title: Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is a systemic inflammatory condition associated with increased cardiovascular risk. This is not fully explained by traditional risk factors, but direct vascular inflammation and aortic stiffening may play a role. We hypothesized that patients with RA exhibit aortic inflammation, which can be reversed with anti-tumor necrosis factor-α therapy and correlates with aortic stiffness reduction.
  
  
  RESULTS
  Aortic inflammation was quantified in 17 patients with RA, before and after 8 weeks of anti-tumor necrosis factor-α therapy by using (18)F-fluorodeoxyglucose positron emission tomography with computed tomography coregistration. Concomitantly, 34 patients with stable cardiovascular disease were imaged as positive controls at baseline. Aortic fluorodeoxyglucose target-to-background ratios (TBRs) and aortic pulse wave velocity were assessed. RA patients had higher baseline aortic TBRs in comparison with patients who have cardiovascular disease (2.02±0.22 versus 1.74±0.22, P=0.0001). Following therapy, aortic TBR fell to 1.90±0.29, P=0.03, and the proportion of inflamed aortic slices (defined as TBR >2.0) decreased from 50±33% to 33±27%, P=0.03. Also, TBR in the most diseased segment of the aorta fell from 2.51±0.33 to 2.05±0.29, P<0.0001. Treatment also reduced aortic pulse wave velocity significantly (from 9.09±1.77 to 8.63±1.42 m/s, P=0.04), which correlated with the reduction of aortic TBR (R=0.60, P=0.01).
  
  
  CONCLUSIONS
  This study demonstrates that RA patients have increased aortic (18)F-fluorodeoxyglucose uptake in comparison with patients who have stable cardiovascular disease. Anti-tumor necrosis factor-α therapy reduces aortic inflammation in patients with RA, and this effect correlates with the decrease in aortic stiffness. These results suggest that RA patients exhibit a subclinical vasculitis, which provides a mechanism for the increased cardiovascular disease risk seen in RA.
authors.affiliation: Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. km391@cam.ac.uk
authors.forename: Kaisa M
authors.initials: KM
authors.lastname: Mäki-Petäjä
authors.forename: Maysoon
authors.initials: M
authors.lastname: Elkhawad
authors.forename: Joseph
authors.initials: J
authors.lastname: Cheriyan
authors.forename: Francis R
authors.initials: FR
authors.lastname: Joshi
authors.forename: Andrew J K
authors.initials: AJ
authors.lastname: Ostör
authors.forename: Frances C
authors.initials: FC
authors.lastname: Hall
authors.forename: James H F
authors.initials: JH
authors.lastname: Rudd
authors.forename: Ian B
authors.initials: IB
authors.lastname: Wilkinson
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000473:pathology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D059289:Vascular Stiffness / Q000502:physiology*; D014657:Vasculitis / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept