Data Sheet 2_Uric acid-to-albumin ratio as a cardiometabolic marker for predicting adverse outcomes in patients with atrial fibrillation: evidence from two independent cohorts.docx

IntroductionAtrial fibrillation (AF) is closely associated with metabolic dysfunction. The uric acid–to–albumin ratio (UAR), integrating oxidative stress, inflammation, and nutritional status, reflect cardiometabolic burden, but evidence linking UAR to AF prognosis remains limited.
MethodsWe analyzed clinical data from 1,908 AF patients at West China Hospital, with external validation from the MIMIC database (n=1,366). Associations were assessed using Kaplan–Meier analyses, restricted cubic splines, and multivariable Cox proportional hazards models. Incremental prognostic value beyond the CHA2DS2-VASc score was evaluated in both cohorts. Exploratory machine learning and SHAP analyses were employed to assess the variable importance of UAR. Subgroup and sensitivity analyses were performed in primary cohort, including additional cardiometabolic adjustment, analyses with cardiac mortality, competing risk models, and longer follow-up.
ResultsBaseline characteristics differed across UAR quartiles, with high UARs associated with substantial burdens of metabolic comorbidities, heart failure, renal dysfunction, and elevated inflammatory and cardiac biomarkers. Mortality was higher in the highest UAR quartile (log-rank P<0.001). In the primary cohort, restricted cubic splines showed a J-shaped association between UAR and 1-year mortality (P for nonlinearity <0.001). In fully adjusted Cox models, UAR (per SD) predicted 1-year all-cause mortality in the primary cohort (HR 1.162, 95% CI 1.036–1.304) and in the MIMIC cohort (HR 1.137, 95% CI 1.092–1.185). Adding UAR to the CHA2DS2-VASc score improved discrimination (C-index 0.654 to 0.692; P = 0.001), reclassification (continuous NRI 0.178), calibration, and clinical net benefit, with consistent incremental performance in the MIMIC cohort. In both cohorts, SHAP analysis consistently identified UAR as one of the major contributors to mortality prediction. Findings were consistent across subgroups and sensitivity analyses.
ConclusionUAR is an independent predictor of mortality in AF and captures cardiometabolic remodeling beyond conventional risk assessment. As a readily available biomarker, UAR may facilitate metabolically guided risk stratification and individualized management in AF populations.