Study Says Test May Surpass Cholesterol as Risk Marker

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 say in a report to be published on Thursday.

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

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Previous research has also found the protein test to be a good measure of risk. The new report, being published 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 researchers, led by Dr. Paul M. Ridker, director of the center for cardiovascular disease prevention at Brigham and Women's Hospital in Boston, found 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 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, with some ready to embrace widespread use of the test and others calling for more research.

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.

The test, for C-reactive protein, is available at many laboratories, but is not in routine use. Experts from the American Heart Association and the Centers for Disease Control and Prevention expect to issue guidelines soon for using the test, the heart association's president, Dr. Robert Bonow, said, adding that the new report would influence the guidelines.

The subjects were 27,939 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 death from cardiovascular disease.

The researchers measured levels of C-reactive protein and LDL cholesterol, the so-called bad cholesterol, that were in blood taken at the beginning of the study. Then, for each substance, they divided the study population into five groups, ranging from the lowest to the highest levels.

Next, they counted the bad events in the various groups.

For LDL cholesterol, women with the highest levels were 1.5 times as likely as those with the lowest levels to have cardiovascular problems.

For C-reactive protein, the risk was greater: women with high levels had 2.3 times the risk of women with low levels. And high C-reactive protein was more dangerous than high LDL cholesterol: compared to high LDL cholesterol, high levels of the protein were linked to about twice the risk of stroke, coronary disease or cardiovascular death.

When the researchers analyzed C-reactive protein and LDL together, they found that women with high levels of both substances had the highest risk. The group with the next highest risk had high C-reactive protein and low LDL — people who might, on a standard exam, be given a clean bill of health based on their low LDL.