Prospective associations of allostatic load with heart failure incidence and prognosis: findings from two national cohorts

Aim: Allostatic load (AL) is a composite measure of cumulative physiological stress, but its role in heart failure (HF) onset and prognosis remains unclear. Methods: We analyzed data from two U.S. cohorts. Logistic regression assessed AL and incident HF in 3,814 adults from the Health and Retirement Study (HRS, 2016–2020). Cox regression examined AL with cardiovascular and all-cause mortality in 1,200 HF patients from the National Health and Nutrition Examination Survey (NHANES, 1999–2010 and 2015–2016). AL was derived from nine biomarkers and categorized as low (0–2), medium (3), or high (≥ 4). Results: In HRS, after full adjustment, high AL was associated with increased incident HF risk versus low AL (OR = 2.07; 95% CI: 1.29–3.32; P = 0.002), with each 1-unit increase raising risk by 30% (P < 0.001). In NHANES, after full adjustment, high AL predicted elevated cardiovascular (HR = 2.03; 95% CI: 1.37–3.03; P < 0.001) and all-cause mortality (HR = 1.70; 95% CI: 1.30–2.22; P < 0.001). Per unit increase, AL raised cardiovascular mortality by 18% and all-cause mortality by 15%. Model performance improved modestly with AL. Conclusions: Elevated AL is independently associated with HF incidence and poorer prognosis, supporting its potential as an integrative biomarker for HF risk stratification and prevention.