Vitamin D status and risk of cardiovascular events: Lessons learned via systematic review and meta-analysis

Accumulating data linking hypovitaminosis D to cardiovascular (CV) events has contributed to large increases in vitamin D testing and supplementation. To evaluate the merits of this practice, we conducted a systematic review with meta-analysis providing a framework for interpreting the literature associating hypovitaminosis D with increased CV events. Prospective studies were identified by search of MEDLINE and EMBASE from inception to January 2010, restricted to English language publications. Two authors independently extracted data and graded study quality. Pooled relative risks (RR) were calculated using a random effects model. Ten studies met criteria for review and 7 were included in meta-analysis. Pooled RR for CV events using FAIR and GOOD quality studies was 1.67 (95% confidence interval, 1.23-2.28) during an average follow-up of 11.8 years. There was evidence of significant heterogeneity across studies (Q statistics = 16.6, P = 0.01, I = 63.8%), which was eliminated after omitting 2 studies identified by sensitivity analysis (RR, 1.34 [1.08-1.67]; P for heterogeneity =0.33). When restricting analysis to GOOD quality studies (RR, 1.27 [1.04-1.56]), no significant heterogeneity was found (P = 0.602). Systematic review identified significant shortcomings in the literature, including variability in defining vitamin D status, seasonal adjustments, defining and determining CV outcomes, and the use of baseline vitamin D levels. In conclusion, a modest increased risk of CV events associated with hypovitaminosis D is tempered by significant limitations within the current literature. These findings underscore the importance of critical appraisal of the literature, looking beyond reported risk estimates before translating results into clinical practice.