Abstract 16816: Plasma Vitamin D Metabolites and Vitamin D Receptor Polymorphisms Are Associated with Risk of Hypertension in Men

Abstract

Introduction: Laboratory and clinical studies have suggested that inadequate vitamin D may be involved in development of hypertension. However, evidence from epidemiologic studies that support a relation between vitamin D metabolism and signaling pathways and risk of hypertension remains limited. Hypothesis: We assessed the hypothesis that plasma vitamin D metabolites, vitamin D receptor (VDR) gene polymorphisms, and their possible interaction are prospectively associated with risk of hypertension in adult men. Methods: We conducted analyses among 1207 men in the Physicians' Health Study who were free of hypertension at baseline and had baseline measurements of major vitamin D metabolites (including plasma 25hydroxy-vitamin D (25(OH)D) and 1,25dihydroxy-vitamin D (1,25(OH) 2 D)) and VDR gene polymorphisms (including Bsm I and Fok I). During 15.3 years of follow-up, 697 out of the 1207 men developed incident hypertension. Results: After adjusting for age, race, exercise, smoking status, alcohol use, body mass index, and history of diabetes and hypercholesterolemia, the multivariable hazard ratios (HR) and 95% confidence intervals (CI) of hypertension were 1.00 (reference), 0.96 (0.71-1.31), 0.71 (0.51-0.98), and 0.86 (0.62-1.18) across season-specific quartiles of 25(OH)D (p, trend: 0.53), and 1.00 (reference), 0.88 (0.63-1.21), 1.09 (0.80-1.50), and 1.17 (0.85-1.60) across quartiles of 1,25(OH) 2 D (p, trend: 0.15). Compared with the VDR Bsm I bb carriers, the HR of hypertension were 1.27 (1.04-1.55) for the bB carriers and 1.19 (0.90-1.56) for the BB carriers. The risk associated with the VDR Bsm I B allele carrier status was particularly strong among men who had 25(OH)D below the median levels (HR: 1.58, 0.98-2.55) but was weaker and not significant among men who had 25(OH)D above the median levels (HR: 1.21, 0.78-1.87) . There was no relation of the VDR Fok I polymorphism or its interaction with vitamin D metabolites with risk of hypertension. Conclusions: In a prospective cohort of US men, plasma concentrations of 25(OH)D but not 1,25(OH) 2 D were inversely associated with risk of hypertension. Men carrying the B allele of VDR Bsm I polymorphism had an increased risk of hypertension, particularly among those with low plasma 25(OH)D level.