Arterial Stiffness in Mild Primary Hyperparathyroidism Mishaela R. Rubin, Mathew S. Maurer, Donald J. McMahon, John P. Bilezikian and Shonni J. Silverberg J. Clin. Endocrinol. Metab. 2005 90:3326-3330 originally published online Mar 15, 2005; , doi: 10.1210/jc.2004-1400 To subscribe to Journal of Clinical Endocrinology & Metabolism or any of the other journals published by The Endocrine Society please go to: http://jcem.endojournals.org//subscriptions/ Copyright © The Endocrine Society. All rights reserved. Print ISSN: 0021-972X. Online 0021-972X/05/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 90(6):3326 –3330 Printed in U.S.A. Copyright © 2005 by The Endocrine Society doi: 10.1210/jc.2004-1400 Arterial Stiffness in Mild Primary Hyperparathyroidism Mishaela R. Rubin, Mathew S. Maurer, Donald J. McMahon, John P. Bilezikian, and Shonni J. Silverberg Departments of Medicine (M.R.R., M.S.M., D.J.M., J.P.B., S.J.S.) and Pharmacology (J.P.B.), College of Physicians & Surgeons, Columbia University, New York, New York 10032 When primary hyperparathyroidism was a more symptomatic dis- justed for, primary hyperparathyroidism was an independent pre- ease, it was often associated with increased cardiovascular risk. As dictor of increased augmentation index (B 3.37; P 0.03). A the clinical manifestations of the disease have changed to a milder, matched-pair analysis showed that 15% of the variance in AIx was more asymptomatic disorder, investigation is shifting to more subtle uniquely accounted for by the presence of primary hyperparathyroid- cardiovascular abnormalities. We measured arterial stiffness in 39 ism. The presence of primary hyperparathyroidism was a stronger patients with mild primary hyperparathyroidism [serum calcium, predictor of elevated AIx than age, gender, smoking, hypertension, 2.66 0.2 mmol/liter (10.7 0.6 mg/dl); PTH, 21.7 9.5 pmol/liter hyperlipidemia, or diabetes mellitus. AIx was also directly correlated (89 39 pg/ml)] and in 134 controls. Arterial stiffness was measured with evidence of more active parathyroid disease, including higher mathematically at the radial artery with a noninvasive device as the PTH levels (r 0.42; P 0.05) and lower bone mineral density at “augmentation index” (AIx). The AIx measures the difference between the distal one-third radius (r 0.33; P 0.05). The diagnosis of the second and first systolic peaks in the pressure waveform and primary hyperparathyroidism was therefore an independent predic- correlates with increased cardiovascular risk. When physiological tor of increased AIx, an early measure of arterial stiffness, and the variables affecting augmentation index and potentially confounding increase was associated with evidence of more active parathyroid cardiovascular risk factors (age, gender, heart rate, height, blood disease. (J Clin Endocrinol Metab 90: 3326 –3330, 2005) pressure, diabetes mellitus, smoking, and hyperlipidemia) were ad- W HEN PRIMARY HYPERPARATHYROIDISM (PHPT) was a more symptomatic disease, it was often associ- ated with increased cardiovascular risk (1, 2). Current data AIx was found previously to be increased in 21 patients with mild PHPT compared with controls by Smith et al. (8). However, AIx is affected by a number of variables, such as about the cardiovascular consequences of PHPT are often con- heart rate and height, which were not fully considered in the flicting, in part due to the decrease in disease severity in the previous study. A higher heart rate lowers AIx because of an United States over the last several decades (3). As the clinical earlier arrival of the reflected wave (9), whereas decreased findings in PHPT have become more subtle over time, the height increases AIx because the site of the reflected wave is investigation of cardiovascular manifestations of the disease closer to the proximal aorta, leading to a greater reflected has turned to less clinically overt abnormalities. In particular, wave (10). Demographic features also limited the interpre- studies of vascular function have