Trimethylamine-N-oxide and 5-year mortality: the role of gut microbiota-generated metabolite from the CORE-Thailand cohort

Abstract

The gut microbiota metabolite trimethylamine-N-oxide (TMAO)—derived from dietary phosphatidylcholine—is mechanistically linked to cardiovascular disease (CVD) and increased cardiovascular risk. This study examined the relationship between fasting plasma TMAO levels and 5-year all-cause mortality in a cohort of patients at high risk of cardiovascular events (CORE-Thailand Registry). Of the 134 patients, 123 (92%) had established cardiovascular disease, and 11 (8%) had multiple risk factors. Fasting plasma TMAO levels were measured using nuclear magnetic resonance spectroscopy. Within this prospective cohort study, the median TMAO was 3.81 μM [interquartile range (IQR) 2.89–5.50 μM], with a mean age of 65 ± 11 years; 61% were men, and 39.6% had type II diabetes. Among 134 patients, 65 (49%) were identified as the high-TMAO group (≥ 3.8 μM), and 69 (51%) were identified as the low-TMAO group (< 3.8 μM). After a median follow-up of 58.8 months, the high-TMAO group was associated with a 2.88-fold increased mortality risk. Following adjustment for traditional risk factors, high-sensitivity cardiac troponin-T, estimated glomerular filtration rate, angiotensin-converting enzyme (ACEI), or angiotensin-receptor blocker (ARB) use, the high-TMAO group remained predictive of 5-year all-cause mortality risk (the high-TMAO vs. the low-TMAO group, adjusted hazard ratio 2.73, 95% CI 1.13–6.54; P = 0.025). Among Thai patients at high risk of cardiovascular events, increased plasma TMAO levels portended greater long-term mortality risk.