Skip Navigation

Cardiovascular Research 1998 40(2):396-401; doi:10.1016/S0008-6363(98)00177-1
© 1998 by European Society of Cardiology
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Neunteufl, T.
Right arrow Articles by Stefenelli, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Neunteufl, T.
Right arrow Articles by Stefenelli, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 1998, European Society of Cardiology

Impairment of endothelium-independent vasodilation in patients with hypercalcemia

Thomas Neunteufl*, Reinhold Katzenschlager, Claudette Abela, Karam Kostner, Bruno Niederle, Franz Weidinger and Thomas Stefenelli

Departments of Cardiology, Vascular Medicine and Surgery, University of Vienna, Vienna, Austria

* Corresponding author. Tel.: +43-1-40400/4614; Fax: +43-1-408-1148.

Received 4 August 1997; accepted 7 April 1998


   Abstract
Top
 Abstract
1 Introduction
 2 Methods
 3 Results
 4 Discussion
 References
 
Objective: Patients with primary hyperparathyroidism (PHPT) and/or hypercalcemia are at increased risk for myocardial ischemia. Whether PHPT is associated with altered endothelium-dependent dilation, vascular smooth muscle cell function, or both is unknown. This study was performed to test the hypothesis that endothelium-dependent, flow-mediated dilation (FMD) and/or endothelium-independent, nitroglycerin-induced dilation (NMD) is impaired in the preclinical phase of vascular disease in patients with PHPT. Methods: Twenty-six PHPT patients (mean±SD; age 55±15y, serum calcium 3.00±0.37 mmol/l, serum phosphate 0.79±0.21 mmol/l, iPTH 249±262 pg/ml) with no evidence of coronary artery disease (CAD) as well as 26 normocalcemic control subjects (CTL; age 51±12y) were studied. FMD following reactive hyperemia and NMD after 0.8 mg nitroglycerin (NTG) were assessed in the brachial artery by using high resolution ultrasound (7MHz). Results: NMD was impaired in PHPT patients compared to CTL (11.9±3.9% vs. 15.6±5.7%; p=0.012). FMD was similar in both study groups (11.6±4.6% vs. 12.6±4.9%; NS). The ratio of FMD to NMD was significantly different between PHPT patients and CTL (0.98±0.19 vs 0.81±0.25, p=0.009). On multiple stepwise regression analysis serum calcium was independently associated with the FMD/NMD ratio (r=0.34, p=0.017). Conclusions: Endothelium-independent vasodilation is impaired in PHPT patients without clinical evidence of coronary artery disease compared to normocalcemic CTL, while endothelium-dependent dilation was similar in both study groups. Thus, altered arterial reactivity in the course of PHPT may predominantly involve the arterial media and not the endothelium as observed previously in patients with various stages of atherosclerosis.

KEYWORDS Flow-mediated dilation; Nitroglycerin-induced vasodilation; Vascular disease; Hypercalcemia; Primary hyperparathyroidism; Ultrasound


   1 Introduction
Top
 Abstract
 1 Introduction
2 Methods
 3 Results
 4 Discussion
 References
 
Patients with primary hyperparathyroidism (PHPT) are at increased risk for premature death particularly from ischemic heart disease [1–3]. Hypercalcemia, associated with PHPT in about 90% [4], is a risk factor for ischemic heart disease [5–7]. Moreover, necropsy analyses of patients with hypercalcemia revealed accelerated deposition of calcium in the media and intima of coronary arteries [7]. However, in PHPT patients myocardial ischemia may be caused by different mechanisms, such as impaired oxygen supply due to the presence of atherosclerotic plaques [6, 7], vasospasm of coronary arteries [8], mediasclerosis leading to reduced coronary vasodilator reserve without significant atherosclerosis [7, 9], and/or increased myocardial oxygen demand in the course of left ventricular hypertrophy [10–13]. Vasomotion may be regulated by various mechanisms affecting the endothelium and/or the arterial smooth muscle cells. In coronary artery disease the endothelium plays a central role in regulation of vasomotion [14–17]. Using high-resolution ultrasound, Celermajer et al. demonstrated that flow-mediated vasodilation (FMD), an endothelium-dependent response [18–20], based on shear stress induced release of endothelium-derived relaxing factor [21, 22], is impaired in the systemic arteries of asymptomatic subjects with hypercholesterolemia, healthy smokers and patients with coronary artery disease [23, 24], while nitroglycerin-induced, endothelium independent dilation (NMD), primarily reflecting vascular smooth muscle function, is preserved. Moreover, endothelial dysfunction in the peripheral circulation is closely related to endothelial dysfunction in the coronary circulation as well as to the extent and severity of coronary artery disease [25, 26]. However, it is unknown whether hypercalcemia and PHPT are associated with endothelial and/or vascular smooth muscle dysfunction. This study was performed to test the hypothesis that endothelium-dependent FMD and/or endothelium-independent NMD is impaired in PHPT patients without clinical evidence of coronary artery disease.


