Abstract 15389: Insulin Like Growth Factor Binding Proteins 1 and 2 Are Prognostic Survival Markers in Intermediate Risk Pulmonary Arterial Hypertension

Abstract

Introduction: Pulmonary arterial hypertension (PH) is an often fatal disease of the pre-capillary pulmonary vasculature. Recognizing high risk PH in ambulatory patients is important for optimization of therapy to improve outcomes. We previously identified insulin like growth factor binding proteins 1 and 2 (IGFBP1, IGFBP2) as prognostic markers in severe PH; here, we evaluated IGFBP1/2 as prognostic markers in PH with intermediate risk features. Methods: A multiplex ELISA assay measured serum IGFBP1/2 in the multicenter PH Biobank (N=2450), and independent validation cohorts (Johns Hopkins, N=145, Vanderbilt N= 128, 388 observations over time). IGFBP1/2 concentrations were compared to hemodynamics, six-minute walk (6MW), and WHO functional class using linear/logistic regression adjusted for age and sex. Time to death/transplant by IGFBP1/2 levels was assessed by Cox proportional hazard models. Analysis was repeated in subjects with low to intermediate risk features defined as WHO functional class 1-2, 6MW >300 m, and NT-proBNP <1500 pg/mL, based on the REVEAL and ERS risk scores. 1, 2 Results: In all cohorts, increased IGFBP1 and IGFBP2 were associated with lower cardiac output, higher mean pulmonary artery pressure and pulmonary vascular resistance (PVR, p<0.05 for all). In each sub-analysis, a higher IGFBP1 and IGFBP2 was associated with lower cardiac output, lower systemic blood pressure, and higher PVR (p<0.05 for all). Higher IGFBP1 and IGFBP2 were associated with shorter time to death/transplant in the overall cohort and each of the intermediate risk PH cohorts (Table 1), although underpowered in the Vanderbilt cohort. Conclusions: Identifying patients who will have adverse outcome in intermediate risk PH has proven challenging. These data suggest IGFBP1/2 are good prognostic markers in PH where functional class and exertional tolerance is preserved. IGFBP1/2 could further discriminate adverse outcomes in patients with low to intermediate risk PH.