title: Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of simvastatin and ezetimibe on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in a cohort of rheumatoid arthritis (RA) patients.
  
  
  BACKGROUND
  Rheumatoid arthritis is a chronic inflammatory condition associated with increased cardiovascular risk. Statins reduce inflammation and disease activity in RA patients, but whether this is due to pleiotropism or cholesterol lowering per se is unclear.
  
  
  METHODS
  Twenty patients received 20 mg simvastatin or 10 mg ezetimibe each for 6 weeks in a randomized double-blind crossover study. Disease activity, blood pressure, aortic pulse wave velocity (PWV), brachial artery flow-mediated dilation (FMD), and serum inflammatory markers were measured before and after each treatment.
  
  
  RESULTS
  Both ezetimibe and simvastatin significantly reduced total cholesterol (-0.62 +/- 0.55 mmol/l and -1.28 +/- 0.49 mmol/l, respectively; p < 0.001), low-density lipoprotein cholesterol (-0.55 +/- 0.55 mmol/l and -1.28 +/- 0.49 mmol/l; p < 0.0001), and C-reactive protein (-5.35 +/- 9.25 mg/l and -5.05 +/- 6.30 mg/l; p < 0.001). Concomitantly, Disease Activity Score (-0.55 +/- 1.01 and -0.67 +/- 0.91; p = 0.002), aortic PWV (-0.69 +/- 1.15 m/s and -0.71 +/- 0.71 m/s; p = 0.001), and FMD (1.37 +/- 1.17% and 2.51 +/- 2.13%; p = 0.001) were significantly improved by both drugs.
  
  
  CONCLUSIONS
  This study demonstrates that both ezetimibe and simvastatin reduce disease activity and inflammatory markers to a similar extent in patients with RA. Therapy is also associated with a concomitant reduction in aortic PWV and improvement in endothelial function. This suggests that cholesterol lowering per se has anti-inflammatory effects and improves vascular function in RA.
authors: Clinical Pharmacology Unit, University of Cambridge, Cambridge, United Kingdom. km391@cam.ac.uk
authors: Kaisa M
authors: KM
authors: Mäki-Petäjä
authors: Anthony D
authors: AD
authors: Booth
authors: Frances C
authors: FC
authors: Hall
authors: Sharon M L
authors: SM
authors: Wallace
authors: John
authors: J
authors: Brown
authors: Carmel M
authors: CM
authors: McEniery
authors: Ian B
authors: IB
authors: Wilkinson
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001011:Aorta / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000503:physiopathology*; D001384:Azetidines / Q000494:pharmacology* / Q000627:therapeutic use; D001783:Blood Flow Velocity; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004548:Elasticity; D004730:Endothelium, Vascular / Q000187:drug effects*; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013314:Stress, Mechanical
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008077:Lipoproteins, LDL; D002097:C-Reactive Protein; D002784:Cholesterol; D019821:Simvastatin; D000069438:Ezetimibe