Two common biomarkers improve prediction of stroke risk
15 January 2009
Two common biomarkers have been shown to improve the ability to
predict who will suffer from a stroke. Results from new research
conducted at the Methodist DeBakey Heart & Vascular Center in Houston
were published in the online version of the journal Stroke.
Stroke is a leading cause of death and disability. Accurate risk
assessment is imperative 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
percent,” said Dr Vijay Nambi, lead author on the study and cardiologist
at the Methodist DeBakey Heart & Vascular Center and Baylor College of
Medicine. “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 Baylor, 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
About the study
Data for the current analysis was 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 a prospective case cohort (n=949) study in 12,762 apparently
healthy, middle-aged men and women in the ARIC study, the researchers
first examined whether Lp-PLA2 and hs-CRP levels improved the area under
the curve (AUC) of receiver operating characteristic 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 three percent of the total
individuals in this study) and furthermore, the majority of reclassified
high-risk individuals (approximately 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
Similarly, as expected from studies with other biomarkers and imaging
tests, very few low-risk individuals (only four percent of this group)
were reclassified, and none were reclassified into the high-risk group.
We feel 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 (two percent to five percent five-year stroke risk).
This study was funded by the National Heart, Lung and Blood Institute
(NHLBI) and by an unrestricted research grant from GlaxoSmithKline. This
was a multi-center study led by investigators at The Methodist Hospital
in Houston. Lp-PLA2 was measured using the PLAC test from diaDexus, Inc.
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