Calcium Supplements Increase Risk of Myocardial Infarction

To the Editor: The cardiovascular safety of calcium supplements has been revisited with a further meta‐analysis,(1) which concludes that calcium supplementation does not increase coronary heart disease in women, without providing data for men. 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. However, in sensitivity analyses, we reported that sex did not interact with the effect of calcium supplements on cardiovascular risk(4) and that the risk of MI from calcium is increased after men or self‐reported events are excluded.(4, 5) The major effect of restricting the analyses to the subgroup of women is a reduction in the power of the analyses, and, for trials that included men and women, potentially introducing bias through loss of the balancing effects of randomization on possible confounders. These, and other major limitations of subgroup analyses, have been well described.(6)