Strong Bones, and Heart Disease, Too
Abstract & Commentary
By Russell H. Greenfield, MD, Editor
Synopsis: A meta-analysis of calcium supplementation studies where vitamin D was not also administered suggests that isolated supplemental calcium may significantly increase the risk of myocardial infarction as well as, to a lesser degree, stroke.
Source: Bolland MJ, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: Meta-analysis. BMJ 2010;341:c3691.
Studies published within the last 5 years have brought to light questions about the safety of calcium supplementation. Perhaps most notably in this regard was a randomized controlled trial of healthy older women where findings suggested that the use of calcium supplementation may be associated with an increased risk of cardiovascular events.1 The authors of that same study sought clarification of the risk:benefit ratio for calcium supplementation and set out to complete a review of the topic that resulted in this current article.
The authors completed a meta-analysis of studies of calcium supplementation (≥ 500 mg elemental calcium/day) for more than 1 year without co-administered vitamin D that included > 100 subjects older than age 40 years. Trials that also employed vitamin D were excluded because vitamin D administration has been associated with decreased mortality, and those focusing on dietary manipulation of calcium intake were likewise not included. Databases combed included Medline, Embase, and the Cochrane Central Register of Controlled Trails. A total of 15 studies met eligibility criteria, 13 of which compared calcium supplements with placebo. The pooled analysis included five studies providing patient level data (> 8,000 subjects with a median follow-up of 3.6 years) and 11 offering trial level data (almost 12,000 subjects, mean duration 4.0 years). Data on cardiovascular outcomes were obtained from death certificates, hospital admissions, and self-report where available, resulting in patient level outcomes data for 63% of participants, complete trial level data for 85% of subjects, and partial trial level data for 93% of participants. Prespecified primary endpoints 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. All-cause mortality was a secondary endpoint.
Results of their analysis were compelling and troubling: 143 people in the five studies that contributed patient level data who had been randomized to receive calcium experienced myocardial infarction compared with only 111 in the placebo group (hazard rate [HR], 1.31; 95% confidence interval [CI], 1.02-1.67). In addition, nonsignificant increases in the incidence of stroke, death, and the composite endpoint of myocardial infarction, stroke, or sudden death were identified. Subgroup analysis indicated that dietary calcium intake that exceeded 805 mg/day was associated with an increased risk of myocardial infarction (HR, 1.87; 95% CI, 1.28-2.67). Recurrent cardiovascular events were likewise more common in those taking calcium supplements. Meta-analysis of the trial level data supported some of the concerns raised by the patient level data, there being an increased risk of myocardial infarction in those taking calcium (pooled relative risk, 1.27; 95% CI, 1.01-1.59), but no increase in the risk of stroke, death, or the combined endpoint. Findings were consistent across studies and were independent of type of supplement, gender, or age. The authors concluded that regular use of calcium supplements without co-administered vitamin D may increase the risk of myocardial infarction and recommended a reassessment of strategies to prevent osteoporosis and the role of calcium supplementation.
Commentary
Calcium supplementation has long been a centerpiece of health promotion, specifically as relates to the prevention of osteoporosis and related fractures. Practitioners have been losing some faith in the agent, however, as a evidence accumulates that suggests its benefit may be at best mild-to-moderate in this regard. The authors of the current study were also troubled by the fact that even though observational data suggest calcium may support vascular health, patients with renal failure receiving calcium supplementation experience accelerated vascular calcification rates and increased mortality. Their meta-analysis of isolated calcium supplementation shows a ~30% increase in the risk of myocardial infarction, and smaller but concerning increased risks of stroke and death. The authors are quick to point out that their findings do not apply to the common practice of employing calcium and vitamin D together, and that in none of the trials was cardiovascular outcome the primary endpoint.
No statistical heterogeneity existed between studies in any of the analyses and compliance rates were generally higher than 75% at the end of the various trials. While meta-analysis is fraught with challenges of proper interpretation, the study authors went out of their way to address issues of potential bias and missing data. This is a strong study presenting data that calls for careful re-evaluation of the way in which calcium supplements are used. Beyond cardiovascular concerns, questions have previously been raised about the potential for an increased risk of prostate cancer with calcium supplementation in non-osteoporotic men.2
When data refute long-held beliefs about the safety and effectiveness of therapies long utilized, practitioners and patients alike are left to ponder how best to move forward. Medical dogma shifts rapidly with new information, as it should when appropriate, but those same shifting sands lead to uncertainty in circumstances where our patients want exactly that certainty. Such is the nature of life and of medical science, where the quest for certainty often leads us no closer to it. Until greater clarity is achieved it seems prudent to recommend that our patients not take calcium supplements unless an appropriate dose of vitamin D is also used.
References
1. Bolland MJ, et al. Vascular events in healthy older women receiving calcium supplementation: Randomized controlled trial. BMJ 2008;336:262-266.
2. Chan JM, et al. Dairy products, calcium and prostate cancer risk in the Physician's Health Study. Am J Clin Nutr 2001;74:549-554.
A meta-analysis of calcium supplementation studies where vitamin D was not also administered suggests that isolated supplemental calcium may significantly increase the risk of myocardial infarction as well as, to a lesser degree, stroke.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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