Submitted to: American Journal of Epidemiology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 11/29/2005
Publication Date: 2/22/2006
Citation: Stranges, S., Marshall, J.R., Trevisan, M., Natarajan, R., Combs, G.F., Farinaro, E., Reid, M.E. 2006. Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analysis in a randomized clinical trial. American Journal of Epidemiology. 163:694-699. Interpretive Summary: This report presents results from the Nutritional Prevention of Cancer Trial concerning the effects of supplemental selenium on cardiovascular disease. More than one thousand subjects were randomly assigned to a daily dose of selenium (200 mcg) or a placebo and followed for an average of over 7 yrs. The results showed that selenium treatment did not affect any aspect of cardiovascular disease, although it reduced cancer risk in this cohort.
Technical Abstract: Background – Despite the documented antioxidant and chemopreventive properties of selenium, studies of selenium and cardiovascular disease (CVD) risk have yielded inconsistent findings. Methods and Results – As part of the Nutritional Prevention of Cancer (NPC) Trial examining the efficacy of selenium supplementation as selenized yeast (200 ug daily) in skin cancer prevention, cardiovascular disease incidence and mortality were assessed as secondary end points. After exclusion of participants with prevalent CVD at baseline, 199 CVD events [total myocardial infarction (MI), stroke, coronary artery bypass graft (CABG), precutaneous transluminal coronary angioplasty (PTCA), and carotid endarterectomy] were newly diagnosed and 71 CVD deaths occurred among 1,004 participants followed for an average of 7.6 years. The effects of treatment overall and within subgroups of baseline plasma selenium were analyzed using incidence rate ratios and Cox proportional hazards (HR) models (adjusted for age, gender, and smoking status). Selenium supplementation was not significantly associated with any of the CVD end points [all CVD: HR = 1.03, 95% confidence interval (CI) = 0.78-1.37; MI: HR = 0.94, 95% CI = 0.61-1.44; stroke: HR = 1.02, 95% CI = 0.63=1.65; all CVD mortality: HR = 1.22, 95% CI = 0.76-1.95]. When analyses were further stratified by the median of baseline plasma selenium concentration, a borderline statistically significant HR was observed for CVD mortality in subjects with baseline plasma selenium below the median (HR = 1.97, 95% CI = 0.99-3.96, P = 0.055). Among the 246 participants who reported prevalent CVD at baseline, no association was found between selenium supplementation and recurrent CVD events. Conclusions – These analyses indicate no overall effect of selenium supplementation on both primary and secondary prevention of CVD.