To investigate whether calcium supplements increase the risk of cardiovascular events.

Patient level and trial level meta-analyses.

Medline, Embase, and Cochrane Central Register of Controlled Trials (1966-March 2010), reference lists of meta-analyses of calcium supplements, and two clinical trial registries. Initial searches were carried out in November 2007, with electronic database searches repeated in March 2010.

Eligible studies were randomized, placebo controlled trials of calcium supplements (. 500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than 1 year. The lead authors of eligible trials supplied data. Cardiovascular outcomes were obtained from self-reports, hospital admissions and death certificates.

Fifteen trials were eligible for inclusion, five with patient level data (8,151 participants, median follow-up 3.6 years, interquartile range 2.7-4.3 years) and 11 with trial level data (11,921 participants, mean duration 4.0 years). In the five studies contributing patient level data, 143 people allocated to calcium had a myocardial infarction compared with 111 allocated to placebo (hazard ratio 1.31, 95% confidence interval 1.02-1.67, p = 0.035). Nonsignificant increases occurred in the incidence of stroke (1.20, 0.96-1.50, p = 0.11), the composite end point of myocardial infarction, stroke, or sudden death (1.18, 1.00 to 1.39, p = 0.057), and death (1.09, 0.96-1.23, p = 0.18). The meta-analysis of trial level data showed similar results: 296 people had a myocardial infarction (166 allocated to calcium, 130 to placebo), with an increased incidence of myocardial infarction in those allocated to calcium (pooled relative risk 1.27, 95% confidence interval 1.01-1.59, p = 0.038).

Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.