title: Endothelial dysfunction in young patients with long-term rheumatoid arthritis and low disease activity.
abstract: OBJECTIVE
  Cardiovascular mortality is excessive in patients with rheumatoid arthritis (RA). It has been proposed that the chronic inflammatory state of RA contributes to accelerated atherosclerosis. The aim of this study was to determine whether endothelial dysfunction, an early sign of arteriosclerosis, is present in young, long-term RA patients receiving standard methotrexate (MTX) therapy. Furthermore, we tested whether etanercept (ENC), a TNF-alpha receptor blocker, resulted in improved endothelial function compared to MTX in the same patients.
  
  
  METHODS
  We studied eight RA patients twice: (1) on MTX and (2) after MTX washout and receiving ENC. Eight healthy volunteers matching for age, gender, height, weight and conventional cardiovascular risk factors served as control (C). All participants received intrabrachial infusions of increasing doses of acetylcholine (ACh, endothelium-dependent vasodilator) and glyceryl-trinitrate (GTN, endothelium-independent vasodilator). Forearm blood flow (FBF) was measured by bilateral venous occlusion plethysmography.
  
  
  RESULTS
  Disease activity of RA was comparably low during both MTX and ENC (DAS 28 3.9+/-0.3 and 3.5+/-0.3). FBF in response to ACh was reduced in RA compared to C (P<0.01). Switching from MTX to ENC failed to improve vascular responsiveness to ACh. GTN comparably increased FBF in all groups.
  
  
  CONCLUSIONS
  Our study for the first time demonstrates that long-term RA is associated with manifested endothelial dysfunction. Switching from MTX to ENC in stable RA patients has no beneficial effect on endothelial function.
authors.affiliation: Medizinische Klinik III/Rheumatology, Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. haensel.s@debitel.net
authors.forename: Sven
authors.initials: S
authors.lastname: Hänsel
authors.forename: Grit
authors.initials: G
authors.lastname: Lässig
authors.forename: Frank
authors.initials: F
authors.lastname: Pistrosch
authors.forename: Jens
authors.initials: J
authors.lastname: Passauer
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D000068800:Etanercept; D005260:Female; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000502:physiology; D006710:Homocysteine / Q000097:blood / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D005996:Nitroglycerin / Q000008:administration & dosage; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects; D012720:Severity of Illness Index; D013995:Time; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D016387:Women's Health
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014665:Vasodilator Agents; D006710:Homocysteine; D005996:Nitroglycerin; D000109:Acetylcholine; D000068800:Etanercept; D008727:Methotrexate