title: Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial.
abstract: BACKGROUND
  There is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the disease. Statins modulate aortic stiffness and have anti-inflammatory properties. A proof-of-principle, double-blind, randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease.
  
  
  METHODS
  Stable patients (n=70) were randomized to simvastatin (active) or placebo. Pre-treatment and post-treatment aortic stiffness, blood pressure, spirometry, and circulating and airway inflammatory mediators and lipids were measured. A predefined subgroup analysis was performed where baseline aortic pulse wave velocity (PWV) was >10 m/sec.
  
  
  RESULTS
  Total cholesterol dropped in the active group. There was no significant change in aortic PWV between the active group and the placebo group (-0.7 m/sec, P=0.24). In those with aortic stiffness >10 m/sec (n=22), aortic PWV improved in the active group compared with the placebo group (-2.8 m/sec, P=0.03). Neither systemic nor airway inflammatory markers changed.
  
  
  CONCLUSIONS
  There was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo, but in those with higher baseline aortic stiffness (a higher risk group) a significant and clinically relevant reduction in PWV was shown.
authors: Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK.
authors: Michelle E
authors: ME
authors: John
authors: Wales Heart Research Institute, Cardiff University, Cardiff, UK.
authors: John R
authors: JR
authors: Cockcroft
authors: Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
authors: Tricia M
authors: TM
authors: McKeever
authors: Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK.
authors: William R
authors: WR
authors: Coward
authors: Wales Heart Research Institute, Cardiff University, Cardiff, UK.
authors: Dennis J
authors: DJ
authors: Shale
authors: Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK.
authors: Simon R
authors: SR
authors: Johnson
authors: Clinical Trials Unit and Department of Obstetrics and Gynaecology, School of Medicine, University of Nottingham, Nottingham, UK.
authors: Jim G
authors: JG
authors: Thornton
authors: Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK.
authors: Timothy W
authors: TW
authors: Harrison
authors: Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK.
authors: Alan J
authors: AJ
authors: Knox
authors: Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK.
authors: Charlotte E
authors: CE
authors: Bolton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D004739:England; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D063177:Pulse Wave Analysis; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D013147:Spirometry; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects*; D014797:Vital Capacity
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D002317:Cardiovascular Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D002784:Cholesterol; D019821:Simvastatin
keywords: arterial stiffness; chronic obstructive pulmonary disease; statins