focused on vascular reactivity, tation of the previous study, because the PHPT subjects were which measures small-vessel, or endothelial, function, as well older than the controls [AIx increases with age because of as vascular compliance and capacitance, measures of large- increased arterial wall thickening and decreased elasticity vessel function (4 – 6). (11)] and had a high frequency of abnormal carbohydrate and Augmentation of the pressure waveform is caused by pe- lipid metabolism, classic cardiovascular risk factors that can ripheral reflection of the initial pressure wave, generated by independently influence vascular stiffness (12–14). Increased ventricular ejection. It is an actual echo of this wave, return- AIx occurs in diabetes mellitus and hypercholesterolemia, ing late in diastole when the arteries are very distensible and probably as a result of alterations in the arterial wall elastin pulse-wave velocity is slow. It returns progressively earlier and collagen (14, 15). Other factors known to increase AIx are during systole as the arteries stiffen and aortic-wave velocity female sex (16), smoking (17), and hypertension (18). The aim increases. The augmentation index (AIx) is measurable of the present study was to examine the augmentation index through identification of the shoulder or early systolic peak in mild PHPT while adjusting for potentially confounding of pressure, which corresponds to peak flow in the aorta, and factors, including age, gender, heart rate, height, blood pres- measurement from this point to the second peak, or shoulder sure, diabetes mellitus, smoking, and hyperlipidemia. of the wave in late systole. AIx has been shown to be a strong, Subjects and Methods independent risk marker for premature coronary artery dis- ease (7). Subjects Thirty-nine consecutive patients (35 females, 4 males) with mild PHPT, as defined by elevated serum calcium and PTH concentrations, First Published Online March 15, 2005 were evaluated in our Metabolic Bone Disease Unit at the time of a Abbreviations: ACE, Angiotensin-converting enzyme; AIx, augmen- routine clinic visit. To exclude patients with such marked hypercalcemia tation index; PHPT, primary hyperparathyroidism. that vascular calcification would be a clearly expected finding, we lim- JCEM is published monthly by The Endocrine Society (http://www. ited PHPT patients to those with serum calcium levels less than 3 endo-society.org), the foremost professional society serving the en- mmol/liter ( 12 mg/dl) and PTH levels less than 50 pmol/liter ( 200 docrine community. pg/ml) by the intact immunoradiometric assay. No exclusion criteria 3326 Rubin et al. • Arterial Stiffness in Hyperparathyroidism J Clin Endocrinol Metab, June 2005, 90(6):3326 –3330 3327 were used. One hundred thirty-four healthy controls (88 females, 46 analysis. With AIx as the dependent variable, the following independent males) were evaluated at a Health Awareness Fair at Columbia Uni- variables were entered in the model, along with a dummy code for the versity. Control subjects were excluded if they reported a history of an presence of a diagnosis of PHPT: age, sex, height, heart rate, systolic and elevated serum calcium. The presence of cardiovascular risk factors diastolic blood pressure, tobacco use, history of hypertension, hyper- including diabetes mellitus, hyperlipidemia, and hypertension, which lipidemia, and diabetes mellitus. P 0.05 was considered significant. can influence augmentation index, was ascertained by questioning in Matched-pair analysis was performed with the use of “propensity addition to medication review. Patients smoking at least one cigarette scores” for the analysis of nonrandomized cohorts (23). A propensity daily for 1 yr within the last 5 yr were considered smokers. Diabetes was score was calculated for each subject (i.e. the likelihood of being in the defined by the use of oral hypoglycemic agents or insulin therapy. PHPT or control group, calculated from a logistic regression model that Hyperlipidemia was