title: Associations among serum trimethylamine-N-oxide (TMAO) levels, kidney function and infarcted coronary artery number in patients undergoing cardiovascular surgery: a cross-sectional study.
abstract: BACKGROUND
  Trimethylamine-N-oxide (TMAO) is a metabolite of phosphatidylcholine generated by gut microbiota and liver enzymes, and has recently been recognized as contributing to atherosclerosis. Elevated serum TMAO levels have been shown to increase the risk of cardiovascular disease (sudden death, myocardial infarction, or stroke) in patients undergoing elective coronary angiography. We aimed to clarify whether TMAO levels are associated with the number of infarcted coronary arteries as a measure of the severity of atherosclerosis, with adjustment using a priori-defined covariates such as kidney function.
  
  
  METHODS
  By conducting a cross-sectional study of 227 patients who underwent cardiovascular surgery for coronary artery disease, valvular heart disease, or aortic disease, the association between serum TMAO levels as measured by HPLC-APCI-MS/MS and the number of infarcted coronary arteries was evaluated using ordered logistic regression models with adjustment of 10 covariates, including chronic kidney disease (CKD) stage. Unadjusted and adjusted odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were determined.
  
  
  RESULTS
  Significantly higher TMAO levels were observed in advanced-stage CKD (p ≤ 0.001). In fully adjusted models with the 10 covariates, a significantly increased number of infarcted coronary arteries was identified in the highest quartile and quintile of TMAO compared to the lowest quartile (OR 11.9; 95 % CI 3.88-36.7, p ≤ 0.001) and quintile (OR 14.1; 95 % CI 3.88-51.2; p ≤ 0.001), respectively, independent of dyslipidemia.
  
  
  CONCLUSIONS
  Higher serum TMAO levels may be associated with advanced CKD stages and with an increased number of infarcted coronary arteries in patients who undergo cardiovascular surgery.
authors.affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.|Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Mafune
authors.affiliation: Core Research Facilities, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.|Department of Anesthesiology, Intensive Care Unit, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tsutsumi
authors.affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.|Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Yamamoto
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yokoyama
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoo
authors.affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan. urashima@jikei.ac.jp.|Department of Molecular Epidemiology, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan. urashima@jikei.ac.jp.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Urashima
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D016017:Odds Ratio; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D012307:Risk Factors; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation; D014656:Vascular Surgical Procedures
chemical_list: D015415:Biomarkers; D008744:Methylamines; C005855:trimethyloxamine
keywords: Cardiovascular disease (CVD); Coronary artery disease (CAD); Glomerular filtration rate (GFR); Trimethylamine-N-oxide (TMAO)