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HOPE

VIEWS: 5 PAGES: 29

									How should we protect
 the diabetic heart?

       Miles Fisher
Royal Alexandra Hospital, Paisley
WHO Definition of Diabetes
Mellitus
• „Diabetes mellitus is a state of chronic
  hyperglycaemia which may result from
  many environmental and genetic
  factors, often acting jointly‟

 WHO Expert Committee on Diabetes
 Mellitus 1980
Re-definition of Diabetes
• „Diabetes is a state of premature
  cardiovascular death which is
  associated with chronic hyperglycaemia
  and may also be associated with
  blindness and renal failure‟

 Miles Fisher, Dublin 1996
 Haffner - Results
incidence
  50
  45
  40                                                   Nondiabetic, no MI
  35                                                   n=1304
  30                                                   Nondiabetic, previous
                                                       MI n=69
% 25
                                                       Diabetic, no MI
  20                                                   n=890
  15                                                   Diabetic, previous MI
  10                                                   n=169
   5
   0
               Fatal and nonfatal MI

            Haffner et al. N Engl J Med 1998; 339: 229-34
Diabetes and heart
abnormalities
• Coronary heart disease
• Specific heart disease of diabetes
• Diabetic autonomic neuropathy
Coronary heart disease and
diabetes
• Studied using
  – epidemiology
  – post-mortem
  – electrocardiography
  – angiography
• Coronary heart disease more prevalent,
  more extensive, more diffuse
• High prevalence of „silent ischaemia‟
Myocardial infarction
• Mortality twice the
  non-diabetic
• Increased „silent‟ or
  painless infarction
• Delay in receiving
  treatment
• Increased
  congestive cardiac
  failure, cardiogenic
  shock, rupture, re-
  infarction
How should we protect the
diabetic heart?
• Treat the diabetes (primary
  prevention)
• Treat the cardiovascular risk factors
• Other preventative measures
• Treat the heart disease

 Miles Fisher Dublin 1996
       “Management of diabetic
       cardiovascular disease”
         SIGN Guideline 19

Primary prevention and risk factor
 management
Treatment of acute myocardial
 infarction and secondary prevention
Implementation of the guideline
Review of the guideline and
 recommendations for research
                            August 1997
Treatment of Type 1 Diabetes
and Heart Disease - DCCT
• Reduction by 41% in risk of all major
  cardiovascular and peripheral vascular
  events combined
• Mortality not significantly different
  between the treatment groups
Treatment of Type 2 Diabetes
and Heart Disease - UKPDS
• Significant reduction in retinopathy,
  microvascular end-points and diabetes
  related end-points
• Non-significant reduction by 16% in risk
  of myocardial infarction (p=0.052)
• Mortality not significantly different
  between the treatment groups
How should we protect the
diabetic heart?
1.   Treat the diabetes (primary prevention)
2.   Treat the cardiovascular risk factors
3.   Other preventative measures
4.   Treat the heart disease
Cardiovascular Risk Factors
and Diabetes
• Data from epidemiological studies including
  Framingham
• Usual risk factors apply - smoking, obesity,
  hypertension, hyperlipidaemia, fibrinogen
• Unique role for diabetes as an independent
  factor
• Evidence supporting response to risk factor
  reduction in diabetes now available for
  hypertension and hyperlipidaemia
HBP Studies in Diabetes
    Completed     Ongoing
•   ABCD        • ALLHAT
•   FACET       • Multiple ongoing
•   HDS           studies including
•   HOT           large numbers of
                  patients with
•   SHEP          diabetes
•   Syst-Eur
Hypertension and Diabetes
Of proven benefit         Caution required
• ACEI                    • Amlodipine
• B-blockers              • Doxazosin
• Diuretics               • Isradipine
• Calcium channel         • Nisoldipine
  blockers (felodipine,
  nitrendipine)
Lipid Studies in Diabetes
    Completed       Ongoing
•   4S          •   ALLHAT
•   CARE        •   CARDS
•   LIPID       •   FIELD
•   VA-HIT      •   LDS
•   DAIS        •   etc
How should we protect the
diabetic heart?
1. Treat the diabetes
2. Treat the cardiovascular risk factors
3. Other preventative measures
   (“primary prevention”)
4. Treat the heart disease
Other Preventative Measures
  Proven              Uncertain
• Aspirin           • Weight loss
• Ramipril (HOPE)   • Exercise
                    • HRT
Aim of the HOPE Study
• To evaluate the efficacy of the ACE
  inhibitor ramipril and the anti-oxidant
  vitamin E in reducing the incidence of
  MI, stroke, or CVD death in people
  considered to be at high risk of CVD




HOPE Study Investigators. Can J Cardiol, 1996
Inclusion Criteria 1
• Patients 55 years of age
• Previous myocardial infarction, PTCA or
  CABG
• Stable or unstable angina
• Peripheral vascular disease
• Stroke


HOPE Study Investigators. Can J Cardiol, 1996
Inclusion Criteria 2
• Diabetes combined with:
    – BP >160mmHg, diastolic>90mmHg, or on
      treatment
    – Total cholesterol >5.2mmol/L
      or HDL <0.9mmol/L
    – Smoking
    – Microalbuminuria
    – Any evidence of previous vascular disease


HOPE Study Investigators. Can J Cardiol, 1996
Primary Endpoint
• All CVD events
• Defined as a combined endpoint of
    – CVD death or
    – MI or
    – Stroke




HOPE Study Investigators. Can J Cardiol, 1996
Effect of Ramipril on CV Events
in Patients With Diabetes
               25

               20   19.8
                                                            Placebo (n=1770)
Patients (%)




                                                            Ramipril (n=1808)
               15          15.3
                                              12.9
                                  9.7                10.2
               10
                                        6.2                     6.1
               5                                                      4.2

               0
                    CV events     CV death           MI           Stroke
                                    Primary endpoint
                     Survival Curves on Primary
                     Outcome - DM
                     0.25
Kaplan-Meier Rates




                                      Ramipril     Placebo
                      0.2
                     0.15
                      0.1
                     0.05
                       0
                            0   500              1000        1500
                                        Days of Follow-up
How should we protect the
diabetic heart?
•   Treat the diabetes
•   Treat the cardiovascular risk factors
•   Other preventative measures (“primary
    prevention”)
•   Treat the heart disease
CHD and diabetes
    Proven               Uncertain
•   Aspirin          •   Other anti-anginal
•   Beta blockade        therapy
•   ACE inhibition   •   ACE receptor
    (CCF)                antagonists
•   CABG             •   Other treatments for
                         CCF
                     •   PTCA?
                     •   Heart
                         transplantation?
MI and diabetes
    Proven/Certain     Uncertain/
•   Aspirin            Controversial
•   Thrombolysis     • Intravenous insulin /
•   Beta blockade      subcutaneous
•   ACE inhibition     insulin
                     • Primary angioplasty
Unanswered questions?
• Should we be screening all patients for
  CHD?
• How to implement guidelines?
• How to avoid polypharmacy/encourage
  compliance (OHAs, statin, ACEI,
  aspirin, etc)?
• What is the role of intravenous insulin
  following myocardial infarction?
Conclusions
• Evidence-based medicine provides
  information on protecting the diabetic
  heart
• Further studies will expand the evidence
  base
• Evidence-based guidelines are
  available
• Implementation is the big challenge

								
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