Molecule Signals Heart Disease in Early Stages

Study found high levels of protein predicted development of cardiovascular trouble

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By
HealthDay Reporter

MONDAY, July 2, 2007 (HealthDay News) -- A molecule that could be a powerful new marker for heart disease and stroke has passed its first real-world test, researchers report.

In an eight-year study, high blood levels of myeloperoxidase (MPO) were closely associated with the early development of heart disease, and its predictive abilities were independent of classic risk factors such as high cholesterol, high blood pressure and diabetes. The finding is detailed in the July 10 issue of the Journal of the American College of Cardiology.

"This is the first time this particular marker has been looked at in an apparently healthy population," said Dr. Stanley L. Hazen, head of the section of preventive cardiology and cardiac rehabilitation at the Cleveland Clinic. His group has been working on MPO for more than a decade.

Hazen has filed for patents on MPO as a biomarker for cardiovascular disease. MPO tests now are available commercially and "at least five pharmaceutical companies are working to develop inhibitors of MPO," Hazen said.

MPO is a protein secreted by white blood cells. It signals inflammation and releases a bleach-like substance that damages the cardiovascular system. "Over a decade ago, our group showed that it is involved in tissue damage," Hazen said. "There are very large research and genetic studies that link MPO to the development of heart disease."

The new report describes use of MPO levels as a screening tool in a healthy population living in Norfolk, England. MPO readings were taken from thousands of residents at the start of the study. Eight years later, the researchers compared those readings in the 1,138 people who had developed coronary artery disease and 2,237 people, matched for age and sex, who had not.

The incidence of heart disease was 49 percent higher in people ranked among the top 25 percent of MPO levels, compared to those in the lowest quarter. Their risk was 36 percent higher when traditional risk factors including cholesterol levels, high blood pressure, smoking and diabetes were taken into account.

"Even if your other biomarkers were normal, if MPO levels were high, you were at higher risk," Hazen said. "The magnitude of the risk is roughly comparable to the risk of elevated LDL cholesterol."

LDL cholesterol collects in fatty plaques that eventually block arteries. It is a major target of medications aimed at reducing risk of heart attack and stroke, most notably statins.

The first commercially available test for MPO levels was approved by the U.S. Food and Drug Administration a year ago, Hazen said. "Its first intended use is for evaluating people with a history of chest pain, people who go to the emergency room or cardiologist," he said. His hope is that it eventually will become a standard screening tool.

"We believe it is potentially of utility for people who you don't know may be at risk," he said.

A high MPO reading now indicates that the physician should concentrate on reducing known risk factors, but MPO itself could eventually become a target of drug treatment, he said.

"One fascinating aspect of this study is that this marker of inflammation precedes by nearly a decade the development of clinical coronary disease," Dr. Christopher Cannon, an associate professor of medicine at Harvard Medical School, said in a statement. "This suggests MPO could be used to catch the disease in a very early stage and help in true prevention of coronary artery disease."

MPO might also be a marker for unstable plaque, deposits that can erupt to emit artery-blocking fragments, Cannon added. "More study is needed, but among hundreds of markers tested to date, MPO looks like a keeper that will one day become part of clinical care," he said.

More information

The known risk factors for cardiovascular disease are described by the American Heart Association.

SOURCES: Stanley L. Hazen, M.D., director, section of preventive cardiology and cardiac rehabilitation, Cleveland Clinic; Christopher Cannon, M.D., associate professor, medicine, Harvard Medical School, Boston; July 10, 2007, Journal of the American College of Cardiology

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