Elevated CRP may indicate stroke-causing plaque

June 23, 2003

DALLAS, June 24 - Elevated levels of a blood-marker for inflammation are associated with a significantly increased risk of stroke among the elderly regardless of the amount of plaque in the arteries leading to the brain, scientists report in today's rapid access issue of Circulation: Journal of the American Heart Association.

The study found that a high C-reactive protein (CRP) level is an independent risk factor for stroke regardless of the thickness of carotid artery walls - which indicates the extent of atherosclerotic plaque in the arteries leading to the brain, says study senior author Mary Cushman, M.D., M.Sc., an associate professor of medicine at the University of Vermont in Burlington.

Cushman believes that elevated CRP may denote plaque instability - plaque likely to rupture and cause a blood clot to form, which can go to the brain resulting in stroke.

The authors believe this is the first prospective study to explore a relationship between CRP and carotid wall thickness.

"We found that while C-reactive protein is an independent risk factor for stroke, it is even more closely related to stroke in people with thicker artery walls than in people with thinner walls," Cushman says.

The study followed 5,417 men and women age 65 or older in the Cardiovascular Health Study, a prospective trial investigating risk factors for cardiovascular disease in the elderly. Participants underwent baseline tests to determine CRP blood levels and carotid ultrasound to determine their carotid wall thickness. Participants were divided into four groups, or quartiles, based on their CRP level.

During 10 years of follow-up, 469 of the participants suffered an ischemic stroke. Ischemic strokes - the most common type of stroke - result from a blockage in an artery that brings blood to a part of the brain.

After accounting for risk factors such as age, high blood pressure and smoking status, researchers determined that people in the highest quartile of CRP levels were 60 percent more likely to have a stroke, compared to those with the lowest CRP levels. People in the second quartile were 19 percent more likely to have a stroke, while those in the third CRP quartile were 5 percent more likely to have a stroke than those with the lowest levels.

The participants were then further divided into three more groups, or tertiles, based on their carotid wall thickness.

Among people with the thinnest carotid walls, there was no significant association between CRP and stroke, the study showed. But among those people in the second and third tertiles, there was a significant association between CRP and stroke.

"This raises the possibility that higher CRP is associated with more active or unstable plaque that is more likely to rupture and cause a stroke," Cushman says.

Despite the findings, people should not necessarily rush to have their carotid wall thickness or CRP levels measured, she adds. Rather, "the findings add to the growing body of evidence that supports using CRP measurements in assessing certain individuals' global cardiovascular disease risk," Cushman says.

Global risk estimation combines information from all existing risk factors, such as elevated LDL cholesterol, high blood pressure and smoking status, to determine a person's overall risk for developing cardiovascular disease in the next 10 years.

"Each new study, as it is evaluated, will allow us to gradually refine the patients most likely to benefit from CRP testing. Thus far, we believe CRP testing may be useful as a discretionary tool for evaluating people with moderate cardiovascular risk," says American Heart Association President-elect Augustus Grant, M.D., Ph.D.
Co-authors are Jie J. Cao, M.D., M.P.H.; Chau Thach, Ph.D.; Teri A. Manolio, M.D., Ph.D.; Bruce M. Psaty, M.D., Ph.D.; Lewis H. Kuller, M.D., Dr. P.H.; Paulo H.M. Chaves, M.D., Ph.D.; Joseph F. Polak, M.D., M.P.H.; Kim Sutton-Tyrrell, Ph.D.; David M. Herrington, M.D., M.H.S.; and Thomas R. Price, M.D.

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