“Taking calcium supplements to improve bone strength in middle-age could put women at higher risk of a heart attack”, the Daily Mail reported today. Other newspapers also described a study that involved nearly 1,500 women in New Zealand. Some reported that this finding appeared to contradict previous evidence that showed benefits in calcium protecting against cardiovascular disease. Many advised people who have been prescribed calcium by their doctor to continue taking it.
The research behind the stories is a well-conducted community based trial. It brings to light a potentially serious adverse effect associated with calcium supplementation. However, the study has limitations including its size. Until a more definitive answer is available - such as one provided by a meta analysis - individuals should be aware of the fine balance between benefit and harm suggested by this study. Anybody with concerns should seek advice from their doctor before changing their calcium intake significantly.
Where did the story come from?
The research was conducted by Dr Mark Boland and colleagues from the University of Auckland in New Zealand. It was supported by grants from the Health Research Council of New Zealand and competing interests were declared. The study was published in the peer-reviewed: The British Medical Journal.
What kind of scientific study was this?
This was a secondary analysis of a randomised controlled trial. The authors had already published the results of their main trial, which looked at the preventive effects of calcium supplementation on bone density and fracture rates in healthy women after the menopause. During that trial and before the analysis of any data on heart disease or stroke, they wrote a detailed plan of their intentions to record the data for this present analysis.
Women were recruited to the study by advertisement and through the post using the electoral roll. In order to qualify, suitable women needed to have had their last period at least five years previously and be aged 55 or more, (meaning they were postmenopausal and had a life expectancy of more than five years). From an assessment of 2,421 women in the clinic, the researchers found 1,471 who agreed to participate and were suitable.
The women were randomly allocated to one of two groups. In the experimental group, the women received 1gram (0.03oz) of elemental calcium daily. This was taken through two tablets of calcium citrate before breakfast and three in the evening. The control group received identical dummy tablets (placebo). The research was double blinded and neither the patients nor the researchers knew who had been allocated to which group. The women were followed up every six months for five years.
The researchers looked for adverse cardiovascular events such as heart attacks, strokes (of all types) angina and death and then analysed the data in three ways. Potentially adverse events that were reported by the women themselves were analysed first. The researchers then checked the medical records at the women’s hospitals and family doctors for confirmation of the event. Finally, a search of the national database of hospital admissions was carried out to identify any events that were unreported by the women.
The researchers used internationally accepted definitions of heart attack and stroke to define the adverse events.
What were the results of the study?
The two groups had similar characteristics to each other at the start of the study. The groups average age was 74.2 compared to 74.3 years and average weight was 66.8 compared to 67 Kg. Less than a quarter of each group smoked.
Over five years of follow-up, 45 heart attacks were self-reported by 31 women in the group taking calcium compared to 19 heart attacks reported by 14 women in the control group. When checking the records at the hospital and GP surgeries the researchers were able to verify fewer events, 24 events in 21 women taking calcium compared to 10 events in 10 women taking placebo. In both these analyses, this was a statistically significant doubling of risk. When the unreported events were added from the national database the increase in risk became less and did not reach statistical significance.
What interpretations did the researchers draw from these results?
The researchers conclude, “Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates. This potentially detrimental effect should be balanced against the likely benefits of calcium on bone.” They acknowledge that some of their findings were not significant (they show a trend).
The authors also compare the results from this trial to their previous trial and report the NNT (Number Needed to Treat). This is an estimated number of patients who need to be treated to cause or prevent one adverse outcome). In this case, the number of women needed to be given calcium supplements for five years to cause one adverse event.
What does the NHS Knowledge Service make of this study?
This was a well-conducted randomised controlled trial, in which the two groups of women were well balanced at the start of the study in terms of risk factors for heart disease and stroke. This increases confidence that the effect demonstrated was not simply due to differences in overall healthiness between the two groups.
- The fact that the women were recruited from the community rather than from attendance at clinics, makes it more likely that these results are applicable to a broader range of normal healthy women. However, as the authors acknowledge, the women were mostly white and 10% of them were over 80 years old, therefore the findings may not necessarily apply to other ages or ethnicities.
- In general, caution should be used when interpreting the results of secondary analyses like this one. However, this study carefully defined its intentions and collected data before the results were known, and this minimises the risks that the results are biased.
- The numbers recruited to this study were thought to be sufficient to detect an effect on bone density and fracture rate. However, by looking at other outcomes such as heart disease, the authors have found the study had a low chance, because of the number of women recruited, of correctly detecting a real difference. The fact that their study was so small may account for the fact that so few of their results were statistically significant.
- The authors compared the results from this trial to the results of their previous trial conducted in the same women and found the balance between risk and benefit to be close. They estimated that, over a five-year period, 44 women would need to take calcium to cause one myocardial infarction, 56 women to cause one stroke, and 29 to cause one cardiovascular event. By comparison, 50 women would need to take calcium to prevent one symptomatic fracture. These estimates of benefit and harm are very similar suggesting that judgment is required by women and their clinicians when deciding whether to take or prescribe calcium.
This study indicates that future research needs to look at cardiovascular events in association with taking calcium supplements. Combining the results of current trials in a systematic review would also be helpful. This study suggests there is a fine balance between benefit and harm through taking calcium supplements. However, people taking these supplements should seek advice from their doctor before changing their calcium intake.
Sir Muir Gray adds...
A systematic review is required.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
BBC News, 16 January 2008
The Daily Telegraph, 16 January 2008
The Times, 16 January 2008
Daily Mail, 16 January 2008
Links to the science
BMJ 2008; Jan 15 [Epub ahead of print]