Abstract 18350: A Composite Risk Score of Biomarkers of Inflammation, Thrombosis, and Cell Stress Pathways Significantly Predict Risk of Adverse Cardiovascular Outcomes
Background: An aggregate biomarker risk score of C-reactive protein (CRP), heat shock protein (HSP)-70, and fibrin degradation products (FDP) significantly predicts adverse outcomes in patients with CAD. Soluble Urokinase Plasminogen Activator Receptor (suPAR) is an inflammatory biomarker that has been associated with incident CVD. We sought to investigate the value of adding plasma suPAR level to the 3 original biomarkers in predicting risk of adverse outcomes.
Methods: 3,280 patients (aged: 62± 11, 83% white, 32% diabetics, 64% with CAD ≥50%) undergoing diagnostic angiography were followed for death and/or MI over median 2.3 yrs. Plasma suPAR (ViroGates, Denmark), and serum CRP, HSP-70, and FDP (Firstmark Inc) were measured using ELISA. Severity of CAD was assessed by the Gensini score. Cox proportional survival and C-statistic analyses were performed adjusting for traditional risk factors, ejection fraction, serum creatinine, and Gensini.
Results: Patients with suPAR level ≥ 3.5ng/ml (ROC cutoff) had a greater CAD burden (Gensini: 49± 68 vs. 41± 64, p=0.003). Plasma suPAR ≥ 3.5 also predicted future death/MI (HR=1.76, p<0.001) after adjustment for all covariates and the 3 biomarkers, CRP, HSP-70, and FDP; the C-statistic improved (0.69 to 0.71, p=0.01). A 4 biomarker aggregate score composed of suPAR, CRP, FDP, and HSP-70 below/above cutoffs significantly predicted risk of death/MI. Thus, compared to those with 0 biomarkers, HR of death/MI for those with 1, 2, 3, or 4 positive biomarkers were: 1.5, 2.1, 4.4, and 7.3 respectively (P<0.001). Addition of the 4-marker score significantly improved the C-statistic compared to a model of traditional factors (0.68 to 0.75, p=0.004).
Conclusion: An aggregate risk score of CRP, HSP-70, FDP, and suPAR representing inflammatory, thrombotic, and cell stress pathways, identifies CAD patients at low and very high risk of death/MI. Thus, the score allows individualization of risk in CAD patients.
- © 2013 by American Heart Association, Inc.