title: Long-term statin therapy in patients with systolic heart failure and normal cholesterol: effects on elevated serum markers of collagen turnover, inflammation, and B-type natriuretic peptide.
abstract: BACKGROUND
  The role of statin therapy in heart failure (HF) is unclear. The amino-terminal propeptide of procollagen type III (PIIINP) predicts outcome in HF, and yet there are conflicting reports of statin therapy effects on PIIINP.
  
  
  OBJECTIVE
  This study determined whether there was an increase in serum markers of inflammation, fibrosis (including PIIINP), and B-type natriuretic peptide (BNP) in patients with systolic HF and normal total cholesterol and determined the effects of long-term treatment with atorvastatin on these markers.
  
  
  METHODS
  Fifty-six white patients with systolic HF and normal cholesterol levels (age 72 [13] years; 68% male; body mass index 27.0 [7.3] kg/m(2); ejection fraction 35 [13]%; 46% with history of smoking) were randomly allocated to atorvastatin treatment for 6 months, titrated to 40 mg/d (A group) or not (C group). Age- and/or sex-matched subjects without HF (N group) were also recruited. Biomarkers were measured at baseline (all groups) and 6 months (A and C groups).
  
  
  RESULTS
  Serum markers of collagen turnover, inflammation, and BNP were significantly elevated in HF patients compared with normal participants (all P < 0.05). There were correlations between these markers in HF patients but not in normal subjects. Atorvastatin treatment for 6 months caused a significant reduction in the following biomarkers compared with baseline: BNP, from median (interquartile range) 268 (190-441) pg/mL to 185 (144-344) pg/mL; high-sensitivity C-reactive protein (hs-CRP), from 5.26 (1.95 -9.29) mg/L to 3.70 (2.34-6.81) mg/L; and PIIINP, from 4.65 (1.86) to 4.09 (1.25) pg/mL (all P < 0.05 baseline vs 6 months). Between-group differences were significant for PIIINP only (P = 0.027). There was a positive interaction between atorvastatin effects and baseline hs-CRP and PIIINP (P < 0.01).
  
  
  CONCLUSIONS
  Long-term statin therapy reduced PIIINP in this small, selected HF population with elevated baseline levels. Further evaluation of statin therapy in the management of HF patients with elevated PIIINP is warranted.
authors.affiliation: HF Unit, St Vincent's University Hospital, Elm Park, Dublin, Ireland.
authors.forename: Esam
authors.initials: E
authors.lastname: Abulhul
authors.forename: Kenneth
authors.initials: K
authors.lastname: McDonald
authors.forename: Ramon
authors.initials: R
authors.lastname: Martos
authors.forename: Dermot
authors.initials: D
authors.lastname: Phelan
authors.forename: J Paul
authors.initials: JP
authors.lastname: Spiers
authors.forename: Martina
authors.initials: M
authors.lastname: Hennessy
authors.forename: John
authors.initials: J
authors.lastname: Baugh
authors.forename: Chris
authors.initials: C
authors.lastname: Watson
authors.forename: Christina
authors.initials: C
authors.lastname: O'Loughlin
authors.forename: Mark
authors.initials: M
authors.lastname: Ledwidge
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood*; D003094:Collagen / Q000097:blood*; D024042:Collagen Type I / Q000097:blood; D015536:Down-Regulation; D005260:Female; D054143:Heart Failure, Systolic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood*; D007494:Ireland; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D020127:Recovery of Function; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D011758:Pyrroles; C052929:collagen type I trimeric cross-linked peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D020097:Natriuretic Peptide, Brain; D003094:Collagen; D002784:Cholesterol; D000069059:Atorvastatin