title: Mycophenolate mofetil for secondary prevention of cardiac allograft vasculopathy: influence on inflammation and progression of intimal hyperplasia.
abstract: BACKGROUND
  Cardiac allograft vasculopathy (CAV) remains the single most important complication impairing long-term survival after heart transplantation (HTx). Intimal hyperplasia as a response to immunologic and non-immunologic injury is involved in the pathogenesis. Because improved immunosuppressive properties with mycophenolate mofetil (MMF) have been shown within the first year, beneficial effects on intimal hyperplasia and systemic inflammation might be found late after HTx as well.
  
  
  METHODS
  After a baseline examination with intravascular ultrasound (IVUS, volumetric assessment) 30 patients (2.0 +/- 1.1 years post-HTx) were prospectively randomized to receive either MMF (2 g/day) or to continue with azathioprine (AZA) as part of a triple immunosuppression protocol with cyclosporine and prednisolone. Markers of systemic inflammation and changes in vascular geometry were evaluated by IVUS after 1 year of follow-up.
  
  
  RESULTS
  With regard to inflammation, significantly lower values were found for high-sensitive C-reactive protein (CRP) in the MMF group (AZA 1.8 +/- 1.2 mg/liter. vs MMF 1.0 +/- 4.1 mg/liter, p = 0.02). Tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6 and transforming growth factor (TGF)-beta did not differ between the groups. IVUS revealed no significant differences between groups. There was a weak trend toward a larger increase in plaque volume (AZA 13 +/- 43 mm(3) vs MMF 27 +/- 41 mm(3), p = 0.33), whereas MMF-treated patients tended to show a small increase in vessel dimensions (AZA +10 +/- 63 mm(3) vs MMF +50 +/- 87 mm(3), p = 0.17).
  
  
  CONCLUSIONS
  Changing immunosuppression from a standard AZA-based regimen to MMF resulted in a decrease in systemic inflammatory activity as indicated by levels of high-sensitive CRP. However, progression of intimal hyperplasia did not differ significantly, and the weak trend toward vascular enlargement could indicate some influence on vascular geometry.
authors.affiliation: Department of Internal Medicine III-Cardiology, Friedrich Schiller University, Jena, Germany. klaus.pethig@t-online.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Pethig
authors.forename: Bernd
authors.initials: B
authors.lastname: Heublein
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wahlers
authors.forename: Olliver
authors.initials: O
authors.lastname: Dannenberg
authors.forename: Petra
authors.initials: P
authors.lastname: Oppelt
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001379:Azathioprine / Q000008:administration & dosage; D002097:C-Reactive Protein / Q000032:analysis; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D016027:Heart Transplantation / Q000000981:diagnostic imaging / Q000401:mortality; D006801:Humans; D006965:Hyperplasia / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007249:Inflammation / Q000188:drug therapy* / Q000517:prevention & control; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010865:Pilot Projects; D011239:Prednisolone / Q000008:administration & dosage; D011446:Prospective Studies; D014463:Ultrasonography
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002097:C-Reactive Protein; D011239:Prednisolone; D009173:Mycophenolic Acid; D001379:Azathioprine