title: The cardiovascular risk marker asymmetric dimethylarginine is elevated in asymptomatic, untreated HIV-1 infection and correlates with markers of immune activation and disease progression.
abstract: BACKGROUND
  As lifespan in HIV infection increases, cardiovascular disease has emerged as a cause of morbidity and mortality. Asymmetric dimethylarginine is an established marker of endothelial dysfunction and predicts cardiovascular events. The role of asymmetric dimethylarginine in HIV-related cardiovascular disease has not been established. Our aim was to determine whether asymmetric dimethylarginine concentrations were elevated in treatment naïve, HIV-infected subjects and to correlate these with markers of immune activation and disease progression.
  
  
  METHODS
  Serum samples were collected from HIV-positive and -negative subjects attending a primary health care clinic over a 12-month period. Asymmetric dimethylarginine concentrations were measured and correlated with CD4 count, viral load, hsCRP, IL-6, IgG, adenosine deaminase and CD8/38 T lymphocytes.
  
  
  RESULTS
  Sixty HIV-positive participants (mean age 32.0 years) and 20 HIV-negative controls (mean age 32.4 years) were studied. All were of black ethnicity. The mean asymmetric dimethylarginine concentration in the infected group measured 0.67 µmol/L (95% CI 0.62-0.72 µmol/L) which was significantly higher than in the control group of 0.48 µmol/L (95% CI 0.40-0.56 µmol/L). Asymmetric dimethylarginine correlated inversely with CD4 counts and positively with IgG, adenosine deaminase and CD8/38 T lymphocytes. No significant correlation was found with hsCRP, IL-6, or viral load.
  
  
  CONCLUSIONS
  We demonstrated that asymmetric dimethylarginine is elevated in HIV infection, in patients with relatively well-preserved CD4 counts not yet on anti-retroviral treatment. We showed significant correlations of asymmetric dimethylarginine with CD8/38 T lymphocytes, IgG and adenosine deaminase, suggesting that T-cell activation and the adaptive immune response underlie asymmetric dimethylarginine elevation in this population.
authors.affiliation: Division of Chemical Pathology, Department of Pathology, University of Stellenbosch and NHLS, Tygerberg Hospital, South Africa.
authors.forename: Careen L
authors.initials: CL
authors.lastname: Hudson
authors.affiliation: Division of Chemical Pathology, Department of Pathology, University of Stellenbosch and NHLS, Tygerberg Hospital, South Africa azemlin@sun.ac.za.
authors.forename: Annalise E
authors.initials: AE
authors.lastname: Zemlin
authors.affiliation: Division of Haematology, Department of Pathology, University of Stellenbosch and NHLS, Tygerberg Hospital, South Africa.
authors.forename: Hayley
authors.initials: H
authors.lastname: Ipp
mesh_terms: D000243:Adenosine Deaminase / Q000097:blood; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000276:immunology; D006679:HIV Seropositivity; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D019562:Viral Load
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D007074:Immunoglobulin G; D015850:Interleukin-6; C018524:N,N-dimethylarginine; D001120:Arginine; D000243:Adenosine Deaminase
keywords: Cardiovascular risk; HIV infection; endothelial dysfunction; inflammation