Published Online
on January 7, 2008

A more recent version of this article appeared on January 29, 2008

This Article Free upon publication Full Text (PDF) All Versions of this Article: 117/4/503    most recent CIRCULATIONAHA.107.706127v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, T. J. Articles by Vasan, R. S. Search for Related Content PubMed PubMed Citation Articles by Wang, T. J. Articles by Vasan, R. S. Related Collections Related Article

Submitted on April 4, 2007
Accepted on November 2, 2007

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.

Key words: cardiovascular diseases • risk factors • vitamin D

Related Article:

Clinical Summaries
Circulation 2008 117: 453-455. [Extract] [Full Text]

This article has been cited by other articles:

				M. L. Melamed, E. D. Michos, and B. Astor 25-Hydroxyvitamin D Levels and All-Cause Mortality--Reply Arch Intern Med, June 8, 2009; 169(11): 1076 - 1076. [Full Text] [PDF]

				A. Zittermann and W. B. Grant 25-Hydroxyvitamin D Levels and All-Cause Mortality Arch Intern Med, June 8, 2009; 169(11): 1075 - 1076. [Full Text] [PDF]

				E. Hagstrom, P. Hellman, T. E. Larsson, E. Ingelsson, L. Berglund, J. Sundstrom, H. Melhus, C. Held, L. Lind, K. Michaelsson, et al. Plasma Parathyroid Hormone and the Risk of Cardiovascular Mortality in the Community Circulation, June 2, 2009; 119(21): 2765 - 2771. [Abstract] [Full Text] [PDF]

				A. Zittermann, S. S. Schleithoff, S. Frisch, C. Gotting, J. Kuhn, H. Koertke, K. Kleesiek, G. Tenderich, and R. Koerfer Circulating Calcitriol Concentrations and Total Mortality Clin. Chem., June 1, 2009; 55(6): 1163 - 1170. [Abstract] [Full Text] [PDF]

				Vitamin D and Health Journal Watch Dermatology, May 22, 2009; 2009(522): 1 - 1. [Full Text]

				M. Matsunawa, Y. Amano, K. Endo, S. Uno, T. Sakaki, S. Yamada, and M. Makishima The Aryl Hydrocarbon Receptor Activator Benzo[a]pyrene Enhances Vitamin D3 Catabolism in Macrophages Toxicol. Sci., May 1, 2009; 109(1): 50 - 58. [Abstract] [Full Text] [PDF]

				W. Janssens, A. Lehouck, C. Carremans, R. Bouillon, C. Mathieu, and M. Decramer Vitamin D Beyond Bones in Chronic Obstructive Pulmonary Disease: Time to Act Am. J. Respir. Crit. Care Med., April 15, 2009; 179(8): 630 - 636. [Abstract] [Full Text] [PDF]

				M. F. Holick MrOs Is D-ficient J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1092 - 1093. [Full Text] [PDF]

				A. H. Lichtenstein Nutrient supplements and cardiovascular disease: a heartbreaking story J. Lipid Res., April 1, 2009; 50(Supplement): S429 - S433. [Abstract] [Full Text] [PDF]

				J. N Artaza and K. C Norris Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells J. Endocrinol., February 1, 2009; 200(2): 207 - 221. [Abstract] [Full Text] [PDF]

				S. van Diepen, S. R. Majumdar, J. A. Bakal, F. A. McAlister, and J. A. Ezekowitz Heart Failure Is a Risk Factor for Orthopedic Fracture: A Population-Based Analysis of 16 294 Patients Circulation, November 4, 2008; 118(19): 1946 - 1952. [Abstract] [Full Text] [PDF]

				D. E. Wallis, S. Penckofer, and G. W. Sizemore The "Sunshine Deficit" and Cardiovascular Disease Circulation, September 30, 2008; 118(14): 1476 - 1485. [Full Text] [PDF]

				D. Wagner, G. Sidhom, S. J. Whiting, D. Rousseau, and R. Vieth The Bioavailability of Vitamin D from Fortified Cheeses and Supplements Is Equivalent in Adults J. Nutr., July 1, 2008; 138(7): 1365 - 1371. [Abstract] [Full Text] [PDF]

				M. D Witham More evidence is needed before general supplementation BMJ, June 28, 2008; 336(7659): 1451 - 1451. [Full Text] [PDF]

				M. F Holick Deficiency of sunlight and vitamin D BMJ, June 14, 2008; 336(7657): 1318 - 1319. [Full Text] [PDF]

				M. L. Melamed, P. Muntner, E. D. Michos, J. Uribarri, C. Weber, J. Sharma, and P. Raggi Serum 25-Hydroxyvitamin D Levels and the Prevalence of Peripheral Arterial Disease: Results from NHANES 2001 to 2004 Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1179 - 1185. [Abstract] [Full Text] [PDF]

				S. Pilz, H. Dobnig, B. Winklhofer-Roob, G. Riedmuller, J. E. Fischer, U. Seelhorst, B. Wellnitz, B. O. Boehm, and W. Marz Low Serum Levels of 25-Hydroxyvitamin D Predict Fatal Cancer in Patients Referred to Coronary Angiography Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1228 - 1233. [Abstract] [Full Text] [PDF]