defined by the use lipid-lowering medication. Hy- included heart rate, height, gender, blood pressure, age, diabetes mel- pertension was defined by either a systolic blood pressure more than 140 litus, smoking, and hyperlipidemia), and the largest number of pairs of mm Hg or diastolic blood pressure more than 90 mm Hg or the use of cases and controls with adjacent propensity scores was used for the antihypertensive medication. Measurements of height and resting heart matched-pair analysis. rate, variables that influence augmentation index, were obtained in each subject. Informed written consent was obtained for each subject, and Results approval for the study was obtained from the Columbia University Institutional Review Board. The characteristics of the PHPT and control groups are shown in Table 1. Mean serum calcium [2.66 0.2 mmol/ Pulse-wave analysis liter (10.7 0.6 mg/dl)] and PTH levels [21.7 9.5 pmol/ Arterial stiffness and central aortic pressure were measured nonin- liter (89 39 pg/ml)] were in the range typical for a cohort vasively by the technique of pulse-wave analysis using the SphygmoCor of patients with mild PHPT. Five patients (13%) had a history apparatus (version 6.01; AtCor, Sydney, Australia) (19). All measure- of nephrolithiasis, although none had active stone disease at ments were taken from the radial artery at the wrist using a microma- the time they were studied. The remaining 34 patients were nometer (SPC-301; Millar Instruments, Houston, TX), applying the prin- asymptomatic. The frequencies of tobacco use, hyperlipid- ciple of applanation tonometry to flatten the artery by gentle pressure. Data were entered directly into a computer and processed by system emia, and diabetes mellitus were similar among the two software to allow accurate on-line recording of the radial artery wave- groups. Compared with the control group, the PHPT group form. The corresponding aortic pressure waveform was then generated was younger, had more women, and had lower peripheral from an averaged radial artery waveform (derived from 11 sec of brachial artery systolic pressures and less frequent histories sequentially recorded radial artery waveforms) using a validated trans- fer function (19 –21). The AIx was determined from a computerized of hypertension. Resting heart rate and peripheral brachial analysis of the central aortic waveform. It is defined as the difference artery diastolic pressure were similar among the two groups. between the first and second peaks of the central arterial waveform, The proportion of patients using angiotensin-converting en- expressed as a percentage of the pulse pressure (19). Larger values of AIx zyme (ACE) inhibitors and blockers did not differ between indicate increased wave reflection from the periphery as a result of the two groups. Serum creatinine was available in 36 of the increased arterial stiffness. Radial blood pressure was calibrated against brachial blood pressure, patients and in 63 of the controls and did not differ between which was measured using conventional mercury sphygmomanometry. the groups (patients, 0.9 0.2 vs. controls, 1.0 1.1 mg/dl; The software allowed for objectivity of measurements by setting quality P 0.4). The 63 controls for whom serum creatinine data control parameters on the radial artery waveform recordings. These were available do not represent a biased, younger sample parameters were mean pulse height and systolic and diastolic variabil- ity. If any of the parameters on a given recording wave were outside the because more than half (n 39) were above the mean age of predetermined acceptable limits ( 100 mV for pulse height, 10% for 67.1 yr of the control population. Indices of PHPT are shown systolic or diastolic variability), then the recording was excluded. Re- in Table 2. producibility of the AIx using the SphygmoCor apparatus was deter- Pulse-wave analysis revealed a higher AIx in the PHPT mined as described previously (22). The precision in our laboratory group (28 10 vs. 25 10%), although it was not