Calcium supplements and MI risk

Do calcium supplements increase the risk of myocardial infarction (MI)? Researchers from New Zealand recently reanalyzed data from the Women's Health Initiative (WHI) in an attempt to answer this question. In 2008 the same group published a randomized, placebo-controlled trial of calcium supplements in nearly 1500 healthy postmenopausal women that showed upward trends in cardiovascular event rates with calcium use (BMJ 2008;336:262-266). The same group subsequently carried out a meta-analysis of cardiovascular events in randomized, placebo-controlled trials of women taking calcium supplementation without vitamin D. In that study, calcium supplementation significantly increased the risk of MI by about 30% (BMJ 2010;341:c3691). Although these studies garnered some interest, they were also viewed with skepticism, and most physicians, especially in this country, did not change their practice of recommending calcium supplementation for postmenopausal women. The New Zealand group then turned to the WHI data, a rather strange place to look considering that one of the main outcomes of WHI was the finding of no adverse effect of calcium and vitamin D on cardiovascular risk. However, the researchers found one major caveat: WHI did not consider whether women were taking calcium on their own prior to entry into the study. The New Zealand group got access to the original NIH data and were able to tease out women who were not using personal calcium supplements at randomization. They found nearly 17,000 women who fit that category. Women in this subgroup who were randomized to calcium and vitamin D had small but significant increased risk for cardiovascular events with hazard ratios that ranged from 1.13-1.22 (P = 0.05 for clinical MI or stroke, P = 0.04 for clinical MI or revascularization). When the WHI data were added to the previously done meta-analysis of three placebo-controlled trials, calcium and vitamin D were found to increase the risk of MI (relative risk [RR] 1.21 [95% confidence interval [CI] 1.01-1.44]; P = 0.04), stroke (1.20 [CI 1.00-1.43], P = 0.05), and the composite of MI or stroke (1.16 [CI 1.02-1.32], P = 0.02). Trial level data was available for more than 28,000 women who were randomly assigned to calcium plus vitamin D or placebo. Calcium or calcium plus vitamin D increased the risk of MI (RR 1.24 [CI 1.07-1.45], P = 0.004) and a composite of MI or stroke (1.15 [CI 1.03-1.27], P = 0.009). The authors conclude that calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially MI. They suggest that a reassessment of the role of calcium supplementation in osteoporosis management is warranted (BMJ 2011;342:d2040 doi:1136/BMJ.d2040, published April 19, 2011). This study has been hotly debated and was even criticized in an editorial in the same issue of BMJ. Nonetheless there is a bit of irony in using WHI data, which are largely responsible for millions of women stopping hormone replacement therapy, to show a relationship between calcium and cardiovascular disease disease. There is no suggestion in any of these data that dietary calcium leads to adverse events. It is postulated that the rapid increases in calcium that occur with calcium supplementation may somehow play a role in increased cardiovascular risk.