Targeted Plasma Metabolomics Reveals Association of Acute Myocardial Infarction Risk with the Dynamic Balance between Trimethylamine-N-oxide, Betaine, and Choline

The relationship between trimethylamine-N-oxide (TMAO), betaine, and choline with acute myocardial infarction (AMI) end point remains unclear. We analyzed plasma TMAO, betaine, and choline concentrations in AMI cases and non-AMI community-dwelling controls by LC-MS/MS to understand how the balance between these metabolites helps to reduce AMI risk. Results showed that the odds ratio (OR) for the highest versus lowest quartiles of betaine was 0.30 (95% CI, 0.10–0.82) after adjustment for AMI risk factors, and the unadjusted OR for quartile 3 versus quartile 1 of TMAO was 2.47 (95% CI, 1.02–6.17) (p < 0.05). The study populations with "high betaine + low TMAO" had a significant protective effect concerning AMI with a multivariable-adjusted OR of 0.20 (95% CI, 0.07–0.55) (p < 0.01). Multivariate linear regression showed that the chronological age was correlated with TMAO concentrations among AMI patients (95% CI, 0.05–3.24, p < 0.01) but not among the controls. This implies a further potential interplay between age and metabolite combination─AMI risk association.