Impairment of endothelium-independent vasodilation in patients with hypercalcemia

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. (C) 1998 Elsevier Science B.V. All rights reserved.