14 (43.8%) of these patients were receiving oral anticoagulants, 17

aspirin or ticlopidine (53.1%) and 1 patient (3.1%) no type of antithrombotic

medication. Conclusions: Neurologic events in patients with AF are more severe

and outcome is significantly poorer than in patients with SR. Anticoagulation as

the effective therapy for primary and secondary prevention of neurologic events

is seriously underused in daily practice



Keywords: acute/ACUTE ISCHEMIC

STROKE/AF/age/anticoagulants/anticoagulation/antithrombotic/ANTITHROM

BOTIC THERAPY/aspirin/atrial

fibrillation/COMMUNITY/dependency/fibrillation/FOLLOW-UP/functional

status/Germany/heart/hospital/HOSPITALS/ischemic/MORTALITY/oral

anticoagulants/outcome/PATTERNS/PREVALENCE/prevention/primary/primar

y and secondary prevention/RISK-FACTORS/secondary/secondary

prevention/severity/sinus

rhythm/status/stroke/survival/therapy/TIA/ticlopidine/transient/transient

ischemic attack/treatment/use/WARFARIN USE



Voller, H., Glatz, J., Taborski, U., Bernardo, A., Dovifat, C., Burkard, G. and Heidinger,

K. (2000), Rationale and design of the self-management of anticoagulation in

patients with non-valvular atrial fibrillation (SMAAF) study. Zeitschrift fur

Kardiologie, 89 (4), 284-288.



Abstract: The objective of this open, randomized, multicenter study is to investigate the

benefits and economic efficiency of self- management of oral anticoagulation in

patients with atrial fibrillation (SMAAF study) in comparison with a group of

patients given conventional care by a general practi tioner or specialist. Two

thousand patients suitable for self-management will be assigned at random to

either the self-management group or the control group. The numbers of

thromboembolic and hemorrhagic complications requiring treatment during the

2-year follow-up period will be recorded as the primary end point. The secondary

endpoint variables will be maintenance of the INR value in the individual target

range, INR variance, the course of complications over time, and the cost

efficiency of self- management compared with the routine procedures. The last

of these parameters will include the diagnostic and/or therapeutic measures

carried out, the duration of inpatient hospital treatment, and the social

consequences (subsequent rehabilitation treatment, inability to work, forced

rentirement). The estimate of the required number of patients was based on the

assumption that during longterm anticoagulant therapy within the framework of

primary and secondary prevention 4 % of patients with chronic non-valvular

atrial fibrillation would have severe thromboembolic of hemorrhagic

complications each year. Since this rate can be halved by selfmanagement, a

one-tailed chi(2)-test of 80 % power and a 5 % significance threshold would

require n = 997 patients per group. The results of the SMAAF study will

establish the socioeconomic benefits of selfmanagement in patients with non-

valvular atrial fibrillation



Keywords: anticoagulant/anticoagulant therapy/anticoagulation/atrial

fibrillation/complications/control/cost/design/fibrillation/Germany/hospital/INR/

non-valvular atrial fibrillation/nonvalvular atrial fibrillation/ORAL

ANTICOAGULATION/prevention/primary/randomized/rehabilitation/secondary

prevention/self-management/STROKE/THERAPY/treatment



Diener, H.C., Darius, H., Bertrand-Hardy, J.M. and Humphreys, M. (2001), Cardiac

events during secondary stroke prevention with dipyridamole. Zeitschrift fur

Kardiologie, 90 (5), 348-351.



Abstract: In a post hoc analysis of the European Stroke Prevention Study 2 (ESPS2), we

investigated whether dipyridamole given as antiplatelet drug in patients with TIA

or stroke increases the risk of cardiac events. ESPS2 was a secondary prevention

trial including 6602 patients with TIA or stroke. Patients were randomized into

one of four treatment arms: 2x25 mg acetylsalicyclic acid (ASA), 2x200 mg slow

release dipyridamole (DP), the combination of DP and ASA and placebo. DP did

not result in a higher number of cardiac events, e.g., angina pectoris, myocardial

infarction or death. The combination of ASA plus DP was superior to either drug

alone in the prevention of strokes



Keywords: acetylsalicyclic acid/angina/angina pectoris/antiplatelet/antiplatelet

drug/aspirin/cardiac/combination/coronary heart

disease/death/dipyridamole/Germany/infarction/myocardial/myocardial

infarction/MYOCARDIAL-ISCHEMIA/prevention/randomized/risk/secondary/s

econdary prevention/secondary stroke prevention/stroke/stroke

prevention/TIA/treatment/trial



Stollberger, C., Finsterer, J., Ernst, G. and Schneider, B. (2002), Is left atrial appendage

occlusion useful for prevention of stroke or embolism in atrial fibrillation?

