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Inflammation Signals May Predict Heart Disease

Studies find two molecules may play key roles

TUESDAY, Nov. 6, 2001 (HealthDayNews) -- Molecules involved in inflammation look promising as risk indicators for coronary artery disease and as targets for treatment, two research teams report.

Scientists at Uppsala University Hospital, in Sweden, find an association between blood levels of interleukin-6 (IL-6), an immune system protein that can drive the inflammatory process, and the risk of death for patients with advanced coronary artery disease. Singling out patients with elevated IL-6 levels for aggressive treatment reduced their death rate, they report.

And researchers at the Cleveland Clinic Foundation say that levels of myeloperoxidase (MPO), an inflammation-causing enzyme produced by the defense system against infection, are much higher in patients with coronary artery disease than in those with healthy arteries.

But an editorial accompanying those reports in the Nov. 7 issue of the Journal of the American Medical Association says the research linking inflammation and coronary artery disease is at an early stage, with years to go before it can be used for prevention and treatment.

IL-6 is one of a family of proteins called cytokines. It induces formation of other molecules that cause inflammation. The Swedish researchers say their work is based on reports that elevated levels of IL-2 are linked to an increased risk of heart attacks and death in patients with severe blockages of heart arteries.

In their study, half of 1,222 patients with severe, unstable coronary artery disease were given aggressive treatment, with either the artery-opening procedure called angioplasty or bypass surgery. The other half were treated less strenuously, with either a blood-thinning drug or a placebo, a necessary part of such a carefully controlled study.

"In patients with high IL-6 levels, an early invasive strategy led to a 5.1 percent absolute or 65 percent relative reduction in 12-month mortality," the researchers say. "At lower IL-6 levels, there was no significant difference in 12-month mortality levels between treatment strategies."

So measuring IL-6 levels can identify those patients with coronary artery disease who are at highest risk and can benefit most from aggressive treatment, they conclude.

The Cleveland Clinic study took a different tack, comparing MPO levels in patients with and without coronary artery disease. The study was done "because a wealth of basic scientific evidence" indicates that MPO plays an important role in generating production of molecules that damage the arteries and lead to heart disease, says Dr. Stanley L. Hazen, professor of cardiology at the Cleveland Clinic Foundation and member of the research team.

"We found that high levels of MPO are highly correlated with the risk of having coronary artery disease, and that high levels of MPO track with levels of coronary artery disease better than traditional risk factors," Hazen says.

The finding is important because "at least 50 percent of people with coronary artery disease have no conventional risk factors. There is a large percentage of patients who are missed by present tests," Hazen says.

And the finding could produce better ways of treating heart disease, he says. MPO appears to generate molecules that damage the arteries, and so drugs that block MPO activity might protect those arteries. "Several pharmaceutical companies are in the process of working on them," Hazen says.

The research is valuable, but it is still very much in the research stage, says Dr. David Vorchheimer, director of the coronary care unit at Mount Sinai School of Medicine, in New York City, and co-author of the editorial.

"We need a sequential series of three steps before this can be applied to clinical practice. First, the molecule has to be proven to be the cause of the disease. Second, we must identify something that inhibits the culprit. Third, a clinical trial needs to be done, designed to show that blocking the culprit molecule reduces the threat," Vorchheimer says.

"Where we are with inflammatory molecules is that we have evidence that persons with coronary artery disease have high levels of them. We don't know that they cause disease; they may just be innocent bystanders, and there is no evidence yet that targeting them will lower the incidence of cardiac events," he says.

What To Do

While research must be encouraged, Vorchheimer says, "We should not overlook what effective methods we have now in overindulgent worship of what's coming down the road." For example, there is much evidence that the family of cholesterol-lowering drugs called statins are not being prescribed enough to people who can benefit from them, he says.

The American Heart Association has information on heart disease risk factors you can change and those you can not.

SOURCES: Interviews with Stanley L. Hazen, M.D., Ph.D., professor of cardiology, Cleveland Clinic Foundation; David Vorchheimer, M.D., director, coronary care unit, Mount Sinai School of Medicine, New York City; Nov. 7, 2001, Journal of the American Medical Association
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