"Upstream markers" provide for early identification of patients at high risk for myocardial necrosis and adverse outcomes

Background: For patients presenting with acute coronary syndrome (ACS) to the emergency department, early identification of those that are at high risk for subsequent myocardial necrosis or adverse outcomes would allow earlier or more aggressive treatment. We determined if a panel of biomarkers can be used to identify high risk patients. Methods: A cohort (84 females/132 males) from our 1996 ACS study population that had EDTA specimens stored (- 70 °C) was selected and the earliest available specimen was analyzed for 11 biomarkers (IL-6, IL-8, MCP-1, VEGF, L-selectin, P-selectin, E-selectin, ICAM-1, VCAM-1, NT-proBNP, cTnT). These data were linked to the existing cTnI and health outcome databases for this population. ROC curve analysis for myocardial necrosis (i.e., peak cTnI > 0.04 μg/l) identified 3 candidate biomarkers. These 3 biomarkers were applied together to generate a panel test (2 of the 3 biomarkers increased for a positive result) and assessed for its ability to identify patients at risk for myocardial necrosis and the combined endpoint of death, myocardial infarction (MI) and heart failure (HF). Results: The panel test (IL-6, NT-proBNP, E-selectin) alone detected 60% (95% CI: 49-69; false positive rate: 26%) of subjects that would be classified with myocardial necrosis. Kaplan-Meier and Cox proportional analyses indicated that patients positive by the biomarker panel (including those with cTnI ≤ 0.04 μg/l) had significantly worse outcomes (death/MI/HF) as compared to those negative by both cTnI and the panel test. Conclusion: A biomarker panel analyzed early after pain onset can identify individuals at risk for both myocardial necrosis and the combined endpoint of death/MI/HF. Additional prospective studies are required to assess this panel for both early MI detection and to further refine which health outcomes (death, MI, HF) are associated with positive panel results.