title: Factors associated with D-dimer levels in HIV-infected individuals.
abstract: BACKGROUND
  Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood.
  
  
  METHODS
  In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol.
  
  
  RESULTS
  Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels.
  
  
  CONCLUSIONS
  D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels.
authors.affiliation: Centre for Health & Infectious Diseases Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Alvaro H
authors.initials: AH
authors.lastname: Borges
authors.affiliation: Research Department of Infection and Population Health, University College London, London, United Kingdom.
authors.forename: Jemma L
authors.initials: JL
authors.lastname: O'Connor
authors.affiliation: Research Department of Infection and Population Health, University College London, London, United Kingdom.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.affiliation: Hennepin County Medical Center, Minneapolis, Minnesota, United States of America; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Jason V
authors.initials: JV
authors.lastname: Baker
authors.affiliation: Veterans Affairs Medical Center, Washington, D. C., United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Vjecha
authors.affiliation: Hospital JM Ramos Mejia, Buenos Aires, Argentina.
authors.forename: Marcelo H
authors.initials: MH
authors.lastname: Losso
authors.affiliation: University of Würzburg Medical Center, Würzburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Klinker
authors.affiliation: Fundación Centro de Estudios Infectológicos, Buenos Aires, Argentina.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Lopardo
authors.affiliation: Centre for Sexual Health & HIV Research, University College London, London, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Williams
authors.affiliation: Centre for Health & Infectious Diseases Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000821:virology; D003430:Cross-Sectional Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D015658:HIV Infections / Q000097:blood* / Q000401:mortality; D006505:Hepatitis / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012737:Sex Factors; D019562:Viral Load
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C508600:IL6 protein, human; D015850:Interleukin-6; C036309:fibrin fragment D; D002097:C-Reactive Protein