   2 Methods
Top
 Abstract
 1 Introduction
 2 Methods
3 Results
 4 Discussion
 References
 
2.1 Subjects
Twenty-six patients (18 women and 8 men; aged 24 to 84 y, mean 55±15 y) who underwent surgery for primary hyperparathyroidism and showed no evidence of coronary artery disease in history, 12-lead electrocardiograph and echocardiographic studies were enrolled into the study. All patients underwent bilateral cervical exploration with removal of pathologically altered parathyroid glands. Three representative sections of paraffin imbedded adenomas were stained with H and E for histological examination. Twenty-six subjects (15 women and 11 men aged 24 to 73 y) who underwent coronary angiography because of atypical chest pain but showed normal coronary arteries as well as normal serum calcium levels served as controls. Levels of serum calcium and phosphate were analyzed by a standard autoanalyzer (SMAC 20 Technicon Autoanalyzer). Immunoreactive intact parathyroid hormone (iPTH; Nichols Institute Diagnostics, San Juan Caistrano, CA) was measured by radioimmunoassay. At least two measurements were averaged.

The investigation conformed with the principles outlined in the Declaration of Helsinki and the study protocol was approved by the local human subjects committee. Written informed consent was obtained from all patients.

2.2 Risk factors
Patients smoking at least one cigarette daily for 1 year within the last 5 years were considered smokers. Subjects currently taking antihypertensive drugs or showing a systolic blood pressure (SBP) ≥145 mmHg and/or a diastolic blood pressure (DBP)≥95 mmHg based on the average of two or more readings taken at each of two or more different days (exception: SBP≥210 mmHg and/or DBP≥120 mmHg) constituted the hypertension group. Hypercholesterolemia was defined as a total serum cholesterol level >5.2 mmol/l.

2.3 Vasodilation and blood flow
Endothelium-dependent FMD following reactive hyperemia and endothelium-independent, NMD were examined in the brachial artery according to the method described by Celermajer et al [23]. Using high resolution ultrasound (Acuson 128XP/10, Mountain View, California, with a 7.0 MHz linear array transducer) measurements of the right brachial artery were taken at rest after lying quietly for at least 10 minutes, after cuff deflation completing supra-systolic compression (250 mmHg for 4.5 min) of the right upper arm and after sublingual application of 0.8 mg nitroglycerin. Scans of the brachial artery were taken proximal to the bifurcation of the radial and the ulnar artery by the same ultrasound operator (R.K.) who was unaware of the patients' diagnoses. Diameter measurements were taken from one media-adventitia interface to the other for at least three times at baseline and every 30 s following reactive hyperemia and after administration of nitroglycerin, which was applied 20 min after cuff deflation to allow arterial diameter to return to baseline [23, 27]. The maximum FMD- and NMD-diameters were calculated as the average of the three consecutive maximum diameter measurements following hyperemia and nitroglycerin, respectively. Vasodilation was then calculated as the percent change in diameter compared to baseline.

In all subjects the maximum flow velocity was measured at rest and within 15 s after cuff deflation. To verify that reactive hyperemia caused similar increases in blood flow in both study groups a flow index was calculated by multiplying the maximum flow velocity by the vessel cross-sectional area (3.14xD2/4). Reactive hyperemia was then calculated as percent change in flow index during hyperemia compared to baseline.

