ORLANDO — Bisphosphonate use was linked with an unexpected, increased risk for aortic valve calcification in women aged 55–64 years in an analysis of about 3,700 women.
The analysis also showed the more expected finding that among older women, aged at least 75, bisphosphonate treatment was linked to a significantly reduced risk for aortic valve calcification. This effect probably occurs because bisphosphonate treatment slows calcium loss from bone, thereby preventing the lost calcium from winding up deposited on valves, Dr. Sammy Elmariah said while presenting a poster at the annual meeting of the American College of Cardiology.
The significantly increased risk for aortic valve calcification among younger women treated with a nitrogen-containing bisphosphonate has no clear explanation. “In my opinion it's due to confounding,” Dr. Elmariah said in an interview. Women younger than 65 who go on bisphosphonate treatment often have a special risk for osteoporosis that may somehow relate to a high level of valve calcification.
He and his associates used data collected in the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study of about 6,800 men and women aged 45–85 recruited from six U.S. communities and sponsored by the National Heart, Lung, and Blood Institute. Among the 3,710 women in MESA, 214 were treated with a nitrogen-containing bisphosphonate, either an oral or intravenous formulation, and the other 3,496 were not receiving a bisphosphonate. The bisphosphonate group included 100 women aged younger than 65.
Cardiovascular calcification was evaluated by electron-beam CT (in three communities) or multidetector row helical CT (at three communities). Aortic-valve calcification was defined as any calcified lesion on an aortic-valve leaflet.
Among women younger than 65, imaging showed aortic valve calcification in 18% of those on a bisphosphonate and in 4% of those not on the drug. In women aged 65 or older, imaging showed a rate of 13% with calcification in the bisphosphonate group and 20% in those not on the drug, reported Dr. Elmariah, a cardiologist at Mount Sinai Medical Center in New York.
In a model that adjusted for age, body mass index, ethnicity, study site, education, income, health insurance, treatment for hypertension or lipid lowering, diabetes, smoking, blood pressure, and cholesterol level, bisphosphonate use was linked with a 3.9-fold increased risk for aortic valve calcification in women younger than 65, a statistically significant association. The vast majority of these women were aged 55–64.
In contrast, among women aged 65 or older, bisphosphonate use was associated with a nonsignificant, 30% reduction in valve calcification. In the subgroup of women aged 75 or older, bisphosphonate use was linked with a significant reduction in the prevalence of valve calcification, a roughly 50% relative risk reduction compared with women not on a bisphosphonate.
The finding warrants further investigation in other groups of women taking bisphosphonates, Dr. Elmariah said. He reported no financial relationships for this study.