title: Clinical improvement in rheumatoid arthritis is associated with healthier microvascular function in patients who respond to antirheumatic therapy.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) mortality. Microvascular endothelial dysfunction occurs early in the development of CV disease and is worsened by inflammation. The effect of drug treatment for RA on microvascular function has been poorly studied. We assessed the effect of antirheumatic treatment on microvascular endothelial function in patients with RA, particularly to examine responders versus nonresponders to therapy.
  
  
  METHODS
  Fifty-one patients with active RA and no previous history of CV disease were assessed at baseline and after 2 and 4 months' therapy with either anti-tumor necrosis factor-alpha drugs (etanercept, n = 27, adalimumab, n = 3) or methotrexate, n = 21. RA disease activity, inflammatory measures, and skin microvascular responses, measured using laser Doppler imaging after iontophoretic delivery of acetylcholine (ACh) and sodium nitroprusside (SNP), were assessed at each study visit.
  
  
  RESULTS
  Disease Activity Score (DAS28) decreased significantly from baseline to visit 2 and 3 (6.04 +/- 1.2, 4.34 +/- 1.3, 4 +/- 1.3, respectively; p < 0.0001). Endothelium-dependent (ACh) and independent (SNP) responses for the whole cohort did not improve significantly after drug treatment (p = 0.250, p = 0.062, respectively). When patients who responded to antirheumatic therapy (n = 31) were analyzed, there were significant improvements in both ACh (p = 0.028) and SNP responses (p = 0.019).
  
  
  CONCLUSIONS
  Microvascular endothelial function improves in patients who respond to antirheumatic therapy. These results support the importance of effective therapy for RA patients in terms of CV effects, which might extrapolate to reduced CV events in the future. Clinical trial registration no. ISRCTN57761809.
authors.affiliation: Vascular and Inflammatory Diseases Research Unit, Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland.
authors.forename: Bernat
authors.initials: B
authors.lastname: Galarraga
authors.forename: Jill J F
authors.initials: JJ
authors.lastname: Belch
authors.forename: Tom
authors.initials: T
authors.lastname: Pullar
authors.forename: Simon
authors.initials: S
authors.lastname: Ogston
authors.forename: Faisel
authors.initials: F
authors.lastname: Khan
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008833:Microcirculation / Q000502:physiology*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate