title: Insulin-Like Growth Factor-Binding Protein-7 as a Biomarker of Diastolic Dysfunction and Functional Capacity in Heart Failure With Preserved Ejection Fraction: Results From the RELAX Trial.
abstract: This study sought to investigate relationships between insulin-like growth factor-binding protein-7 (IGFBP7) and parameters of diastolic function or functional capacity in patients with heart failure and preserved ejection fraction (HFpEF) who were randomized to receive sildenafil or placebo.
  
  
  
  IGFBP7 was previously found to be associated with diastolic function in heart failure with reduced ejection fraction, but it is unclear whether these associations are present in HFpEF.
  
  
  
  At baseline and 24 weeks, IGFBP7, imaging studies, and peak oxygen consumption (Vo2max) were obtained and compared in 160 patients with HFpEF who were randomized to receive sildenafil or placebo.
  
  
  
  Patients with supramedian baseline IGFBP7 concentrations were older, had signs of systemic congestion and worse renal function, and had higher concentrations of prognostic heart failure biomarkers including amino-terminal pro-B-type natriuretic peptide (p < 0.05). Higher baseline IGFBP7 was modestly correlated with worse diastolic function: higher E velocity (Spearman correlation [ρ] = 0.40), E/E' (ρ = 0.40), left atrial volume index (ρ = 0.39), and estimated right ventricular systolic pressure (ρ = 0.41; all p < 0.001) and weakly correlated with transmitral E/A (ρ = 0.26; p = 0.006). Notably, change in IGFBP7 was significantly correlated with change in E, E/A, E/E', and right ventricular systolic pressure. Elevated baseline IGFBP7 was associated with lower baseline Vo2max(13.2 vs. 11.1 ml/min/kg; p < 0.001), and change in IGFBP7 was weakly inversely correlated with change in Vo2max(ρ = -0.19; p = 0.01). Subjects receiving sildenafil had a decrease in IGFBP7 over 24 weeks, in contrast to placebo-treated patients (median change in IGFBP7 -1.5 vs. +13.6 ng/ml; p < 0.001).
  
  
  
  In patients with HFpEF, IGFBP7 may be a novel biomarker of diastolic function and exercise capacity.
authors.affiliation: VA CT Healthcare System, West Haven, Connecticut; Yale University School of Medicine New Haven, Connecticut.
authors.forename: Parul U
authors.initials: PU
authors.lastname: Gandhi
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Gaggin
authors.affiliation: Mayo Clinic Rochester, Minnesota.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.affiliation: Mayo Clinic Rochester, Minnesota.
authors.forename: Horng H
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Semigran
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Liu
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts. Electronic address: jjanuzzi@partners.org.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D054144:Heart Failure, Diastolic / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010101:Oxygen Consumption; D010446:Peptide Fragments / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D000068677:Sildenafil Citrate / Q000627:therapeutic use; D013318:Stroke Volume; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; D010446:Peptide Fragments; D014665:Vasodilator Agents; C102529:insulin-like growth factor binding protein-related protein 1; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000068677:Sildenafil Citrate
keywords: biomarkers; diastolic function; heart failure with preserved ejection fraction; insulin-like growth factor–binding protein 7