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

• Published in: The American heart journal Vol. 236; pp. 80 - 86
• Main Authors: Tang, W.H. Wilson, Li, Xinmin S., Wu, Yuping, Wang, Zeneng, Khaw, Kay-Tee, Wareham, Nicholas J., Nieuwdorp, Max, Boekholdt, S. Matthijs, Hazen, Stanley L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2021; Elsevier Limited
• Subjects: 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; United Kingdom; United Kingdom > UK; Europe
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2021.01.020

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.