2.4 Statistics
Results are expressed as mean±standard deviation (SD). Differences between the two groups were analyzed using Student's t-test for continuous variables and X2 test for categoric variables. Univariate analyses of the effects of serum phosphate, serum calcium, iPTH, age, resting diameter and cardiovascular risk factors on NMD, FMD and FMD/NMD were performed with linear regression. The interactions between NMD and FMD/NMD and serum phosphate, serum calcium, age, resting diameter and the total number of risk factors were examined using multiple stepwise regression analysis. Inter- and intraobserver variability were estimated using full nested analysis of variance. Differences were considered significant at p<0.05.

2.5 Analyses of intra- and interobservervariability
In this study all subjects were investigated by the same ultrasound operator (R.K.). However, to examine intra- as well as interobserver variability eight subjects underwent four scans. Repeat examinations were periodically performed (1 h time interval) by two independent observers in alternating order.

The mean range of intraobserver difference for measurements of baseline diameter was 0.10±0.07%, that of%FMD 2.4±2.2%, and that of%NMD 2.7±1.9%. The variability among repeated measurements by the same observer was 4.4% of total variability (variance component for patient+variance component for measure) for baseline diameter, 11.2% for%FMD and 10.2% for%NMD.

The mean interobserver difference for the measurements of baseline diameter was 0.13±0.07%, of%FMD 2.8±1.7% and of%NMD 3.0±1.8%. The variance component for observer did not noticeably contribute to the total variability.


   3 Results
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
4 Discussion
 References
 
3.1 Clinical and biochemical characteristics
Histology revealed a single chief-cell adenoma in 20 patients, parathyroid hyperplasia in 3 patients and oxiphilic adenoma in 3 patients. The clinical and biochemical characteristics of patients with hyperparathyroidism and CTL are summarized in Table 1.


View this table:
[in this window]
[in a new window]

  		Table 1 Characteristics of the study groups

 
3.2 Vasodilation and blood flow responses
At baseline brachial artery diameters were comparable in PHPT patients and CTL (4.1±0.8, range 2.7 to 5.4 mm vs 3.9±0.8, range 2.7 to 5.3 mm; NS). In response to similar increases in brachial blood flow (from 322±142 to 699±282 ml/min vs 310±139 to 673±310 ml/min; NS) PHPT patients dilated from 4.1±0.8 mm to 4.6±0.8 mm and CTL from 3.9±0.8 mm to 4.4±0.8 mm. FMD values calculated from these data were similar in both study groups (11.6±4.6%; range 2.4 to 22.5% in PHPT patients vs 12.6±4.9%; range 4.6 to 26.1% in CTL; NS) (Table 2, Fig. 1).


View this table:
[in this window]
[in a new window]

  		Table 2 Results of ultrsound measurements in the brachial artery

 

Figure 1
View larger version (11K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Flow-mediated vasodilation (FMD) in 26 patients with primary hyperparathyroidism (PHPT) and 26 normocalcemic control subjects (CTL).

 
After sublingual application of 0.8mg NTG PHPT patients dilated from 4.1±0.8 to 4.6±0.8mm and CTL from 3.9±0.8 to 4.5±0.8 mm. NMD was significantly reduced in PHPT patients compared to CTL (11.9±3.9, range 4.5 to 22% vs 15.6±5.7, range 8.3 to 30.9%; p=0.012) (Table 2, Fig. 2). The ratio of FMD to NMD was significantly different between PHPT patients and CTL (0.98±0.19 vs 0.81±0.25, p=0.009).


Figure 2
View larger version (12K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Nitroglycerin-induced vasodilation (NMD) in 26 patients with primary hyperparathyroidism (PHPT) and 26 normocalcemic control subjects (CTL).

