title: Pleiotropic effects of atorvastatin in heart failure: role in oxidative stress, inflammation, endothelial function, and exercise capacity.
abstract: BACKGROUND
  Increased oxidative stress, a common feature in chronic heart failure, has been associated with inflammation, endothelial dysfunction, and extracellular matrix degradation. Statins have known anti-inflammatory and anti-oxidant effects; however, their role in chronic heart failure is still controversial.
  
  
  METHODS
  This was a prospective study of 38 patients with stable systolic chronic heart failure. Patients received a 4-week placebo course, followed by atorvastatin 20 mg/day for 8 weeks. Oxidative stress, inflammation and remodeling markers, brachial artery flow-mediated vasodilation, and 6-minute walk test were evaluated at baseline, 4, and 8 weeks.
  
  
  RESULTS
  Mean age was 58 +/- 12. Mean left ventricular ejection fraction was 27% +/- 12%. No significant differences were observed between measurements at baseline and after placebo. Atorvastatin induced a significant decrease of matrix metalloproteinase-9 activity, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-6, and malondialdehyde, and a significant increase of endothelial superoxide dismutase activity when compared with placebo. No differences in tissue inhibitor of matrix metalloproteinase and matrix metalloproteinase-2 activities were observed. Atorvastatin use was associated with an improved flow-dependent brachial vasodilation and exercise capacity in the 6-minute walk test.
  
  
  CONCLUSIONS
  In chronic heart failure patients, atorvastatin therapy is associated with a decrease of inflammation and extracellular matrix remodeling, improving both endothelial function and exercise capacity.
authors: Departamento de Enfermedades Cardiovasculares, Hospital Clínico, Pontificia Universidad Católica de Chile, Santiago, Chile. pcastro@med.puc.cl
authors: Pablo F
authors: PF
authors: Castro
authors: Rodrigo
authors: R
authors: Miranda
authors: Hugo E
authors: HE
authors: Verdejo
authors: Douglas
authors: D
authors: Greig
authors: Luigi A
authors: LA
authors: Gabrielli
authors: Hernán
authors: H
authors: Alcaino
authors: Mario
authors: M
authors: Chiong
authors: Carlos
authors: C
authors: Bustos
authors: Lorena
authors: L
authors: Garcia
authors: Rosemarie
authors: R
authors: Mellado
authors: José Luis
authors: JL
authors: Vukasovic
authors: Ivan
authors: I
authors: Godoy
authors: Sergio
authors: S
authors: Lavandero
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000378:metabolism; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D017079:Exercise Tolerance; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011446:Prospective Studies; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014664:Vasodilation; D016138:Walking
chemical_list: D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin