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A growing body of evidence supports an association between vitamin D and cardiovascular disease. However, the mechanisms underlying this association are unknown. From 2000 to 2002, we identified 946 participants with stable cardiovascular disease in San Francisco, California, and followed them prospectively for cardiovascular events (heart failure, myocardial infarction, stroke, or cardiovascular death). We then examined the extent to which the association was attenuated by adjustment for poor health behaviors, comorbid health conditions, and potential biological mediators. During a median follow-up period of 8.0 years (through August 24, 2012), 323 subjects (34.1%) experienced a cardiovascular event. Following adjustment for sociodemographic factors, season of blood measurement, health behaviors, and comorbid conditions, 25-hydroxyvitamin D levels under 20 ng/mL remained independently associated with cardiovascular events (hazard ratio = 1.30, 95% confidence interval: 1.01, 1.67). However, after further adjustment for potential biological mediators, the independent association was no longer present (hazard ratio = 1.11, 95% confidence interval: 0.85, 1.44). Parathyroid hormone, a potentially modifiable biological factor downstream from 25-hydroxyvitamin D, was responsible for the majority of this attenuation. These findings highlight the need for randomized controlled trials to determine whether vitamin D supplementation in persons with deficiency could be beneficial for the primary or secondary prevention of cardiovascular events.

Vitamin D Deficiency and Cardiovascular Events in Patients With Coronary Heart Disease: Data From the Heart and Soul Study