Monday August 2 2010

“Calcium pills increase risk of heart attacks,” BBC News reported. It said a study has found that people taking the supplements are 30% more likely to have a heart attack.

This research combined the results from 11 placebo-controlled trials of calcium supplementation. Researchers looked at the numbers of heart attacks and strokes in 11,921 participants over an average of four years. In total, 296 people had a heart attack, of whom 166 were taking calcium supplements compared to 130 taking placebo.

This was a well-conducted review but its results should be treated with some caution. None of these trials originally aimed to investigate cardiovascular health and they used a variety of methods to assess and report their outcomes.

On this basis, people advised to take calcium by a doctor should not stop taking the supplement without consulting their GP first.

The researchers’ conclusions seem appropriate: given these findings and the widespread use of calcium supplementation, “a reassessment of the role of calcium supplements in the management of osteoporosis is warranted”.

The research did not look at dietary calcium or calcium supplements in combination with vitamin D, so the safety of these is not in question.

 

Where did the story come from?

Researchers from University of Auckland, University of Aberdeen and the Dartmouth Medical School in the US conducted this study, which was funded by the Health Research Council of New Zealand and the University of Auckland, School of Medicine Foundation. It was published in the British Medical Journal.

In general, the news reports have correctly reflected the findings of this review.

 

What kind of research was this?

This was a systematic review and meta-analysis designed to investigate whether calcium supplements increase the risk of cardiovascular events such as a heart attack and stroke.

There is evidence that calcium supplements slightly reduce the risk of bone fracture, but previous research has also suggested they may also cause vascular calcification (hardening of the arteries), thereby increasing the risk of adverse heart events.

A systematic review that identifies all trials relevant to the use of a treatment for a particular condition is the best way of combining the evidence on its safety and effectiveness. Meta analyses, which combine the results of several individual trials, often have inherent limitations due to differences in study populations, methods, follow-up and assessment of outcomes.

 

What did the research involve?

The researchers carried out a search for trials across the medical databases Medline, Embase and the Cochrane Central Register of Controlled Trials, in addition to looking at the reference lists of previous meta-analyses published since 1990 and two clinical trial registries.

To be eligible for inclusion, the studies had to be randomised controlled trials comparing calcium supplements (at least 500 mg/day) with inactive placebo. The studies had to have included 100 or more participants aged over 40 and to have followed them up for more than a year. The researchers excluded trials investigating the use of calcium plus vitamin D, those that had used dietary modification rather than supplements, and trials in which the participants were taking calcium for any disease other than osteoporosis.

The researchers contacted lead authors of the individual trials to obtain individual patient data. If this was not available they relied on summaries of the trial results. The researchers were interested in any cardiovascular events that occurred during the studies and that were recorded in medical records, obtained from self-reports, hospital admissions or death certificates. They were particularly interested in the time between starting calcium supplementation and the patients’ first heart attack, stroke or sudden death. When calculating associations between these outcomes and calcium supplementation they took into account possible confounders including age, sex, smoking, diabetes and high blood pressure.

 

What were the basic results?

A total of 15 studies met the inclusion criteria, but only 11 had cardiovascular data available and were included in the results.

Five of the studies had data available at the individual patient level and covered a total 8,151 people who were followed for an average of 3.6 years. In these trials, 143 people allocated to calcium had a heart attack compared with 111 in the placebo groups, which equates to a 31% increased risk of heart attack (hazard ratio 1.31, 95% confidence interval 1.02 to 1.67). There was no significant increase in risk of stroke, sudden death or the combined outcome of heart attack, stroke or sudden death.

Summary outcomes as a whole (rather than data on individual participants only) was available for 11 studies, covering 11,921 participants followed for an average of four years. In total, 296 people had a heart attack. Of these, 166 were taking calcium compared with 130 taking placebo. This analysis gave similar findings, with a 27% increased risk of heart attack with use of calcium (relative risk 1.27, 95% confidence interval 1.01 to 1.59), but no increased risk of stroke, sudden death or the combined outcome.

 

How did the researchers interpret the results?

The researchers conclude that calcium supplements are associated with an increased risk of heart attack. They say that as calcium supplements are widely used, “these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population”. They advise that “a reassessment of the role of calcium supplements in the management of osteoporosis is warranted”.

 

Conclusion

This well-conducted review has important findings. Calcium supplements are widely used among elderly people, particularly postmenopausal women, to try to reduce their risk of fractures due to loss of bone mineral density.

Points to take into consideration:

• The researchers tried to obtain detailed information on cardiovascular outcomes for individual study participants. However, this level of detail was not always available and they reported that they only managed to obtain this data for 63% of the participants across all identified trials. Where this information was not available, the researchers used either the participants’ self-reports, hospital admissions or death certificates. As such, the reliability of the source data could be considered to have a variable reliability.
• Research methods varied between individual trials, and there were different lengths of follow-up and quality of reporting. For example, a clear explanation of the randomisation method was available for only seven trials, and assessors were only blind to drug allocation in two trials.
• None of the included trials were originally set up to investigate cardiovascular events, and caution is always needed when using trial data to make conclusions on anything other than what the trial was originally designed to examine.
• Although there was a roughly 30% increased risk of heart attack with use of calcium, the actual numbers are still relatively small. There were 296 heart attacks among 11,921 people across calcium and placebo groups (2.5% overall; 1.4% in the calcium group versus 1.1% in the placebo group). The authors estimate that by incorporating the patient level data here with other trial results, treatment of 1,000 people with calcium for five years would cause an additional 14 heart attacks, 10 strokes, and 13 deaths, while preventing 26 fractures.
• The trial participants were mainly female.
• The results cannot be generalised to the use of calcium combined with vitamin D as this was not investigated here.

The researchers’ conclusions seem appropriate, that given these findings and the widespread use of calcium supplementation, “a reassessment of the role of calcium supplements in the management of osteoporosis is warranted.”

However, as the British Heart Foundation says, people who have been advised by their doctor to take calcium should not stop taking the supplement without consulting their doctor first.