Study Says a Protein May Be Better Than Cholesterol in Predicting Heart Disease Risk

By DENISE GRADY

n inexpensive blood test for a protein linked to artery disease may be better than a cholesterol test at predicting a person's risk for a heart attack or stroke, researchers are reporting today.

The test, for the substance, C-reactive protein, may help identify people who have an increased risk even though they do not have high cholesterol. About half of the people with heart disease have normal cholesterol levels, a finding that has led many researchers to suspect that other factors must play a role in cardiovascular disease.

Recognizing risk can help determine whether patients need to do things like change their diets, lose weight, exercise more or take medication.

Previous reports have also found the protein test to be a good measure of risk. The new report, being published today in The New England Journal of Medicine, is considered the strongest evidence yet because the study was large, with 27,939 women, and tracked their health for eight years. The results are thought to apply equally to men.

The researchers, led by Dr. Paul M. Ridker, director of the center for cardiovascular disease prevention at Brigham and Women's Hospital in Boston, concluded that women with high C-reactive protein were twice as likely to have a heart attack or stroke as women with high cholesterol.

"This is a very powerful and I would even argue overwhelming demonstration of the fact that it's time to move beyond cholesterol if we're trying to prevent this disease," Dr. Ridker said.

Other researchers had varying opinions about the blood test, with some ready to embrace widespread use and others calling for more research. It was one of the battery of tests performed during President Bush's annual physical exam in August; his level was low.

Dr. Eric Topol, chief of cardiology at the Cleveland Clinic, who was not part of Dr. Ridker's study, said, "This is the time to make the call for using this test, not in every patient, but in a large proportion as a routine evaluation."

At his clinic, Dr. Topol said, the test costs only $8 and has been used often for several years. He said he thought it would eventually be included in the blood tests now done routinely during checkups.

Dr. Topol also said that at cardiology conferences, where the test is commonly offered free, he had seen doctors line up to find out their levels.

The protein is measured in milligrams per liter of blood, and the lower the level, the better, Dr. Topol said. A high level is more than 4.0.

Dr. Lori Mosca, director of preventive cardiology at New York Presbyterian Hospital, said the test had predictive value, but, she added, "I don't think we're ready to make the leap to routine screening."

Dr. Mosca, who wrote an editorial accompanying Dr. Ridker's article, said it was too soon for routine screening because studies had not been done to determine whether lowering C-reactive protein would lower a person's risk.

The same measures already used to treat and prevent heart disease — including exercise, weight loss, aspirin, smoking cessation and the statin drugs that are widely used to lower cholesterol — also lower levels of the protein.

Dr. Mosca said she did use the test in some patients, particularly those who had some risk factors but were borderline cases in terms of whether they needed drug treatment.

Dr. James Cleeman, coordinator of the National Cholesterol Education Program at the National Heart Lung and Blood Institute, expressed views similar to Dr. Mosca's and said his group would not recommend routine use of the test now. But that could change, he said.

Experts from the American Heart Association and the Centers for Disease Control and Prevention expect to issue guidelines soon for using the test, said Dr. Robert Bonow, president of the heart association. He said Dr. Ridker's report would influence the guidelines.

Even researchers who do not think the test is ready for the public said the study was extremely important in helping to explain the development of heart disease. C-reactive protein is a measure of inflammation, which in recent years has become the focus of intense research in cardiology. Normally, it is the body's way of protecting itself against injury and infection; it involves a cascade of reactions by the immune system. But if inflammation becomes chronic or turns against a person's own tissues, disease can result.

Many researchers think chronic inflammation plays a major part in artery disease, heart attacks and strokes. Inflammation inside arteries is thought to contribute to heart attacks and strokes by causing cholesterol deposits in the artery walls to rupture and bleed. Blood clots then form, blocking the vessels and cutting off the blood supply to portions of the heart or brain.

C-reactive protein, Dr. Topol said, "is a window into the process of arterial inflammation, a very important insight that we otherwise can't get."

Dr. Ridker said, "From 25 to 30 million healthy, middle-aged Americans are at far higher risk than they and their doctors understand them to be, because we're not taking inflammatory factors into account."

The subjects in his study were women 45 and older who were healthy and already participating in a study that tracked the development of heart disease. The women gave blood samples when they entered the study, and researchers followed their health for an average of eight years. During that time, 571 women had heart attacks, strokes, procedures to open blocked coronary arteries or died from cardiovascular disease.

The researchers measured levels of C-reactive protein and LDL cholesterol, the so-called bad cholesterol, in the blood taken at the beginning of the study. High levels of the protein were more dangerous than high LDL cholesterol: compared with high cholesterol, high protein was linked to about twice the risk of stroke, coronary disease or cardiovascular death.