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 (≥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.

Relationships between vascular calcification, calcium metabolism, bone density, and fractures

“…(7)(8)(9) Calcium supplements also have been associated with increased cardiovascular event rates in a randomized, controlled trial in older women (10) and subsequent meta-analysis. (11) The mechanism of the association between calcium metabolism and vascular disease is unknown. The process of vascular calcification is thought to be similar to bone formation, (12,13) and since calcium supplements increase bone mineral density (BMD), (14,15) they also may increase vascular calcification.…”

Calcium Supplements Increase Risk of Myocardial Infarction

“…In their analyses of calcium monotherapy and MI, the authors identified only one trial (with four MIs) published after our metaanalysis, (2) explaining the similarity of results (Lewis, (2) and when self-reports are excluded (RR 1.33 [1.03-1.73]). (5) In their analyses of calcium plus vitamin D, the authors included two trials not in our meta-analysis, (3) one trial with one MI, and the second a trial by Larsen and colleagues.…”

“…Their conclusion is at odds with that of our meta-analyses, which reported that calcium increased the risk of myocardial infarction (MI) and possibly stroke in men and women together. (2,3) There are important differences between approaches to the meta-analyses. In the current article and previously, the authors suggest that including men and self-reported events may have explained the increased risk of MI from calcium.…”

“…Surprisingly, the authors also did not seek data for their primary endpoint from our previous trial, which would have increased the size of their data set of calcium monotherapy trials by about 40%. (8) In addition, a group that previously supplied individual patient data for our meta-analysis did not agree to participate in the Lewis meta-analysis.In their analyses of calcium monotherapy and MI, the authors identified only one trial (with four MIs) published after our metaanalysis, (2) In their analyses of calcium plus vitamin D, the authors included two trials not in our meta-analysis, (3) one trial with one MI, and the second a trial by Larsen and colleagues. (9) The latter was an open-label study of multifactorial interventions, one of which included calcium and vitamin D, administered to people living in different regions of the city.…”

“…In their analyses of calcium monotherapy and MI, the authors identified only one trial (with four MIs) published after our metaanalysis, (2) In their analyses of calcium plus vitamin D, the authors included two trials not in our meta-analysis, (3) one trial with one MI, and the second a trial by Larsen and colleagues. (9) The latter was an open-label study of multifactorial interventions, one of which included calcium and vitamin D, administered to people living in different regions of the city.…”