Calcium supplementation has been widely used in the United States as a means to reduce fracture risk and prevent or treat osteoporosis. Current osteoporosis guideline recommendations encourage preventive supplementation in those over 50 if dietary calcium intake is inadequate (< 1,200 mg /day).1 The benefits of calcium intake have also been linked to potential protection against vascular disease, since high calcium intake is associated with an increased ratio of high density lipoprotein cholesterol to low density lipoprotein cholesterol.2 Conversely, excessive calcium intake has proven detrimental for hemodialysis patients. Elevated serum calcium levels in this population lead to vascular calcification, a risk factor associated with future cardiovascular events. A recent study has also linked calcium supplementation with increases in cardiovascular event rates in postmenopausal women (albeit not statistically significant).2 The potential for heightened cardiovascular risk brings the role of calcium supplementation into question.
To further investigate the association between calcium supplementation and risk of myocardial infarction and cardiovascular events, Mark J Bolland and colleagues conducted a meta-analysis of calcium supplementation in randomized controlled trials (RCT).3 The authors searched Medline, Embase, and Cochrane Central Register of Controlled Trials (1966-March 2010) for RCTs of calcium supplementation. Overall, fifteen trials met eligibility criteria for inclusion (randomized, double blind, placebo controlled, elemental calcium supplementation (≥ 500 mg/d), ≥ 100 participants of mean age > 40 yrs, participants of either sex studies, and study duration > 1 yr). Of the fifteen eligible trials, eleven were able to provide data on myocardial infarction and cardiovascular events. Cardiovascular outcomes were obtained from hospital admissions, death certificates, and, in large part, from patient self reports. Patient level data was accessible for five of the studies (8,151 participants), and a separate meta-analysis was conducted for trial level data provided by all eleven studies (11,921 participants). The pre-specified primary endpoints for the study were time to first myocardial infarction, time to first stroke, and time to first event for the composite endpoint of myocardial infarction, stroke, or sudden death. The secondary endpoint was time to death (all cause mortality).
Results were presented separately for patient and trial level data. During the median 3.6 years of follow-up for the trials providing 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). All other primary and secondary endpoints demonstrated non-significant increases in incidence: stroke (HR 1.20, CI 0.96 to 1.50, P= 0.11); composite endpoint (HR 1.18, CI 1.00 to 1.39, P=0.057); death (HR 1.09, CI 0.96 to 1.23, P= 0.18). Results for trial level data, covering a mean duration of 4.0 years, mirrored that of the patient level data; 166 people allocated to calcium experienced myocardial infarction versus 130 people allocated to placebo (pooled relative risk 1.27, CI 1.01 to 1.59, P= 0.038).
Based on these data, the authors concluded that calcium supplementation, without the cardioprotective effect of vitamin D, increases incidence of myocardial infarction. A meta-analysis of RCT data provides high quality evidence that, in the current study, ...