Zeitschrift fur Kardiologie, 91 (5), 376-379.



Abstract: Since in atrial fibrillation more than 90% of the thrombi are located in the left

atrial appendage, an "elimination" of the left atrial appendage, either by resection

or occlusion, seems an attractive alternative to oral anticoagulation. Although

frequently regarded as an useless appendage, data from animal and human

investigations show that the left atrial appendage may play an important role in

the maintenance and regulation of the cardiac function, especially in arterial

hypertension, atrial fibrillation, coronary heart disease, valvular heart disease and

heart failure. Elimination of the left atrial appendage may impede thirst in

hypovolemia, deteriorate hemodynamic responses to volume or pressure

overload, decrease cardiac output and promote heart failure. Instead of

preventing stroke, the consequences of left atrial appendage elimination may

create new risk factors for stroke and thus might induce more harm than benefit

to patients with atrial fibrillation. As long as the physiologic and

pathophysiologic role of the left atrial appendage is not fully understood, left

atrial appendage elimination should not be an alternative to oral anticoagulation



Keywords: animal/anticoagulation/APPENDECTOMY/arterial/arterial

hypertension/atrial/atrial appendage/atrial fibrillation/Austria/cardiac/cardiac

output/coronary heart disease/disease/embolism/fibrillation/heart/heart

disease/heart failure/human/hypertension/hypovolemia/left atrial

appendage/MAZE

PROCEDURE/MORPHOLOGY/NATRIURETIC-PEPTIDE/OBLITERATION/

oral anticoagulation/prevention/RISK/risk factors/risk factors for

stroke/stroke/stroke Maze procedure/TRANSESOPHAGEAL

ECHOCARDIOGRAPHY/transesophageal echocardiography



Schneider, J., Voit, R., Debus, S., Vanseil, B. and Franke, S. (1995), Carotid

Endarterectomy with Routine Shunting, A Safe Method for Reducing the Risk of

Stroke - Results of 11 Years Experience with 546 Consecutive Elective

Operations. Zentralblatt fur Chirurgie, 120 (8), 624-629.



Abstract: The operative removal of haemodynamical significant carotid artery stenosis

by endarterectomy nowadays is one of the vascular surgical standard procedures.

Purpose of the operation is prevention of ischemic strokes, For a long-term

prognostic advantage the patient has to take the risk of perioperative mortality

and morbidity. While efforts are being made to minimize this risk, the question

of optimal surgical strategy has not get finally been solved. Since 1982 in our

hospital all carotid endarterectomies are carried out with routine insertion of an

intraluminal shunt. The distal intima step of the internal carotid artery is secured

by a running suture and closure of the longitudinal arteriotomy is accomplished

by dacron patch plasty. In this manner 546 successive operations have been

performed under general anaesthesia until 1993. Intra- and postoperative

mortality,vas 0,9% with an ischemic cerebral infarction rate of 1,8% . According

to the preoperative stage of cerebrovascular insufficiency the frequencies for

mortality and perioperative ischemic stroke were 0,6% and 1,3% for CVI I, 0,4%

and 0,7% for CVI II and 2,8% and 5,7% for CVI IV. Apart from perioperative

mortality for patients with CVI IV, these complication rates are clearly below the

suggested limits of the Ad hoc Commitee on Carotid Surgery Standards by the

Stroke Council of the American Heart Association. Routine use of a temporary,

intraluminal shunt in carotid artery operations therefore can be considered as a

safe measure, with complication rates still not underbid by those achieved with

intraoperative cerebral monitoring and selective shunting



Keywords: carotid/CAROTID ENDARTERECTOMY/CAROTID

STENOSIS/CEREBROVASCULAR INSUFFICIENCY

(CVI)/endarterectomy/INTRALUMINAL SHUNTING/ischemic

stroke/morbidity/mortality/prevention/risk/stroke/vascular



Mast, H., Chambless, L.E., Mohr, J.P. and Toole, J.F. (1996), Endarterectomy for

asymptomatic carotid artery stenosis - Results of the ACAS-study. Zentralblatt

fur Chirurgie, 121 (12), 1033-1035.



