Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis

Abstract

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

Design: Patient level and trial level meta-analyses.

Data sources: 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.

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

Results: 15 trials were eligible for inclusion, five with patient level data (8151 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 to 1.67, P=0.035). Non-significant increases occurred in the incidence of stroke (1.20, 0.96 to 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 to 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 to 1.59, P=0.038).

Conclusions: 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.

Fig 1 Flowchart of studies. Initial search was in November 2007: 9358 reports were identified, 173 reports of potentially relevant studies retrieved, 150 reports excluded, and 23 reports of 15 individual studies identified. Search was updated in March 2010: a further 2005 reports were identified and 17 reports retrieved but no new studies identified

Fig 2 Cumulative incidence of myocardial infarction, stroke, composite of myocardial infarction, stroke, or sudden death, and death by treatment allocation in five studies that contributed patient level data

Fig 3 Random effects models of effect of calcium supplementation on cardiovascular events and death. Full data were available from these eight trials, but some trials do not appear in the figures because no events occurred during the trial: no myocardial infarctions occurred in the study by Reid 1993 or Bonnick 2007, no strokes occurred in the study by Reid 2008, and no deaths occurred in the study by Reid 1993. Data on composite end point were not available for the study by Bonnick 2007 or Lappe 2007. Grant 2005 is a Randomised Evaluation of Calcium or Vitamin D (RECORD) study calcium versus placebo arms, and Grant 2005 vitamin D is a RECORD study calcium plus vitamin D versus vitamin D plus placebo arms