Oxidative balance score as a predictor of MASLD-CVD comorbidity risk and mortality: Insights from traditional and machine learning approaches.

Background: Oxidative stress underlies both metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular disease (CVD). The oxidative balance score (OBS) quantifies systemic oxidative stress from pro-/antioxidant exposures, but its role in MASLD-CVD comorbidity is unknown. Methods: We analyzed 19,993 adults from NHANES 1999-2018. Multinomial logistic and Cox regression assessed OBS associations with comorbidity risk and all-cause mortality. Machine learning and SHAP interpretability analysis identified key predictors, and bioinformatics explored mechanistic pathways. Results: Lower OBS quartiles were associated with higher odds of prevalent MASLD (Q1 OR = 1.31), CVD (Q1 OR = 1.95), and MASLD-CVD comorbidity (Q1 OR = 2.15). Each unit increase in OBS reduced mortality risk (MASLD-CVD: HR = 0.98; MASLD: HR = 0.98; CVD: HR = 0.99). Critical OBS thresholds were identified: OBS<8.73 increased mortality risk in MASLD patients (HR = 1.09), while OBS≥8.73 was protective (HR = 0.96). For MASLD-CVD, OBS = 21 optimally stratified mortality risk (log-rank P = 0.0018). SHAP analysis revealed the nonlinear contributions of key dietary/lifestyle factors. The key pro-oxidant factors may contribute to comorbidity development through IL-17 and insulin resistance pathways, as suggested by bioinformatics analysis. Conclusions: OBS enables risk stratification for MASLD-CVD comorbidity, but external validation is required before clinical application.