"Although a number of medications are known to reduce the incidence of stroke, national screening guidelines for cholesterol are based only on the risk for developing heart disease and do not include stroke," said Christie Ballantyne, MD, director of the Center for Cardiovascular Disease Prevention at the Methodist DeBakey Heart Center and Baylor College of Medicine in Houston, and lead author of the study. "The lack of association between lipid levels and future ischemic stroke has made identifying patients at risk for stroke a challenge to the medical community. Our findings suggest that a panel of Lp-PLA2 and CRP may help identify those high risk individuals, so that proactive measures can be taken to lower those risks and avoid a stroke."
The NHLBI's Atherosclerosis Risk in Communities (ARIC) study followed 12,762 apparently healthy bi-racial middle-aged men and women for six to eight years to evaluate incidence of major cardiovascular events. The case-cohort analysis, evaluating the relationship of Lp-PLA2 and CRP levels to ischemic stroke, was coordinated by Dr. Ballantyne at the Methodist DeBakey Heart Center and also involved researchers from the University of North Carolina at Chapel Hill, Johns Hopkins School of Public Health, University of Minnesota, The National Institutes of Health and University of Texas.
Lp-PLA2 levels were assessed using the diaDexus PLAC® test, the first blood test approved by the FDA to aid in predicting ischemic stroke associated with atherosclerosis. CRP was measured using an assay from Denka Seiken.
Using a Cox proportional hazards model, the study demonstrated that Lp-PLA2 was independently associated with ischemic stroke after adjusting for age, sex, race and confounders including LDL-cholesterol, HDL-cholesterol, diabetes, smoking, hs-CRP levels and blood pressure. Additionally, the effect of Lp-PLA2 in combination with CRP was highly significant. Individuals with the highest levels of both Lp-PLA2 and CRP had an 11.38-fold (95% CI 3.13-41.41) increased risk of suffering an ischemic stroke during the study, compared to individuals with the lowest levels of Lp-PLA2 and CRP. Notably, LDL-cholesterol levels did not differ between incident stroke cases and non-cases and, in fully adjusted models, LDL-cholesterol, HDL-cholesterol and triglycerides were not associated with increased risk for stroke consistent with previous reports. 2
"Stroke is the third largest killer in the United States. The PLAC test will help improve identification of the high risk patients, allowing physicians to implement basic prevention strategies and potentially reduce the number of strokes that occur each year," said Richard B. Lanman, MD, Executive Vice President and Chief Medical Officer of diaDexus. "Additional analyses have shown that Lp-PLA2 has the unique capability of predicting future ischemic stroke and in combination with more traditional risk factors, particularly blood pressure measurements, it allows physicians to identify those stroke prone hypertensive patients who may benefit from more aggressive treatment programs."
Stroke is a leading cause of serious long-term disability. Each year approximately 700,000 strokes occur, 88% of which are ischemic strokes. While elevated cholesterol levels are directly linked to heart disease, no such relationship has been established for stroke.
This study was supported by the National Institutes of Health (NIH) and an unrestricted grant from GlaxoSmithKline.
diaDexus, Inc., a privately held biotechnology company based in South San Francisco, California, is focused on the discovery, development and commercialization of novel, patent-protected diagnostic and therapeutic products with high clinical value. The PLAC® test, developed by diaDexus, Inc., is a blood test cleared by the U.S. Food and Drug Administration to aid in the prediction of an individual's risk for a coronary or ischemic stroke event, in conjunction with clinical evaluation and patient risk assessment. For more information about the PLAC® test visit www.plactest.com. More information about the company may be found at www.diaDexus.com.
About the Methodist DeBakey Heart Center
The Methodist DeBakey Heart Center is a world-renowned organization that is consistently ranked among the top heart centers in the nation. Located in Houston, Texas, the Methodist DeBakey Heart Center combines research, prevention, diagnostic care, surgery and rehabilitation services in a coordinated multi-disciplinary program with one focus: delivering compassionate, effective care and treatment to patients with heart disease. For more information about the Methodist DeBakey Heart Center, visit www.debakeyheartcenter.com.
1. Ballantyne C, Hoogeveeen R, Bang H, 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; 165:1-7.
2. Shahar E, Chambless LE, Rosamond WD, et al. Plasma lipid profile and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2003; 34:623-631.