Assessment of multiple cardiac biomarkers in non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 Trial

Aims The aim of this study is to simultaneously evaluate the incremental prognostic value of multiple cardiac biomarkers reflecting different underlying pathophysiological processes in a well-characterized population of patients with non-ST-segment acute coronary syndrome (NSTE-ACS). Methods and results We measured cardiac troponin I (cTnI), N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein, and myeloperodixase (MPO) among 4352 patients with NSTE-ACS in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischaemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial and followed them for a mean of 343 days. When added individually to a multivariable model adjusted for clinical characteristics, the risk of cardiovascular (CV) death rose in a stepwise fashion with increasing quartiles of each biomarker, and when using their pre-defined cut-points [HRadj 2.71 (P < 0.001) for cTnI >= 0.03 ng/mL; HRadj 3.01 (P < 0.001) for NT-proBNP >= 400 pg/mL; HRadj 1.45 (P = 0.019) for high-sensitivity (hs) C-reactive protein >= 15 mg/L; and HRadj 1.49 (P = 0.006) for MPO >= 670 pmol/L]. After including all biomarkers, only NT-proBNP and cTnI were independently associated with CV death, and only cTnI with myocardial infarction (MI). The addition of NT-proBNP to a model adjusted for TIMI risk score incorporating cTnI significantly improved both the discrimination and re-classification of the model for CV death and heart failure (HF) while there was no such improvement after the addition of either MPO or hs-C-reactive protein. Conclusion In this study of over 4300 patients presenting with NSTEACS, we found that both cTnI and NT-proBNP offer prognostic information beyond that achieved with clinical risk variables for CV death, MI, and HF. Myeloperoxidase and hs-C-reactive protein, while independently associated with some adverse CV outcomes, did not provide substantial incremental prognostic information when evaluated together with cTnI and NT-proBNP.