From Gut to Heart: TMAO as a Predictive Marker for Cardiovascular Risk

Background: Trimethylamine N-oxide (TMAO), a metabolite produced by gut microbiota from dietary nutrients such as choline and carnitine, has emerged as a potential biomarker linking the gut microbiome to cardiovascular disease (CVD). This review synthesizes findings from 31 studies examining the association between circulating TMAO levels and cardiovascular outcomes. Objective: To evaluate the prognostic value of plasma or serum TMAO concentrations in predicting major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular mortality. Methods: Studies were identified through a systematic search and screened based on inclusion criteria that required human populations, quantification of blood-based TMAO, and analysis of cardiovascular outcomes. A total of 31 studies published in the last 5 years were included. Results: Elevated TMAO levels were consistently associated with increased risk of cardiovascular events across both general and high-risk populations, including individuals with coronary artery disease, heart failure, and diabetes. Hazard ratios for adverse outcomes ranged from 1.5 to 3.5 in most studies, even after adjustment for traditional risk factors such as lipid levels and renal function. Some studies also observed additive risk when TMAO elevation coexisted with metabolic comorbidities. Conclusion: TMAO demonstrates strong potential as an independent biomarker for cardiovascular risk stratification. Its integration into clinical practice could enhance precision prevention strategies. However, further research is needed to standardize cut-off levels and explore whether interventions that reduce TMAO levels can improve outcomes.