Insulin-like growth factor binding Protein-4: A novel indicator of pulmonary arterial hypertension severity and survival

Guillermo Torres, Jun Yang, Megan Griffiths, Stephanie Brandal, Rachel Damico, Dhananjay Vaidya, Catherine E. Simpson, Michael W. Pauciulo, William C. Nichols, David D. Ivy, Eric D. Austin, Paul M. Hassoun, Allen D. Everett

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Proteomic analysis of patients with pulmonary arterial hypertension (PAH) has demonstrated significant abnormalities in the insulin-like growth factor axis (IGF). This study proposed to establish associations between a specific binding protein, insulin-like growth factor binding protein 4 (IGFBP4), and PAH severity as well as survival across varying study cohorts. In all cohorts studied, serum IGFBP4 levels were significantly elevated in PAH compared to controls (p < 0.0001). IGFBP4 concentration was also highest in the connective tissue-associated PAH (CTD-PAH) and idiopathic PAH subtypes (876 and 784 ng/mL, median, respectively). After adjustment for age and sex, IGFBP4 was significantly associated with worse PAH severity as defined by a decreased 6-min walk distance (6MWD), New York heart association functional class (NYHA-FC), REVEAL 2.0 score and higher right atrial pressures. In longitudinal analysis provided by one of the study cohorts, IGFBP4 was prospectively significantly associated with a shorter 6MWD, worse NYHA-FC classification, and decreased survival. Cox multivariable analysis demonstrated higher serum IGFBP4 as an independent predictor of survival in the overall PAHB cohort. Therefore, this study established that higher circulating IGFBP4 levels were significantly associated with worse PAH severity, decreased survival and disease progression. Dysregulation of IGF metabolism/growth axis may play a significant role in PAH cardio-pulmonary pathobiology.

Original languageEnglish (US)
Article numbere12235
JournalPulmonary Circulation
Volume13
Issue number2
DOIs
StatePublished - Apr 2023

Keywords

  • biomarker
  • outcomes
  • prognosis
  • proteomics

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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