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on March 19, 2007

Hypertension. 2007
Published online before print March 19, 2007, doi: 10.1161/HYPERTENSIONAHA.107.087288
A more recent version of this article appeared on May 1, 2007
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Submitted on January 9, 2007
Revised on January 22, 2007

Plasma 25-Hydroxyvitamin D Levels and Risk of Incident Hypertension

John P. Forman*; Edward Giovannucci; Michelle D. Holmes; Heike A. Bischoff-Ferrari; Shelley S. Tworoger; Walter C. Willett; and Gary C. Curhan

From the Channing Laboratory (J.P.F., E.G., M.D.H., S.S.T., W.C.W., G.C.C.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; the Renal Division (J.P.F., G.C.C.), Brigham and Women’s Hospital, Boston, Mass; the Departments of Epidemiology (J.P.F., S.S.T., W.C.W., G.C.C.) and Nutrition (E.G., W.C.W.), Harvard School of Public Health, Boston, Mass; and the Department of Rheumatology and Institute for Physical Medicine (H.A.B.-F.), University Hospital, Zurich, Switzerland.

* To whom correspondence should be addressed. E-mail: jforman{at}partners.org.

Abstract--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.


Key words: vitamins • epidemiology • hypertension • risk factors • human




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