Allostatic Load as a Mediator of Adverse Social Determinants of Health and Incident Heart Failure

Background Adverse social determinants of health (SDOH) are independently associated with incident heart failure (HF), but the mechanisms underlying this relationship are unknown. Allostatic load (AL)—the cumulative physiologic burden of chronic stress—may represent an etiologic mechanism. We examined whether AL mediates the association between adverse SDOH and incident HF. Methods and Results We examined 13,529 REGARDS participants aged 45-64 years who were free of HF at baseline. Adverse SDOH burden was defined as a count among factors based on the Healthy People 2030 framework. AL was calculated using 11 physiologic markers across cardiovascular, metabolic, immune, and inflammatory systems. The primary outcome was adjudicated incident HF hospitalization or death (ascertained between 2003 and 2021). Mediation was assessed using Inverse Odds Weighting with Cox proportional hazards models, adjusted for age, sex, and geographic region. Over a median follow-up period of 14.30 years (interquartile range (IQR): 7.71–16.40), 500 participants experienced incident HF events. Higher adverse SDOH count was associated with increased HF risk in a stepwise fashion. AL mediated 18.87% of the association between ≥3 adverse SDOH and HF (indirect effect hazard ration (HR): 1.30 [1.14–1.47]) and 13.32% of the association for 2 adverse SDOH. No mediation was observed for 1 adverse SDOH. Conclusions AL partially mediates the relationship between adverse SDOH burden and incident HF. These findings highlight AL as a potential underlying mechanism by which adverse SDOH exerts a negative effect on health.