Abstract 14691: Sex Differences in the Prognostic Value of N-Terminal Brain Natriuretic Peptide in Pulmonary Arterial Hypertension

Abstract

Introduction: Pulmonary arterial hypertension (PAH) causes right heart failure (HF) and mainly affects females, but males have worse survival. Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP), along with N-terminal BNP (NTproBNP), are secreted from cardiomyocytes upon stretch and are important biomarkers in HF. Sex differences are observed in NTproBNP levels and prognostic value in left HF, but unknown in right HF. The aim was to assess sex differences in NTproBNP levels and prognostic value in PAH from a translational perspective. Methods: We screened patients with baseline NTproBNP measurements and right heart catheterization between 2002 and 2020. Induced pluripotent stem cells (iPSCs) from 1 male and 1 female PAH-patients were differentiated into cardiomyocytes (iPSC-CMs), and stretched for 24h at 1Hz and 10% on the Flexcell FX-6000 system (N=2). Gene expression analyses were performed on static and stretched samples. Results: 266 patients (N=106 male, N=166 female) were included. Median baseline NTproBNP levels were similar in male and female patients (1118 vs 832 ng/ml, P=0.58). We risk stratified patients on NTproBNP according to the guidelines and assessed differences in 1-year survival. In males highest 1-year mortality was observed in low and low-intermediate risk groups (16,4% and 7.7%, respectively) vs females (4.7% and 4.2%, respectively) (Figure1 A,B). Preliminary results indicate ~2x higher BNP mRNA expressions on male vs female patients (0.80 vs 0.37, N=3 male and N=3 female, P=0.018), after mechanical stretch (Figure1 C). Conclusions: Although no sex differences were observed in NTproBNP plasma levels, it had different prognostic value in male and female patients. Furthermore, in vitro male iPSC-CMs had higher BNP levels after stretch compared to female iPSC-CMs.