An Integrated Model of Cardiotoxicity: Interaction of Age, Sex, and Genetic Polymorphisms in Patients with Acute Leukemia

Background: Cardiotoxic complications represent a major challenge in patients receiving anticancer therapy and may be influenced by interactions among demographic and genetic factors contributing to structural, functional, and electrophysiological myocardial abnormalities. This study aimed to evaluate the effects of age, sex, and genetic polymorphisms on the development of cardiotoxic complications in patients with acute leukemia. Methods: A total of 89 patients aged 18–78 years underwent electrocardiography, echocardiography, and molecular genetic analyses of polymorphisms in GPX4, SOD2, COL1A1, CAT, EDN1, and COMT. Results: Left ventricular hypertrophy (LVH) was detected in 58.4% of patients, reduced left ventricular ejection fraction (LVEF < 50%) in 23.6%, arrhythmias in 46.1%, and ischemic myocardial changes in 28.1%. Older age was significantly associated with LVH, reduced LVEF, and ischemic myocardial changes (all p < 0.05). Sex-specific differences showed a higher prevalence of rhythm disturbances in women and ischemic myocardial changes in men than in women. Individual genetic polymorphisms were significantly associated with specific cardiac phenotypes. Furthermore, combined genetic risk, defined as the presence of two or more unfavorable alleles, was significantly associated with higher rates of LVH, arrhythmias, and impaired myocardial contractility. Multivariate logistic regression identified COMT Val158Met, COL1A1 C1997A, SOD2 C14510A, and EDN1 Lys198Asn as independent genetic predictors of cardiotoxic complications. Conclusions: These findings support a polygenic model of cardiotoxicity and highlight the potential value of integrating demographic and genetic factors for personalized cardiovascular risk stratification, early detection, and prevention of treatment-related cardiac complications.

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