title: Hepatoma-derived Growth Factor Predicts Disease Severity and Survival in Pulmonary Arterial Hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a fatal disease, and pulmonary microvascular remodeling is an important contributor to PAH development. Therefore, we hypothesized that a circulating angiogenic factor could predict disease severity and survival.
  
  
  
  We sought to assess the relationship of serum hepatoma-derived growth factor (HDGF) with PAH disease severity and survival.
  
  
  
  Using a newly developed enzyme-linked immunosorbent assay, we evaluated circulating HDGF levels in two independent PAH cohorts and two different characterized control cohorts. Clinical and laboratory data were also used to assess the value of HDGF as a PAH prognostic biomarker.
  
  
  
  Serum HDGF levels were significantly elevated in two independent PAH cohorts. Importantly, serum HDGF levels were not elevated in a noncardiac chronic disease cohort. Further, patients with elevated HDGF had significantly lower exercise tolerance, worse New York Heart Association functional class, and higher levels of N-terminal pro-brain natriuretic peptide. HDGF was a strong predictor of mortality, with an unadjusted hazard ratio of 4.5 (95% confidence interval, 1.9-10.3; P = 0.003 by log-rank test). In multivariable Cox proportional hazards models, elevated HDGF levels predicted decreased survival after being adjusted for age, PAH subtype, invasive hemodynamics, and N-terminal pro-brain natriuretic peptide.
  
  
  
  Elevated HDGF was associated with worse functional class, exertional intolerance, and increased mortality in PAH, suggesting HDGF as a potential biomarker for predicting mortality and as having possible diagnostic value for distinguishing PAH from non-PAH. HDGF may add additional value in PAH risk stratification in clinical trials and may represent a potential target for future PAH drug development.
authors.affiliation: 1 Division of Pediatric Cardiology.
authors.forename: Jun
authors.identifier: 0000-0001-9273-4578
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1 Division of Pediatric Cardiology.
authors.forename: Melanie K
authors.identifier: 0000-0001-5453-425X
authors.initials: MK
authors.lastname: Nies
authors.affiliation: 2 Division of Pediatric Hematology, Department of Pediatrics.
authors.forename: Zongming
authors.initials: Z
authors.lastname: Fu
authors.affiliation: 3 Division of Pulmonary and Critical Care Medicine, Department of Medicine, and.
authors.forename: Rachel
authors.initials: R
authors.lastname: Damico
authors.affiliation: 4 Department of Emergency Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Frederick K
authors.initials: FK
authors.lastname: Korley
authors.affiliation: 3 Division of Pulmonary and Critical Care Medicine, Department of Medicine, and.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hassoun
authors.affiliation: 5 Department of Pediatric Cardiology, Children's Hospital Colorado, Denver, Colorado; and.
authors.forename: David D
authors.initials: DD
authors.lastname: Ivy
authors.affiliation: 6 Division of Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Austin
authors.affiliation: 1 Division of Pediatric Cardiology.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Everett
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012720:Severity of Illness Index; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor
keywords: biomarker; enzyme-linked immunosorbent assay; hepatoma-derived growth factor; pulmonary arterial hypertension; survival