title: Plasma levels of trimethylamine-N-oxide are confounded by impaired kidney function and poor metabolic control.
abstract: BACKGROUND
  After ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk.
  
  
  METHODS
  A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease.
  
  
  RESULTS
  Betaine concentrations in males were significantly higher than in females (42.0 vs. 35.9 μmol/L; p < 0.001). Plasma concentrations of TMAO but not of betaine or choline were higher in patients with diabetes compared to euglycemic patients (2.39 vs. 0.980 μmol/L; p = 0.001) as well as in patients with metabolic syndrome as compared to patients without metabolic syndrome (2.37 vs. 1.43 μmol/L; p = 0.002). Plasma concentrations of TMAO or choline increased significantly with decreasing renal function (Spearman's rho: -0.281; p < 0.001). However, plasma levels of TMAO or betaine were associated with neither a history of myocardial infarction nor the angiographically assessed presence of coronary heart disease, nor incident cardiovascular events during 8 years of follow-up. Plasma levels of choline were significantly lower in patients with a history of acute myocardial infarction as compared to those without such history (10.0 vs. 10.8 μmol/L; p = 0.045).
  
  
  CONCLUSIONS
  Plasma levels of TMAO are confounded by impaired kidney function and poor metabolic control but are not associated with the history, presence or incidence of symptoms or events of coronary heart disease.
authors.affiliation: Institute of Clinical Chemistry, University Hospital and University of Zurich, Zurich, Switzerland.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Mueller
authors.affiliation: Institute of Clinical Chemistry, University Hospital and University of Zurich, Zurich, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Allenspach
authors.affiliation: Institute of Clinical Chemistry, University Hospital and University of Zurich, Zurich, Switzerland; Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
authors.forename: Alaa
authors.initials: A
authors.lastname: Othman
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Saely
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors.forename: Axel
authors.initials: A
authors.lastname: Muendlein
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors.forename: Alexander
authors.initials: A
authors.lastname: Vonbank
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Heinz
authors.initials: H
authors.lastname: Drexel
authors.affiliation: Institute of Clinical Chemistry, University Hospital and University of Zurich, Zurich, Switzerland. Electronic address: arnold.voneckardstein@usz.ch.
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
mesh_terms: D000368:Aged; D001622:Betaine / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002794:Choline / Q000097:blood; D002853:Chromatography, Liquid; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008744:Methylamines; D001622:Betaine; C005855:trimethyloxamine; D002794:Choline
keywords: Betaine; Cardiovascular risk; Choline; Kidney function; Metabolic control; TMAO