Biomarkers Found To Improve Prediction of Stroke Risk

Two common biomarkers have now been shown to improve the ability to predict who will suffer from a stroke.

Stroke is the third-leading cause of death in the United States alone, and a leading cause of disability. Accurate risk assessment is essential because stroke is preventable with medical therapy and lifestyle changes. "If we can identify increased risk for stroke, we can recommend, exercise, smoking cessation, and cholesterol and blood pressure medication to reduce a person's risk for stroke by more than 30%,” said Dr. Vijay Nambi, lead author on the study and cardiologist at the Methodist DeBakey Heart & Vascular Center (Houston, TX, USA). "Adding these two biomarkers to traditional risk assessment tools improves our ability to do that.”

"The study found that adding two biomarkers associated with inflammation, lipoprotein-associated phospholipase A2 [Lp-PLA2], and high-sensitivity C-reactive protein (CRP), to traditional risk factor assessment for stroke changed the risk category in which some patients were placed,” said Dr. Christie Ballantyne, director of the Center for Cardiovascular Disease Prevention at the Methodist DeBakey Heart & Vascular Center, and senior investigator in the study. "The greatest impact was on patients who, with traditional risk assessment, were placed into the intermediate risk category. With the addition of the biomarkers, Lp-PLA2 and CRP testing, 39% of those patients were reclassified into a lower or higher risk group.”

Traditional risk factors for stroke include high blood pressure, smoking, high cholesterol, diabetes, obesity, and other hereditary factors. Data for the current analysis were gathered from the Atherosclerosis Risk in Communities (ARIC) study. The ARIC study is a prospective biracial study of atherosclerotic cardiovascular disease incidence; 15,792 individuals, initially aged 45 to 64 years, were recruited between 1987 and 1989 from four communities in the United States.

In the prospective case cohort (n = 949) group in 12,762 apparently healthy, middle-aged men and women in the ARIC study, the researchers first assessed whether Lp-PLA2 and hs-CRP levels improved the area under the curve (AUC) of receiver operating characteristic (ROC) curves for five-year ischemic stroke risk. They then examined how Lp-PLA2 and hs-CRP levels altered classification of individuals into low-, intermediate-, or high-risk categories compared with traditional risk factors.

C-reactive protein and Lp-PLA2 have been associated with stroke in several studies. This new analysis now suggests that these biomarkers modestly improve ischemic stroke risk prediction and offer the most improvement when combined.

As has been seen with the addition of biomarkers in coronary heart disease risk prediction, the intermediate-risk group had the greatest reclassification with approximately 39% of the individuals reclassified into lower or higher risk groups. Although approximately 33% of the high-risk individuals were reclassified to a lower risk, the overall number of individuals in the high-risk group was very small (only 3% of the total individuals in this study) and furthermore, most of reclassified high-risk individuals (about 98%) were reclassified to the intermediate risk group. Given the known benefits of lifestyle modification and pharmacotherapy in high-risk individuals based on traditional risk factors alone, these individuals should continue to be treated as high risk.

Similarly, as expected from studies with other biomarkers and imaging tests, very few low-risk individuals (only 4% of this group) were reclassified, and none were reclassified into the high-risk group. The investigators believed that from a clinical point of view, the measurement of these biomarkers for further stratification of clinical stroke risk should only be considered in individuals who have intermediate risk based on TRF alone (2-5% five-year stroke risk).

Results from new research were published in December 18, 2008, online version of the journal Stroke.

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Methodist DeBakey Heart & Vascular Center