Focus on the Clinical Evidence on Stroke and Lp-PLA2

Stroke is the third leading cause of death in the United States, and a leading cause of severe, long-term disability. Nearly 90% strokes are ischemic, of atherosclerotic origin. Yet predictive models used in cardiovascular disease, such as the Framingham Risk Score and Adult Treatment Panel III (ATP III), have determined all patient risk estimates and treatment recommendations entirely on coronary heart disease outcomes and do not include stroke. While increased cholesterol levels have been strongly associated with CHD event rates, lipids have not been shown to be a predictor for stroke events. While the lack of association between stroke and cholesterol levels makes the identification of patients at high risk for stroke challenging, numerous pharmacologic agents have been shown to be beneficial in reducing the incidence of primary ischemic stroke.

The ARIC Stroke Study

A case-cohort evaluation based on the Atherosclerosis Risk in Communities (ARIC) Study

  • NIH-sponsored study in four U.S. communities on 12,773 African-American and Caucasian men and women, ages 45-65
  • Lp-PLA2 was evaluated to determine its ability to predict future stroke
  • Approximate six-year follow-up period
  • A total of 194 cases of ischemic stroke

Conclusions
As seen in a number of other studies, lipid levels were not considerably different between stroke and non-stroke individuals in the ARIC cohort. But Lp-PLA2 levels were significantly higher in stroke cases than non-stroke subjects. Elevated Lp-PLA2 levels presented an almost twofold increase in stroke risk, regardless of other risk factors.

Further analyses showed that individuals with the highest levels of Lp-PLA2 and systolic blood pressure were at the greatest risk of suffering an ischemic stroke, conferring an over sixfold increase in stroke risk.1

The Rotterdam Study

A case-cohort examination of the Rotterdam Study

  • Ongoing population-based observational study of 7,983 men and women (begun in 1990)
  • Represents 78 percent of the inhabitants age 55 and older of a suburb of Rotterdam
  • A total of 110 cases of ischemic stroke

Conclusions
In the Rotterdam analysis, the association of Lp-PLA2 with ischemic stroke was statistically significant and independent of other cardiovascular risk factors. Participants with the highest Lp-PLA2 activity had a 77 percent greater risk of ischemic stroke compared with those with the lowest Lp-PLA2 activity, after adjusting for other cardiovascular risk factors.2

  

  1. Ballantyne CM, Hoogeveen RC, Heejung B, et al. Lipoprotein-Associated Phospholipase A2, High-Sensitivity C-Reactive Protein, and Risk for Incident Ischemic Stroke in Middle-aged Men and Women in the Atherosclerosis Risk in Communities (ARIC) Study. Arch Intern Med. 2005;165:2479-2484.
  2. Oei HH, van der Meer IM, Hofman A, et al. Lipoprotein-Associated Phospholipase A2 Activity Is Associated With Risk of Coronary Heart Disease and Ischemic Stroke: The Rotterdam Study. Circulation. 2005;111:570-575.

The PLAC test can help identify stroke-prone hypertensive patients

Lp-PLA2 in ischemic stroke from the Rotterdam Study