The use of calcium supplements, common among the elderly today, was linked with an elevated risk for cardiovascular death in men, a new study found.
Compared with men who did not take calcium supplements, those taking more than 1,000 mg per day had a 20 percent higher risk of dying from cardiovascular disease, Qian Xiao of the National Cancer Institute in Bethesda, Md., and colleagues reported in JAMA Internal Medicine.
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Early studies suggested that calcium supplementation might provide cardiovascular benefits through blood pressure or lipid effects, but more recent analyses have suggested that the supplements might actually be harmful to cardiovascular health.
To clarify these discrepancies, Xiao and colleagues analyzed data from the National Institutes of Health-AARP Diet and Health Study, which enrolled almost 600,000 adults ages 50 to 71 in 1995 and 1996.
At baseline, participants completed a questionnaire detailing their eating habits, medical history, and lifestyle.
Among the 388,229 participants included in the analysis, 56 percent of women and 23 percent of men reported using calcium supplements, while 58 percent and 56 percent reported taking multivitamins that contained calcium.
Those in the highest quintile of calcium supplement use were more often white, college-educated, and physically active, and were less likely to be smokers or to have a high intake of red meat and dietary fat.
During 12 years of follow-up, 7,904 men and 3,874 women died of cardiovascular disease.
Along with the increased risk for all cardiovascular disease deaths and heart disease deaths in men, calcium supplementation also was associated with an elevated risk for death from cerebrovascular disease, but the relative risk did not reach statistical significance.
This may have resulted from there being only 36 cases of fatal cerebrovascular events, according to the researchers.
In contrast to men, no increased risks with supplementation were seen for women.
For total calcium intake -- dietary plus supplementation -- men in the highest quintile of intake again were at increased risk for all cardiovascular disease mortality and death from heart disease.
They also had a nonsignificant increase for cerebrovascular death.
Total calcium intake was not linked with increased cardiovascular mortality in women.
The researchers also analyzed the data for individuals taking calcium-only supplements, to rule out possible effects from other micronutrients contained in multivitamin supplements, and found that once again there was an increase in the risk of death from cardiovascular disease in the study population.
They then looked for interactions between calcium supplement use and a number of other factors such as age, smoking, body mass index, and dyslipidemia, and found a significant interaction for men with smoking.
In women, they noted an interaction for calcium use and past smoking and high cholesterol.
The researchers noted that the different risks for men and women were "intriguing," in light of the fact that a reanalysis of data from the Women's Health Initiative identified "modest" increases in risk for cardiovascular events, particularly myocardial infarction, in supplement users.
The increased risk seen only for men in this study may have been because they began taking the supplements at older ages, and women who tend to use calcium for longer periods may "have achieved calcium balance and stable calcium levels long before the study, and the effect of calcium supplement became less profound," the researchers wrote.
A possible reason for why calcium might influence the cardiovascular system is through calcification of the coronary arteries.
"Vascular calcification is an actively regulated process that not only shares key proteins and pathways but is also intricately intertwined with bone mineralization," Xiao and colleagues explained.
However, because of the multiplicity of biological effects of calcium, further research into mechanisms of action are needed, they noted.
Limitations of the study included a lack of information on the duration of calcium use and family history of heart disease, as well as self-report of supplementation.
"Given the extensive use of calcium supplement in the population, it is of great importance to assess the effect of supplemental calcium use beyond bone health," the authors concluded.
In an invited commentary, Susanna C. Larsson of the Karolinska Institute in Stockholm also called for additional studies to more clearly establish the benefits or risks of calcium.
"Meanwhile, a safe alternative to calcium supplements is to consume calcium-rich foods, such as low-fat dairy foods, beans, and green leafy vegetables, which contain not only calcium but also a cocktail of essential minerals and vitamins," Larsson advised.