Trimethylamine N-oxide is associated with long-term mortality risk: the multi-ethnic study of atherosclerosis.

Abstract

AIMS:

Little is known about associations of trimethylamine N-oxide (TMAO), a novel gut microbiota-generated metabolite of dietary phosphatidylcholine and carnitine, and its changes over time with all-cause and cause-specific mortality in the general population or in different race/ethnicity groups. The study aimed to investigate associations of serially measured plasma TMAO levels and changes in TMAO over time with all-cause and cause-specific mortality in a multi-ethnic community-based cohort.

METHODS AND RESULTS:

The study included 6,785 adults from the Multi-Ethnic Study of Atherosclerosis. TMAO was measured at baseline and year 5 using mass spectrometry. Primary outcomes were adjudicated all-cause mortality and cardiovascular disease (CVD) mortality. Secondary outcomes were deaths due to kidney failure, cancer, or dementia obtained from death certificates. Cox proportional hazards models with time-varying TMAO and covariates assessed the associations with adjustment for sociodemographics, lifestyles, diet, metabolic factors, and comorbidities. During a median follow-up of 16.9 years, 1704 participants died and 411 from CVD. Higher TMAO levels associated with higher risk of all-cause mortality [hazard ratio (HR): 1.12, 95% confidence interval (CI): 1.08-1.17], CVD mortality (HR: 1.09, 95% CI: 1.00-1.09), and death due to kidney failure (HR: 1.44, 95% CI: 1.25-1.66) per inter-quintile range, but not deaths due to cancer or dementia. Annualized changes in TMAO levels associated with higher risk of all-cause mortality (HR: 1.10, 95% CI: 1.05-1.14) and death due to kidney failure (HR: 1.54, 95% CI: 1.26-1.89) but not other deaths.

CONCLUSION:

Plasma TMAO levels were positively associated with mortality, especially deaths due to cardiovascular and renal disease, in a multi-ethnic US cohort.

• Authors: Meng Wang, Xinmin S Li, Zeneng Wang, Marcia C de Oliveira Otto, Rozenn N Lemaitre, Amanda Fretts, Nona Sotoodehnia, Matthew Budoff, Ina Nemet, Joseph A DiDonato, Wai Hong Wilson Tang, Bruce M Psaty, David S Siscovick, Stanley L Hazen, Dariush Mozaffarian
• Journal: European heart journal (Eur Heart J) Vol. 44 Issue 18 Pg. 1608-1618 (05 07 2023) ISSN: 1522-9645 [Electronic] England
• PMID: 36883587 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• trimethyloxamine
• Biomarkers
• Methylamines

Topics

• Adult
• Humans
• Risk Factors
• Biomarkers
• Methylamines (metabolism)
• Cardiovascular Diseases
• Renal Insufficiency (etiology)
• Atherosclerosis (complications)
• Neoplasms (complications)
• Dementia