 
On univariate analysis within PHPT patients, both, NMD and FMD were related to the serum phosphate level (vs NMD, r=0.36, p=0.05 and vs FMD, r=0.45, p=0.03) as well as to the resting diameter (vs NMD, r=–0.38, p=0.04 and vs FMD, r=–0.39, p=0.04). A significant inverse correlation was found between the serum phosphate level and the resting diameter (r=–0.41, p=0.04). Correlations between the impairment of NMD and the serum calcium levels, iPTH concentrations, age and cardiovascular risk factors like hypercholesterolemia, hypertension, smoking and diabetes did not reach statistical significance.

Univariate analysis including PHPT patients and CTL revealed significant correlations between NMD and the resting diameter (r=–0.55, p=0.0001) as well as between NMD and the serum phosphate level (r=0.36, p=0.017). No significant correlation was found between serum calcium levels and the impairment of NMD (r=–0.28, p=0.06).

On multiple stepwise regression analysis the resting diameter was independently associated with NMD, within PHPT patients (r=–0.37, p=0.04) and CTL (r=–0.51, p=0.002). No significant correlation was found between the impairment of NMD and the serum phosphate level, serum calcium level, age and the total number of risk factors.

On multivariate analysis (including PHPT patients and CTL) significant correlation was found between the FMD/NMD ratio and the serum calcium level (r=0.34, p=0.017), but not between FMD/NMD and age, resting diameter, serum phosphate and total number of risk factors.


   4 Discussion
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
References
 
The present study shows that endothelium-independent vasodilation of the brachial artery is impaired in PHPT patients without clinical evidence of CAD. In contrast, endothelium-dependent FMD was preserved in PHPT patients compared to normocalcemic CTL with a similar risk factor profile. The ratio FMD/NMD, which was also different between study groups, was independently associated with the serum calcium level. Within PHPT patients NMD and FMD were inversely correlated with the serum phosphate level.

Calcification of the mitral and aortic valves, calcific deposits in the myocardium, left ventricular hypertrophy and myocardial ischemia represent cardiac manifestations of PHPT [28–30]. Some authors suggest that a high incidence of ischemic heart disease in PHPT patients is due to the presence of atherosclerotic plaques [6, 7]and/or vasospasm of coronary arteries [8]while others discuss the importance of mediasclerosis leading to reduced coronary vasodilator response [9, 10]. In the present study we used a test, previously described by Celermajer et al [23], to distinguish endothelial dysfunction from altered reactivity of the smooth muscle cells caused by mediasclerosis.

There is evidence that vascular smooth muscle cells [31]as well as cardiac myocytes [32]are targets for PTH. PTH increases receptor mediated [Ca2+]i of cardiac myocytes which is due to augmented entry of calcium into myocytes as well as to mobilization of calcium from the sarcoplasmatic reticulum by a calcium-induced calcium release mechanism [32]. As a result of this calcium overload myocytes may get damaged [33]. On the other hand, necropsy analyses of patients with chronic hypercalcemia revealed accelerated deposition of calcium not only in myocardial fibers but also in the media and intima of coronary arteries [7]. The present study extends these findings by revealing impaired endothelium-independent vasodilation in PHPT patients without clinical evidence of ischemic heart disease and without medial calcification noted on ultrasound. Moreover, within PHPT patients and CTL the ratio of FMD to NMD was independently correlated with the serum calcium level. Taken together, previous observations and the present data suggest that morphologic and functional alterations of vascular smooth muscle cells lead to impaired vasoreactivity of the brachial artery in PHPT patients prior to arterial medial calcification detectable on ultrasound and prior to clinical symptoms of coronary artery disease.

