title: Relationship between total bilirubin and endothelial function, inflammation and oxidative stress in HIV-infected adults on stable antiretroviral therapy.
abstract: OBJECTIVE
  Enhanced inflammation is evident in HIV infection, even with virological suppression. Outside HIV infection, studies show an independent association between higher total bilirubin and better endothelial function as well as a lower prevalence of coronary heart disease, possibly as a consequence of the anti-inflammatory and antioxidant effect of bilirubin. The aim of this study was to determine whether such an association exists in HIV-infected individuals.
  
  
  METHODS
  A cross-sectional study was performed in HIV-1-infected adults on stable antiretroviral therapy (ART) to determine if a relationship exists between total bilirubin and endothelial function [flow-mediated dilation (FMD) of the brachial artery], inflammation [interleukin-6 (IL-6), soluble tumour necrosis factor receptors, C-reactive protein, and adhesion molecules], coagulation markers (fibrinogen and D-dimer) and oxidative stress (F (2) -isoprostanes). Endpoints were compared based on total bilirubin levels and atazanavir status using distributionally appropriate, two-sample tests. Correlation coefficients were determined between total bilirubin and endpoints. Linear regression was used to model the relationship between total bilirubin (and atazanavir status) and FMD.
  
  
  RESULTS
  A total of 98 adults were included in the study. Total bilirubin was higher in the atazanavir group when compared to the non-atazanavir group [median (interquartile range) 1.8 (1.1-2.6) vs. 0.6 (0.4-1.4) mg/dL; P < 0.01] as were insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) and fibrinogen. Total bilirubin was positively correlated with fibrinogen and was not correlated with other outcomes. After adjustment, neither total bilirubin nor atazanavir status was associated with FMD.
  
  
  CONCLUSIONS
  In virologically suppressed, HIV-infected adults on stable ART, neither total bilirubin nor atazanavir use was associated with improved endothelial function as measured using FMD, inflammation or oxidative stress as measured using biomarkers.
authors.affiliation: MetroHealth Medical Center, Cleveland, OH 44106, USA.
authors.forename: Co
authors.initials: C
authors.lastname: Hileman
authors.forename: Ct
authors.initials: C
authors.lastname: Longenecker
authors.forename: Tl
authors.initials: T
authors.lastname: Carman
authors.forename: Gl
authors.initials: G
authors.lastname: Milne
authors.forename: D E
authors.initials: DE
authors.lastname: Labbato
authors.forename: Nj
authors.initials: Nj
authors.lastname: Storer
authors.forename: Ca
authors.initials: C
authors.lastname: White
authors.forename: Ga
authors.initials: G
authors.lastname: McComsey
mesh_terms: D000328:Adult; D000069446:Atazanavir Sulfate; D001663:Bilirubin / Q000097:blood*; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006679:HIV Seropositivity / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014664:Vasodilation
chemical_list: D015815:Cell Adhesion Molecules; D028441:F2-Isoprostanes; D005338:Fibrin Fibrinogen Degradation Products; D017320:HIV Protease Inhibitors; D015850:Interleukin-6; D009842:Oligopeptides; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C036309:fibrin fragment D; D000069446:Atazanavir Sulfate; D005340:Fibrinogen; D002097:C-Reactive Protein; D001663:Bilirubin