Abstract: Objective: To determine the effect of endarterectomy on the primary

prevention of ischemic stroke in patients with asymptomatic carotid artery

stenosis. Methods: In a prospective, randomized, multicenter trial 1659 patients

with asymptomatic carotid stenosis of 60 % or more were studied in two

treatment arms (endarterectomy: n=825; medical therapy: n=834). Endpoints

were: (1) ischemic stroke in the vascular territory of the study artery, (2) any

perioperative stroke or any perioperative death. Results: The Kaplan-Meier

5-year-risk estimation showed a relative risk reduction of 53% (confidence

interval: 22 %-72 %) for patients in the surgical arm. The combined

perioperative morbidity and mortality rate was 2.3 %. Conclusion:

Endarterectomy of asymptomatic carotid artery stenosis performed with a

perioperative complication rate of less than 3% reduces the 5-year risk of

ipsilateral stroke



Keywords: asymptomatic/carotid/carotid artery/carotid artery stenosis/carotid

stenosis/endarterectomy/ischemic/ischemic

stroke/morbidity/mortality/prevention/primary prevention/randomized/relative

risk/risk/stroke/symptomatic carotid artery

stenosis/therapy/thromboendarterectomy/treatment/vascular



Schweiger, H. (2000), Natural history of carotid artery stenosis and indication for

surgery. Zentralblatt fur Chirurgie, 125 (3), 221-227.



Abstract: Atherosclerotic stenoses of the internal carotid artery are often the underlying

cause for ischemic stroke. Several studies show a strong correlation between the

grade of stenosis and stroke risk. When cerebral symptoms occur in patients with

a carotid artery stenosis of 60% or more the risk of stroke within the following

12 months is over 10%. Large randomised studies show that patients with a high

grade carotid artery stenosis benefit clearly from carotid endarterectomy.

Surgical treatment reduces stroke risk by more than 70% in these patients.

Symptomatic patients with stenoses less than 40% do not benefit by

endarterectomy even when surgical complication rate is low. The benefit of

carotid endarterectomy is proven for asymptomatic stenoses, too. Zn

asymptomatic patients, however, an operative procedure is justified only when

surgical complication rate is 3% or less



Keywords: asymptomatic/ASYMPTOMATIC PATIENTS/BRUITS/carotid/carotid

artery/carotid artery stenosis/carotid

endarterectomy/cerebral/DISEASE/ENDARTERECTOMY/Germany/history/ind

ication for surgery/internal carotid artery/ischemic/ischemic stroke/natural

course/OCCLUSION/PREVENTION/risk/stenosis/STROKE/surgery/treatment/

TRIAL



Reber, P.U., Ghisletta, N., Hakki, H., Zwahlen, I., Baumgartner, I. and Kniemeyer, H.W.

(2001), Assessment of intraoperative duplexsonography during carotid

endarterectomy. Zentralblatt fur Chirurgie, 126 (12), 969-974.



Abstract: Introduction: Carotid endarterectomy (CEA) for prevention of strokes

mandates a high amount of experience and a meticulous surgical technique.

Intraoperative morphologic as well as hemodynamic monitoring of the

endarterectomized arteries is rarely performed. The purpose of this study was to

determine the value of intraoperative colour-coded-duplex-sonography to

recognize eventual intraoperative technical problems that might result in serious

cerebral damage. Methods: Prospective analysis of the medical data of all

patients who underwent CEA for treatment of high-grade carotid stenosis

between 1996 and 1999. Adequacy of the repair was assessed intraoperatively by

duplexsonography. Results: Of 142 consecutive patients with a median age of 68

(43-84) years, 104 (73%) were men and 38 (27%) were women. 9 patients (6%)

had bilateral CEAs. intraoperative duplexsonography revealed abnormalities

during 11 (7%) of 151 CEAs. 4(3%) were considered major and underwent

immediate revision. There was one (0.7%) temporary neurologic deficit

(hyperperfusion syndrome) and 2 (1.3%) cases of fatal intracerebral hemorrhage.

6 (4%) postoperative surgical complications occurred, i.e. 3 cases of major

wound hematoma (with revision) and 3 cases of temporary cranial nerve palsy.

Median length of follow-up was 11 (3-35) months. No late neurologic event

occurred during follow-up. 5 (3%) patients developed asymptomatic restenosis.

Discussion: Routine intraoperative duplexsonography is a valuable and reliable

diagnostic tool to detect correctable technical problems during CEA that

subsequently may lead to neurological deficits, fatal stroke or a high incidence of

restenosis



Keywords: age/ANGIOSCOPY/arteries/ARTERY/asymptomatic/carotid/carotid

artery/carotid endarterectomy/carotid

stenosis/cerebral/complications/diagnostic/duplex

sonography/endarterectomy/FOLLOW-UP/hematoma/hemorrhage/incidence/intr

acerebral/intracerebral

hemorrhage/medical/men/monitoring/postoperative/prevention/restenosis/results/

STENOSIS/STROKE/Switzerland/TECHNICAL DEFECTS/treatment/women



Stolyarova, L.G., Kadykov, A.S., Chernikova, L.A., Razinkina, T.P. and Shvedkov, V.V.

(1989), Prevention and Treatment of Contractures in Post-Stroke Arthropathies.

Zhurnal Nevropatologii I Psikhiatrii Imeni S S Korsakova, 89 (9), 63-65



Vereschagin, N.V. and Varakin, Y.Y. (1996), Prophylaxis of acute cerebrovascular

disorders: Theory and reality. Zhurnal Nevropatologii I Psikhiatrii Imeni S S

Korsakova, 96 (5), 5-9.

Abstract: It would be valid to conduct prophylaxis of acute cerebrovascular disturbances

(ACVD) in the context of state Integral program of prophylaxis of the main

noninfectious diseases. Its basic principles are: control of risk factors, Integral

approach and priority of populational strategy. The main medical directions of

ACDV prophylaxis are: control of arterial hypertension and prevention of

cardioembolic insult in patients with heart rhythm disorders. It is also possible to

prevent repeated ACDV in patients with transitory Ischemic attacks and minor

Insults. The best result is prognosed in combination of the state policy of

providing the healthy mode of life of population and medical prophylaxis of

ACVD in high risk groups



Keywords: acute/arterial hypertension/cerebrovascular/cerebrovascular

disorders/control/CORONARY

HEART-DISEASE/diseases/heart/hypertension/MORTALITY/prevention/proph

ylaxis/risk/risk factors/STROKE



Pokrovsky, A.V., Dzhibladze, D.N., Orekhov, P.Y., Lagoda, O.V. and Shekhonin, B.V.

(1998), Clinical course of restenoses after carotid endarterectomy. Zhurnal

Nevropatologii I Psikhiatrii Imeni S S Korsakova, 98 (1), 10-15.



Abstract: Angiologic and neurologic examinations, ultrasonic dopplerography were

performed in 89 patients after operation of carotid endarterectomy. Period of

observation was 6-182 months after operation (61 months on the average).

Positive clinical effect (absence of disorders of cerebral circulation -DCC) was

achieved in 91% of cases. The frequency of both repeated transitory ischemic

attacks and the strokes was 9%, the best frequency being in patients with initially

asymptomatic course. It was found that the degree of restenosis directly

correlated with frequency of neurologic symptom development: there were no

repeated DCC in normal state of the operated artery. Meanwhile DCC frequency

was less than 4% In cases with the degree of restenoses less than 60% and was

equal to 15,8% in more than 60% restenoses. DCC were more frequently found

in occlusion of internal carotid artery. Rather favourable course of restenoses of

carotid artery was also conditioned by low content of the plaques dangerous in

terms of embolism. Progression of atherosclerotic damages in other parts of

extracranial arteries promoted clinical manifestation of cerebral ischemia.

Moreover, negative neurologic dynamics developed in 7% Of the patients with

restenoses less than 60%, and in 13,8% of cases with restenoses more than 60%.

