title: Neutral effect on markers of heart failure, inflammation, endothelial activation and function, and vagal tone after high-dose HMG-CoA reductase inhibition in non-diabetic patients with non-ischemic cardiomyopathy and average low-density lipoprotein level.
abstract: OBJECTIVE
  This study sought to determine the effect of aggressive 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy on surrogate markers in non-ischemic cardiomyopathy (NICM) patients and average low-density lipoprotein (LDL) concentrations.
  
  
  BACKGROUND
  The effects of statins may well go beyond lipid lowering, and these pleiotropic effects may be of benefit in the treatment of heart failure.
  
  
  METHODS
  Fifteen patients with NICM on standard maximized heart failure medication were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial. Patients received 80 mg atorvastatin (ATV) or matching placebo for a 12-week treatment period with a minimum of an 8-week washout period. The following surrogate markers were evaluated: N-terminal-pro brain natriuretic peptide, high-sensitivity C-reactive protein, oxidized LDL antibody, soluble receptor tumor necrosis factor, tumor necrosis factor-alpha, circulating levels of vascular adhesion molecule-1, intercellular adhesion molecule-1, P-selectin, non-invasive endothelial function studies, and heart rate variability.
  
  
  RESULTS
  After ATV therapy, there was a significant decrease in LDL concentration from 110 +/- 27 mg/dl to 55 +/- 18 mg/dl (p < 0.05). There were no differences between ATV and placebo with regard to the surrogate markers measured.
  
  
  CONCLUSIONS
  Based on these findings, it seems that the administration of high-dose statins to a heart failure population with modest LDL levels and no other indication for statin therapy was neither beneficial nor detrimental as determined by surrogate marker measures. Further studies are needed to determine whether there is an appropriate patient population and optimal dose (LDL concentration) for the treatment of systolic heart failure with statin therapy.
authors.affiliation: University of Michigan, College of Pharmacy, Ann Arbor, Michigan 48109-1065, USA. bbleske@umich.edu
authors.forename: Barry E
authors.initials: BE
authors.lastname: Bleske
authors.forename: John M
authors.initials: JM
authors.lastname: Nicklas
authors.forename: Robert L
authors.initials: RL
authors.lastname: Bard
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brook
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Bliden
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000188:drug therapy*; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; D019007:P-Selectin; D010446:Peptide Fragments; D018124:Receptors, Tumor Necrosis Factor; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein