title: Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis.
abstract: BACKGROUND
  The excess in cardiovascular risk in patients with rheumatoid arthritis provides a strong rationale for early therapeutical interventions. In view of the similarities between atherosclerosis and rheumatoid arthritis and the proven benefit of angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease, it was the aim of the present study to delineate the impact of ramipril on endothelial function as well as on markers of inflammation and oxidative stress in patients with rheumatoid arthritis.
  
  
  RESULTS
  Eleven patients with rheumatoid arthritis were included in this randomized, double-blind, crossover study to receive ramipril in an uptitration design (2.5 to 10 mg) for 8 weeks followed by placebo, or vice versa, on top of standard antiinflammatory therapy. Endothelial function assessed by flow-mediated dilation of the brachial artery, markers of inflammation and oxidative stress, and disease activity were investigated at baseline and after each treatment period. Endothelial function assessed by flow-mediated dilation increased from 2.85+/-1.49% to 4.00+/-1.81% (P=0.017) after 8 weeks of therapy with ramipril but did not change with placebo (from 2.85+/-1.49% to 2.84+/-2.47%; P=0.88). Although systolic blood pressure and heart rate remained unaltered, diastolic blood pressure decreased slightly from 78+/-7 to 74+/-6 mm Hg (P=0.03). Tumor necrosis factor-alpha showed a significant inverse correlation with flow-mediated dilation (r=-0.408, P=0.02), and CD40 significantly decreased after ramipril therapy (P=0.049).
  
  
  CONCLUSIONS
  Angiotensin-converting enzyme inhibition with 10 mg/d ramipril for 8 weeks on top of current antiinflammatory treatment markedly improved endothelial function in patients with rheumatoid arthritis. This finding suggests that angiotensin-converting enzyme inhibition may provide a novel strategy to prevent cardiovascular events in these patients.
authors.affiliation: Cardiovascular Centre, Cardiology, University Hospital, Rämistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Flammer
authors.forename: Isabella
authors.initials: I
authors.lastname: Sudano
authors.forename: Frank
authors.initials: F
authors.lastname: Hermann
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
authors.forename: Adrian
authors.initials: A
authors.lastname: Forster
authors.forename: Michel
authors.initials: M
authors.lastname: Neidhart
authors.forename: Peter
authors.initials: P
authors.lastname: Künzler
authors.forename: Frank
authors.initials: F
authors.lastname: Enseleit
authors.forename: Daniel
authors.initials: D
authors.lastname: Périat
authors.forename: Matthias
authors.initials: M
authors.lastname: Hermann
authors.forename: Juerg
authors.initials: J
authors.lastname: Nussberger
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Luscher
authors.forename: Roberto
authors.initials: R
authors.lastname: Corti
authors.forename: Georg
authors.initials: G
authors.lastname: Noll
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000453:epidemiology; D050197:Atherosclerosis / Q000453:epidemiology / Q000517:prevention & control*; D015415:Biomarkers; D002478:Cells, Cultured; D018592:Cross-Over Studies; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects; D017257:Ramipril / Q000008:administration & dosage*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors; D016896:Treatment Outcome; D014471:Umbilical Veins / Q000166:cytology; D014657:Vasculitis / Q000453:epidemiology / Q000517:prevention & control*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D017257:Ramipril