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  February 2006
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Biomarkers may predict risk of stroke

by Ross Tomlin

Christie Ballantyne, M.D.
Christie Ballantyne, M.D.

Inflammatory markers found in the blood may help identify middle-aged men and women at increased risk for ischemic stroke, according to a study in today's issue of Archives of Internal Medicine, a JAMA/Archives journal. The finding is part of a long-term study funded by the National Institutes of Health and was conducted primarily at Baylor College of Medicine in Houston.

"We think that the enzyme lipoprotein-associated phospholipase A2 (Lp-PLA2) which is measured by the PLAC test may be a link between lipoproteins and vascular inflammation, and we found that Lp-PLA2 is additive to C-reactive protein, a measure of inflammation, for the prediction of stroke," said Christie Ballantyne, M.D., lead author of the Atherosclerosis Risk in Communities study and a professor of medicine at BCM.

CRP levels

Ballantyne and researchers at five other institutions, including The University of Texas Health Science Center at Houston, examined levels of C-reactive protein (CRP) and Lp-PLA2 to determine if they are associated with increased risk for the kind of stroke that develops when a blood clot blocks flow through a blood vessel supplying blood to an area of the brain. The authors report that levels of CRP and Lp-PLA2 were higher in middle-aged Americans who subsequently had this kind of stroke than in those who did not.

CRP and Lp-PLA2 levels may provide additional information that can be added to that associated with traditional risk factors for stroke such as diabetes, high blood pressure, age, and race regardless of cholesterol levels. Ballantyne's past involvement in ARIC has shown that both CRP and Lp-PLA2 play a role in predicting heart disease affecting the coronary arteries that provide blood to the heart muscle. However, their role in predicting this disease is only significant when there are normal levels of low-density lipoproteins (LDL) or, "bad" cholesterol.

False sense of health

"Someone may be falsely reassured that if they have a normal cholesterol, they don't have an increased risk for stroke," said Ballantyne, whose Atherosclerosis Clinical Research Laboratory serves as the core laboratory for the ARIC study. "The enzyme, Lp-PLA2, is predictive of stroke. Low density lipoprotein (the so-called bad cholesterol) is not."

The ARIC study researchers followed 12,762 apparently healthy middle-aged men and women for about six years. The final sample size for the analysis was 960, including 194 ischemic stroke cases and 766 non-cases. In addition to the NIH, funding for this ancillary observation of the ARIC study came from the pharmaceutical company GlaxoSmithKline.

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 between the ages of 45 and 64, according to background information in the article. Preexisting data shows that weight loss can lower blood pressure and CRP levels, reducing the risk for stroke.

Future studies will determine whether selective inhibition of Lp-PLA2 or reduction and/or inhibition of CRP reduces ischemic stroke and whether cholesterol-lowering drugs like statins and fibrates are more effective for stroke prevention in patients with elevated levels of Lp-PLA2.

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.

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