Abstract 4147205: Characterization of plasma proteome perturbations to distinguish thrombotic myocardial infarction from non-thrombotic myocardial injury and chronic coronary artery disease.

Background: The distinction between thrombotic myocardial infarction (TMI) and non-thrombotic myocardial injury (nTMi) is crucial, given their varied etiologies, unique treatment approaches, and higher misclassification in clinical setting. In this study, we compared plasma proteome among individuals with TMI, nTMi, and chronic coronary artery disease (cCAD). Methods: Mass spectrometry-based proteomic analysis was conducted in 173 patients (84 with TMI, 36 with nTMi, and 51 with cCAD) who underwent coronary angiography (T 0 - acute time) and had an average 3-month post-procedure follow-up (T fu, quiescent state). Initially, we assessed temporal change from T 0 to T fu in proteomic profile in TMI group to identify proteins elevated during acute thrombosis. Subsequently, we compared these proteins’ levels at the acute phase across all groups to find differentially expressed proteins. We used hierarchical Bayesian models to analyze protein abundances, considering study group, time-point, and their interaction, with random effects for individual variability. Statistical significance was determined using Bayesian factor analysis with a threshold of BF > 150. Results: Proteomic profiling of plasma samples quantified 1,756 proteins. In TMI, 141 proteins varied significantly between T 0 and T fu . Proteins related to platelet activation, hemostasis, cell adhesion, and tissue remodeling were elevated. In contrast, proteins associated with extracellular matrix remodeling, cell adhesion, receptor signaling, and growth factor binding were reduced. Notably, six proteins showed differences when comparing TMI to nTMi. Specifically, Decorin, Myoglobin, and C-reactive protein levels were elevated during T 0 , while the others were decreased in TMI group. Comparing TMI to cCAD, 47 proteins differed significantly ( Figure 1A ). Conclusion: Our unique study design, using patients as their own controls, helped us in identifying distinct proteomic signature that can offers a promising set of noninvasive biomarkers for differentiating between TMI from other myocardial injury events.