Why do some people develop ]]>cardiovascular disease]]> (CVD) and others do not? While lifestyle (i.e., diet, exercise, smoking) is certainly an important factor, genes also have a significant role to play.

Recent research suggests that estrogen may be involved in cardiovascular risk. But the findings have not been consistent. Some studies have indicated that higher levels of estrogen in the blood may be protective against CVD, but others show estrogen may increase the risk of certain cardiovascular events.

Researchers believe variations in estrogen receptor genes may help explain these inconsistencies. Estrogen receptors are activated by estrogen to regulate various genes. Since estrogen receptors are found in a wide range of body tissues, they may be involved in regulating some cardiovascular risk factors. Several small studies have linked a variation in the estrogen receptor gene ( ESR1 ) to an increased risk for CVD and ]]>atherosclerosis]]> .

A new study in the November 5, 2003 issue of the Journal of the American Medical Association found that people with a certain variation in the ESR1 gene were twice as likely to develop CVD, and three times as likely to have a ]]>heart attack]]> , compared with people with other variations.

About the Study

This study included 1,739 unrelated men and women from the Framingham Heart Study (875 men and 864 women).

Researchers analyzed the participants’ blood samples to identify three combinations of two ESR1 gene variations: CC, CT, or TT. They were guessing that the CC combination would associate most closely with CVD.

This study lasted from 1971 to 1998, during which participants were examined every two years. Examinations included ]]>blood pressure measurements]]> , fasting blood glucose levels, ]]>cholesterol tests]]> , smoking status checks, and body mass index (BMI, a measure of weight in relation to height) calculations. The participants provided information about their CVD history at each visit.

The researchers calculated how many participants developed the following CVD-related conditions during the course of the study:

  • Total CVD conditions (heart attack, ]]>angina]]> , and/or other symptoms of vascular problems)
  • Major CVD conditions (acute heart attack, vascular problems identified by an ]]>electrocardiogram]]> , death due to coronary heart disease, or a blockage in an artery leading to the brain)
  • Acute heart attack

The Findings

Twenty percent of the participants carried the CC genotype. During the course of the study, 54 men and 5 women had a heart attack. Of the participants who had a heart attack, 37% carried the CC genotype.

The researchers found that the participants who had a CC genotype were three times as likely to develop major CVD and twice as likely to have an acute heart attack as participants with CT or TT variants. The CC genotype had no effect, however, on the risk for total CVD.

When the results were calculated separately for men and women, the men’s results remained significant. Since the number of CVD events among women was so small, however, the researchers were not able to study the women separately.

How Does This Affect You?

These findings suggest that variations in the ESR1 gene may help explain why blood levels of estrogen increase the risk of CVD for some people, but not others. The CC variation is common; 20% of the participants in this study carried it.

Whether the CC variation facilitates the development of atherosclerosis or accelerates the occurrence of CVD events (i.e., heart attack, ]]>stroke]]> ), the researchers still aren’t sure. Whatever the mechanism, these findings support the notion that the CC variation significantly increases the risk for major CVD and heart attack.

How is this related to previous findings about estrogen and CVD? Hormone replacement therapy (HRT, a combination of estrogen and progestin) was once thought to decrease the risk of heart disease in postmenopausal women. But a recent report from the Women’s Health Initiative (WHI) trial indicated that HRT might actually increase the risk of heart disease in postmenopausal women, especially during the first year of taking it. Given the results of the current study, variations in the estrogen receptor gene may explain these inconsistent findings.

This study indicates the need for future research on the association between estrogen and CVD susceptibility. More studies are needed to determine if, in fact, the CC genotype also increases the risk for CVD in women. In the near future, it may be possible for doctors to genetically screen patients to see if they are more susceptible to CVD based on their ESR1 gene status. And, in the distant future, doctors may even prescribe medications or offer gene therapy to help their genetically susceptible patients prevent or delay heart attacks and strokes.