title: Osteoprotegerin, but Not Receptor Activator for Nuclear Factor-κB Ligand, is Associated With Subclinical Coronary Atherosclerosis in HIV-Infected Men.
abstract: BACKGROUND
  Abnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease (CVD) pathogenesis in the general population.
  
  
  OBJECTIVE
  To determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis.
  
  
  METHODS
  Cross-sectional study nested within the Multicenter AIDS Cohort Study.
  
  
  METHODS
  Four US academic medical centers.
  
  
  METHODS
  There were 578 HIV-infected and 344 HIV-uninfected men.
  
  
  METHODS
  Coronary artery calcium (CAC) was measured by noncontrast cardiac computed tomography, and coronary stenosis and plaque characteristics (composition, presence, and extent) were measured by coronary computed tomography angiography. All statistical models were adjusted for traditional CVD risk factors.
  
  
  RESULTS
  OPG concentrations were higher, and RANKL concentrations were lower among HIV-infected men compared with HIV-uninfected men (P < 0.0001 each). Among HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis >50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with the extent of both CAC and calcified plaque, but not with their presence. RANKL concentrations were not associated with plaque presence or the extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque.
  
  
  CONCLUSIONS
  OPG and RANKL are dysregulated in HIV-infected men, and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men.
authors.affiliation: *Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; †Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; ‡Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA; §Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; and ‖Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA.
authors.forename: Kerunne S
authors.initials: KS
authors.lastname: Ketlogetswe
authors.forename: Rebeccah
authors.initials: R
authors.lastname: McKibben
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Xuihong
authors.initials: X
authors.lastname: Li
authors.forename: Adrian S
authors.initials: AS
authors.lastname: Dobs
authors.forename: Matthew
authors.initials: M
authors.lastname: Budoff
authors.forename: Mallory D
authors.initials: MD
authors.lastname: Witt
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Palella
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kingsley
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002118:Calcium / Q000032:analysis; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000150:complications*; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D014057:Tomography, X-Ray Computed; D014481:United States
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D002118:Calcium