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Elevated LpPLA2 predictive of recurrent stroke

Issue: April 2006

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Elevations of LpPLA₂ may be predictive of recurrent ischemic stroke, according to data from the Northern Manhattan Study.

Mitchell S.V. Elkind, MD, said that levels of the lipoprotein-associated phospholipase A₂ enzyme were previously found to be predictive of first stroke. The retrospective data he presented at the American Stroke Association’s International Stroke Conference were drawn from a cohort of the Northern Manhattan Study (NOMAS) and suggest that LpPLA₂ may also predict a recurrent stroke.

These results “require further confirmation in prospective trials,” said Elkind, an assistant professor of neurology at Columbia University’s Division of Stroke and Critical Care.

The Northern Manhattan Study

NOMAS, an ongoing epidemiological study since 1990, focuses on stroke risk factors in different race and ethnic groups. Elkind said he and his colleagues tested the blood samples of 467 patients enrolled in NOMAS who had an initial ischemic stroke. Fifty-three percent were Hispanic, 27% were black, and 18% white. All were aged older than 40, and 55% were women.

Researchers assessed LpPLA₂ levels using the PLAC test (diaDexus), approved by the FDA for predicting ischemic stroke. The study demonstrated that increased levels of LpPLA₂ were associated with risk for recurrent stroke after adjusting for demographics, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation and coronary disease. Eighty of the 467 patients had had a recurrent stroke after an average of four years of follow-up.

Elkind said that high sensitivity C-reactive protein (hsCRP) levels were predictive of mortality in this study but not of recurrent stroke risk. CRP levels increase during illness and particularly after a stroke. Levels of LpPLA₂, however, are not as affected by stroke but are “tied in with future stroke,” he said.

Even though the results must be confirmed in prospective clinical trials, Elkind said, these findings may “warrant a more aggressive approach to managing risk factors following a stroke,” possibly including a higher dose of statins, even if cholesterol levels are not elevated. Drugs to inhibit this enzyme are in development, he said.

Predictive of CAD in women

Research presented at the American Heart Association Scientific Sessions 2005 indicated that LpPLA₂ is an independent predictor of CAD in women, particularly women older than age 65. Jeffrey Anderson, MD, professor of internal medicine at the University of Utah, said that in postmenopausal women, the enzyme was more strongly predictive of CAD risk than CRP.

Investigators also reported that LpPLA₂ stratified by glucose levels predicted CAD in intermediate fasting glycemic status and diabetes. – by Kathy Holliman

For more information:

• Elkind MS, Coates K, Tai W, et al. Lipoprotein-associated phospholipase A2 and C-reactive protein as predictors of stroke recurrence and death: the Northern Manhattan Study. Presented at the American Stroke Association’s International Stroke Conference 2006. Feb. 16-18, 2006. Kissimmee, Fla.