statistically between repeated measurements of the AIx is 2.2 1.5% (mean differ- ence sd). significant without adjustment for factors that influence AIx. Biochemical and densitometric measurements TABLE 1. Characteristics of subjects and controls Biochemical and densitometric measurements were obtained at the PHPT Controls time of the study visit or within the 6 months preceding the visit. Serum (n 39) (n 134) total calcium was measured by automated techniques (Technicon In- struments, Tarrytown, NY). Serum PTH was measured by immunora- Age (yr) 63.3 8.8 67.1 11a diometric assay (Nichols Institute Diagnostics, San Jaun Capistrano, Female 35 (90) 88 (66)a CA). Bone-specific alkaline phosphatase activity was measured by a Height (cm) 163.6 7.0 165.2 9.0 solid phase, two-site immunoradiometric assay (Hybritech Inc., San Resting heart rate (bpm) 71.4 11 72.6 11 Diego, CA). Urinary N-telopeptide excretion was measured by a com- Brachial systolic blood 126.4 16.6 142.7 20.0a petitive-inhibition ELISA (Ostex, Seattle, WA). Bone mineral density pressure (mm Hg) was obtained by dual-energy x-ray absorptiometry (model QDR-4500 Brachial diastolic blood 77.4 10 77.7 13 bone densitometer; Hologic, Waltham, MA.) pressure (mm Hg) Tobacco use 3 (8) 4 (3) Hypertension 15 (39) 86 (64)a Statistical analyses Hyperlipidemia 15 (39) 38 (28) Diabetes mellitus 3 (8) 11 (8) All statistical analyses were performed using SPSS for Windows Antihypertensive 12 (31) 44 (33) (version 11.0; SPSS, Chicago, IL). All continuous data are presented as medications mean value sd, and all categorical data are reported as percentage or B blockers 4 10 absolute number. Student’s t tests and Fisher’s exact tests were used to ACE inhibitors 5 8 assess differences between groups. A Pearson’s correlation coefficient was used to assess the relationship between variables. The multivariate Data are expressed as the mean SD or number (%). a relationship among variables was evaluated by multiple-regression P 0.05. 3328 J Clin Endocrinol Metab, June 2005, 90(6):3326 –3330 Rubin et al. • Arterial Stiffness in Hyperparathyroidism TABLE 2. Biochemical and densitometric indices in PHPT presence of PHPT. Having PHPT was a stronger predictor of subjects elevated AIx than age, gender, smoking, hypertension, hy- PHPT Normal perlipidemia, or diabetes mellitus. (n 39) range For the PHPT group, a significant positive correlation was Serum calcium (mmol/liter) 2.66 0.2 2.1–2.4 noted between PTH concentration and AIx (r 0.42; P PTH (pmol/liter) 21.7 9.5 2.4 –15.9 0.05) (Fig. 1A). A hallmark of target organ involvement in Urinary calcium (mg/24h) 191.3 99 300 PHPT is a reduction in cortical bone density as measured at Lumbar spine BMD (gm/cm2) 0.920 0.22 the distal one-third of the radius. When this feature of PHPT T score 1.48 1.5 Total hip BMD (gm/cm2) 0.760 0.15 was studied in relationship to the AIx, the r value was sig- T score 1.52 1.1 nificant (r 0.33; P 0.05) (Fig. 1B). There was no asso- Distal forearm BMD (gm/cm2) 0.614 0.11 ciation between AIx and serum or urinary calcium, markers T score 1.48 1.4 of bone turnover, or bone mineral density at the lumbar spine Urinary NTX (nmol/liter BCE) 50.5 31 20 –50 or femoral neck (data not shown). (n 11) BSAP (ng/ml) (n 13) 18.5 10 8.0 –16.6 Discussion Data are expressed as the mean SD. BMD, Bone mineral density; NTX, N-telopeptide; BSAP, bone-specific alkaline phosphatase. Although symptomatic PHPT has been associated with adverse cardiovascular consequences, it is unclear whether Because large-artery stiffness can be influenced by a variety mild PHPT has similar effects. We found that, when potential of physical and metabolic factors and because the control physiological confounders and classical cardiovascular risk group was significantly older and more hypertensive, a mul- factors were taken into account, the diagnosis of PHPT was tiple-regression analysis was performed in which the fol- an independent predictor of increased AIx, an early measure lowing factors potentially altering central