Abstract 17447: Effects of Inflammatory Biomarkers on Epigenetic Age Acceleration in Adult Congenital Heart Disease

Abstract

Introduction: DNA methylation (DNAm) changes reflect alterations in the immune response to cardiac surgery in older adults. However, the role of inflammation on epigenetic age acceleration (EAA) in adults with congenital heart disease (ACHD) who underwent palliative cardiac surgery during childhood is unknown. Hypothesis: ACHD patients with Fontan(F) procedures would have advanced EAA due to higher DNAm predicted IL-6 and CRP levels compared to healthy adults or ACHD patients who underwent single surgery as an infant, likely capturing chronic inflammation associated with the abnormal pathophysiologic state. Methods: A case-control study in young adults (aged 20-30 years) with Fontan circulation or single surgery (SS) as an infant at a tertiary ACHD hospital. DNAm were measured by the EPIC Array. DNAm predicted IL-6 and CRP level differences were tested by robust linear model (rlm) adjusted for age, sex, cell types, and self-reported ethnicity. EAAs were calculated by extracting residuals by regressing epigenetic ages on chronological age in linear regression models. EAA differences were tested by rlm adjusted for the same covariates. Contribution analysis was performed to determine contribution of IL-6 and CRP to EAA. Results: Thirteen Fontan patients (6 female: 7 male, median age: 23) and 5 SS patients (3 female: 2 male, median age: 23) were compared with 20 age-matched controls (15 female: 5 male, median age: 27). Each subgroup had a predominant white race and non-Hispanic ethnicity. The F group has a statistically higher predicted IL-6 and CRP level (p<0.001). Also, the F group had significantly higher EAA for mortality predictor Grimage (p<0.001) and PhenoAge (p<0.001). Conclusions: Patients who underwent Fontan procedure experience advanced EAA contributed by inflammatory biomarkers at a young age. Future studies evaluating the key predictors that drive EAA difference is needed to understand the impact of chronic alteration of physiology.