Abstract

Background: Experimental studies suggest that vitamin D may potentially prevent the development of hypertension through down-regulation of the renin-angiotensin system. However, evidence from epidemiologic studies remains limited. Objective: In parallel nested case-control studies of women from the Women’s Health Study (WHS) and men from the Physicians’ Health Study (PHS) with >10 years follow-up, we examined the prospective associations between the circulating biomarkers of vitamin D status with risk of hypertension, as well as the inter-relation between vitamin D biomarkers and renin production. Methods: In each cohort, 500 incident hypertension cases and 500 controls were randomly selected from participants who were free of cardiovascular disease, cancer, and hypertension and provided bloods at baseline. Hypertension cases were identified based on self-reported blood pressure, physician’s diagnosis, or medication use. Controls were matched to cases on gender, age, race, follow-up time, and month of blood draw. Baseline plasma 25(OH)-vitamin D, parathyroid hormone (PTH), and total renin (pro-renin plus active renin) concentrations were measured. Analyses were first performed in each cohort separately and, given the similar results, finally combined for both cohorts. Results: Baseline concentrations of 25(OH)-vitamin D (mean of 26.6 vs. 27.0 ng/mL) and PTH (32.6 vs. 32.2 pg/mL) were similar in hypertension cases and controls. In the crude matched model, the risk of hypertension did not change with 25(OH)-vitamin D or PTH concentrations. Additional adjustment for other known hypertension-related risk factors minimally affected the associations. After adjusting for baseline smoking, alcohol use, exercise, menopausal status and hormone therapy use among women, body mass index, and history of diabetes and hypercholesterolemia, the relative risks of incident hypertension across increasing quintiles of 25(OH)-vitamin D were 1.00, 1.42 (95% CI: 0.94-2.16), 0.94 (95% CI: 0.60-1.48), 0.99 (95% CI: 0.61-1.61), and 1.03 (95% CI: 0.63-1.69) (p, trend, 0.48), and across increasing quintiles of PTH were 1.00, 1.26 (95% CI: 0.83-1.92), 0.91 (95% CI: 0.60-1.40), 1.10 (95% CI: 0.70-1.71), 0.92 (95% CI: 0.59-1.44) (p, trend, 0.50). These associations were similar in men and women. Among controls, plasma 25(OH)-vitamin D was inversely correlated with PTH (Pearson r: -0.24, p<0.0001), while neither 25(OH)-vitamin D (r: -0.02, p=0.53) nor PTH (r: -0.01, p=0.69) was correlated with total renin concentrations. Conclusions: In prospective cohorts of men and women, we found no association between either baseline plasma 25(OH)-vitamin D or PTH with the risk of hypertension, or between either 25(OH)-vitamin D or PTH with total renin concentration. More research is needed to further elucidate the specific effect of vitamin D in the development of hypertension.

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