Epigenetic changes, such as DNA methylation (DNAm), offer a measure of biological age distinct from chronological age. DNAm PhenoAge is one such biomarker that is more strongly related to morbidity, mortality, and physical function than chronological age. More accurate risk stratification methods are needed for ASD surgeries, where complications remain difficult to predict with an increasingly aged population. A multicenter ASD registry was queried. DNAm PhenoAge was calculated as per Levine et al. (6). Multivariable logistic regression examined the associations of DNAm PhenoAge and chronological age with perioperative adverse events (AE). The relative improvements in model discrimination, fit, and classification performance were compared. Adjusted odds ratios compared the risk of 55 versus 75 years for each age metric. Laboratory data were available for 200 patients. Mean DNAm PhenoAge was lower than chronological (DNAm PhenoAge, 53.7 ± 18.1; chronological, 61.1 ± 15.4; p < 0.001; 95% CI, 6.3-8.5). DNAm PhenoAge models demonstrated numerically higher discrimination for all outcomes examined (AUC range, 0.701-0.823 vs. 0.671-0.767), although no DeLong comparisons were statistically significant (all p > 0.05). Model fit consistently favored DNAm PhenoAge (ΔAIC, 4.41-7.08), with NRI ranging from 0.198 to 0.500. For most adverse events, DNAm PhenoAge demonstrated adjusted odds ratios that were comparable to or greater than those observed for chronological age. In this exploratory study, DNAm PhenoAge demonstrated associations with several postoperative adverse events. Although differences in discrimination were not statistically significant, improvements were consistently observed across multiple complementary measures of model performance. The generally consistent direction of improved model performance suggests that DNAm PhenoAge warrants further study as a candidate biomarker for perioperative risk stratification (level of evidence, 3).
