The Actively Secreted Plasma ExtraCellular Vesicle Troponin (ASPECT) Study: Circulating Troponin in Extracellular Vesicles Across Cardiovascular Disease Cohorts

Cardiac troponin is essential for diagnosing myocardial infarction, yet high-sensitivity assays frequently detect troponin elevations in non-ischemic contexts, complicating clinical decision-making. We investigated extracellular vesicle-associated (EV) versus non-vesicular (NEV) troponin in plasma samples from 266 participants across acute and chronic heart failure, type 1 and type 2 MI, hypertrophic cardiomyopathy, end-stage kidney disease, healthy individuals, and exercise states. EV troponin was negligible in necrosis-dominant conditions (MI, kidney disease) but constituted up to 40-50% of total troponin in chronic heart failure or hypertrophic cardiomyopathy and nearly 100% in healthy or exercise cohorts. Unlike plasma troponin, EV troponin weakly correlated with natriuretic peptides or renal indices, suggesting a distinct release mechanism linked to chronic stress or physiological turnover. These findings highlight the potential for EV troponin to distinguish active, non-necrotic processes from acute injury. Further study may clarify its prognostic utility and refine current diagnostics and risk stratification. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=162 HEIGHT=200 SRC="FIGDIR/small/25340197v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@269101org.highwire.dtl.DTLVardef@1fa0f19org.highwire.dtl.DTLVardef@1f5376corg.highwire.dtl.DTLVardef@9d515_HPS_FORMAT_FIGEXP M_FIG C_FIG