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

• Published in: Circulation (New York, N.Y.) Vol. 146; no. Suppl_1; p. A15389
• Main Authors: Griffiths, Megan, Simpson, Catherine, Yang, Jun, Torres, Guillermo, Vaidya, Dhananjay, Brandal, Stephanie, Pauciulo, Michael, Damico, Rachel L, Hassoun, Paul, Ivy, Dunbar D, Austin, Eric, Rosenzweig, Erika, Nichols, Bill, Everett, Allen D
• Format: Journal Article
• Language: English
• Published: Lippincott Williams & Wilkins 08.11.2022
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.146.suppl_1.15389

IntroductionPulmonary 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. MethodsA 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 ResultsIn 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. ConclusionsIdentifying 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.