Moreover, PTH is known to be a vasodilator [34]. A functional endothelium was not required for this relaxing effect [35]but increases in intracellular cyclic AMP concentrations were temporally and quantitatively correlated with PTH induced smooth muscle relaxation [31]. Moreover, Ellison et al demonstrated that vasoactive analogues of PTH like human PTH (1–34) significantly increased urinary phosphorus excretion. Indeed, baseline brachial artery diameter was inversely correlated with serum phosphate levels, indicating both, a vasodilating effect of PTH leading to a larger baseline diameter as well as a phosphaturic effect of PTH resulting in serum phosphate reduction. However, as we measured iPTH and not PTH (1–34) no significant correlation was found between baseline diameter and PTH. Thus, one could speculate that the impairment of NMD in PHPT patients could be accounted for by a lager arterial size. Indeed, PHPT patients showed a tendency towards a larger brachial artery diameter compared to CTL; this difference, however, was not statistically significant. Moreover, the baseline diameter was inversely correlated with both, NMD and FMD in accordance with previous studies [26, 36, 37]and due to a formal correlation between the percent change in brachial artery diameter and the baseline diameter. For example if there were a constant difference between the baseline diameter and the NTG diameter the correlation between NMD and the baseline diameter would be identical to the correlation between NMD and 1/baseline diameter. Thus, a larger baseline diameter, which is related to NMD as well as to FMD, cannot explain an impairment of NMD that is out of proportion to the impairment of FMD.

A possible drawback may be the argument that CTL subjects undergoing coronary angiography because of atypical chest pain may have endothelial dysfunction even in the absence of angiographically detectable coronary artery disease. Thus, impairment of FMD in PHPT patients in addition to impaired NMD could have been masked by impaired FMD in CTL. However, the risk factor burden (total number of risk factors) was similar in both study groups.

These results suggest that patients with PHPT and/or hypercalcemia develop smooth muscle cell dysfunction in the preclinical phase of vascular disease. We conclude that altered arterial reactivity in the course of PHPT may predominantly involve the arterial media and not the endothelium as observed in patients with vascular risk factors such as hypercholesterolemia and smoking. It remains to be shown whether successful parathyroidectomy has a beneficial effect on arterial reactivity in PHPT patients.

Time for primary review 30 days.


