Plasma 25-hydroxyvitamin D levels and risk of incident hypertension

Hydroxylation of 25( OH) D to 1,25-dihydroxyvitamin D and signaling through the vitamin D receptor occur in various tissues not traditionally involved in calcium homeostasis. Laboratory studies indicate that 1,25-dihydroxyvitamin D suppresses renin expression and vascular smooth muscle cell proliferation; clinical studies demonstrate an inverse association between ultraviolet radiation, a surrogate marker for vitamin D synthesis, and blood pressure. We prospectively studied the independent association between measured plasma 25-hydroxyvitamin D [ 25( OH) D] levels and risk of incident hypertension and also the association between predicted plasma 25( OH) D levels and risk of incident hypertension. Two prospective cohort studies including 613 men from the Health Professionals' Follow-Up Study and 1198 women from the Nurses' Health Study with measured 25( OH) D levels were followed for 4 to 8 years. In addition, 2 prospective cohort studies including 38 388 men and 77 531 women with predicted 25( OH) D levels were followed for 16 to 18 years. During 4 years of follow-up, the multivariable relative risk of incident hypertension among men whose measured plasma 25( OH) D levels were < 15 ng/mL (ie, vitamin D deficiency) compared with those whose levels were >= 30 ng/mL was 6.13 (95% confidence interval [CI]: 1.00 to 37.8). Among women, the same comparison yielded a relative risk of 2.67 ( 95% CI: 1.05 to 6.79). The pooled relative risk combining men and women with measured 25( OH) D levels using the random-effects model was 3.18 ( 95% CI: 1.39 to 7.29). Using predicted 25( OH) D levels in the larger cohorts, the multivariable relative risks comparing the lowest to highest deciles were 2.31 ( 95% CI: 2.03 to 2.63) in men and 1.57 ( 95% CI: 1.44 to 1.72) in women. Plasma 25( OH) D levels are inversely associated with risk of incident hypertension.