Abstract
BACKGROUND: Allostatic load (AL) is a measurement of physiological burden of chronic stress, operationalized using a composite score derived from biomarkers from multiple physiologic systems. The relationship between AL and anthracycline cardiotoxicity is unclear. METHODS AND RESULTS: We included consecutive adult patients who underwent anthracycline-based chemotherapy from 2016 to 2019 for any type of cancer. Patients with preexisting heart failure and lack of AL score measures were excluded from the analysis. A composite AL score was calculated using 9 biomarkers tested before initiating chemotherapy. The end point was the development of cardiotoxicity (defined as clinical heart failure or drop in left ventricular ejection fraction≥10% to <50%). A total of 718 patients were included in the analysis (29% Non-Hispanic White, 31% Non-Hispanic Black, 40% Hispanic). The mean AL score was 2.4±1.4 and it was significantly higher in Non-Hispanic Black and Hispanic patients compared with Non-Hispanic White patients (2.5±1.3 in Non-Hispanic Black versus 2.4±1.3 in Hispanic versus 2.1±1.5 in Non-Hispanic White, P=0.031). In patients who developed cardiotoxicity, AL score was significantly higher than patients without cardiotoxicity (2.7±1.4 versus 2.3±1.3, P=0.006). AL score was independently associated with incident anthracycline cardiotoxicity after adjusting for race and ethnicity, age, sex, cardiovascular risk factors, anthracycline dose, baseline left ventricular ejection fraction, cancer type, and cancer metastasis (hazard ratio 1.20 per 1 AL score increase [95% CI, 1.02-1.43], P=0.033). AL score remained significantly associated with anthracycline cardiotoxicity after additional adjustment of social determinants of health. CONCLUSIONS: AL score can be a potential important prognostic marker in the prediction of cardiotoxicity in patients with cancer undergoing cardiotoxic treatment independent of social determinants of health.