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 40-60% of total troponin in chronic heart failure or hypertrophic cardiomyopathy; in healthy controls and athletes, troponin concentrations were near or below the detection limit, though detectable troponin was predominantly EV-associated. Unlike plasma troponin, EV troponin weakly correlated with natriuretic peptides or renal indices, suggesting a distinct release mechanism linked to chronic stress or physiological processes. 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.