title: Plasma Trimethylamine N-Oxide, a Gut Microbe-Generated Phosphatidylcholine Metabolite, Is Associated With Atherosclerotic Burden.
abstract: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is associated with adverse outcomes.
  
  
  
  This study sought to examine the relationship between plasma TMAO levels and the complexity and burden of CAD and degree of subclinical myonecrosis.
  
  
  
  We studied 353 consecutive stable patients with evidence of atherosclerotic CAD detected by elective coronary angiography between 2012 and 2014. Their high-sensitivity cardiac troponin T (hs-cTnT) levels were measured. SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) scores and lesion characteristics were used to quantify atherosclerotic burden. Fasting plasma TMAO was measured by mass spectrometry.
  
  
  
  In this prospective cohort study, the median TMAO level was 5.5 μM (interquartile range [IQR]: 3.4 to 9.8 μM), the median SYNTAX score was 11.0 (IQR: 4.0 to 18.5), and 289 (81.9%), 40 (11.3%), and 24 (6.8%) patients had low (0 to 22), intermediate (23 to 32), and high (≥33) SYNTAX scores, respectively. Plasma TMAO levels correlated (all p < 0.0001) with the SYNTAX score (r = 0.61), SYNTAX score II (r = 0.62), and hs-cTnT (r = 0.29). Adjusting for traditional risk factors, body mass index, medications, lesion characteristic, renal function, and high-sensitivity C-reactive protein, elevated TMAO levels remained independently associated with a higher SYNTAX score (odds ratio [OR]: 4.82; p < 0.0001), SYNTAX score II (OR: 1.88; p = 0.0001), but were not associated with subclinical myonecrosis (OR: 1.14; p = 0.3147). Elevated TMAO level was an independent predictor of the presence of diffuse lesions, even after adjustments for traditional risk factors and for hs-cTnT (OR: 2.05; 95% confidence interval: 1.45 to 2.90; p = 0.0001).
  
  
  
  Fasting plasma TMAO levels are an independent predictor of a high atherosclerotic burden in patients with CAD.
authors.affiliation: Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; Queen Sirikit Heart Center of the Northeast, Department of Medicine, Faculty of Medicine, Khon Kaen University, Thailand.
authors.forename: Vichai
authors.initials: V
authors.lastname: Senthong
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Xinmin S
authors.initials: XS
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Timothy
authors.initials: T
authors.lastname: Hudec
authors.affiliation: Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: John
authors.initials: J
authors.lastname: Coughlin
authors.affiliation: Department of Mathematics, Cleveland State University, Cleveland, Ohio.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Bruce
authors.initials: B
authors.lastname: Levison
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Zeneng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.affiliation: Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: tangw@ccf.org.
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D012720:Severity of Illness Index; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D008744:Methylamines; D020107:Troponin T; C005855:trimethyloxamine
keywords: SYNTAX score; diffuse; focal; myonecrosis; risk factors; troponin T