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Inflammatory markers may help predict stroke risk in middle-aged people

The JAMA Network Journals

CHICAGO - In addition to traditional risk factors such as diabetes, high blood pressure, age, and race, a particular enzyme and protein found in the blood may help identify middle-aged men and women at increased risk for ischemic stroke, according to a study in the November 28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

An estimated 700,000 strokes occur each year in the United States, making stroke the third leading cause of death and the leading cause of neurologic disability. Almost a third of strokes occur in people under the age of 65, according to background information in the article. Measurement of inflammatory markers has been reported to identify individuals at increased risk for ischemic stroke, which develops when a blood vessel supplying blood to an area of the brain becomes blocked by a blood clot.

Christie M. Ballantyne, M.D., of Baylor College of Medicine and Methodist DeBakey Heart Center, Houston, Texas, and colleagues examined levels of two inflammatory markers--C-reactive protein (CRP) and the enzyme lipoprotein-associated phospholipase A2 (Lp-PLA2)--to determine if they are associated with increased risk for incident ischemic stroke. The researchers conducted a prospective case-cohort study of 12,762 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study, who were observed for about six years. The final sample size for the analysis was 960, including 194 ischemic stroke cases and 766 non-cases.

The authors report that levels of Lp-PLA2 and CRP were higher in middle-aged Americans who subsequently had an ischemic stroke than in those who did not.

"Mean Lp-PLA2 and CRP levels adjusted for sex, race, and age were higher in the 194 stroke cases than the 766 non-cases, whereas low-density lipoprotein cholesterol (LDL-C) level was not significantly different," the authors write.

"Individuals with high levels of both CRP and Lp-PLA2 were at the highest risk after adjusting for traditional risk factors compared with individuals with low levels of both, whereas others were at intermediate risk," they continue.

"In summary, Lp-PLA2 and CRP levels may be complementary to traditional risk factors to identify middle-aged individuals at increased risk for stroke," the authors conclude. "Future studies should determine whether selective inhibition of Lp-PLA2 or reduction and/or inhibition of CRP reduces ischemic stroke and whether statins and/or fibrates [two types of cholesterol-lowering drugs] are more effective for stroke prevention in patients with elevated levels of Lp-PLA2."


(Arch Intern Med. 2005;165:2479-2484. Available pre-embargo to the media at

Editor's Note: Dr. Ballantyne has received grant and/or research support from AstraZeneca, diaDexus, Gene Logic, GlaxoSmithKline, Integrated Therapeutics, Kos, Merck, Novartis, Pfizer, Reliant, Sankyo Pharma, and Schering-Plough; he has served as consultant for AstraZeneca, Bayer, Merck, Novartis, Pfizer, Reliant, and Schering-Plough; and he currently serves or has served on the speakers bureau for AstraZeneca, Bristol Myers-Squibb, Kos, Merck, Novartis, Pfizer, Reliant, Sanofi-Synthelabo, and Schering-Plough. The ARIC Study is carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute, Bethesda, Md. This research was also supported by an unrestricted research grant from GlaxoSmithKline, Research Triangle Park, N.C.

Editorial: When Is a New Prediction Marker Useful?

In an accompanying editorial, Archives of Internal Medicine Editor Philip Greenland, M.D., and Patrick G. O'Malley, M.D., Walter Reed Army Medical Center, write that epidemiologic studies, such as that by Ballantyne and colleagues, are most useful for identifying potential new risk predictors or new potential approaches to treatment requiring further confirmatory observational studies or future clinical trials.

"From the Ballantyne et al study, it is unclear how useful CRP or Lp-PLA2 level will be for improving risk prediction vs. traditional risk factors alone," they write. "Simply showing statistical independence, as recently discussed in an Archives review article, is not adequate for demonstrating clinical utility for risk prediction."

(Arch Intern Med. 2005;165: 2454-2456. Available pre-embargo to the media at

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