hemodynamic in- of arterial stiffness. The relationship between this measure- dices were entered into the model: presence of PHPT, heart ment and classical indices of parathyroid disease activity, rate, height, gender, blood pressure, age, diabetes mellitus, namely PTH level and distal forearm bone density, help to smoking, and hyperlipidemia. With these adjustments, there substantiate the likelihood that mild PHPT can be associated was a significant relationship between PHPT and AIx. The with cardiovascular abnormalities. presence of PHPT was an independent predictor of increased Symptomatic PHPT has been associated with vascular and AIx (B 3.37; P 0.03). PHPT remained an independent myocardial calcification, arrhythmias, hypertension, and left predictor of AIx in the subgroup of patients with asymp- ventricular hypertrophy (24) (25). Epidemiological studies in tomatic disease (n 34; B 3.17; P 0.05). The attributable Scandinavian populations with PHPT support an increase in unique contribution of the presence of PHPT to the variance cardiovascular mortality (26 –29). In contrast to the European in AIx (r2) in this sample, after controlling for other variables, studies, the only study of a largely asymptomatic American was 5%. Details of this model are shown in Table 3. The cohort found markedly reduced cardiovascular mortality presence of PHPT contributed to the risk of arterial stiffness (relative risk 0.6) (3). In populations characterized primarily more than other known risk factors, including diabetes mel- by asymptomatic disease, evidence for cardiovascular involve- litus, hyperlipidemia, smoking, and diastolic blood pressure. ment has therefore turned to more subtle manifestations. An- When the analysis was performed with only female subjects, atomic parameters, for example, have been measured with the the same pattern of multiple-regression results was seen use of high-resolution carotid ultrasonography (30). Carotid (data not shown). intima-medial thickness was markedly increased in 20 patients A matched-pair analysis was also performed in the 28 with PHPT compared with controls (1.6 0.5 vs. 0.68 0.3) (31). pairs with matched propensity scores (pairs of patients and In populations in which the serum calcium did not extend to the control subjects comparable with regard to heart rate, height, markedly abnormal range, it was shown, in contrast, that ca- gender, blood pressure, age, diabetes mellitus, smoking, and rotid intima-medial thickness is not affected by PHPT (4, 6, 32, hyperlipidemia in a logistic regression model). When the 33). The suggestion is that only in those with severe hypercal- original regression analysis was repeated on this restricted cemia or in those with established cardiovascular risk factors is sample of matched pairs, 83% of the variance in AIx was one likely to find evidence for cardiovascular involvement in accounted for, and 15% was uniquely accounted for by the PHPT. Although these data are supported by a recent study by TABLE 3. Multiple-regression summary for the dependent variable AIx (r2 0.58) Independent variable B SE t value P less than Height (cm) 0.35 0.09 3.98 0.01 Heart rate (bpm) 0.43 0.06 7.25 0.01 Systolic blood pressure (mm Hg) 0.18 0.05 3.59 0.01 Female gender 4.78 1.81 2.65 0.01 Presence of PHPT 3.37 1.52 2.21 0.03 Presence of diabetes mellitus 5.08 1.98 2.56 0.01 Age (increase per decade) 0.96 0.70 1.38 0.18 Smoking 3.60 2.67 1.38 0.17 Presence of hyperlipidemia 1.61 1.26 1.32 0.19 Diastolic blood pressure (mm Hg) 0.02 0.07 0.29 0.77 Rubin et al. • Arterial Stiffness in Hyperparathyroidism J Clin Endocrinol Metab, June 2005, 90(6):3326 –3330 3329 was an independent predictor of increased AIx. Although the controls were older and more hypertensive than the patients with PHPT, these differences, if anything, would tend to bias our results toward minimizing differences rather than es- tablishing them. Other cardiovascular risk factors associated with increased AIx, including smoking, diabetes mellitus, and hypercholesterolemia, were