Abstract
Background: This study investigated the value of trimethylamine oxide (TMAO) and its precursors in secondary prevention for patients with acute myocardial infarction (AMI). Methods: We retrospectively enrolled patients diagnosed with AMI. The associations of TMAO and its precursors with endpoint events were estimated by Cox proportional hazards models. Results: During a median follow-up of 6.4 years, 319 (32.0%) major adverse cardiovascular event (MACE) occurred in the 996 patients enrolled. After adjusting for traditional risk factors, the risk of MACE, cardiac death, and recurrent MI increased by 28% (HR 1.28, 95% CI 1.10-1.49), 44% (HR 1.44, 95% CI 1.12-1.84), and 27% (HR 1.27, 95% CI 1.04-1.55), respectively, per one increment in ln-transformed TMAO. After adjustment for the levels of its precursors, the relationship between TMAO and MACE was still significant. Choline was associated with MACEs, all-cause mortality, cardiac death, and risk of recurrent MI after adjusting for the levels of the remaining metabolites, in addition to traditional risk factors. The overall ability to predict all-cause mortality was better for the choline model than for the TMAO model (continuous NRI 0.185, p = 0.007; IDI 0.030, p = 0.020). Mediation effect analysis showed that the mediating effect of TMAO on choline and the risk of all-cause mortality was 11.39% (95% CI 0.0209-0.2200, p = 0.016), suggesting the existence of a choline activity pathway that is independent of the TMAO pathway. Conclusions: TMAO and choline were associated with an increased risk of MACE in patients with AMI, and choline had better predictive power.