Trimethylamine N-Oxide and Lactate in Individuals With High and Low Atherogenic Risks

ABSTRACT Cardiovascular disease remains a leading cause of global mortality, with traditional lipid profiling serving as the cornerstone for atherogenic risk assessment. However, emerging evidence suggests that additional metabolic biomarkers may provide deeper insights into cardiovascular pathophysiology and risk stratification. This cross-sectional study investigated the relationship between serum concentrations of trimethylamine N-oxide (TMAO) and lactate in individuals stratified by atherogenic risk using triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratios. A total of 105 participants were enrolled and classified into low-risk (n=51) and high-risk (n=54) groups based on established TG/HDL-C ratio cut-off values. Comprehensive assessments included anthropometric measurements (weight, height, waist, hip, and neck circumferences), hemodynamic parameters (blood pressure and pulse rate), lipid profiles, liver function tests, and serum concentrations of TMAO and lactate. The study revealed significantly elevated serum TMAO concentrations in the high-risk group (242.13 ± 9.66 µmol/L) compared to low-risk individuals (229.40 ± 13.75 µmol/L; p = 0.026), suggesting a potential mechanistic link between gut microbiome-derived metabolites and atherogenic processes. Concurrently, lactate levels were significantly higher in high-risk participants (3.78 ± 2.53 mmol/L vs 3.53 ± 3.19 mmol/L; p = 0.009), which may reflect altered cellular metabolism, impaired mitochondrial function, or a shift toward anaerobic glycolysis in tissues of individuals with elevated cardiovascular risk. As expected, the high-risk group demonstrated a pronounced atherogenic lipid profile characterized by significantly elevated total cholesterol (6.81 ± 0.19 mmol/L vs 6.37 ± 0.10 mmol/L), triglycerides (2.79 ± 0.51 mmol/L vs 2.54 ± 0.21 mmol/L), LDL/HDL ratio (3.90 ± 0.17 vs 3.14 ± 0.09), and reduced HDL cholesterol (1.11 ± 0.01 mmol/L vs 1.25 ± 0.03 mmol/L). Interestingly, despite these metabolic differences, liver function parameters (AST, ALT, and AST/ALT ratios) remained comparable between groups, and most anthropometric measures showed no significant differences, with the notable exception of hip circumference, which was significantly lower in the high-risk group (97.2 ± 2.4 cm vs 103.4 ± 1.1 cm; p = 0.023), possibly indicating altered fat distribution xi patterns. These findings collectively suggest that TMAO and lactate may serve as valuable adjunctive metabolic biomarkers for cardiovascular risk assessment, potentially reflecting distinct pathophysiological processes including gut dysbiosis, endothelial dysfunction, and metabolic dysregulation that contribute to atherogenesis beyond conventional lipid abnormalities.