Inflammation Marker Signals Stroke Risk in Healthy Middle-Aged Men

DALLAS, April 8 – High levels of the inflammation marker C-reactive protein (CRP) in healthy, middle-aged men signals an increased risk of ischemic stroke in later life, according to a 20-year follow-up study reported in today’s rapid access issue of Circulation: Journal of the American Heart Association.

In this study, men with few cardiovascular risk factors but with the highest CRP levels studied had a 3.8-fold increased incidence of stroke in 10 to 15 years compared to men with the lowest levels, says lead author J. David Curb, M.D., of the Pacific Health Research Institute and the Department of Geriatric Medicine and Medicine at the University of Hawaii in Honolulu.

The study is the longest and most complete follow-up of the association between CRP and stroke, Curb says.

Researchers examined data from the Honolulu Heart Program, an ongoing study of 8,006 men of Japanese descent that began in 1965. The men were between the ages of 48 and 70 when CRP was measured. They underwent comprehensive physical exams and testing for cardiovascular disease at enrollment and have undergone similar examinations regularly since then.

In 20 years of follow-up, there were 259 strokes. The researchers compared these cases with 1,348 men who did not have a stroke. The men were divided into four groups (quartiles) based on their CRP levels. The lowest quartile had CRP levels from 0.1 to 0.32 milligrams per liter (mg/L). CRP levels in the highest quartile ranged from 1.01 to 79.2 mg/L.

The harmful effects of high CRP levels are “stronger in middle-aged men, men without hypertension or diabetes and in those who were nonsmokers,” Curb says. He speculates that this may be because inflammation’s effect on stroke risk is overshadowed by risk factors such as hypertension and diabetes.

In men age 48-55 in the highest quartile of CRP levels, the odds of stroke in 10 to 15 years increased three-fold compared with men with the lowest CRP levels at baseline. For nonsmokers with elevated CRP, risk of stroke was 5.8-fold compared with men with the lowest CRP levels.

Associations were not significant in past and current smokers, in men older than 55, and in those with hypertension or diabetes.

Inflammation may trigger stroke because it causes cell growth, cholesterol accumulation and plaque formation on the interior of blood vessels. Ruptured plaque can travel through the blood vessels, lodge in tiny vessels of the brain and cause an ischemic stroke.

Apparently healthy women with high CRP may also be at risk of stroke, Curb says. Other population-based research, such as the Framingham Study and the Women’s Health Study, indicate that associations between CRP levels and stroke in men are also likely to apply to women.

It is still too soon to draw firm conclusions about CRP levels and stroke risk, Curb cautions. “Whether CRP levels can be used as a clinical screen to identify an increased risk of cardiovascular disease in otherwise healthy adults . . . warrants additional consideration.”

Co-authors are Robert D. Abbott, Ph.D.; Beatriz L. Rodriguez, M.D., Ph.D.; Pamela Sakkinen, M.D., MPH; Jordan S. Popper, M.D.; Katsuhiko Yano, M.D. and Russell P. Tracy, Ph.D.

The study was partly funded by the National Heart, Lung, and Blood Institute; National Institute on Aging; and the American Heart Association.

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