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25-Hydroxyvitamin D Levels and the Risk of Stroke: A Prospective Study and Meta-analysis

Background and Purpose— Despite evidence suggesting that vitamin D deficiency may lead to elevated cardiovascular disease risk, results regarding the association of 25-hydroxyvitamin D (25[OH]D) levels with stroke risk are inconclusive. We aimed to examine this association in a prospective study in women and to summarize all existing data in a meta-analysis. Methods— We measured 25(OH)D levels among 464 women who developed ischemic stroke and an equal number of control subjects who were free of stroke through 2006 in the Nurses' Health Study (NHS). We searched MEDLINE and EMBASE for articles published through March 2011 that prospectively evaluated 25(OH)D levels in relation to stroke. Results— After multivariable adjustment for lifestyle and dietary covariates, lower 25(OH)D levels were associated with an elevated risk of ischemic stroke in the NHS: the OR (95% CI) comparing women in the lowest versus highest tertiles was 1.49 (1.01–2.18; Ptrend=0.04). We found 6 other prospective studies that examined 25(OH)D in relation to stroke outcomes. After pooling our results with these prospective studies that included 1214 stroke cases in total, low 25(OH)D levels were associated with increased risk of developing stroke outcomes in comparison to high levels: the pooled relative risk (95% CI) was 1.52 (1.20–1.85; I2=0.0%, Pheterogeneity=0.63). In 2 studies that explicitly examined ischemic stroke, this association was 1.59 (1.07–2.12; I2=0.0%, Pheterogeneity=0.80). Conclusions— These data provide evidence that low vitamin D levels are modestly associated with risk of stroke. Maintaining adequate vitamin D status may lower the risk of stroke in women.