on January 7, 2008
Published online before print January 7, 2008, doi: 10.1161/CIRCULATIONAHA.107.706127
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Submitted on April 4, 2007
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 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.
Accepted on November 2, 2007
Vitamin D Deficiency and Risk of Cardiovascular Disease
Thomas J. Wang MD*,
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.
Key words: cardiovascular diseases • risk factors • vitamin D
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|
|
|
|
|
|
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|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
 |
|
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|
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|
|
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|
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|
|
 |
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