Biomarkers Identify Distinct Biological Signatures of Eccentric Hypertrophy in Elite Athletes: A Sex-Specific...

Background and Objectives: Eccentric hypertrophy (EH) represents a common physiological cardiac adaptation in athletes, particularly in endurance disciplines. However, the biological correlates underlying EH and potential sex-specific differences remain poorly understood. This study aimed to investigate clinical, echocardiographic, and biochemical determinants of EH in a large cohort of elite athletes. Materials and Methods: We evaluated 2522 elite athletes undergoing pre-participation screening for Olympic competitions. Athletes were classified according to cardiac geometry into EH or normal geometry (NG) based on echocardiographic parameters. Clinical, anthropometric, echocardiographic, and biochemical variables were compared between groups. Univariate and multivariable logistic regression analyses were performed to identify independent predictors of EH. Results: EH was present in 601 athletes (23.8%) and was more prevalent in endurance sports (51.1% vs. 14.3%, p < 0.0001). Athletes with EH showed greater cardiac chamber dimensions and mass, with preserved systolic and diastolic function. Several biomarkers differed between groups, including higher AST, ALT, CPK, eosinophils, and HDL, and lower creatinine and TSH in EH (all p < 0.01). Following multivariable analysis, lower creatinine (OR 0.28, 95% CI 0.14-0.52, p < 0.0001), higher AST (OR 1.02, 95% CI 1.02-1.03, p < 0.0001), and higher eosinophil count (OR 1.12, 95% CI 1.06-1.20, p < 0.0001) independently predicted EH. The model showed moderate discrimination (AUC 0.72). Sex-stratified analyses showed different biomarker associations with EH in men (creatinine and AST) and women (eosinophils and HDL), with similar model performance (AUC 0.71 vs. 0.73). Conclusions: EH in elite athletes is associated with distinct biological signatures reflecting multiple physiological pathways. Notably, sex-specific patterns emerge, suggesting different mechanisms underlying cardiac adaptation in male and female athletes.