title: Microbiota-Dependent Marker TMAO Is Elevated in Silent Ischemia but Is Not Associated With First-Time Myocardial Infarction in HIV Infection.
abstract: OBJECTIVE
  HIV infection is associated with increased risk of coronary heart disease beyond that explained by traditional risk factors, and altered gut microbiota has been proposed as a potential trigger. Trimethylamine-N-oxide (TMAO) is a proatherogenic substance formed in the liver from trimethylamine, exclusively generated by gut microbiota from dietary phosphatidylcholine. We aimed to investigate whether TMAO is associated with subclinical and clinical coronary heart disease in HIV infection.
  
  
  METHODS
  Two previously described cohorts were examined as follows: (1) cross-sectional cohort of HIV-infected persons and uninfected controls with known atherosclerotic plaque burden as assessed by myocardial perfusion scintigraphy, coronary artery calcium score, and intima-media thickness and (2) nested case-control study of HIV-infected persons with first-time myocardial infarction (MI) compared with HIV-infected persons without MI, assessed at 4 time points from before initiation of antiretroviral therapy (ART) to last sample before the case's MI (median: 51, range: 0-239 days).
  
  
  RESULTS
  There was no difference in plasma TMAO when comparing HIV-infected persons and uninfected controls. TMAO was elevated in HIV-infected persons with myocardial perfusion defects but was not associated with coronary artery calcium score, intima media thickness, or Framingham risk score. In the nested case control study, plasma TMAO was not associated with first-time MI. However, TMAO increased after ART introduction and was associated with the use of protease inhibitors in both cohorts.
  
  
  CONCLUSIONS
  TMAO was elevated in HIV-infected persons with myocardial perfusion defects, but was not associated with first-time MI. Our data question TMAO as a useful biomarker of cardiovascular risk in HIV infection, at least in ART-treated individuals.
authors.affiliation: *Department of Infectious Diseases; †Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen; ‡Department of Infectious Diseases, Hvidovre University Hospital, Copenhagen, Denmark; §Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet; ‖Department of Clinical Science, University of Bergen; ¶Department of Heart Disease, Haukeland University Hospital; #Research Institute of Internal Medicine; **Institute of Clinical Medicine; ††K.G. Jebsen Inflammatory Research Center; and ‡‡Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Haissman
authors.forename: Andreas
authors.initials: A
authors.lastname: Knudsen
authors.forename: Hedda
authors.initials: H
authors.lastname: Hoel
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjær
authors.forename: Ulrik S
authors.initials: US
authors.lastname: Kristoffersen
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
authors.forename: Terese L
authors.initials: TL
authors.lastname: Katzenstein
authors.forename: Asbjørn
authors.initials: A
authors.lastname: Svardal
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Anne-Mette
authors.initials: AM
authors.lastname: Lebech
authors.forename: Susanne D
authors.initials: SD
authors.lastname: Nielsen
authors.forename: Marius
authors.initials: M
authors.lastname: Trøseid
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000150:complications / Q000382:microbiology; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000382:microbiology; D006801:Humans; D007511:Ischemia / Q000150:complications* / Q000382:microbiology; D008297:Male; D008744:Methylamines / Q000378:metabolism*; D064307:Microbiota; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications* / Q000382:microbiology; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000382:microbiology; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008744:Methylamines; C005855:trimethyloxamine; C023336:trimethylamine