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Misconceptions about Cholesterol and Stroke

by: Richard B. Lanman, MD

Stroke is the third leading cause of death in the United States, and a leading cause of severe, long-term disability. About 700,000 Americans will suffer a stroke this year and 500,000 of those will be first attacks. Yet predictive models used in cardiovascular disease, such as the Framingham Risk Score and the 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 coronary heart disease event rates, lipids have not been shown to be a predictor for stroke events.1 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 stroke.

Growing evidence in vascular biology suggests that Lp-PLA2 (lipoprotein-associated phospholipase A2, an enzyme carried predominantly on the low-density

lipoprotein cholesterol (LDL-C) particle, may play a key role in promoting atherogenesis.2 Lp-PLA2 remains latent until LDL undergoes oxidative modification, at which point it generates two bioactive mediators believed to be associated with the formation of inflamed, rupture-prone plaque.3 Findings from NHLBI's Atherosclerosis Risk in Communities (ARIC) study demonstrate a strong independent correlation between elevated Lp-PLA2 levels and incidence of ischemic stroke. Individuals with high Lp-PLA2 levels were found to have a twofold risk increase of ischemic stroke.

Further analyses were performed to determine if Lp-PLA2 was predictive across the complete range of systolic blood pressure (SBP) values in the population. Findings suggest that Lp-PLA2 and blood pressure are additive in their ability to predict risk for ischemic stroke events. Individuals with the highest levels of Lp-PLA2 and SBP were at a greater than sixfold increased risk of suffering an ischemic stroke compared to those with low levels of both.

While no consistent correlation exists between cholesterol levels and stroke incidence, statin therapy is associated with a significant reduction in stroke events across all cholesterol levels.4,5 Reduction in stroke observed in various statin trials may be a direct result of atherosclerotic disease regression, plaque stabilization, endothelial dysfunction, or some other unexplained mechanism. Levels of Lp-PLA2 are significantly reduced by statin therapy and could be a possible mechanism by which statins reduce stroke incidence.6

The PLAC test is a simple blood test cleared by the FDA for the quantitative determination of Lp-PLA2 in human serum and plasma as an aid in predicting risk for ischemic stroke associated with atherosclerosis. With a clear picture of patient cardiovascular risk, physicians can more accurately determine what type of goals and treatment programs patients will need to minimize the risk of having a stroke. The PLAC test is currently available through clinical laboratories nationwide. Please visit or call 1-877-PLACTEST for more information.


1. Prospective Studies Collaboration. Cholesterol, diastolic blood pressure, and stroke: 13,000 strokes in 450,000 people in 45 prospective cohorts. Lancet. 1995;346:1647-1653.

2. PLAC test package insert.

3. Kolodgie FD, Burke AP, Taye A, Liu W, Sudhir K, Virmani R. Lipoprotein-associated phospholipase A2 is highly expressed in macrophages of coronary lesions prone to rupture. [Abstract 1183, Scientific Sessions of the American Heart Association, Nov 2004. New Orleans, La.] Circulation. 110 Suppl 3:246-247.

4. Sever PS, Dahlof B, Poulter NR, et al; ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomized controlled trial. Lancet. 2003;361:1149-1158.

5. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.

6. Schaefer EJ, McNamara JR, Asztalos BF, et al. Effects of atorvastatin versus other statins on fasting and postprandial C-reactive protein and lipoprotein-associated phospholipase A2 in patients with coronary heart disease versus control subjects. Am J Cardiol. 2005;95:1025-1032.

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