Association of the trimethylamine N-oxide with cardiovascular risk and vascular alterations in middle-aged patients with risk factors for cardiovascular diseases

Biosci Rep. 2024 Apr 29;44(5):BSR20232090. doi: 10.1042/BSR20232090.

Abstract

Background: Trimethylamine N-oxide (TMAO) is synthesized by the intestinal microbiota and is an independent predictor of cardiovascular disease (CVD). However, its underlying mechanisms remain unclear. We investigated TMAO levels across different CVD-risk patient groups, and evaluated associations between TMAO and vascular alterations (e.g., arterial stiffness, intima-media thickness [IMT], and the presence and grade of carotid artery plaques [CAPs]).

Methods: We examined 95 patients (58.5 ± 7.3 years): 40 with clinical atherosclerotic cardiovascular disease (ASCVD), 40 with atherosclerosis risk factors (RF), and 15 controls. Arterial stiffness was measured by Carotid-Femoral Pulse Wave Velocity (C-F PWV). B-mode ultrasound was used to evaluate the presence and grade of CAPs and carotid IMT (CIMT). TMAO was measured by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and results were presented as the median (interquartile range).

Results: TMAO levels were higher in patients with ASCVD (251.5 [164.5] µg/l) when compared with patients with RFs (194.0 [174] µg/l, P=0.04) and controls (122.0 (77) µg/l, P<0.001). A significant correlation was observed between TMAO and PWV (r = 0.31, P=0.003), which was not confirmed after adjustment for RFs. TMAO levels were significantly correlated with plaque score (r = 0.46, P<0.001) and plaque height (r=0.41, P=0.003), and were independent predictors for grade III plaques (odds ratio [OR] = 1.002, confidence interval (CI) 95%: 1.000047-1.003, P=0.044).

Conclusions: TMAO levels are increased with expanded CVD risk. Across different types of vascular damage, TMAO is associated with atherosclerotic changes.

Keywords: Arterial Stiffness; Atherosclerosis risk factors; Carotid artery plaques; Intestinal Microbiota; Trimethylamine N-oxide.

MeSH terms

  • Aged
  • Atherosclerosis / blood
  • Atherosclerosis / diagnostic imaging
  • Biomarkers / blood
  • Cardiovascular Diseases* / etiology
  • Carotid Artery Diseases / blood
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Intima-Media Thickness*
  • Case-Control Studies
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Male
  • Methylamines* / blood
  • Middle Aged
  • Plaque, Atherosclerotic
  • Risk Factors
  • Vascular Stiffness*

Substances

  • Methylamines
  • trimethyloxamine
  • Biomarkers