title: Anti-inflammatory treatment improves high-density lipoprotein function in rheumatoid arthritis.
abstract: Patients with rheumatoid arthritis (RA) are at increased cardiovascular risk. Recent studies suggest that high-density lipoprotein (HDL) may lose its protective vascular phenotype in inflammatory conditions. However, the effects of common anti-inflammatory treatments on HDL function are not yet known.
  
  
  
  We compared the function of HDL in 18 patients with RA and 18 matched healthy controls. Subsequently, patients were randomised to (methotrexate+infliximab (M+I) (5 mg/kg)) or methotrexate+placebo (M+P) infusions for 54 weeks. At week 54 and thereafter, all patients received infliximab therapy until completion of the trial (110 weeks), enabling assessment of the impact of 1 year of infliximab therapy in all patients. HDL functional properties were assessed at baseline, 54 weeks and 110 weeks by measuring the impact on endothelial nitric oxide (NO) bioavailability and superoxide production (SO), paraoxonase activity (PON-1) and cholesterol efflux.
  
  
  
  All HDL vascular assays were impaired in patients compared with controls. After 54 weeks, NO in response to HDL was significantly greater in patients who received M+I compared with those who received M+P. Endothelial SO in response to HDL was reduced in both groups, but PON-1 and cholesterol efflux remained unchanged. All vascular measures improved compared with baseline after ≥1 infliximab therapy in the analysis at 110 weeks. No significant trend was noted for cholesterol efflux.
  
  
  
  HDL function can be improved with anti-inflammatory treatment in patients with RA. The M+I combination was superior to the M+P alone, suggesting that the tumour necrosis factor-α pathway may have a role in HDL vascular properties.
authors.affiliation: Vascular Physiology Unit, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Francis
authors.initials: F
authors.lastname: O'Neill
authors.affiliation: Vascular Physiology Unit, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Marietta
authors.initials: M
authors.lastname: Charakida
authors.affiliation: Institute of Structural & Molecular Biology and London Centre for Nanotechnology, University College London, London, UK.
authors.forename: Eric
authors.initials: E
authors.lastname: Topham
authors.affiliation: Vascular Physiology Unit, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Eve
authors.initials: E
authors.lastname: McLoughlin
authors.affiliation: Vascular Physiology Unit, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Neha
authors.initials: N
authors.lastname: Patel
authors.affiliation: Vascular Physiology Unit, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Sutill
authors.affiliation: Institute of Structural & Molecular Biology and London Centre for Nanotechnology, University College London, London, UK.
authors.forename: Christopher W M
authors.initials: CWM
authors.lastname: Kay
authors.affiliation: Periodontology Unit, Department of Clinical Research, University College London Eastman Dental Institute, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: D'Aiuto
authors.affiliation: Department of Cardiology, Charite Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Taylor
authors.affiliation: Vascular Physiology Unit, Institute of Cardiovascular Science, University College London, London, UK.|National Institute for Cardiovascular Outcomes Research, University College London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Deanfield
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008075:Lipoproteins, HDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D008075:Lipoproteins, HDL; D000069285:Infliximab; D008727:Methotrexate