The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta-Analysis of Randomized Controlled Trials

Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta-analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta-analyses. We, therefore, undertook a meta-analysis of randomized controlled trials with placebo or no-treatment control groups to determine if these supplements increase all-cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random-effects meta-analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96-1.09; p=0.51). Seventeen trials contributed all-cause mortality data with pooled RR of 0.96 (95% CI, 0.91-1.02; p=0.18). Heterogeneity among the trials was low for both primary outcomes (I-2=0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92-1.26; p=0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95-1.24; p=0.22) and chronic CHD 0.92 (95% CI, 0.73-1.15; p=0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all-cause mortality risk in elderly women. (c) 2014 American Society for Bone and Mineral Research.