Brain-Derived Neurotrophic Factor in Acute Coronary Syndromes: Beyond Diagnosis Toward Biological Phenotyping and Risk Stratification

Acute coronary syndromes (ACS) remain time-critical clinical emergencies in which early diagnosis and accurate risk stratification determine management and outcomes. Although symptoms, electrocardiography, and high-sensitivity cardiac troponin (hs-cTn) provide a reliable framework for detecting myocardial injury, they offer limited insight into plaque instability, thromboinflammatory activity, vascular repair, and post-infarction remodeling. In this narrative review, we examine the biological rationale and current clinical evidence supporting brain-derived neurotrophic factor (BDNF) as a candidate biomarker in ACS, with particular attention to pre-analytical, analytical, and phenotypic sources of heterogeneity. Available studies show that circulating BDNF concentrations vary substantially according to biological matrix, timing of sampling, ACS subtype, and assay methodology, which likely contributes to inconsistent findings across cohorts. Overall, current evidence does not support BDNF as a diagnostic alternative to hs-cTn in rule-in or rule-out pathways. However, BDNF may have value in biological phenotyping and risk stratification by reflecting platelet activation, endothelial dysfunction, inflammatory signaling, and remodeling processes after ACS. Further progress will require standardized pre-analytical procedures, separate assessment of mature BDNF and proBDNF, serial sampling, and validation in large multicenter studies.