Subgroup analysis for the risk of cardiovascular disease with calcium supplements

Calcium supplements have been reported to increase the risk of myocardial infarction (MI). We wished to determine whether the effects of calcium supplements on cardiovascular risk vary across different population groups. We modeled the effect of calcium (with or without vitamin D) on the time to incident cardiovascular events in pre-specified subgroups based on age, dietary calcium intake, body mass index, smoking history, history of hypertension, diabetes and prevalent cardiovascular disease, using interaction terms in Cox proportional hazards models in two randomized controlled trial data sets—our re-analysis of the Women's Health Initiative Calcium and Vitamin D study (WHI CaD), and our pooled patient-level meta-analysis of trials of calcium supplements with or without vitamin D. For women in WHI CaD not taking calcium supplements at randomization (n=16 718), we found no significant interactions between treatment allocation, the risk of MI, stroke or coronary revascularization, or any of the baseline variables. In the pooled patient-level data set of six trials of calcium with or without vitamin D (n=24 869), there were also no significant interactions between treatment allocation, risk of MI or stroke, and any of the baseline variables. We found no evidence that the increased cardiovascular risk from calcium supplements differs across varying patient subpopulations. These findings suggest that targeted prescription of calcium supplements to specific population subgroups, such as younger people and those with low dietary calcium intake, should not be endorsed.