Increasing trimethylamine N-oxide levels as a predictor of early neurological deterioration in patients with acute ischemic stroke

Background and aims: Trimethylamine N-oxide (TMAO), a pro-atherosclerotic intestinal microbiota metabolite, has mechanistic links to atherosclerosis development and cardiovascular diseases. In this study, we aimed to investigate whether serum TMAO levels could predict early neurological deterioration (END) after acute ischemic stroke. Methods: We prospectively recruited patients with first-ever ischemic stroke and hospitalized within 24 h of symptoms onset during Mar 2018 to Mar 2019. Plasma TMAO levels were quantified using stable isotope dilution high-performance liquid chromatography with tandem mass spectrometry after admission. END was defined as an increase in the total National Institutes of Health Stroke Scale by 2 or more points within 3 days. Results: Of the 362 patients included, END was diagnosed in 97 subjects (26.8%). The median TMAO concentrations were 4.8 mu mol/L, with tertile levels as follows: first tertile (<3.9 mu mol/L), second tertile (3.9-5.6 mu mol/L), and third tertile (>5.6 mu mol/L). Patients with END showed higher levels of TMAO (median 5.0 vs. 4.5 mu mol/L, P = 0.005) at admission. In univariate logistic analysis, elevated plasma levels of TMAO [odd ratios for highest tertile vs. lowest tertile, 2.14; 95% confidence interval, 1.19-3.82] was a significant predictor of END in patients with ischemic stroke. This association remained significant after controlling for confounders in multivariate logistic analysis. Multiple-adjusted spline regression model further confirmed the dose-response relationship between TMAO levels and END (P < 0.001 for linearity). Conclusions: Our study indicated that increasing TMAO levels at admission might be associated with END after acute ischemic stroke.