Abstract P205: Multiple Biomarkers for the Prediction of Ischemic Stroke: The PRIME Study
Objective: The simultaneous assessment of multiple biomarkers from distinct biological pathways has been hypothesized to enhance cardiovascular risk stratification. We simultaneously evaluated 14 biomarkers for risk prediction of ischemic stroke including 9 novel biomarkers of hemostasis, inflammation and endothelial activation as well as 5 chemokines and adipocytokines previously identified to be associated with ischemic stroke in the PRIME study.
Methods: PRIME is a multicenter prospective cohort study of 9,771 healthy men 50-59 years of age who were followed up over 10 years. In a nested case-control study, 95 ischemic stroke cases were matched with 190 controls. Plasma concentrations of the following biomarkers were measured in samples obtained at baseline examination: fibrinogen, von Willebrand factor antigen, plasminogen activator inhibitor-1, high-sensitivity C-reactive protein, interleukin-6, E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, regulated on activation normal T-cell expressed and secreted, interferon-gamma-inducible-protein-10, resistin, adipsin and total adiponectin. We estimated hazard ratios (HRs) of ischemic stroke per standard deviation increase in biomarker levels using conditional logistic regression analysis. The predictive value of biomarkers was evaluated by the area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI), categorical based on risk tertiles and continuous.
Results: In a single multivariable model adjusted for traditional risk factors, fibrinogen (HR, 1.53; 95% CI, 1.03-2.28), E-selectin (HR, 1.76; 95% CI, 1.06-2.93), interferon-gamma-inducible-protein-10 (HR, 1.72; 95% CI, 1.06-2.78), resistin (HR, 2.86; 95% CI, 1.30-6.27) and total adiponectin (HR, 1.82; 95% CI, 1.04-3.19) were significantly associated with ischemic stroke. When separately included into a traditional risk factor model (AUC=0.679; 95% CI, 0.612-0.745), only E-selectin and resistin significantly increased the AUC to 0.785 (p=0.004) and 0.788 (p=0.008), respectively and yielded a categorical NRI of 29.9% (p=0.001) and 28.4% (p=0.002), respectively. The simultaneous inclusion of E-selectin and resistin in the traditional risk factor model resulted in an AUC of 0.824 (95% CI, 0.770-0.887; p<0.001) and a categorical NRI of 41.4% (p<0.001). Results were consistent when using continuous NRI.
Conclusion: The simultaneous evaluation of multiple biomarkers from distinct biological pathways including hemostasis, inflammation and endothelial activation with chemokines and adipocytokines revealed that E-selectin and resistin provided incremental and additive value to traditional risk factors in risk prediction of ischemic stroke. Further studies are needed to confirm these study results in cohorts with broader age range, women and other ethnic groups.
- © 2013 by American Heart Association, Inc.