Association Between Plasma Trimethylamine N-Oxide (TMAO) Levels and Subclinical Atherosclerosis in Asymptomatic Adults

Background: Trimethylamine N-oxide (TMAO), a microbiota-derived metabolite in the gut, has recently become a putative biomarker of cardiovascular disease (CVD). Nonetheless, there is little evidence that plasma TMAO levels are linked with increased carotid intima-media thickness (CIMT) in individuals without symptoms. The study aimed to assess the association between plasma TMAO concentration and subclinical atherosclerosis in seemingly healthy adults. Methods: The study used a hospital-based cross-sectional observational design with asymptomatic adults aged 25 to 60 years without a known history of cardiovascular disease. There was a collection of demographic and clinical data, such as age, sex, body mass index (BMI), smoking status, hypertension, diabetes, and dyslipidemia. Venous blood samples were collected after fasting, and plasma TMAO was measured by enzyme-linked immunosorbent assay (ELISA). CIMT measured by ultrasound was used to assess subclinical atherosclerosis. Correlation and regression analyses were conducted to assess the association between TMAO and CIMT. Results: There was a strong, positive, and statistically significant correlation between plasma TMAO levels and CIMT (r = 0.771, p < 0.001). TMAO was also associated with age (r = 0.587) and BMI (r = 0.234), with moderate and weak associations, respectively. The multiple regression analysis showed that age had the strongest association with CIMT, followed by TMAO and BMI. Higher TMAO and CIMT levels were observed in males and in individuals with multiple cardiometabolic comorbidities (e.g., hypertension, diabetes, and dyslipidemia), as well as those with higher red meat intake. Conclusion: Plasma TMAO levels were significantly associated with increased CIMT in asymptomatic adults. These findings suggest a potential link between gut microbiota-derived metabolites and increased CIMT. However, due to the cross-sectional design, causality and predictive utility cannot be established, and longitudinal studies are required.