Abstract 17619: A Validated, Modifiable, and Actionable Pathway-Specific Aggregate Biomarker Risk Score Predicts Risk of Cardiovascular Outcomes in Patients with Coronary Artery Disease: Findings from the BARI 2D Trial

Background: A biomarker risk score (BRS) comprised of C-reactive protein, Fibrin-Degradation products, and Heat Shock Protein-70 predicted MI and death in patients with CAD. Here, we sought to: a) validate the BRS in the BARI 2D cohort, b) investigate the impact of intensive medical therapy (IMT) on biomarkers, and c) examine whether the BRS is modifiable and, if so, whether the new BRS predicts altered risk. Methods: 2032 diabetic subjects with CAD were enrolled in the BARI 2D trial and followed for 5.3 yrs. Biomarkers were tested in 1304 subjects at 1-year after IMT targeting hyperglycemia and cardiac risk factors. BRS was computed by counting the number of biomarkers above predefined levels that previously discriminated high/low risk groups (CRP>3 mg/L, HSP-70>0.313 ng/ml, and FDP>1 μg/ml). Results: High levels of individual biomarkers at baseline and the BRS predicted risk of all events in models adjusted for cardiovascular risk factors. Compared to those with BRS of 0, adjusted hazard ratios for death were 1.75, 2.49, and 3.99 for those with BRS of 1, 2, and 3, respectively (p≤0.01 for all). All biomarkers were significantly lower at 1 year (Δ CRP=-1.2±3.5 mg/dl, Δ HSP-70=-0.36±1.2 ng/ml, and Δ FDP=-0.24±1.45 μg/ml; p=0.0001 for all). The new BRS at 1-year also predicted risk of events; a 1-year BRS of 2-3 had a 4-year mortality rate of 21% compared to 7.1% for BRS of 0 (>80% decreased their BRS. The 4-year death/MI rates were 34.2% for those with BRS of 2-3 at 1 year and 19% in those with a decline (p=0.0025), Figure. Conclusion: The BARI 2D results validate the ability of the BRS to predict outcomes. Moreover, IMT decreases the BRS and re-classifies risk, such that those with a decreased BRS have improved prognosis, and vice versa. The BRS is a validated tool that can be modified by therapy, with new values reflecting altered risk, thereby providing actionable information in targeting therapy for individual patients.