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, or 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 were 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," said Erin D. Michos, assistant professor of
medicine at the Johns Hopkins University
School of Medicine and its Heart and Vascular Institute, in
an interview. "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."
The study assessed whether sex hormones affect the
risk of atherosclerosis using data from
the Multi-Ethnic Study of Atherosclerosis, or 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 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 Johns 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 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. 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. 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 added that the role that sex hormones play in
cardiovascular disease is complex, with
often diverse and contradictory effects. While the Johns
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 are
Dhananjay Vaidya, Sherita Hill Golden and
Pamela Ouyang, all of Johns Hopkins; Susan R. Heckbert, of
the University of Washington; and Mary
Cushman, of the University of Vermont.