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Circulation. 2008
Published online before print January 7, 2008, doi: 10.1161/
CIRCULATIONAHA.107.706127

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:
tjwang[at]partners.org.

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 (<15 ng/mL, <10
ng/mL). Multivariable Cox regression models were adjusted for
conventional risk factors. Overall, 28% of individuals had levels <15
ng/mL, and 9% had levels <10 ng/mL. During a mean follow-up of 5.4
years, 120 individuals developed a first cardiovascular event.
Individuals with 25-OH D <15 ng/mL had a multivariable-adjusted hazard
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 <15 ng/mL
and 1.80 (95% confidence interval 1.05 to 3.08) for levels <10 ng/mL
(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.