Calcium supplementation significantly increased the risk of a myocardial infarction among healthy postmenopausal women, compared with those taking placebo, in a secondary analysis of an osteoporosis study.
Physicians should consider this increased cardiovascular risk against other clinical benefits of calcium supplementation in older women until confirmatory studies can be completed, the authors suggested.
“It is an important finding because so many women are prescribed calcium supplements,” Dr. Rita F. Redberg said in an interview. “I would not recommend calcium supplementation based on this finding. This raises enough concern. With any supplement, you have to show evidence of benefit without risk,” said Dr. Redberg, who was not involved in the study.
The HDL to LDL cholesterol ratios improved among the 732 women who took daily calcium supplementation, compared with the 739 participants who took placebo. This suggests that a different mechanism spurred the increase in myocardial infarction.
“This is an interesting point. It shows that just improving cholesterol does not reduce the risk of a heart attack,” said Dr. Redberg, a Robert Wood Johnson Foundation health policy fellow and director of women's cardiovascular services at the University of California, San Francisco. “It was the same finding with estrogen: It lowered LDL, increased HDL, but did not reduce the number of heart attacks in studies.”
The current findings contrast with previous suggestions of cardiovascular benefit from calcium supplementation. One study found that calcium increases the HDL:LDL cholesterol ratio by almost 20% (Am. J. Med. 2002;112:343-7).
In addition, a one-third decrease in deaths from cardiovascular events was observed among women who had the greatest intake of calcium from either diet or supplements in the Iowa Women's Health Study (Am. J. Epidemiol. 1999;149:151-61).
Following completion of a 5-year osteoporosis study (Am. J. Med. 2006;1119:777-85), Dr. Mark J. Bolland and his associates at the University of Auckland (New Zealand) reassessed their data to compare cardiovascular events. Women were randomized to 1 g/day of elemental calcium (Citracal) or placebo. All of the 1,471 participants were postmenopausal for at least 5 years and older than age 55 years at baseline, and 10% of those were older than age 80 at baseline.
Death, sudden death, myocardial infarction, angina, other chest pain, stroke, and transient ischemic attacks events were recorded every 6 months. In all, 336 women stopped taking the calcium and 296 stopped taking the placebo before the study end.
A total of 21 of the 732 women in the calcium group experienced 24 myocardial infarctions, a statistically significant difference vs. 10 of the 739 in the placebo group who had 10 such events. A composite end point of sudden death, myocardial infarction, angina, or chest pain was also higher in the calcium group (155 events among 87 women) vs. the placebo group (135 events among 93 women).
No significant differences were found in angina, chest pain, transient ischemic attack, stroke, or sudden death events between groups. There were 34 deaths in the calcium group and 29 in the placebo, a nonsignificant difference.
Dr. Redberg was not surprised by the elevated MI risk. She said research by Dr. Linda Demer, vice chair of medicine at the University of California, Los Angeles, has indicated increased cardiovascular risk associated with calcium.
“It's called the calcium paradox. Women lose calcium from their bones as they get older and it ends up in their arteries and the lining of their vessel walls, leading to accelerated atherosclerosis,” Dr. Redberg said. “This study is a confirmation of that hypothesis, that calcium can end up in the walls of your arteries.” Dr. Redberg is also a professor of medicine at the University of California, San Francisco.
The mean age was 74 years and participants were white, a possible limitation for generalizing results to other ages or racial groups, the authors said.
However, Dr. Redberg said that the inclusion of older women in the study is a strength because they are the most likely to be prescribed calcium supplements. It is very unusual for studies to include people older than age 80, she added.
'It is an important finding because so many women are prescribed calcium supplements.' DR. REDBERG