Calcium Supplements May Increase MI Risk in Healthy Older Women

By Judith Groch
AUCKLAND, New Zealand, Jan 16 -- Healthy older women taking high-dose calcium supplements had a significantly increased risk of myocardial infarction, investigators here found. MI was twice as common in women taking one gram of elemental calcium daily than in those taking a placebo, Ian R. Reid, M.D., of the University of Auckland, and colleagues reported online in BMJ.
However, the researchers cautioned, this potentially detrimental effect should be balanced against the likely benefits of calcium on bone.
These findings do not permit definitive conclusions but do flag cardiac health as an area of concern in relation to calcium use, the investigators wrote.
Evidence has suggested that high calcium intake might protect against vascular disease by increasing the ratio of HDL to LDL cholesterol. However, the researchers said, evidence from controlled trials supporting this theory is lacking.
So they did a secondary analysis of 1,471 healthy postmenopausal women, mean age 74, who had previously taken part in a randomized study to assess the effect of calcium on bone density and fracture rates.
Of the participants, 739 were randomized to placebo and 732 to one gram of elemental calcium daily as citrate. They took two tablets (each containing 200 mg elemental calcium) before breakfast and three in the evening and were followed for five years. A food frequency questionnaire was also used to assess dietary calcium intake.
In what they termed an adjudication of the primary findings, the researchers also reviewed the patients' medical records completed by the family doctor or hospital. For women who died during the study, they reviewed hospital records or death certificates, and for unreported events during the study, they searched a national database of hospital admissions for cardiovascular events.
The researchers found no difference between groups in the number of women experiencing any cardiovascular event (angina, chest pain, MI, or sudden death); however, MI was more commonly and significantly reported in the calcium group than in the placebo group (45 events in 31 women taking calcium versus 19 in 14 in the placebo group, P=0.01).
The composite endpoint of myocardial infarction, stroke, or sudden death was also more common in the calcium group (101 events in 69 women versus 54 events in 42 women, P=0.008).
After adjudication, myocardial infarction remained twice as common in the calcium group (24 events in 21 women versus 10 events in 10 women, relative risk: 2.12, 95% confidence interval: 1.01 to 4.47).
For the composite end point of sudden death, myocardial infarction, or stroke, 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group (relative risk: 1.47, 95% CI: 0.97 to 2.23).
When unreported events were added from the national database of hospital admissions in New Zealand, the risks changed. The relative risk of myocardial infarction was attenuated but still significant: 1.49 (95% CI: 0.86 to 2.57) and the composite end point was 1.21 (95% CI: 0.84 to 1.74, P=0.043).
However, adjudicated values for individual vascular events showed that only MI rates were significant (P=0.058).
The number of events were not significant for stroke alone (37 events in 34 women in the calcium group versus 26 in 25 women (P=0.15)), or for sudden death (three women in the calcium group versus six in the placebo group (P=0.36)).
That calcium supplementation might have adverse effects on vascular disease incidence is of concern because the morbidity and mortality that would follow from even a small adverse effect on vascular event rates is such that the beneficial effects of calcium supplementation on bone loss would be rapidly counterbalanced, the researchers said.
For example, the number of women needed to treat for five years to cause one myocardial infarction was 44, to cause one stroke was 56, and to cause one cardiovascular event was 29. By comparison the number needed to treat to prevent one symptomatic fracture was 50.
Dr. Reid and his team noted that these results are not conclusive, but finding an adverse trend in vascular events with calcium supplementation is not necessarily surprising. Calcium supplements acutely elevate serum calcium levels, possibly accelerating vascular calcification, which is predictive of vascular event rates, they said.
High calcium intake has also been associated with brain lesions on MRI and vascular calcification and mortality in dialysis patients, the researchers said.
The trend to more frequent cardiac events in the calcium group does not seem to be secondary to changes in lipids or other risk factors, they added, because calcium supplementation was associated with beneficial trends in levels of HDL and LDL cholesterol in the present study, they added.
Weaknesses of the study included its small size for a study with cardiovascular endpoints. The cohort comprised elderly (10% over 80 at baseline) and white women, so that the results may not be generalizable to other ages and racial groups.
The study was supported by the Health Research Council of New Zealand. Mission Pharmacal supplied the calcium citrate tablets and placebo.
Dr. Reid has received research support from and acted as a consultant for Fonterra and Mission Pharmacal. No other conflicts were reported.
Additional source: BMJ Online FirstSource reference: Bolland M, et al "Vascular events in healthy older women receiving calcium supplementation: randomized controlled trial" BMJ Online First 2008; DOI: 10.1136/bmj.39440.525752.BE.