   References
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
 References
 

  1. Ronni-Sivula H. The state of health of patients previously operated on for primary hyperparathyroidism compared with rendomized controls. Ann Chir Gynaecol (1985) 74:60–65.[Medline]
  2. Palmer M, Adami H.-O, Bergström R, Akerström G, Ljunghall S. Mortality after surgery for primary hyperparathyroidism: a follow up of 441 patients operated on from 1956 to 1979. Surgery (1987) 102:1–7.[Web of Science][Medline]
  3. Niederle B, Roka R, Woloszczuk W, et al. Successful parathyroidectomy in primary hyperparathyroidism: a clinical follow up study of 212 consecutive patients. Surgery (1987) 102:903–909.[Web of Science][Medline]
  4. Christensson T, Hellström K, Wengle B, Alveryd A, Wikland B. Prevalence of hypercalcaemia in a health screening in Stockholm. Acta Med Scand (1976) 200:131–137.[Web of Science][Medline]
  5. Palmer M, Adami H.-O, Bergström R, et al. Survival and renal function in untreated hypercalcaemia. Population-based cohort study with 14 years of follow up. Lancet (1987) 1:59–62.[Web of Science][Medline]
  6. Fleckenstein A, Frey M, Zorn J, Fleckenstein-Grün G. The role of calcium in the pathogenesis of experimental arteriosclerosis. Trends Pharmacol Sci (1987) 8:496–501.[CrossRef]
  7. Roberts W.C, Waller B.F. Effects of chronic hypercalcaemia on the heart. An analysis of 18 necropsy patients. Am J Med (1981) 71:371–384.[CrossRef][Web of Science][Medline]
  8. Slavich G.A, Antonucci F, Sponza E. Primary hyperparathyroidism and angina pectoris. Int J Cardiol (1988) 19:266–267.[CrossRef][Web of Science][Medline]
  9. Barson A.J, Campbell R.H.A, Langley F.A, Milner R.D.G. Idiopathic arterial calcification of infancy without intimal proliferation. Virchows Arch (1976) 372:167–173.[CrossRef][Web of Science]
  10. Symons C, Fortune F, Greenbaum R.A, Dandona P. Cardiac hypertrophy, hypertrophic cardiomyopathy, and hyperparathyroidism – an association. Br Heart J (1985) 54:539–542.[Abstract/Free Full Text]
  11. Janssens S, DeGeest H, Decramer M. Hypertrophic cardiomyopathy caused by hyperparathyroidism. Report of case and review of the literature. Acta Cardiol (1987) 12:287–293.
  12. Diamon T.H, Kawalsky D.L, van der Merwe T.L, Myburgh D.P. Hypercalcaemia due to parathyroid adenoma and hypertrophic cardiomyopathy. A case report. S Afr Med J (1987) 71:448–449.[Web of Science][Medline]
  13. Harnett J.D, Parfrey P.S, Griffiths S.M, et al. Left ventricular hypertrophy in end-stage renal disease. Nephron (1988) 18:107–115.
  14. Furchgott R.F, Zawadzki J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature (1980) 288:373–376.[CrossRef][Medline]
  15. Ross R. The pathogenesis of atherosclerosis: an update. New Engl J Med (1986) 314:488–500.[Web of Science][Medline]
  16. Healy B. Endothelial cell dysfunction: an emerging endocrinopathy linked to coronary disease. J Am Coll Cardiol (1990) 16:349–356.[Abstract]
  17. Meredith I.T, Yeung A.C, Weidinger F.F, et al. Role of impaired endothelium-dependent vasodilation in ischemic manifestations of coronary artery disease. Circulation (1993) 87(suppl V):V56–V66.
  18. Pohl U, Holtz J, Busse R, Bassenge E. Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension (1986) 8:37–44.[Abstract/Free Full Text]
  19. Holtz J, Förstermann U, Pohl U, Giesler M, Bassenge E. Flow-dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs: effects of cyclooxygenase inhibition. J Cardiovasc Pharmacol (1984) 6:1161–1169.[Web of Science][Medline]
  20. Rubanyi G.M, Romero J.C, Vanhoutte P.M. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol (1986) 250:H1145–H1149.[Medline]
  21. Lieberman E.H, Knab S.T, Creager M.A. Nitric oxide mediates the vasodilator response to flow in humans (Abstract). Circulation (1994) 90(suppl_I):I–138.
  22. Joannides R, Haefeli W.E, Linder L, et al. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation (1995) 91:1314–1319.[Abstract/Free Full Text]
  23. Celermajer D.S, Sorensen K.E, Gooch V.M, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet (1992) 340:1111–1115.[CrossRef][Web of Science][Medline]
  24. Celermajer D.S, Sorensen K.E, Georgakopoulos D, et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation (1993) 88:2149–2155.[Abstract/Free Full Text]
  25. Anderson T.J, Uehata A, Gerhard M.D, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol (1995) 26:1235–1241.[Abstract]
  26. Neunteufl T, Katzenschlager R, Hassan A, et al. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis (1997) 129:111–118.[CrossRef][Web of Science][Medline]
  27. Correti M.C, Plotnick G.D, Vogel R.A. Technical aspects of evaluating brachial artery vasodilatation using high-frequency ultrasound. Am J Physiol (1995) 268(Heart Circ Physiol 37):H1397–H1404.[Web of Science][Medline]
  28. Niederle B, Stefenelli T, Glogar D, et al. Cardiac calcific deposits in patients with primary hyperparathyroidism: Preliminary results of a prospective echocardiographic study. Surgery (1990) 108:1052–1057.[Web of Science][Medline]
