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

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 to 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.