The conclusion was made about efficiency of carotid endarterectomy in patients

with atherosclerotic damages of carotid arteries. For prevention of repeated DCC

it is recommended both to perform conservative therapy after the operation and

to examine dynamically the patients using ultrasonic dopplerography beginning 6

months after the operation



Keywords: ARTERY STENOSIS/carotid/carotid arteries/carotid

endarterectomy/cerebral/cerebral

ischemia/development/DISEASE/embolism/endarterectomy/ischemia/MANAGE

MENT/META-ANALYSIS/OCCLUSION/POLYTETRAFLUOROETHYLENE

PATCH/prevention/RECURRENT STENOSIS/STROKE/TERM

FOLLOW-UP/therapy/ultrasonic/VEIN PATCH ANGIOPLASTY



Stakhovskaya, L.V., Kvasova, O.V., Pryanikova, N.A., Efremova, N.M. and Skvortsova,

V.I. (2000), The application of dipyridamole (curantyl) for the secondary

prevention of ischemic stroke. Zhurnal Nevropatologii I Psikhiatrii Imeni S S

Korsakova, 100 (4), 28-31



Keywords: dipyridamole/ischemic/ischemic stroke/prevention/secondary

prevention/stroke



Stakhovskaya, L.V., Pryanikova, N.A., Kvasova, O.V., Guseva, O.I., Buvaltsev, V.I. and

Skvortsova, V.I. (2001), Comparative analysis of treatment with either

dipyridamol or combination dipyridamol plus aspirin in patients selected for

secondary stroke prevention. Zhurnal Nevropatologii I Psikhiatrii Imeni S S

Korsakova, 66-71.



Abstract: 57 patients were treated with dipyridamol (225 mg/day) alone and in

combination with aspirin (150 mg/ and 50 mg/day respectively) since the 15th

day of stroke onset. 16 patients were enrolled as controls. Development of

vascular events and results of spontaneous and ADP induced aggregation rates

were assessed. We found that such therapy applied for six months could prevent

the development of myocardial infarction, ischemic stroke and other vascular

events whereas in 19% of patients who weren't treated recurrent ischemic stroke

occurred. It is shown that both monotherapy with dipyridamol and combination

therapy with dipyridamol+aspirin has stabilized aggregation within normal

parameters by the middle of the treatment course irrespectively of platelet

functional activity registered before treatment start



Keywords: ADP/aggregation/aspirin/combination/combination

therapy/development/infarction/ischemic/ischemic stroke/myocardial/myocardial

infarction/PLATELET-AGGREGATION/prevention/secondary/secondary stroke

prevention/stroke/stroke prevention/therapy/treatment/vascular



Olbinskaya, L.I. (2001), Therapy of arterial hypertension and stroke prevention. Zhurnal

Nevropatologii I Psikhiatrii Imeni S S Korsakova, 45-47



Keywords: arterial

hypertension/BLOOD-PRESSURE/DISEASE/hypertension/prevention/RISK/str

oke/stroke prevention



Harakoz, O.S., Kanorsky, S.G., Schelchkova, I.S. and Kizhvatova, N.V. (2001), First

results of stroke register in Krasnodar. Zhurnal Nevropatologii I Psikhiatrii

Imeni S S Korsakova, 26-30.



Abstract: The stroke register started in Krasnodar revealed that the age- standardized

stroke morbidity in male patients was 232.3 in 1998, among female - 146.6 per

100 000 (p<0.01), and mortality - 90.4 and 69.5 for 100 000, respectively

(p<0.05). At the age before 50 mortality among males is 1.8 times higher, aged

50-69 - in 1.4 times higher than in females of the same ages, but after 70 years

old, vice versa, it is 1.6 times lower. 39.7% patients were admitted to the hospital,

62.1% of them had mild and moderate stroke. 74.7% patients with severe stroke

were treated. In these cases mortality was 61.4% while that in in- patient, 17.8%

(p<0.01). Hypertension appeared to be the main risk factor of stroke (65.7%).

