Allostatic Load in Adults with Congenital Heart Disease: A Multi-Cohort Analysis of the All of Us Research Program

Background. Adults with congenital heart disease (CHD) are a growing population and face unique challenges as they age. Unlike acquired diseases that disrupt a previously healthy baseline, CHD is developmentally embedded. Allostatic load, the multi-system biological "wear and tear" exacted by the continuous cost of coping, offers a framework for indexing this lifelong psychophysiological stress. Methods. We analyzed 14,469 adults from the All of Us Research Program: non-syndromic CHD (n = 6,810), acquired heart disease (AHD; n = 2,264), non-cardiac chronic illness (n = 4,331), and a general population comparison cohort (GP; n = 1,064). Using a standardized operationalization, allostatic load was scored across five biomarker domains (AL5, range 0-5). A pre-specified primary test compared adjusted AL5 between CHD and GP. Exploratory analyses examined clinical predictor of this gap and whether baseline subjective health predicted prospective AL5 change, utilizing strictly matched biomarkers across timepoints to prevent substitution artifacts. Results. Adults with CHD carried significantly higher allostatic load than the general population comparison cohort (adjusted difference +0.30 AL5 units, 95% CI 0.24-0.37, p < .001). Cumulative comorbidity and cardiac medication burden explained most of this gap. Congenital anatomical complexity did not independently predict this burden. In a prospective subsample (n = 8,031, mean follow-up 2.7 years), worse baseline mental health predicted increases in allostatic load over time in CHD. Baseline physical health showed no such prospective association. The general population and acquired heart disease cohorts demonstrated the inverse dissociation: subjective physical health predicted these longitudinal physiological changes. Conclusions. Adults with CHD carry an elevated allostatic burden dictated by the cumulative cost of acquired medical and treatment intensity. The original congenital anatomy does not predict this accumulation. Furthermore, subjective mental health prospectively tracks future increases in allostatic load in CHD. This dissociation is absent in adult-onset acquired heart disease, suggesting that the mental aspects of coping with CHD may impact outcomes above and beyond those with acquired heart disease. These findings position psychological care as a potentially physiologically consequential intervention.