Traditional risk-factor scoring misses one-third of women vulnerable to coronary heart disease

December 16, 2005

Traditional risk-factor scoring fails to identify approximately one-third of women likely to develop coronary heart disease (CHD), the leading cause of death of women in the United States, according to a pair of reports from cardiologists at Johns Hopkins.

"Our best means of preventing coronary heart disease is to identify those most likely to develop the condition, and intervene with lifestyle changes and drug treatment before symptoms start to appear," says the senior author of both studies, cardiologist Roger Blumenthal, M.D., an associate professor and director of the Ciccarone Preventive Cardiology Center at The Johns Hopkins University School of Medicine and its Heart Institute. "The goal is to strongly consider therapies, such as aspirin, cholesterol-lowering medications and, possibly, blood pressure medications for individuals at higher risk, so that heart attacks will be less likely to occur in the future."

The Hopkins findings, the latest of which appear in the American Heart Journal online Dec. 16, is believed to be one of the first critical assessments of the Framingham Risk Estimate (FRE) as the principal test for early detection of heart disease. The researchers wanted to determine why many of these women at risk for heart disease are not identified earlier.

The FRE is a total estimate of how likely a person is to suffer a fatal or nonfatal heart attack within 10 years, and it is based on a summary estimate of major risk factors for coronary heart disease, such as age, blood pressure, blood cholesterol levels and smoking.

However, Blumenthal says, many women with cardiovascular problems go undetected despite use of the Framingham score. While the death rate for men from cardiovascular disease has steadily declined over the last 20 years, the rate has remained relatively the same for women, he says.

In their latest report, the Hopkins researchers examined the risk of premature CHD in women whose average age was 50 and who were participating in the Sibling and Family Heart Study, a long-term study of how heart disease develops among family members. Study subjects had no symptoms of heart disease, but had a sibling who had been hospitalized for a coronary event, such as a heart attack before age 60.

The researchers calculated each woman's Framingham score and found that 98 percent were gauged to be at very low risk for future CHD, with an FRE of less than 6 percent, while only 2 percent of participants were judged to be at intermediate risk for future CHD, with an FRE between 10 percent and 20 percent.

When the results were contrasted with evidence gleaned from CT-scan measurements of calcium build-up in the arteries, the researchers found that one-third of women originally classified as very low risk actually had coronary atherosclerosis, a hardening and narrowing of the arteries that can lead to heart attacks if not controlled with drug therapy along with diet, exercise and other lifestyle changes. Indeed, 12 percent of women in the study had advanced stages of atherosclerosis, while another 6 percent had severe calcium build-up.

"We wanted to verify if the Framingham score truly captured who was most at risk, but it turns out to have underestimated a large number of those who should be considered for preventive therapies," says Blumenthal.

According to the researchers, performing cardiac CT scans on everyone with a low Framingham score is not a practical option for improving upon traditional risk-factor screening. To better determine who should get scanned, even if they have a low risk assessment, the Hopkins team began to search for additional predictors of who was most at risk. They found that people with two or more risk factors, such as obesity, smoking or metabolic syndrome, plus a family history for heart disease were those most likely to have a high calcium score. It is this group, the researchers say, who should be considered for a fast cardiac CT scan regardless of low Framingham scores and if the physician or patient is unsure about the need to go on long-term preventive therapies.

In a related, second investigation, published online in the May edition of the journal Atherosclerosis, the Hopkins team analyzed the Framingham scores of 2,447 women age 45 to 65, all of whom were participating in another long-term study in Ohio of adults referred by a physician for a cardiac risk assessment.

Again, when the FRE results were compared to calcium scores, 84 percent (408 of 489) of those classified as low risk by FRE actually had some coronary atherosclerosis. Twenty percent of those who were classified at intermediate risk by FRE had signs of advanced atherosclerosis.

"Our results show that if a CT scan had not been performed in addition to traditional risk-factor scoring, a large number of women would have missed the chance to begin preventive therapies," says cardiologist Erin Michos, M.D., a clinical research fellow at Hopkins and its Heart Institute. Michos led both Hopkins studies.

"For some women, especially those with a family history of heart disease and multiple risk factors for it, additional screening using CT scan and calcium scoring may be warranted," she adds.
Funding for these studies, whose data analyses took place between January 2003 and November 2004, was provided by the National Institutes of Health, including the National Institute of Nursing Research and the National Heart, Lung and Blood Institute, the Johns Hopkins General Clinical Research Center and the Maryland Athletic Club Charitable Foundation.

Other researchers involved in the two studies were Khurram Nasir, M.D., M.B.A.; Joel Braunstein, M.D.; John Rumberger, M.D.; Matthew Budoff, M.D.; Wendy Post, M.D.; Chandra Vasamreddy, M.D.; Diane Becker, M.P.H., Sc.D.; Lisa Yanek, M.P.H.; Taryn Moy, M.S.; Elliot Fishman, M.D.; and Lewis Becker, M.D.

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