title: Rheumatoid arthritis is associated with increased aortic pulse-wave velocity, which is reduced by anti-tumor necrosis factor-alpha therapy.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is associated with increased cardiovascular risk, which is not explained by traditional cardiovascular risk factors but may be due in part to increased aortic stiffness, an independent predictor of cardiovascular mortality. In the present study, our aim was to establish whether aortic stiffness is increased in RA and to investigate the relationship between inflammation and aortic stiffness. In addition, we tested the hypothesis that aortic stiffness could be reduced with anti-tumor necrosis factor-alpha (TNF-alpha) therapy.
  
  
  RESULTS
  Aortic pulse-wave velocity (PWV), augmentation index, and blood pressure were measured in 77 patients with RA and in 142 healthy individuals. Both acute and chronic inflammatory measures and disease activity were determined. The effect of anti-TNF-alpha therapy on PWV and endothelial function was measured in 9 RA patients at 0, 4, and 12 weeks. Median (interquartile range) aortic PWV was significantly higher in subjects with RA than in control subjects (8.35 [7.14 to 10.24] versus 7.52 [6.56 to 9.18] m/s, respectively; P = 0.005). In multiple regression analyses, aortic PWV correlated independently with age, mean arterial pressure, and log-transformed C-reactive protein (R2 = 0.701; P < 0.0001). Aortic PWV was reduced significantly by anti-TNF-alpha therapy (8.82+/-2.04 versus 7.94+/-1.86 versus 7.68+/-1.56 m/s at weeks 0, 4, and 12, respectively; P < 0.001); concomitantly, endothelial function improved.
  
  
  CONCLUSIONS
  RA is associated with increased aortic stiffness, which correlates with current but not historical measures of inflammation, suggesting that increased aortic stiffness may be reversible. Indeed, anti-TNF-alpha therapy reduced aortic stiffness to a level comparable to that of healthy individuals. Therefore, effective control of inflammation may be of benefit in reducing cardiovascular risk in patients with RA.
authors.affiliation: Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Box 110, Cambridge CB2 2QQ, United Kingdom.
authors.forename: Kaisa M
authors.initials: KM
authors.lastname: Mäki-Petäjä
authors.forename: Frances C
authors.initials: FC
authors.lastname: Hall
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Booth
authors.forename: Sharon M L
authors.initials: SM
authors.lastname: Wallace
authors.lastname: Yasmin
authors.forename: Philip W P
authors.initials: PW
authors.lastname: Bearcroft
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Harish
authors.forename: Anita
authors.initials: A
authors.lastname: Furlong
authors.forename: Carmel M
authors.initials: CM
authors.lastname: McEniery
authors.forename: John
authors.initials: J
authors.lastname: Brown
authors.forename: Ian B
authors.initials: IB
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure; D004198:Disease Susceptibility / Q000503:physiopathology; D004548:Elasticity; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007249:Inflammation / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000627:therapeutic use*; D012044:Regression Analysis; D012307:Risk Factors; D053319:Tumor Necrosis Factor Decoy Receptors
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D009363:Neoplasm Proteins; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D053319:Tumor Necrosis Factor Decoy Receptors; D000068800:Etanercept