title: Endothelial function is impaired in HIV-infected patients with lipodystrophy.
abstract: BACKGROUND
  Data supporting a link between body-fat distribution changes and cardiovascular disease risk in HIV-infected patients are scarce and contradictory. We evaluated endothelial dysfunction, an early event in the development of atherosclerosis, and pro-atherosclerotic plasma biomarkers in HIV-infected patients with lipodystrophy.
  
  
  METHODS
  HIV-infected patients with and without lipodystrophy were prospectively enrolled. Endothelial function was measured through flow-mediated dilatation (FMD) of the brachial artery. Plasma levels of several biomarkers of inflammation, endothelial activation and coagulation associated with adipose tissue and endothelial dysfunction were determined.
  
  
  RESULTS
  The study included 110 patients, 55 of them with lipodystrophy. FMD was significantly lower in patients with lipodystrophy than in those without lipodystrophy (median [IQR] 3.1% [0.4-8.9] versus 6.3% [3.3-10.7]; P=0.004). Patients with isolated lipoatrophy exhibited the lowest FMD (2.6% [0-6.6]; P(Kruskal-Wallis)=0.02). Lipodystrophy was associated with significantly higher plasma levels of interleukin 6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1) and lower levels of adiponectin; severe lipodystrophy was associated with higher concentrations of vascular cell adhesion molecule 1 (sVCAM-1). There was an inverse correlation between FMD and IL-6 (Spearman's rho =-0.26; P=0.007). In a multivariate regression model with the lowest quartile of FMD as the dependent variable and lipodystrophy, traditional cardiovascular risk factors, 10-year Framingham risk score, pro-atherosclerotic biomarkers and HIV-related variables as predictors, the only independent predictor of endothelial dysfunction was lipodystrophy (odds ratio 5.22, 95% confidence interval 1.76-15.46; P=0.003).
  
  
  CONCLUSIONS
  Lipodystrophy is associated with endothelial dysfunction, independently of the presence of traditional cardiovascular risk factors. This finding and the accompanying profile of pro-atherosclerotic biomarkers support an increased cardiovascular risk in HIV-infected patients with lipodystrophy.
authors.affiliation: Infectious Diseases Unit, Hospital General Universitario de Elche, Department of Clinical Medicine, University Miguel Hernández, Elche, Alicante, Spain. marmasia@ya.com
authors.forename: Mar
authors.initials: M
authors.lastname: Masiá
authors.forename: Sergio
authors.initials: S
authors.lastname: Padilla
authors.forename: Natalia
authors.initials: N
authors.lastname: García
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Jarrin
authors.forename: Enrique
authors.initials: E
authors.lastname: Bernal
authors.forename: Natividad
authors.initials: N
authors.lastname: López
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Hernández
authors.forename: Félix
authors.initials: F
authors.lastname: Gutiérrez
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D050218:Body Fat Distribution; D001916:Brachial Artery / Q000166:cytology / Q000503:physiopathology; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011446:Prospective Studies; D012307:Risk Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D019010:Vascular Cell Adhesion Molecule-1