Abstract 13128: IGFBP8 as a Novel Biomarker for Hemodynamics and Functional Status in Pulmonary Arterial Hypertension

Abstract

Background: Previous studies have shown that insulin-like growth factor binding proteins (IGFBPs) are correlated with pulmonary artery hypertension (PAH) disease severity. IGFBP8 has been shown in- vitro to be associated with pulmonary vessel remodeling and PAH in gene deletion experiments. However, no studies have evaluated IGFBP8 levels in adults with PAH. Research Question: This study sought to assess if IGFBP8 concentrations are elevated in patients with PAH and if levels are associated with survival, hemodynamic, and clinical PAH measurements. Methods: Serum IGFBP8 was measured in 2,763 adults with PAH and 92 adult controls. Two PAH cohorts and two control cohorts were used for analysis. A Mann-Whitney U test was used to compare IGFBP8 levels in PAH and controls. Samples were adjusted for age and sex using linear and logistic regression for continuous and categorical variables, respectively. IGFBP8 levels in the PAH cohort were compared to mean right atrial (mRAP), mean pulmonary artery pressures (mPAP), pulmonary vascular resistance (PVR) and functional measures such as six-minute walk distance (6-MWD), and New York Heart Association Functional Class (NYHA FC). Analysis of composite outcome (death or transplant) was conducted using a Cox proportional hazard model. Results: IGFBP8 levels were higher in PAH vs controls patients (Figure 1B, p<0.0001). Among PAH patients, for every natural log unit higher, IGFBP8 was associated with death or transplant with Cox proportional hazard ratio of 1.313 (95% CI 1.034-1.666; p=0.025). Higher IGFBP8 levels were associated with lower 6-MWD (p=0.035) and increased NYHA FC (p=0.026). Hemodynamically, increased IGFBP8 levels were associated with lower cardiac index (p=0.014), increased mRAP (p=0.012) and lower stroke volume (p=0.002) but not mPAP or PVR (Figure 1A). Conclusions: IGFBP8 is a novel biomarker in PAH. Higher levels are associated with worse survival, worse hemodynamics, and poor functional status.