Cardiac biomarkers in athletes and active individuals: a clinical review of exercise-induced elevations and diagnostic interpretation

Figure 1. Comparative causes, release kinetics, and clinical interpretation of increases in NP (BNP, NT-proBNP) and cTn (cTnI, cTnT) after acute, intensive exercise. Different mechanisms are triggered by hemodynamic and metabolic stressors: reversible membrane permeability and cytosolic leakage from the sarcomere (troponin) in response to myocyte stretch, and neurohormonal activation (NPs). Peak time (cTn: 1-5h; NPs: 0-4h) and return to baseline (cTn: 24-72h; NPs: 24-72h) are two important differences. Serial sampling is necessary for clinical interpretation: pathogenic elevations persist for more than 72 hours, with increasing patterns and symptoms, whereas physiological (benign) elevations return to baseline within 24 to 72 hours, with normal ECG and imaging (Martinez et al., 2021; Cirer-Sastre et al., 2022; Omran et al., 2022; Shi et al., 2022).

Figure 2. NcRNAs, as cardiovascular biomarkers, are released during exercise. Exercise that is intense or prolonged causes metabolic and hemodynamic stress, thereby stimulating the release of ncRNAs from cardiac and vascular cells. Exercise-responsive lncRNAs (MALAT1, Mhrt, Chast) serve as transcriptional controllers, ceRNAs, and epigenetic regulators (Lee et al., 2003; Zeng and Cullen, 2003; Lee et al., 2004; Faller and Guo, 2008; Morlando et al., 2008). While chronic exercise modifies different sets of miRNAs (miR-139, miR-143, miR-223, miR-330), acute exercise quickly mobilizes miRNAs (miR-21, miR-146a, miR-221, miR-222) (Ultimo et al., 2018). EXOs and EVs encapsulate both miRNAs and lncRNAs to ensure their steady circulation. Early subclinical damage identification, left ventricular hypertrophy type differentiation, and hypertrophic cardiomyopathy screening are examples of clinical value that remain in the exploratory stage and require validation (de Gonzalo-Calvo et al., 2018; Barber et al., 2019; Ma and Liao, 2019; Hu et al., 2021, 2026).

Figure 3. Exercise-induced cardiac biomarkers in four domains: present constraints and potential remedies. Clinical (no sport-specific cutoffs, 76–96% of athletes exceeding myocardial infarction thresholds, multi-marker strategies adding no value, absence of validated return-to-play algorithms); methodological/design (small sample sizes, short follow-up durations, lack of comparison with CMR gold standard); technical (non-standardized pre-analytical protocols, variability in EV and miRNA methods, requirement for invasive blood sampling); and individual diversity (high inter-individual variability, lack of re-regulation data, no personalized baseline reference values). Athlete-specific 99th percentiles, multifaceted ML models, AI-driven decision support, large multicenter cohorts with 5–10 year follow-up, direct biomarker comparison with CMR (T1 mapping and late gadolinium enhancement), MISEV-aligned guidelines, locked-in assays, and saliva-based POC testing (validated for cTnI, emerging for miRNAs) are some of the suggested solutions. Prevention-first personalized sports medicine, which integrates individual molecular profiles, individualized exercise prescriptions, personalized…