Multicomponent-based analyses of ACS-patient-derived extracellular vesicles as likely tools for tailored interventional approaches.

Reliable predictive biomarkers to reduce unnecessary coronary angiograms (CAGs) in non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA) patients displaying high-risk features are still lacking. Here, we show that profiling patient-derived circulating extracellular vesicles (EVs) can not only improve their risk stratification but also reduce unnecessary CAGs. Analysis of EVs and their miR cargo revealed that CD62p+EVs enriched in miR-130a-3p correlated with the absence of non-critical coronary artery disease (CAD). Proteomic analysis identified nine proteins differentially enriched in patients with or without critical-CAD (NO CAD), irrespective of their diagnosis. Multivariate analysis identified miR-130a-3p (odds ratio [OR]:0.35 [0.19-0.67]), phospholipid transfer protein (OR 0.96 [0.94-0.98]), and subunit beta of mitochondrial trifunctional enzyme (OR:0.96 [0.94-0.98]) as predictors of NO CAD. Furthermore, EV-miR-130a-3p enrichment predicted the absence of multivessel disease (OR:0.46 [0.23-0.90]). These findings establish EV profiling as a valuable tool for stratifying and optimizing the clinical management of patients with acute coronary syndrome.