Association of Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide with First Ischemic Stroke

J Atheroscler Thromb. 2021 Apr 1;28(4):320-328. doi: 10.5551/jat.55962. Epub 2020 Jul 9.

Abstract

Aim: We aimed to investigate the relationship of trimethylamine N-oxide (TMAO) concentrations with ischemic stroke in a large-scale case-control study conducted among the hospital-based general population.

Methods: We recruited 953 case-control sex- and age-matched pairs, and cases were confined to first acute ischemic stroke in this study. Fasting plasma TMAO was measured using high-performance liquid chromatography-tandem mass spectroscopy. Conditional logistic regression analysis was conducted to calculate odds ratios (OR) for the association of plasma TMAO with ischemic stroke.

Results: We found that plasma TMAO concentrations in patients with ischemic stroke were significantly higher than that in the control group (median: 2.85 µmol/L vs. 2.33 µmol/L, P<0.001). In multivariable conditional logistic regression models, higher plasma TMAO concentrations were associated with increased odds of ischemic stroke [fully adjusted OR for highest vs. lowest TMAO quartile: 1.81; 95% confidence interval (CI): 1.27, 2.59; P for trend <0.001]. The multivariable-adjusted OR for ischemic stroke per 1 µmol/L increment of plasma TMAO was 1.05 (95% CI: 1.02, 1.08). Additionally, the positive association also persisted in subgroups stratified by age, sex, body mass index, smoking status, alcohol habits, history of diabetes, and history of hypertension.

Conclusions: This study suggested a positive association between plasma TMAO and ischemic stroke. Further studies are required to explore the role of plasma TMAO concentrations in predicting stroke risk.

Keywords: Case–control study; Ischemic stroke; Trimethylamine N-oxide.

MeSH terms

  • Age Factors
  • Alcohol Drinking / epidemiology
  • Body Mass Index
  • Case-Control Studies
  • China / epidemiology
  • Chromatography, Liquid / methods
  • Correlation of Data
  • Diabetes Mellitus / epidemiology
  • Female
  • Humans
  • Hypertension / epidemiology
  • Ischemic Stroke* / blood
  • Ischemic Stroke* / diagnosis
  • Ischemic Stroke* / epidemiology
  • Male
  • Methylamines / blood*
  • Middle Aged
  • Risk Factors
  • Sex Factors
  • Smoking / epidemiology
  • Tandem Mass Spectrometry / methods

Substances

  • Methylamines
  • trimethyloxamine