Trimethylamine N-oxide (TMAO) for risk stratification after acute ischemic stroke: Results from the BIOSIGNAL cohort study

INTRODUCTION: Recent studies in stroke patients from predominantly Asian populations have underscored the significance of trimethylamine N-oxide (TMAO) as a valuable blood biomarker for predicting incident strokes and major adverse cardiovascular events (MACE). However, its prognostic role after ischemic stroke in other populations is not yet comprehensively investigated. PATIENTS AND METHODS: We measured plasma TMAO levels in 1726 acute ischemic stroke patients (within 24 h from symptom onset) from the multicenter BIOSIGNAL cohort. Using cox and logistic regression models adjusting for demographic and vascular risk factors, we investigated the association of TMAO with recurrent stroke, MACE within 365 days and functional outcome at 90 days after stroke. RESULTS: TMAO levels were not associated with any risk of recurrent stroke (n = 108, unadj. HR per unit increase of log (TMAO) 1.15, 95% CI 0.88-1.51, adjust. HR 1.07, 95% CI 0.78-1.47) or MACE (n = 309, unadj. HR of log (TMAO) 1.10,95% CI 0.91-1.3, adjust. HR 0.90, 95% CI 0.74-1.09). There was an univariable positive association between higher TMAO plasma levels and unfavorable functional outcome, this association remained statistically significant in the multivariable analysis (unadj. OR of log (TMAO) 1.56, 95% CI 1.34-1.81, adjust. OR 1.28, 95% CI 1.04-1.57). CONCLUSION: In this large cohort of acute stroke patients from a predominantly White population, TMAO had no independent association with either recurrent stroke, or MACE or death. In univariable, and multivariable analysis, there was a significant association between TMAO and unfavorable functional outcome, which might not be clinically significant due to its low effect size. Therefore, TMAO seems not to be a clinically relevant biomarker for risk stratification after stroke.