Calcium Can Break Your Heart

Abstract & Commentary

By Allan J. Wilke, MD, MA, Chair, Department of Integrative Medicine, Ross University School of Medicine, Commonwealth of Dominica. Dr. Wilke reports no financial relationship to this field of study.

Synopsis: Calcium supplementation without vitamin D supplementation is associated with an increased risk of myocardial infarction.

Source: Bolland MJ, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: Meta-analysis. BMJ 2010 Jul 29;341:c3691; doi: 10.1136/bmj.c3691.

Physicians commonly recommend calcium supplements to combat osteoporosis and osteopenia. High dietary calcium intake is associated with improved vascular health.1 On the other hand, calcium supplementation in patients with kidney failure, whether on dialysis or not, is associated with accelerated vascular calcification.2 With this backdrop of uncertainty, these researchers performed a meta-analysis to determine the effects of calcium supplementation on cardiovascular disease.

They searched for randomized, double-blind, placebo-controlled studies of calcium supplementation in doses ≥ 500 mg/day with participants who were ≥ age 40 years. The trials had to include at least 100 participants and had to last at least 1 year. They excluded studies that administered vitamin D with calcium vs placebo, but included studies that gave vitamin D to both groups, reasoning that vitamin D supplementation alone is associated with reduced cardiovascular disease mortality.3 Studies were also excluded if the calcium supplementation was by dietary modification or if the subjects had major systemic diseases besides osteoporosis. They identified 15 trials that met their criteria. The lead authors of these studies were asked for patient-level data; if those data were not available, the researchers used summary data. The endpoints of interest were time to first myocardial infarction (MI), time to first stroke (CVA), time to first event of the composite of MI, CVA, or sudden death, and time to death (all-cause mortality).

Five studies had patient-level data. The patients' median age was 75 years, and more than three-quarters were female. They were overwhelmingly white (> 97%). The median calcium intake was 805 mg/day. The hazard ratio (HR) for MI was 1.31 (95% confidence interval [CI], 1.02-1.67), favoring subjects randomized to placebo. Similarly, the HR for CVA was 1.20 (CI, 0.96-1.50), for the composite endpoint 1.18 (CI, 1.00-1.39), and for all-cause mortality 1.09 (CI, 0.96-1.23). When the participants were grouped into those who took less or more than the median calcium intake, the HR was 1.85 (CI, 1.28-2.67) for those who took more and 0.98 (CI 0.69-1.38) for those who took less. The same results were obtained when the studies that had trial-level data only were analyzed.

Commentary

How should we interpret the results of this meta-analysis? I think the most conservative interpretation is that there is an association between calcium supplementation and MI. The HR for MI reached statistical significance, while the HRs for CVA, the composite endpoint, and all-cause mortality did not, although the trend favored placebo over calcium. Additionally, there was a dose-response favoring those who took less than the median. Although the results have biologic plausibility (possible mechanisms of action are vascular calcification and elevated serum calcium levels4), the study design does not allow for conclusions about causation.

We must be careful not to assume that calcium plus vitamin D supplementation avoids this problem. This was not studied. Nor should we tar all calcium intake with the same brush. Dietary calcium has many benefits.5

The hazard ratios are not very large, but the number of people taking calcium supplementation is. Vitamin D supplementation prevents nonvertebral fracture.6 Calcium supplementation does not reduce, and possibly increases, the risk of hip fracture and has a neutral effect on nonvertebral fractures.7 The researchers suggest that "a reassessment of the role of calcium supplementation in the prevention and treatment of osteoporosis is warranted." I agree. The most prudent approach would be to: 1) ask your patients if they are taking calcium supplements, 2) encourage them to switch to low-fat dairy products, and 3) if they are reluctant to stop taking calcium supplements, recommend that they also take vitamin D supplements.

References

1. Bostick RM, et al. Relation of calcium, vitamin D, and dairy food intake to ischemic heart disease mortality among postmenopausal women. Am J Epidemiol 1999;149:151-161.

2. Burke SK. Arterial calcification in chronic kidney disease. Semin Nephrol 2004;24:403-407.

3. Wang L, et al. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med 2010;152:315-323.

4. Reid IR, et al. Does calcium supplementation increase cardiovascular risk? Clin Endocrinol (Oxf) 2010 Feb 23; Epub ahead of print.

5. Leyva M. The role of dietary calcium in disease prevention. J Okla State Med Assoc 2003;96:272-275.

6. Bischoff-Ferrari HA, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: A meta-analysis of randomized controlled trials. Arch Intern Med 2009;169:551-561.

7. Bischoff-Ferrari HA, et al. Calcium intake and hip fracture risk in men and women: A meta-analysis of prospective cohort studies and randomized controlled trials. Am J Clin Nutr 2007;86:1780-1790.