1,25-Dihydroxy vitamin D and coronary microvascular function

PURPOSE: The active form of vitamin D (1,25(OH)(2)D) contributes to blood flow regulation in skeletal muscle. The aim of the present study was to determine whether this hormone also modulates coronary physiology, and thus whether abnormalities in its bioavailability contribute to excess cardiovascular risk in patients with disorders of mineral metabolism. METHODS: As a clinical model of the wide variability in 1,25(OH)(2)D bioavailability, we studied 23 patients (62 ± 8 years) with suspected primary hyperparathyroidism referred for myocardial perfusion imaging because of atypical chest pain and at least one cardiovascular risk factor. Dipyridamole and baseline myocardial blood flow indexes were assessed on G-SPECT imaging of (99m)Tc-tetrofosmin, with normalization of the myocardial count rate to the corresponding first-transit counts in the pulmonary artery. Coronary flow reserve (CFR) was defined as the ratio between dipyridamole and baseline myocardial blood flow indexes. In all patients, parathyroid hormone, 25-hydroxy vitamin D (25(OH)D) and 1,25(OH)(2)D serum levels were determined. RESULTS: Primary hyperparathyroidism was eventually diagnosed in 15 of the 23 patients. The mean 25(OH)D concentration was relatively low (21 ± 10 ng/mL) while the concentrations of 1,25(OH)(2)D varied widely but within the normal range (mean 95 ± 61 pmol/L). No patient showed reversible perfusion defects on G-SPECT. CFR was not correlated with either the serum concentration of 25(OH)D nor that of parathyroid hormone, but was strictly correlated with the serum level of 1,25(OH)(2)D (R = 0.8, p < 0.01). Moreover, patients with a 1,25(OH)(2)D concentration below the median value (86 pmol/L) had markedly lower CFR than the other patients (1.48 ± 0.40 vs. 2.51 ± 0.63, respectively; p < 0.001). CONCLUSION: Bioavailable 1,25(OH)(2)D modulates coronary microvascular function. This effect might contribute to the high cardiovascular risk of conditions characterized by chronic reduction in bioavailability of this hormone.