Sex hormones may affect atherosclerosis

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Naturally produced sex hormones may influence the risk and progression of atherosclerosis, or hardening of the arteries, Johns Hopkins researchers report in a recent study.

The findings may help explain the increased risk men have of developing heart disease, which runs about twofold higher than women’s heart disease risk worldwide.

The study suggests that older women who produce a relatively high amount of estrogen are more likely to develop coronary artery calcium (CAC), a component of the fatty plaque that builds up in blood vessels and hardens arteries. Older men with relatively high amounts of testosterone are also more likely to develop CAC. However, once CAC is present, higher testosterone appears to help prevent CAC from progressing too quickly in men’s arteries. These findings will be presented Nov. 11 at the American Heart Association’s annual Scientific Sessions in New Orleans.

“We know many things that increase the risk of cardiovascular disease, such as high cholesterol and diabetes,” says Erin D. Michos, M.D., M.H.S., assistant professor of medicine at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute. “But 10 percent to 20 percent of people who get heart disease don’t have these risk factors, so we need to understand other factors that might be involved. Our results suggest that someday, in addition to testing your cholesterol and blood sugar levels to assess your heart disease risk, your doctor may want to measure your sex hormone levels as well.”

The study assessed whether sex hormones affect the risk of atherosclerosis using data from the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing study that’s been tracking 6,814 patients of four different races since 2000 to determine factors that influence risk of developing cardiovascular disease. The MESA study recruited healthy people from six different communities across the United States. Through a baseline assessment and regular checkups, researchers track each volunteer to learn what factors affect a person’s risk of developing cardiovascular disease or progressing once the disease develops.

For the Hopkins study, researchers used data from 2,700 male and 1,646 postmenopausal female MESA participants who did not use hormone replacement therapy. At the beginning of the study, participants answered detailed questionnaires about their demographics and medical history, and they received a basic health assessment measuring their height, weight and blood pressure. Participants also received a CT scan measuring their baseline level of CAC and had their blood drawn to measure blood concentrations of various sex hormones, including estradiol, the dominant type of estrogen in women, and testosterone, the dominant sex hormone in men. About half of the participants had a second CT scan 18 months later. The other half had their second scan 37 months after the initial scan.

Taking into account factors known to affect atherosclerosis risk, such as age, body mass index, blood pressure, and exercise and smoking habits, Michos and her colleagues assessed whether there was a correlation between changes in CAC between patients’ two scans and their levels of sex hormones. In women who had no baseline CAC, the researchers found that women with higher amounts of estrogen were 30 percent more likely to develop CAC by their second scan than women with lower levels of estrogen. This risk was most pronounced in women older than 65 years of age. Levels of estrogen did not seem to significantly affect whether CAC increased in women who already had CAC at baseline.

In those men who had no CAC at baseline, the researchers found that men with higher testosterone levels were 48 percent more likely to develop CAC than those with the lowest testosterone levels, with the risk greatest among men older than 55 years of age. In men who already had CAC at baseline, higher testosterone levels appeared to have a protective effect, reducing the chances that CAC measurements would increase at follow-up.

Michos adds that the role that sex hormones play in cardiovascular disease is complex, with often diverse and contradictory effects. While the Hopkins study looked at early atherosclerosis in the coronary arteries, sex hormones may also affect heart disease risk through other mechanisms, including influencing inflammation, blood clotting, and whether blood vessels are constricted or relaxed. In the future, she and her colleagues plan to study how sex hormone levels might affect the risk of specific cardiovascular incidents, such as heart attacks and strokes, in men and women.

MESA is funded by the National Heart, Lung and Blood Institute, a member of the National Institutes of Health.

Other researchers who participated in this study include Dhananjay Vaidya, Ph.D., M.P.H., Sherita Hill Golden, M.D., M.H.S., and Pamela Ouyang, M.B.B.S., all of the Johns Hopkins University School of Medicine; Susan R. Heckbert, M.D., Ph.D., of the University of Washington; and Mary Cushman, M.D., of the University of Vermont.

(Presentation title: Sex Hormones and the Risk of Coronary Artery Calcium Progression in the Multi-Ethnic Study of Atherosclerosis)


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