not significantly different between patients and controls. The control subjects did not appear to have a greater degree of renal insufficiency, an important indicator of comorbidity that can be associated with increased AIx. There was also no difference in propor- tion of use of ACE inhibitors or blockers in the two groups. Moreover, all cardiovascular risk factors were adjusted for in the multiple-regression analysis, which showed that PHPT contributed 5% of the variance in arterial stiffness. The pres- ence of PHPT contributed to the risk of arterial stiffness more than other known risk factors, including diabetes mellitus, hyperlipidemia, smoking, and diastolic blood pressure. The strength of the association between PHPT and AIx was fur- ther enhanced when pairs of patients and control subjects well matched with regard to age, gender, heart rate, height, blood pressure, diabetes mellitus, smoking, and hyperlipid- emia were considered. In that analysis, 15% of the variance in AIx was uniquely accounted for by the presence of PHPT. Having PHPT was a stronger predictor of elevated AIx than FIG. 1. A, A significant positive correlation was noted between AIx age, gender, smoking, hypertension, hyperlipidemia, or di- and PTH levels (r 0.42; P 0.05). The horizontal lines delineate abetes mellitus. the normal range of PTH (10 – 65 pg/ml); the relationship with AIx We also found that AIx was directly correlated with evi- extends linearly into the normal range of PTH. B, A significant neg- dence of more active parathyroid disease. The increased ar- ative correlation was noted between AIx and the one-third radius T score (r 0.33; P 0.05). terial stiffness in the presence of higher PTH levels and greater cortical demineralization is consistent with overall Fallo et al.,(34) that study was limited in the scope of the analysis greater target organ involvement that now could include the of the carotid artery. vasculature as well. This relationship extended into the “nor- Arterial stiffness is a strong, early predictor for cardio- mal” range of PTH, but, for these subjects with hypercalce- vascular disease. The normal central aortic pressure wave is mia, levels of PTH, even if normal, are decidedly abnormal. composed of a forward-traveling wave generated by left However, we did not find an association between AIx and ventricular ejection and a later-arriving reflected wave from serum or urinary calcium levels. Whether PTH has an effect the periphery. As arterial stiffness increases, transmission on the vasculature independent of ambient calcium levels velocity of both forward and reflected waves increase, which (36) is unknown. causes the reflected wave to arrive earlier in the central aorta In conclusion, PHPT was an independent predictor of and augment pressure in late systole. This earlier arrival, increased AIx, an early measure of arterial stiffness, and the measured as the AIx, is associated with several cardiovas- increase was associated with evidence of more active para- cular risk factors (35), including age, smoking, hypertension, thyroid disease. Additional studies are needed to establish diabetes mellitus, and hypercholesterolemia. Other factors whether the vasculature should become another key target that can influence AIx include heart rate and height (9, 10). organ for evaluation of patients with mild, asymptomatic ACE inhibitors decrease AIx through vasodilatation, PHPT. whereas blockers increase AIx by a reduction in heart rate. In mild PHPT, AIx was found previously to be increased in Acknowledgments a study by Smith et al. (8). However, heart rate and height were not controlled for. In addition, a younger control group Received July 16, 2004. Accepted March 3, 2005. was used, in whom the AIx might be lower simply as a Address all correspondence and requests for reprints to: Shonni J. Silverberg, M.D., Columbia University, College of Physicians & Sur- function of age (11). Finally, subjects with PHPT were over- geons, Department of Medicine, PH8-864, 630 West 168th Street, New represented with respect to the expected incidence in this York, New York 10032. E-mail: email@example.com. population of diabetes mellitus and elevated total choles- terol, risk factors that can independently influence vascular References stiffness (12–14). 