A statistical approach to evaluate the performance of cardiac biomarkers in predicting death due to acute myocardial infarction: time-dependent ROC curve

Authors: EDA KARAİSMAİLOĞLU, ZELİHA GÜNNUR DİKMEN, FİLİZ AKBIYIK, AHMET ERGUN KARAAĞAOĞLU

Abstract: Background/aim: Myoglobin, cardiac troponin T, B-type natriuretic peptide (BNP), and creatine kinase isoenzyme MB (CK-MB) are frequently used biomarkers for evaluating risk of patients admitted to an emergency department with chest pain. Recently, time- dependent receiver operating characteristic (ROC) analysis has been used to evaluate the predictive power of biomarkers where disease status can change over time. We aimed to determine the best set of biomarkers that estimate cardiac death during follow-up time. We also obtained optimal cut-o values of these biomarkers, which di erentiates between patients with and without risk of death. A web tool was developed to estimate time intervals in risk. Materials and methods: A total of 410 patients admitted to the emergency department with chest pain and shortness of breath were included. Cox regression analysis was used to determine an optimal set of biomarkers that can be used for estimating cardiac death and to combine the signi cant biomarkers. Time-dependent ROC analysis was performed for evaluating performances of signi cant biomarkers and a combined biomarker during 240 h. e bootstrap method was used to compare statistical signi cance and the Youden index was used to determine optimal cut-o values. Results: Myoglobin and BNP were signi cant by multivariate Cox regression analysis. Areas under the time-dependent ROC curves of myoglobin and BNP were about 0.80 during 240 h, and that of the combined biomarker (myoglobin + BNP) increased to 0.90 during the rst 180 h. Conclusion: Although myoglobin is not clinically speci c to a cardiac event, in our study both myoglobin and BNP were found to be statistically signi cant for estimating cardiac death. Using this combined biomarker may increase the power of prediction. Our web tool can be useful for evaluating the risk status of new patients and helping clinicians in making decisions.

Keywords: Time-dependent ROC curve, cardiac biomarkers, B-type natriuretic peptide, creatine kinase isoenzyme MB, troponin T, myoglobin

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