Selenium and coronary heart disease: a meta-analysis

Background: It is hypothesized that low selenium concentrations are associated with an increased risk of cardiovascular disease and that selenium supplements prevent coronary heart disease. Objective: The objective was to perform a meta-analysis on the association of selenium biomarkers with coronary heart disease end-points in observational studies and on the efficacy of selenium supplements in preventing coronary heart disease endpoints in randomized trials. Design: The MEDLINE and the Cochrane Library databases were searched for studies conducted from 1966 through 2005. Relative risks were pooled by using an inverse-variance weighted random-effects model. Results: Twenty-five observational studies (14 cohort and 11 case-control studies) that measured blood or toenail selenium concentrations and 6 randomized trials that evaluated supplements containing selenium met our inclusion criteria. The pooled relative risk in a comparison of the highest with the lowest selenium concentration categories was 0.85 (95% CI: 0.74, 0.99) in cohort studies and 0.43 (0.29, 0.66) in case-control studies. In observational studies, a 50% increase in selenium concentrations was associated with a 24% (7%, 38%) reduction in coronary heart disease risk. In randomized trials, the pooled relative risk in a comparison of supplements containing selenium with placebo was 0.89 (0.68, 1.17). Conclusions: Selenium concentrations were inversely associated with coronary heart disease risk in observational studies. Because observational studies have provided misleading evidence for other antioxidants, the validity of this association is uncertain. Few randomized trials have addressed the cardiovascular efficacy of selenium supplementation, and their findings are still inconclusive. Evidence from large ongoing trials is needed to establish low selenium concentrations as a cardiovascular disease risk factor. Currently, selenium supplements should not be recommended for cardiovascular disease prevention.