1. Roberts WC, Waller BF 1981 Effect of chronic hypercalcemia on the heart. An In the present study, AIx was compared in 39 patients with analysis of 18 necropsy patients. Am J Med 71:371–384 mild PHPT and 134 healthy controls. When physiological 2. Herrmann G, Hehrmann R, Scholz HC, Atkinson M, Lichtlen P, von zur Muhlen A, Hesch RD 1986 Parathyroid hormone in coronary artery disease— variables affecting AIx and potentially confounding classical results of a prospective study. J Endocrinol Invest 9:265–271 cardiovascular risk factors were taken into account, PHPT 3. Wermers RA, Khosla S, Atkinson EJ, Grant CS, Hodgson SF, O’Fallon WM, 3330 J Clin Endocrinol Metab, June 2005, 90(6):3326 –3330 Rubin et al. • Arterial Stiffness in Hyperparathyroidism Melton III LJ 1998 Survival after the diagnosis of hyperparathyroidism: a 20. Karamanoglu M, O’Rourke MF, Avolio AP, Kelly RP 1993 An analysis of the population-based study. Am J Med 104:115–122 relationship between central aortic and peripheral upper limb pressure waves 4. Nilsson IL, Aberg J, Rastad J, Lind L 1999 Endothelial vasodilatory dysfunc- in man. Eur Heart J 14:160 –167 tion in primary hyperparathyroidism is reversed after parathyroidectomy. 21. Pauca AL, O’Rourke MF, Kon ND 2001 Prospective evaluation of a method Surgery 126:1049 –1055 for estimating ascending aortic pressure from the radial artery pressure wave- 5. Neunteufl T, Katzenschlager R, Abela C, Kostner K, Niederle B, Weidinger form. Hypertension 38:932–937 F, Stefenelli T 1998 Impairment of endothelium-independent vasodilation in 22. Wilkinson IB, Fuchs SA, Jansen IM, Spratt JC, Murray GD, Cockcroft JR, patients with hypercalcemia. Cardiovasc Res 40:396 – 401 Webb DJ 1998 Reproducibility of pulse wave velocity and augmentation index 6. Kosch M, Hausberg M, Vormbrock K, Kisters K, Rahn KH, Barenbrock M measured by pulse wave analysis. J Hypertens 16:2079 –2084 2000 Studies on flow-mediated vasodilation and intima-media thickness of the 23. D’Agostino Jr RB 1998 Propensity score methods for bias reduction in the brachial artery in patients with primary hyperparathyroidism. Am J Hypertens comparison of a treatment to a non-randomized control group. Stat Med 13:759 –764 17:2265–2281 7. Weber T, Auer J, O’Rourke MF, Kvas E, Lassnig E, Berent R, Eber B 2004 24. Clemens TL, Broadus AE 2001 Physiologic actions of PTH and PTHrp. In: Arterial stiffness, wave reflections, and the risk of coronary artery disease. Bilezikian JP, Marcus R, Levine MA, eds. The parathyroids. New York: Aca- Circulation 109:184 –189 demic; 261–273 8. Smith JC, Page MD, John R, Wheeler MH, Cockcroft JR, Scanlon MF, Davies 25. Garcia de la Torre N, Wass JA, Turner HE 2003 Parathyroid adenomas and JS 2000 Augmentation of central arterial pressure in mild primary hyperpara- cardiovascular risk. Endocr Relat Cancer 10:309 –322 thyroidism. J Clin Endocrinol Metab 85:3515–3519 26. Ljunghall S, Jakobsson S, Joborn C, Palmer M, Rastad J, Akerstrom G 1991 9. Wilkinson IB, Mohammad NH, Tyrrell S, Hall IR, Webb DJ, Paul VE, Levy Longitudinal studies of mild primary hyperparathyroidism. J Bone Miner Res T, Cockcroft JR 2002 Heart rate dependency of pulse pressure amplification 6(Suppl 2):S111–S116; discussion S121–S124 and arterial stiffness. Am J Hypertens 15(1 Pt 1):24 –30 27. Hedback G, Oden A 1998 Increased risk of death from primary hyperpara- 10. Kelly RP, Millasseau SC, Ritter JM, Chowienczyk PJ 2001 Vasoactive drugs thyroidism—an update. Eur J Clin Invest 28:271–276 influence aortic augmentation index independently of pulse-wave velocity in 28. Stefenelli T, Abela C, Frank H, Koller-Strametz J, Globits S, Bergler-Klein healthy men. Hypertension 37:1429 –1433 J, Niederle B 1997 Cardiac abnormalities in patients with primary hyperpara- 