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Vitamin D for cardiovascular disease prevention


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Circulation. 2008

Published online before print January 7, 2008, doi: 10.1161/



Vitamin D Deficiency and Risk of Cardiovascular Disease


Thomas J. Wang MD*, Michael J. Pencina PhD, Sarah L. Booth PhD, Paul

F. Jacques DSc, Erik Ingelsson MD, PhD, Katherine Lanier BS, Emelia J.

Benjamin MD, MSc, Ralph B. D'Agostino PhD, Myles Wolf MD, MMSc, and

Ramachandran S. Vasan MD

From the Framingham Heart Study, Framingham, Mass (T.J.W., M.J.P.,

E.I., K.L., E.J.B., R.B.D., R.S.V.); Cardiology Division (T.J.W.) and

Renal Division (M.W.), Department of Medicine, Massachusetts General

Hospital, Harvard Medical School, Boston, Mass; Statistics and

Consulting Unit, Department of Mathematics (M.J.P., R.B.D.), Boston

University, Boston, Mass; Jean Mayer US Department of Agriculture

Human Nutrition Research Center on Aging (S.L.B., P.F.J.), Tufts

University, Boston, Mass; and Sections of Cardiology and Preventive

Medicine (E.J.B., R.S.V.), Boston Medical Center, Boston University

School of Medicine, Boston, Mass.


* To whom correspondence should be addressed. E-mail:



Background--Vitamin D receptors have a broad tissue distribution that

includes vascular smooth muscle, endothelium, and cardiomyocytes. A

growing body of evidence suggests that vitamin D deficiency may

adversely affect the cardiovascular system, but data from longitudinal

studies are lacking.


Methods and Results--We studied 1739 Framingham Offspring Study

participants (mean age 59 years; 55% women; all white) without prior

cardiovascular disease. Vitamin D status was assessed by measuring 25-

dihydroxyvitamin D (25-OH D) levels. Prespecified thresholds were used

to characterize varying degrees of 25-OH D deficiency (

ng/mL). Multivariable Cox regression models were adjusted for

conventional risk factors. Overall, 28% of individuals had levels

ng/mL, and 9% had levels

years, 120 individuals developed a first cardiovascular event.

Individuals with 25-OH D

ratio of 1.62 (95% confidence interval 1.11 to 2.36, P=0.01) for

incident cardiovascular events compared with those with 25-OH D 15 ng/

mL. This effect was evident in participants with hypertension (hazard

ratio 2.13, 95% confidence interval 1.30 to 3.48) but not in those

without hypertension (hazard ratio 1.04, 95% confidence interval 0.55

to 1.96). There was a graded increase in cardiovascular risk across

categories of 25-OH D, with multivariable-adjusted hazard ratios of

1.53 (95% confidence interval 1.00 to 2.36) for levels 10 to

and 1.80 (95% confidence interval 1.05 to 3.08) for levels

(P for linear trend=0.01). Further adjustment for C-reactive protein,

physical activity, or vitamin use did not affect the findings.


Conclusions--Vitamin D deficiency is associated with incident

cardiovascular disease. Further clinical and experimental studies may

be warranted to determine whether correction of vitamin D deficiency

could contribute to the prevention of cardiovascular disease.

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