Despite the patient's well awareness of this disease (81.8%) 65.2% patients

refused to take hypotensive therapy and only 16.9% afflicted with stroke later

were regularly treated in appropriate way



Keywords: age/aged/awareness/CARDIOVASCULAR-DISEASE/CEREBRAL

INFARCTION/disease/HEART-DISEASE/hospital/HYPERTENSION/hypotens

ive

therapy/MEN/morbidity/MORTALITY/MYOCARDIAL-INFARCTION/PREV

ENTION/risk/risk factor/RISK-FACTORS/stroke/therapy/WOMEN



Preobrazhensky, D.V., Sidorenko, B.A., Batyraliev, T.A., Nosenko, N.S. and Pataraya,

S.A. (2002), Primary prevention of cerebral stroke. Part I. Zhurnal

Nevropatologii I Psikhiatrii Imeni S S Korsakova, 19-23.



Abstract: Prevalence of stroke in Russia is compared to that in North American and

West European developed countries. The lifestyle modification is highlighted as

beneficial both for primary and secondary stroke prevention. The randomized

controlled trials concerned with antihypertensive therapy influence on the risk of

stroke were reviewed. Diuretics, beta-blockers, ACE inhibitors and calcium

antagonists are concluded to be equipotent for stroke prevention in patients with

arterial hypertension



Keywords: ACE inhibitors/ACE inhibitors and calcium

antagonists/ANTIHYPERTENSIVE THERAPIES/antihypertensive

therapy/antihypertensive treatment/arterial/arterial hypertension/beta-

blockers/beta-blockers/BLOOD-PRESSURE/calcium/calcium

antagonists/calcium-antagonists/cerebral/diuretics/hypertension/lifestyle/lifestyle

modification/lifestyle modifications/METAANALYSIS/North

American/prevention/primary/primary prevention/randomized/RANDOMIZED

CONTROLLED TRIALS/RISK/risk factors/secondary/secondary stroke

prevention/stroke/stroke prevention/therapy/trials



Fedin, A.I., Efimov, V.S., Kashezheva, A.Z. and Kromm, M.A. (2002),

Hyperhomocysteinemia as a risk factor for stroke. Zhurnal Nevropatologii I

Psikhiatrii Imeni S S Korsakova, 24-28.



Abstract: The importance of stroke investigation stipulates by higher prevalence and

morbidity of the disease as well as severe disablement of patients.

Atherosclerotic plaques and major arteries stenosis, arterial hypertension, arterial

aneurisms, etc., are reported to be the most known etiological factors for stroke.

Arterial hypertension, smoking, diabetes mellitus, older age, physical activity

reduction, obesity, hyperlipoproteinemia with distinct increase of total blood

cholesterol and low and very low density lipoproteins are considered as most

known risk factors for stroke irrespective of its subtypes. For the last years, an

association between intracerebral arteries thrombosis development and abnormal

metabolism of amino acid methionine and its metabolite homocysteine has been

studied intensively. The article addresses the biochemical aspects of this

phenomenon and main etiological causes both of genetic and iatrogenic origin.

Much attention is drawn to prevention and treatment of hyperhomocysteinemia.

The relationship between a chain of atherosclerotic processes development and

oxidative stress activation in relation to cell membrane lipids, extracerebral

hyperhomocysteinemia symptoms is shown. Modem mechanisms of

hemocoagulation system activation in hyperhomocysteinemia are regarded



Keywords: activation/age/arterial/arterial

hypertension/arteries/atherosclerosis/causes/cholesterol/development/diabetes/di

abetes mellitus/disease/genetic/homocysteine/HOMOCYSTEINE

METABOLISM/hyperhomocysteinemia/hypertension/intracerebral/lipids/lipopr

oteins/main head artery

stenosis/mechanisms/metabolism/methionine/morbidity/obesity/oxidative

stress/physical activity/PLASMA

HOMOCYSTEINE/prevalence/prevention/risk/risk factor/risk factors/risk

factors for stroke/smoking/stenosis/stress/stroke/stroke

prevention/symptoms/thrombosis/treatment/VASCULAR-DISEASE



Kharakoz, O.S., Chirva, N.N., Kanorsky, S.G., Ovcharov, V.K. and Skvortsova, V.I.

(2002), Secondary stroke prevention: the advantages of care in neurological

center for specialized outpatient treatment. Zhurnal Nevropatologii I Psikhiatrii

Imeni S S Korsakova, 59-61.



