title: Role of T-Cell Dysfunction, Inflammation, and Coagulation in Microvascular Disease in HIV.
abstract: Compared to uninfected adults, HIV-infected adults on antiretroviral therapy are at increased risk of cardiovascular disease. Given the increase in T-cell dysfunction, inflammation, and coagulation in HIV infection, microvascular dysfunction is thought to contribute to this excess cardiovascular risk. However, the relationships between these variables remain undefined.
  
  
  
  This was a cross-sectional study of 358 HIV-infected adults from the SCOPE cohort. Macrovascular endothelial function was assessed using flow-mediated dilation of the brachial artery and microvascular function by reactive hyperemia. T-cell phenotype was determined by flow cytometry. Plasma markers of inflammation (tumor necrosis factor-α, interleukin-6, high-sensitivity C-reactive protein, sCD14) and coagulation (fibrinogen, D-dimer) were also measured. In all HIV+ subjects, markers of inflammation (tumor necrosis factor-α, high-sensitivity C-reactive protein), coagulation (D-dimer) and T-cell activation (CD8+PD1+, CD4+interferon+cytomegalovirus-specific) were associated with worse reactive hyperemia after adjusting for traditional cardiovascular risk factors and co-infections. In treated and suppressed subjects, tumor necrosis factor-α and CD8+PD1+ cells remained associated with worse reactive hyperemia after adjustment. Compared to the untreated subjects, CD8+PD1+ cells were increased in the virally suppressed group. Reactive hyperemia was predictive of flow-mediated dilation.
  
  
  
  CD8+PD1+ cells and tumor necrosis factor-α were associated with microvascular dysfunction in all HIV+ subjects and the treated and suppressed group. Additionally, D-dimer, high-sensitivity C-reactive protein, sCD-14, and interleukin-6 were associated with microvascular dysfunction in all HIV+ subjects. Although T-cell dysfunction, inflammation, and microvascular dysfunction are thought to play a role in cardiovascular disease in HIV, this study is the first to look at which T-cell and inflammatory markers are associated with microvascular dysfunction in HIV-infected individuals.
authors.affiliation: Department of Medicine, University of California, San Francisco, CA.
authors.forename: Arjun
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Department of Medicine, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, CA.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Medicine, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, CA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Hur
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA.
authors.forename: Danny
authors.initials: D
authors.lastname: Li
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA.
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.affiliation: The Positive Health Program, San Francisco General Hospital, San Francisco, CA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA priscilla.hsue@ucsf.edu.
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hsue
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000276:immunology*; D001916:Brachial Artery / Q000276:immunology / Q000503:physiopathology; D002097:C-Reactive Protein / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000276:immunology; D005340:Fibrinogen / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D006940:Hyperemia; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008833:Microcirculation / Q000276:immunology*; D055806:Microvessels; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014664:Vasodilation
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C036309:fibrin fragment D; D005340:Fibrinogen; D002097:C-Reactive Protein
keywords: 
  HIV
  ; coagulation; immune system; inflammation; microcirculation