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A Prospective Study

Edward Giovannucci, MD, ScD; Yan Liu, MS; Bruce W. Hollis, MD, PhD; Eric B. Rimm, ScD

Arch Intern Med. 2008;168(11):1174-1180.

Background  Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans.

Methods  We assessed prospectively whether plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with risk of coronary heart disease. A nested case-control study was conducted in 18 225 men in the Health Professionals Follow-up Study; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection. The blood samples were returned between April 1, 1993, and November 30, 1999; 99% were received between April 1, 1993, and November 30, 1995. During 10 years of follow-up, 454 men developed nonfatal myocardial infarction or fatal coronary heart disease. Using risk set sampling, controls (n = 900) were selected in a 2:1 ratio and matched for age, date of blood collection, and smoking status.

Results  After adjustment for matched variables, men deficient in 25(OH)D (15 ng/mL [to convert to nanomoles per liter, multiply by 2.496]) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D (30 ng/mL) (relative risk [RR], 2.42; 95% confidence interval [CI], 1.53-3.84; P < .001 for trend). After additional adjustment for family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, marine -3 intake, low- and high-density lipoprotein cholesterol levels, and triglyceride levels, this relationship remained significant (RR, 2.09; 95% CI, 1.24-3.54; P = .02 for trend). Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels (22.6-29.9 ng/mL: RR, 1.60 [95% CI, 1.10-2.32]; and 15.0-22.5 ng/mL: RR, 1.43 [95% CI, 0.96-2.13], respectively).

Conclusion  Low levels of 25(OH)D are associated with higher risk of myocardial infarction in a graded manner, even after controlling for factors known to be associated with coronary artery disease.

Author Affiliations: Departments of Nutrition (Drs Giovannucci and Rimm and Ms Liu) and Epidemiology (Drs Giovannucci and Rimm), Harvard School of Public Health, Boston, Massachusetts; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (Drs Giovannucci and Rimm); and Department of Pediatrics, Medical University of South Carolina, Charleston (Dr Hollis).

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