A study provides more evidence that high levels of C-reactive protein can spell trouble.

A new report strengthens the case that high blood levels of the inflammation-related molecule called C-reactive protein (CRP) signal impending danger for the arteries, even when someone shows no other signs of trouble.

Otherwise healthy men with high levels of CRP had a significantly increased risk of ischemic stroke, the kind that happens when a blood vessel bursts, says a report in the April 8 issue of Circulation. The research is based on the decades-long Honolulu Heart Program.

Men with the highest blood levels of CRP when the study began had a 3.8-fold increased incidence of stroke over the next 10 to 15 years compared to men with the lowest levels, says the report by Dr. J. David Curb and his colleagues at the Pacific Health Research Institute.

The most striking finding was that the elevated risk associated with high CRP levels was "strongest in the healthier group of men, those without high blood pressure or diabetes, those who don't smoke," says Robert D. Abbott, a professor of biostatistics at the University of Virginia who has been with the study since its inception.

For example, the incidence of stroke over 10 to 15 years for nonsmokers with the highest levels of CRP was 5.8-fold higher than that of nonsmokers with the lowest CRP levels.

The implication for prevention of heart disease and stroke is that "when you find someone with elevated CRP who is still healthy, you should look harder for things that might increase risk, such as physical inactivity or an unhealthy diet, and work on them," Abbott says.

The evidence calling for an effort to reduce CRP levels in those men is not yet in and won't be for a number of years, says Dr. Robert C. Pasternak, director of preventive cardiology at Massachusetts General Hospital and a spokesman for the American Heart Association. A large trial to see whether reducing CRP levels reduces cardiovascular risk has just started to enroll people and is scheduled to run for five years, he says.

An expert panel of the American Heart Association recently declared elevated blood CRP levels to be a "marker" of cardiovascular risk, but stopped short of including it as a "risk factor" on the list of conditions that call for treatment -- high blood pressure, smoking and the like.

What doctors should do now for someone with elevated CRP is work harder on the known risk factors, stressing the effort to keep blood pressure under control, increase physical activity and stop smoking, Pasternak says.

As a research effort, the one strong point of the Hawaiian study is that it has followed its participants, more than 8,000 men of Japanese ancestry, for so long, Pasternak says. "This is probably the longest follow-up of all the studies," he says.

It's also interesting that the CRP-risk relationship was found in this particular ethnic group, an indication that the relationship holds true throughout society, Pasternak says.

SOURCES: Robert D. Abbott, Ph.D., professor, biostatistics, University of Virginia, working in Honolulu; Robert C. Pasternak, M.D., director, preventive cardiology, Massachusetts General Hospital, Boston; April 8, 2003, Circulation

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