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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Tang, WH Wilson 
Li, Xinmin S 
Wu, Yuping 
Wang, Zeneng 
Khaw, Kay-Tee 

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.

Description

Keywords

Aged, Case-Control Studies, Choline, Coronary Artery Disease, Correlation of Data, Female, Gastrointestinal Microbiome, Healthy Volunteers, Humans, Male, Methylamines, Middle Aged, Predictive Value of Tests, Prognosis, Risk Factors, United Kingdom

Journal Title

Am Heart J

Conference Name

Journal ISSN

0002-8703
1097-6744

Volume Title

236

Publisher

Elsevier BV
Sponsorship
Medical Research Council (G1000143)
Cancer Research Uk (None)
MRC (MC_UU_00006/1)
Medical Research Council (G0401527)
Medical Research Council (MR/N003284/1)
Medical Research Council (G0401527/1)