Abstract

Background: A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system, but data from longitudinal studies are lacking. Circulating 25-hydroxyvitamin D3 (25[OH]D), the most commonly used index of vitamin D status, is converted to the active hormone 1,25-dihydroxyvitamin D3 (1,25[OH]2D), which, operating through the vitamin D receptor, inhibits in vitro cell proliferation, induces differentiation and apoptosis, and may protect against coronary heart disease (CHD). Therefore, the aim was to prospectively assess the association between serum (25[OH]D) concentrations and incident CHD. Methods: Using a case-cohort design, serum levels of (25[OH]D) were measured in 1,783 subjects (964 men, 819 women) selected from a source population of 9,300 middle-aged participants in the population-based MONICA/KORA Augsburg studies. Results: A total of 298 CHD cases (225 male, 73 female) were identified over an 11-year average follow-up period. We found a significant interaction of the effects of vitamin D with sex. After adjustment for age, survey, and season of blood sampling, the hazard ratio (HR) and 95% confidence interval (CI) comparing tertile extremes of serum levels of (25[OH]D) was 0.32 (0.16-0.65) (p for trend=0.001) in women, and 0.56 (0.38-0.82) (p-trend=0.005) in men. Further adjustment for standard cardiovascular risk factors (including BMI, smoking, physical activity, alcohol, systolic blood pressure, total cholesterol/HDL-cholesterol ratio, and parental history) slightly attenuated the association in women (HR: 0.39 [0.18-0.84] p-trend=0.013, and strongly in men (HR: 0.76 [0.49-1.17] p-trend=0.215). After additional adjustment for C-reactive protein, interleukin-6, ICAM-1, and IP-10, the effect remained significant in women (HR: 0.42 [0.19-0.93] p-trend=0.028) while it was further reduced in men (HR: 0.84 [0.52-1.35] p-trend=0.461). Conclusions: Our findings suggest that higher vitamin D status is associated with decreased risk of CHD. This effect seems to be particularly pronounced in women. Further clinical and experimental studies are needed to investigate the sex differences and whether or not correction of vitamin D deficiency could contribute to the prevention of CHD.

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