Abstract: In neurological center for specialized course outpatient treatment, a higher

level of medical care, comparing to general clinics, is provided for post- stroke

patients. The continuous antiaggregants intake and modern antihypertensive

therapy allowed to reduce significantly a frequency of secondary stroke in

comparison to standard care for such patients in general outpatient clinics (4.6%

versus 24% during a year; p<0.05). A combined treatment in neurological center

promoted a decrease of neurological deficit in 92.6% of all the cases. Positive

experience of the secondary stroke prevention unit gives grounds for its

introduction in clinical practice



Keywords: antihypertensive therapy/center of specialized outpatient treatment/clinical

practice/medical/prevention/secondary/secondary stroke prevention/stroke/stroke

patients/stroke prevention/THERAPY/TIA/treatment



Vizir, V.A. and Berezin, A.E. (2002), The influence of lacidipin on brain hemodynamics

in patients with arterial hypertension due to carotid artery stenosis. Zhurnal

Nevropatologii I Psikhiatrii Imeni S S Korsakova, 45-51.

Abstract: Eighteen pairs of patients, 18 men and 18 women, aged 57 years, with arterial

hypertension (AH) of 15.7 year duration, were ascertained. Each patient with AH

and carotid artery stenosis has been matched with the patient without carotid

artery stenosis for gender, age, illness duration, degree of target organs damage

and All severity. All the patients were treated with lacidipin in average dosage 6

mg per day for 2-13 weeks. The cerebral blood flow state was evaluated using

duplex insonation with color pulse wave and energetic Doppler. The results

obtained revealed that the lacidipin dosage used in the study promoted an

adequate control over arterial pressure in the AH patients with- or without

carotid artery stenosis. The drug application reduces an exuberant perfusion in

stenosis side of the middle cerebral artery. Lacidipin usage in patients with AH

due to carotid artery stenosis may be taken into account in cerebral stroke

prevention



Keywords: age/aged/arterial/arterial hypertension/brain/brain

hemodynamics/carotid/carotid artery/carotid artery stenosis/cerebral/cerebral

artery/cerebral blood

flow/control/Doppler/duplex/gender/hemodynamics/hypertension/ISCHEMIC

STROKE/lacidipin/men/middle cerebral artery/MILD

HYPERTENSION/prevention/RISK/severity/stenosis/stroke/stroke

prevention/treatment/TRIAL/women



Gorbacheva, F.E., Buvaltsev, V.I., Natyazhkina, G.M., Matveeva, L.A., Kvasov, V.T.,

Telysheva, J.B. and Nosko, V.N. (2002), Effect of nebivolol on systemic and

cerebrovascular hemodynamics in patients with cerebrovascular lesions and

arterial hypertension. Zhurnal Nevropatologii I Psikhiatrii Imeni S S Korsakova,

52-56.



Abstract: The effect of nebivolol on cerebrovascular blood flow state was studied in 25

patients with discirculatory encephalopathy (DEP) due to arterial hypertension

and cerebrovascular artherosclerosis after transient ischemic attacks (TIAs) and

with residual stroke symptoms in the subcompensation stage. Major

cerebrovascular arteries blood flow was studied using triplex ultrasonic scanning

and regional blood flow - with radionuclide Tc-99m scintigraphy.

Atherosclerotic stenosis (30- 70% of extra- and intra-cerebral arteries up to

occlusion) has been detected in the majority of the patients. Monotherapy with

nebivolol in dosage 2.5-5 mg per day for 8 weeks had hypotensive effect without

severe bradycardia and cerebrovascular hemodynamic deterioration. Significant

cerebrovascular blood flow improvement has been found in the patients with

TIAs. Therefore, nebivolol therapy proved to have a hypotensive effect and

improve cerebrovascular hemodynamics



Keywords: arterial/arterial

hypertension/arteries/artherosclerosis/cerebrovascular/cerebrovascular blood

flow/hemodynamics/hypertension/intracerebral/ischemic/nebivolol/residual/seco

ndary stroke prevention/stenosis/stroke/symptoms/therapy/transient/transient

ischemic attacks/treatment/ultrasonic