ABSTRACT NUMBER: ESOC2026A1462 TRIMETHYLAMINE N-OXIDE AND FUNCTIONAL OUTCOMES AFTER ACUTE ISCHEMIC STROKE: CONSISTENCY ACROSS SUBTYPES AND INCREMENTAL PROGNOSTIC VALUE

Abstract Background and aims Early prognostic stratification after acute ischemic stroke (AIS) would benefit from biomarkers that reflect thrombo-inflammatory biology. Trimethylamine-N-oxide (TMAO), a gut microbiota–derived metabolite, has been linked to platelet reactivity and systemic inflammation. Methods In a prospective cohort of 322 AIS patients from a single tertiary center, fasting plasma TMAO was measured at admission and analyzed as both continuous and categorical variables. The primary outcome was assessed using the 90-day modified Rankin scale (mRS). Associations were evaluated with proportional-odds modes adjusted for demographics, vascular risk factors, renal function, treatments and TOAST subtypes. Incremental predictive value was examined via area under curve (AUC), continuous net reclassification improvement (NRI)/ integrated discrimination index (IDI), and decision-curve analysis (DCA). Results AIS Patients had higher fasting TMAO than matched controls (p<0.001). Higher TMAO was independently associated with a worse mRS distribution: per two-fold increase, common adjuster odds ratio (aOR) 1.54 (95% confidence interval [CI] 1.34–1.76; by tertiles, T3 vs T1 aOR 5.05 (95%CI 2.93–8.69). The association was consistent across TOAST subtypes (interaction p=0.70). Adding TMAO modestly improved discrimination (ΔAUC=0.027) but significantly enhanced reclassification (NRI=0.618, IDI=0.051) with small threshold-relevant gains on DCA. TMAO also correlated strongly with CRP and systemic immune-inflammation index. Conclusions Elevated admission TMAO is associated with poorer functional recovery after AIS, independent of stroke subtype and clinical predictors. TMAO may represent a cross-etiological prognostic biomarker aligned with thrombo-inflammatory pathways, warranting validation in larger multicenter cohorts. Conflict of interest Eung-Joon Lee: Nothing to disclose Figure 1 - belongs to Conclusions