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

Esam Abulhul, Kenneth McDonald, Ramon Martos, Dermot Phelan, J Paul Spiers, Martina Hennessy, John Baugh, Chris Watson, Christina O'Loughlin, Mark Ledwidge

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

OBJECTIVES: 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.

Original languageEnglish
Pages (from-to)91-100
Number of pages10
JournalClinical Therapeutics
Volume34
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Atorvastatin Calcium
  • Biomarkers
  • Chi-Square Distribution
  • Cholesterol
  • Collagen
  • Collagen Type I
  • Down-Regulation
  • Female
  • Heart Failure, Systolic
  • Heptanoic Acids
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Inflammation Mediators
  • Ireland
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain
  • Peptide Fragments
  • Peptides
  • Procollagen
  • Prospective Studies
  • Pyrroles
  • Recovery of Function
  • Stroke Volume
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Ventricular Function, Left

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