Background: Assessing high-risk mortality in acute coronary syndrome (ACS) patients, encompassing ST-Elevation Myocardial Infarction (STEMI), Non-ST-Elevation Myocardial Infarction (NSTEMI), and Unstable Angina Pectoris (UAP), is crucial. However, the prognostic significance of hematological parameters in predicting high-risk mortality in ACS patients remains uncertain despite advancements in ACS research. Aim: The aim was to investigate prognostic significance of hematological parameters troponin, Creatine Kinase-MB (CKMB), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocyte-to-Lymphocyte Ratio (MLR), Basophil-to-Lymphocyte Ratio (BLR), and Eosinophil-to-Lymphocyte Ratio (ELR) levels in predicting high-risk mortality in ACS patients. Methods: In this retrospective observational study, data from medical records of 115 patients with ACS, including 40 with STEMI, 38 with NSTEMI, and 37 with UAP, were analyzed. Patients were selected using stratified random sampling, whereby five patients were randomly chosen each month from January 2021 to December 2022 while maintaining a 1:1:1 ratio of selection. Results: Troponin (r=0.519) and NLR (r=0.484) showed moderate positive correlations with high-risk STEMI mortality. Meanwhile, troponin (r=0.387), NLR (r=0.279), PLR (r=0.276), MLR (r=0.250), BLR (r=0.237), and ELR (r=-0.344) were found to be significantly correlated with high-risk ACS mortality. Troponin, CKMB, NLR, and MLR were significant (AUC>0.7) for high-risk STEMI mortality, and Troponin, NLR, and MLR were significant for high-risk ACS mortality. The results of the multivariate regression analysis indicated that only Troponin (OR:2.049; 95%CI: 1.802 – 8.218; p=0.014), NLR (OR:1.652; 95%CI: 1.306 – 7.753; p=0.030), and MLR (OR:4.067; 95%CI: 1.182 – 13.987; p =0.026) were capable of predicting high-risk ACS mortality. Sub-group analysis showed an increased risk of ACS mortality by GRACE score >140 in patients with elevated levels of Troponin (OR:2.787; 95%CI: 1.032 – 7.524; p

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