Journal Article

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

Wang, Zeneng, Nieuwdorp, Max, Hazen, Stanley L., Tang, W.H. Wilson, Khaw, Kay-Tee, Wu, Yuping, Wareham, Nicholas J., Li, Xinmin S., Boekholdt, S. Matthijs

2021

Overview

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. 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). 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.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Aged / Arteriosclerosis / Atherosclerosis / Betaine / Cardiovascular disease / Cardiovascular diseases / Case-Control Studies / Chemical vapor deposition / Choline / Choline - blood / Chromatography / Confidence intervals / Coronary artery / Coronary artery disease / Coronary Artery Disease - diagnosis / Coronary Artery Disease - epidemiology / Coronary Artery Disease - metabolism / Coronary vessels / Correlation of Data / Female / Gastrointestinal Microbiome - physiology / Health risks / Healthy Volunteers / Heart diseases / Hospitals / Humans / Intestinal microflora / Investigations / Male / Mass spectrometry / Metabolism / Metabolites / Methylamines - blood / Microbiota / Middle age / Middle Aged / Mortality / Nutrients / Plasma / Plasma levels / Population studies / Population-based studies / Precursors / Predictive Value of Tests / Prognosis / Risk analysis / Risk Factors / Scientific imaging / Thromboembolism / Thrombosis / Trimethylamine / United Kingdom - epidemiology