Plasma trimethylamine N-oxide (TMAO) levels predict future risk of coronary artery disease in apparently healthy individuals in the EPIC-Norfolk prospective population study.

Abstract

BACKGROUND:

Recent studies show a mechanistic link between gut microbiota-dependent formation of the atherosclerosis- and thrombosis-promoting metabolite trimethylamine N-oxide (TMAO) and cardiovascular disease (CVD). The clinical utility of TMAO in apparently healthy subjects for predicting incident CVD risks is unclear.

METHODS AND RESULTS:

In the EPIC-Norfolk community-based study, we examined baseline fasting levels of TMAO and two of its nutrient precursors, choline and betaine, in a case:control design study comparing apparently European healthy middle-aged participants who subsequently develop CVD (Cases, n = 908) vs those who did not (Controls, n = 1,273) over an ensuing average follow-up period of 8 years. In participants who developed CVD vs controls, higher plasma TMAO (3.70 [IQR 2.50-6.41]μM vs 3.25 [IQR 2.19-52,1.15]μM; P < .001) and choline levels (9.09 [IQR 7.87-10.53]μM vs 8.89 [IQR 7.66-10.13]μM; P = .001) were observed. Following adjustments for traditional risk factors, elevated TMAO (adjusted odds ratio (OR) 1.58 [95% confidence interval (CI) 1.21-2.06], P < .001) and choline levels (adjusted OR 1.31 [95%CI 1.00-1.72], P < .05) remained predictive of incident CVD development. The clinical prognostic utility of TMAO remained significant and essentially unchanged regardless of the level of cutoff chosen between 1.5 uM (10%ile) to 10.5 uM (90%ile).

CONCLUSION:

In apparently healthy participants of the community-based middle-aged EPIC-Norfolk population, elevated plasma levels of the gut microbe-dependent metabolite TMAO, and its nutrient precursor choline, predict incident risk for CVD development independent of traditional risk factors.

• Authors: W H Wilson Tang, Xinmin S Li, Yuping Wu, Zeneng Wang, Kay-Tee Khaw, Nicholas J Wareham, Max Nieuwdorp, S Matthijs Boekholdt, Stanley L Hazen
• Journal: American heart journal (Am Heart J) Vol. 236 Pg. 80-86 (06 2021) ISSN: 1097-6744 [Electronic] United States
• PMID: 33626384 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Methylamines
• trimethyloxamine
• Choline

Topics

• Aged
• Case-Control Studies
• Choline (blood)
• Coronary Artery Disease (diagnosis, epidemiology, metabolism)
• Correlation of Data
• Female
• Gastrointestinal Microbiome (physiology)
• Healthy Volunteers
• Humans
• Male
• Methylamines (blood)
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Risk Factors
• United Kingdom (epidemiology)