Low-affinity insulin-like growth factor binding protein 7 and its association with pulmonary arterial hypertension severity and survival

Guillermo Torres, Andrew C. Lancaster, Jun Yang, Megan Griffiths, Stephanie Brandal, Rachel Damico, Dhananjay Vaidya, Catherine E. Simpson, Lisa J. Martin, Michael W. Pauciulo, William C. Nichols, D. Dunbar Ivy, Eric D. Austin, Paul M. Hassoun, Allen D. Everett
Johns Hopkins University. University of Texas Southwestern Medical Center. Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine. Children’s Hospital Colorado. Vanderbilt University Medical Center.
United States

Pulmonary Circulation
Pulm Circ 2023; 13
DOI: 10.1002/pul2.12284

Abstract
Insulin-like growth factor (IGF) binding proteins (IGFBPs) are a family of growth factor modifiers, some of which are known to be independently associated with pulmonary arterial hypertension (PAH) survival. IGF factor binding protein 7 (IGFBP7) is a unique low-affinity IGFBP that, independent of IGF, stimulates prostacyclin production. This study proposed to establish associations between IGFBP7 and PAH severity and survival, using enrollment and longitudinal samples. Serum IGFBP7 levels were significantly elevated in patients with PAH compared to controls. After adjusting for age and sex, logarithmic increases in IGFBP7 were associated with a 20 m shorter six-minute walk distance (6MWD; p < 0.001), a 2-3 mmHg higher mean right atrial pressure (p < 0.001 and 0.02), and a higher likelihood of a greater REVEAL 2.0 risk category placement (p < 0.001). Kaplan-Meier analysis demonstrated significantly decreased survival with IGFBP7 above the median and Cox multivariable analysis adjusted for age and sex, demonstrated higher serum IGFBP7 was an independent predictor of survival. Though the exact mechanism is still unknown, given IGFBP7’s role as a prostacyclin stimulant, it has potential use as a therapeutic target for disease modulation.

Category
Acquired Patient Factors Associated with Pulmonary Vascular Disease
Potential Biomarkers Associated with Pulmonary Vascular Disease

Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease

Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication

Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes

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