  29. Stefenelli T, Mayr H, Bergler-Klein J, et al. Primary Hyperparathyroidism: Incidence of cardiac abnormalities and partial reversibility after successful parathyroidectomy. Am J Med (1993) 95:197–202.[CrossRef][Web of Science][Medline]
  30. Stefenelli T, Abela C, Frank H, et al. Cardiac abnormalities in patients with primary hyperparathyroidism: Implications for follow-up. J Clin Endocrinol Metab (1997) 82:106–112.[Abstract/Free Full Text]
  31. Nickols G.A. Actions of parathyroid hormone in the cardiovascular system. Blood Vessels (1987) 24:120–124.[Web of Science][Medline]
  32. Smogorzewski M, Zayed M, Zhang Y.B, Roe J, Massry S.G. Parathyroid hormone increases cytosolic calcium concentration in adult rat cardiac myocytes. Am J Physiol (1993) 264:H1998–2006.[Web of Science][Medline]
  33. Bogin E, Massry S.G, Harary I. Effect of parathyroid hormone on rat heart cells. J Clin Invest (1981) 67:1215–1227.[Web of Science][Medline]
  34. Saglikes Y, Massry S.G, Iseki K, Nadler J.L, Campese V.M. Effect of PTH on blood pressure and response to vasoconstrictor agonists. Am J Physiol (1985) 248:F674–F681.[Web of Science][Medline]
  35. Nickols G.A, Nana A.D, Nickols M.A, DiPette D.J, Asimakis G.K. Hypotension and cardiac stimulation due to the parathyroid hormone-related protein, humoral hypercalcemia of malignancy factor. Endocrinology (1989) 125:834–841.[Abstract/Free Full Text]
  36. Celermajer D.S, Sorensen K.E, Spiegelhalter D.J, et al. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol (1994) 24:471–476.[Abstract]
  37. Celermajer D.S, Sorensen K.E, Bull C, Robinson J, Deanfield J.E. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol (1994) 24:1468–1474.[Abstract]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
S. J. Silverberg, E. M. Lewiecki, L. Mosekilde, M. Peacock, and M. R. Rubin
Presentation of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Third International Workshop
J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 351 - 365.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
H. Volzke, D. M. Robinson, T. Spielhagen, M. Nauck, A. Obst, R. Ewert, B. Wolff, H. Wallaschofski, S. B. Felix, and M. Dorr
Are serum thyrotropin levels within the reference range associated with endothelial function?
Eur. Heart J., January 2, 2009; 30(2): 217 - 224.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. R. Rubin, M. S. Maurer, D. J. McMahon, J. P. Bilezikian, and S. J. Silverberg
Arterial Stiffness in Mild Primary Hyperparathyroidism
J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3326 - 3330.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
M. L. Bots, J. Westerink, T. J. Rabelink, and E. J.P. de Koning
Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response
Eur. Heart J., February 2, 2005; 26(4): 363 - 368.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
P. Andersson, E. Rydberg, and R. Willenheimer
Primary hyperparathyroidism and heart disease -- a review
Eur. Heart J., October 2, 2004; 25(20): 1776 - 1787.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
S. Y. Chan, G. B. J. Mancini, L. Kuramoto, M. Schulzer, J. Frohlich, and A. Ignaszewski
The prognostic importance of endothelial dysfunction and carotid atheromaburden in patients with coronary artery disease
J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1037 - 1043.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. Fallo, G. Camporese, E. Capitelli, G. M. Andreozzi, F. Mantero, and F. Lumachi
Ultrasound Evaluation of Carotid Artery in Primary Hyperparathyroidism
J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2096 - 2099.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
Shonni J. Silverberg;
Cardiovascular Disease in Primary Hyperparathyroidism
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3513 - 3514.
[Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. C. Smith, M. D. Page, R. John, M. H. Wheeler, J. R. Cockcroft, M. F. Scanlon, and J. S. Davies
Augmentation of Central Arterial Pressure in Mild Primary Hyperparathyroidism
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3515 - 3519.
[Abstract] [Full Text]

Home page
 Cardiovasc ResHome page
M. Kosch, M. Hausberg, K. Vormbrock, K. Kisters, G. Gabriels, K. Heinz Rahn, and M. Barenbrock
Impaired flow-mediated vasodilation of the brachial artery in patients with primary hyperparathyroidism improves after parathyroidectomy
Cardiovasc Res, September 1, 2000; 47(4): 813 - 818.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
T. Neunteufl, U. Priglinger, S. Heher, M. Zehetgruber, G. Soregi, S. Lehr, K. Huber, G. Maurer, F. Weidinger, and K. Kostner
Effects of vitamin E on chronic and acute endothelial dysfunction in smokers
J. Am. Coll. Cardiol., February 1, 2000; 35(2): 277 - 283.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Neunteufl, T.
Right arrow Articles by Stefenelli, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Neunteufl, T.
Right arrow Articles by Stefenelli, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?