eMedinewS Editorial

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Calcium builds bones but may weaken heart

Medpage Today: A re–examination of the Women’s Health Initiative study revealed a modest increase in risk of MI and stroke for those taking calcium supplements, with or without vitamin D. The Women’s Health Initiative Calcium/Vitamin D Supplementation (WHI CaD) Study originally found no risk associated with the supplements after studying more than 36,000 patients over seven years.

However, 54% and 47% of those participants were taking personal calcium and vitamin D supplements, respectively, effectively rendering the trial a comparison of higher dose and lower dose calcium and vitamin D for most of the participants, according to Mark J. Bolland, senior research fellow at the University of Auckland, New Zealand, and colleagues. The findings suggest the use of these supplements in managing osteoporosis should be re–assessed, researchers reported online today in the BMJ.

In the new study, researchers analyzed data from 16,718 women who were not taking personal calcium supplements at the start of the trial and found that those allocated to combined calcium and vitamin D supplements were at an increased risk of cardiovascular events, especially MI. By contrast, in women who were taking calcium supplements before entering the trial, combined calcium and vitamin D supplements did not alter their cardiovascular risk.

In women not taking calcium at baseline, the hazard ratios with calcium and vitamin D were 1.16 (P=0.04) for the composite endpoint of clinical MI or coronary revascularization; 1.16 (P=0.05) for clinical MI or stroke; 1.22 (P=0.05) for MI; and 1.13 to 1.20 for the other cardiovascular endpoints. By contrast, in women taking personal calcium supplements, the hazard ratios for these endpoints with calcium and vitamin D were 0.83 to 1.08. Researchers also found no relation between the dose of the supplements and the cardiovascular risk. The authors suspect that the abrupt change in blood calcium levels after taking a supplement causes the adverse effect, rather than it being related to the total amount of calcium consumed.

“The process of vascular calcification is a complex, regulated process similar to osteogenesis,” they wrote. “It is possible that the increase in serum calcium concentrations from calcium supplements influences vascular calcification by altering regulators of calcification such as fetuin A, pyrophosphate, and bone morphogenic protein–7, or by directly binding to the calcium–sensing receptor that is expressed on vascular smooth muscle cell.”

Bolland and colleagues said that this analysis by itself does not provide definitive evidence regarding calcium supplements and cardiovascular risk. However, the researchers also pooled previously unpublished data from two other placebo–controlled trials of calcium and vitamin D, with consistent increases in the risk of MI and stroke.

To further bolster the evidence, Bolland et al. suggested that a similar risk is evident from 13 other trials, involving 29,000 people altogether, including studies involving calcium monotherapy.

The size of this increase (in risk) is modest, about 25% to 30% for myocardial infarction and 15% to 20% for stroke, but, because of the widespread use of calcium supplements either alone or with vitamin D, even small increases in cardiovascular disease incidence may translate to a substantial population burden of disease, particularly in older age groups.

The risk to benefit profile is unfavorable. Treating 1,000 patients with calcium or calcium and vitamin D for five years would cause an additional six myocardial infarctions or strokes (number needed to harm of 178) and prevent only three fractures (number needed to treat of 302).

Dr KK Aggarwal
Editor in Chief