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

## TL;DR

This study found that TMAO levels in blood are not useful for predicting stroke recurrence or cardiovascular risks in White patients after an acute ischemic stroke.

## Contribution

The study evaluates TMAO's role in risk stratification after stroke in a predominantly White population, contrasting with prior findings in Asian populations.

## Key findings

- TMAO levels were not associated with recurrent stroke or major adverse cardiovascular events.
- Higher TMAO levels were linked to worse functional outcomes in both univariable and multivariable analyses.
- The observed association with functional outcomes had a low effect size, suggesting limited clinical relevance.

## Abstract

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.

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.

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).

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.

Graphical abstract