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. 2008 Jan;387(1-2):133-8.
doi: 10.1016/j.cca.2007.09.023. Epub 2007 Oct 3.

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

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

Peter A Kavsak et al. Clin Chim Acta. 2008 Jan.

Abstract

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 degrees 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 microg/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 < or =0.04 microg/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.

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Figures

Fig. 1
Fig. 1
Kaplan–Meier curves using the early specimen concentrations for classification of subjects positive by the panel test and/or troponin with a peak cTnI >0.04 μg/l (n=74, Group 1); subjects with both a negative panel test and cTnI in the early specimen, but with a peak cTnI >0.04 μg/l (n=18,Group 3); subjects positive for the panel test with a peak cTnI ≤0.04 μg/l (n=29, Group 2), and subjects negative by both tests with a peak TnI ≤ 0.04 μg/l (n=84, Group 4).
Fig. 2
Fig. 2
Kaplan–Meier curves using the early specimen concentrations in those subjects with detectable peak cTnI concentrations (≥0.02 μg/l; n=161). Subjects were classified based on being positive for both tests in the first specimen (n=54, Group C — positive panel and detectable cTnI (≥0.02 μg/l) at presentation), positive only for the panel test (n=24, Group B — positive panel test and a cTnI concentration that is not detectable (≤ 0.01 μg/l) at presentation), positive only for TnI (n=42, Group A — a cTnI concentration that is detectable (≥0.02 μg/l) with a negative panel test at presentation) or negative by both tests (n=41, Group D — negative cTnI (≤0.01 μg/l) and negative panel test at presentation but with a subsequent peak cTnI that is detectable, i.e. ≥0.02 μg/l).

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References

    1. Apple FS, Wu AH, Mair J, et al. Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome. Clin Chem. 2005;51:810–24. - PubMed
    1. Jaffe AS, Babuin L, Apple FS. Biomarkers in acute cardiac disease: the present and the future. J Am Coll Cardiol. 2006;48:1–11. - PubMed
    1. Jaffe AS. Cardiovascular biomarkers: the state of the art in 2006. Clin Chim Acta. 2007;381:9–13. - PubMed
    1. Lindmark E, Diderholm E, Wallentin L, Siegbahn A. Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease. JAMA. 2001;286:2107–13. - PubMed
    1. Jernberg T, Lindahl B, Siegbahn A, et al. N-Terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease. J Am Coll Cardiol. 2003;42:1909–16. - PubMed

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