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Inflammation Molecules Signal Heart Risk

Role in medical practice not yet clear

MONDAY, Oct. 20, 2003 (HealthDayNews) -- Inflammation is starting to look even more important as a factor in heart disease and stroke, say researchers who report that measuring blood levels of inflammation-related molecules can be better indicators of cardiovascular risk for some people than such well-established risk factors as high blood pressure or cholesterol levels.

In a study of more than 2,200 healthy people over the age of 70, blood levels of two inflammation-related molecules, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), were sometimes better predictors of future trouble than the conventional risk factors, says a report in the Oct. 21 issue of Circulation.

Inflammation is the body's response to an injury, such as infection. Studies in the past few years have shown that inflammation somehow plays a role in atherosclerosis, the buildup of fatty deposits in blood vessels that can lead to heart attacks, strokes and other cardiovascular problems.

Most research has concentrated on one molecule, C-reactive protein, as a marker of inflammation. A number of studies have shown that high blood levels of C-reactive protein are associated with an increased risk of cardiovascular disease. The new study says that IL-6 and TNF-alpha are stronger predictors of trouble than C-reactive protein.

In the Health, Aging and Body Composition study, done at the Wake Forest University School of Medicine, the researchers tracked the medical history of the 2,225 participants for an average of 42 months after measuring their blood levels of C-reactive protein, IL-6 and TNF- alpha.

People with the highest IL-6 levels were two to five times more likely to have a heart attack, stroke or other cardiovascular episode than those with the lowest levels, the researchers say. High blood levels of TNF-alpha increased the risk of heart disease by 79 percent and of heart failure by 121 percent. High levels of C-reactive protein increased the risk of heart failure by 160 percent compared to those with low levels, but they did not significantly raise the risk of a first stroke or heart attack.

As expected, the incidence of cardiovascular disease was high for people with the conventional risk factors -- smoking, high blood pressure, high cholesterol and the like. But for participants free of those risk factors, the inflammation-related molecules were better predictors of heart disease.

Nevertheless, it will be a while before measurements of inflammation markers are widely used, says study author Dr. Matteo Cesari, a junior investigator at Wake Forest's Sticht Center on Aging.

"It doesn't mean that high blood pressure and cholesterol are not worthwhile to measure," Cesari says. "They do lose some of their power to predict cardiovascular events in older people, so adding these measurements might help improve the evaluation of patients so we will be able to define their risk at an earlier stage of cardiovascular disease."

One practical issue is that tests to measure the inflammation-related molecules are not widely available, although they are being used in some larger medical centers, Cesari says.

Asked when measurements of inflammation markers might enter general medical practice, Dr. Richard C. Pasternak, an associate professor of medicine at Harvard Medical School and a spokesman for the American Heart Association, says, "Not soon."

"This is the beginning, not the end," Pasternak says. "We are just beginning to accept the use of C-reactive protein in limited circumstances in some patients."

The basic problem is that cardiologists don't understand the relationship between inflammation and heart disease, so the inflammation marker tests "still don't directly inform us about how to handle our patients," he says.

By contrast, many studies show that lowering blood pressure and cholesterol levels and treating other established risk factors can help patients, so "for people at increased risk by whatever measure is used, we should first try all the risk-lowering strategies we already know about," Pasternak says.

More information

An overview of the current status of inflammation and C- reactive protein in heart disease can be found at the American Heart Association, which also has a page on other risk factors for heart disease.

SOURCES: Matteo Cesari, M.D., junior investigator, Sticht Center on Aging, Wake Forest University School of Medicine, Winston Salem, N.C.; Richard C. Pasternak, M.D., associate professor, medicine, Harvard Medical School, Boston; Oct. 21, 2003, Circulation
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