11. Vaitkevicius PV, Fleg JL, Engel JH, O’Connor FC, Wright JG, Lakatta LE, Yin thyroidism: implications for follow-up. J Clin Endocrinol Metab 82:106 –112 FC, Lakatta EG 1993 Effects of age and aerobic capacity on arterial stiffness in 29. Nilsson IL, Yin L, Lundgren E, Rastad J, Ekbom A 2002 Clinical presentation healthy adults. Circulation 88(4 Pt 1):1456 –1462 of primary hyperparathyroidism in Europe—nationwide cohort analysis on 12. Tanokuchi S, Okada S, Ota Z 1995 Factors related to aortic pulse-wave mortality from nonmalignant causes. J Bone Miner Res 17(Suppl 2):N68 –N74 velocity in patients with non-insulin-dependent diabetes mellitus. J Int Med 30. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson Jr SK Res 23:423– 430 1999 Carotid-artery intima and media thickness as a risk factor for myocardial 13. Salomaa V, Riley W, Kark JD, Nardo C, Folsom AR 1995 Non-insulin-de- infarction and stroke in older adults. Cardiovascular Health Study Collabo- pendent diabetes mellitus and fasting glucose and insulin concentrations are rative Research Group. N Engl J Med 340:14 –22 associated with arterial stiffness indexes. The ARIC Study. Atherosclerosis 31. Nuzzo V, Tauchmanova L, Fonderico F, Trotta R, Fittipaldi MR, Fontana D, Risk in Communities Study. Circulation 91:1432–1443 Rossi R, Lombardi G, Trimarco B, Lupoli G 2002 Increased intima-media 14. Henry RM, Kostense PJ, Spijkerman AM, Dekker JM, Nijpels G, Heine RJ, thickness of the carotid artery wall, normal blood pressure profile and normal Kamp O, Westerhof N, Bouter LM, Stehouwer CD 2003 Arterial stiffness left ventricular mass in subjects with primary hyperparathyroidism. Eur J increases with deteriorating glucose tolerance status: the Hoorn Study. Cir- Endocrinol 147:453– 459 culation 107:2089 –2095 32. Barletta G, De Feo ML, Del Bene R, Lazzeri C, Vecchiarino S, La Villa G, 15. Wilkinson IB, Prasad K, Hall IR, Thomas A, MacCallum H, Webb DJ, Brandi ML, Franchi F 2000 Cardiovascular effects of parathyroid hormone: a Frenneaux MP, Cockcroft JR 2002 Increased central pulse pressure and aug- study in healthy subjects and normotensive patients with mild primary hy- mentation index in subjects with hypercholesterolemia. J Am Coll Cardiol perparathyroidism. J Clin Endocrinol Metab 85:1815–1821 39:1005–1011 33. Kosch M, Hausberg M, Barenbrock M, Posadzy-Malaczynska A, Kisters K, 16. Hayward CS, Kelly RP 1997 Gender-related differences in the central arterial Rahn KH 2001 Arterial distensibility and pulse wave velocity in patients with pressure waveform. J Am Coll Cardiol 30:1863–1871 primary hyperparathyroidism before and after parathyroidectomy. Clin 17. Stefanadis C, Tsiamis E, Vlachopoulos C, Stratos C, Toutouzas K, Pitsavos Nephrol 55:303–308 C, Marakas S, Boudoulas H, Toutouzas P 1997 Unfavorable effect of smoking 34. Fallo F, Camporese G, Capitelli E, Andreozzi GM, Mantero F, Lumachi F 2003 on the elastic properties of the human aorta. Circulation 95:31–38 Ultrasound evaluation of carotid artery in primary hyperparathyroidism. 18. Duprez DA, De Buyzere ML, Verloove HH, Kaufman JM, Van Hoecke MJ, J Clin Endocrinol Metab 88:2096 –2099 Clement DL 1996 Influence of the arterial blood pressure and nonhemody- 35. Nichols WW, Singh BM 2002 Augmentation index as a measure of peripheral namic factors on regional arterial wall properties in moderate essential hy- vascular disease state. Curr Opin Cardiol 17:543–551 pertension. J Hum Hypertens 10:251–256 36. Piovesan A, Molineri N, Casasso F, Emmolo I, Ugliengo G, Cesario F, Bor- 19. O’Rourke MF, Gallagher DE 1996 Pulse wave analysis. J Hypertens Suppl retta G 1999 Left ventricular hypertrophy in primary hyperparathyroidism. 14:S147–S157 Effects of successful parathyroidectomy. Clin Endocrinol (Oxf) 50:321–328 JCEM is published monthly by The Endocrine Society (http://www.endo-society.org), the foremost professional society serving the endocrine community.
Pages to are hidden for
"Arterial Stiffness in Mild Primary Hyperparathyroidism"Please download to view full document