Increased Levels of Runt-Related Transcription Factor 2 Are Associated With Poor Survival of Patients With Idiopathic Pulmonary Arterial Hypertension

Abstract

Runt-related transcription factor 2 (RUNX2) plays a pivotal role in the pathogenesis of pulmonary arterial hypertension (PAH); yet, whether circulating levels of RUNX2 can predict survival of patients with idiopathic PAH (IPAH) is still unclear. The present study aimed to investigate the correlation between circulating levels of RUNX2 and survival of patients with IPAH. Blood samples were collected from 46 incident patients with IPAH and 30 healthy controls in Shanghai Pulmonary Hospital. Levels of RUNX2 were measured using ELISA. Linear regression and cox proportional hazards analysis were performed to assess the prognostic value of RUNX2 levels in predicting survival using the Kaplan–Meier method. Nonsurvivors had significantly shorter 6MWD, higher levels of NT-proBNP, increased mRAP, mPAP, mPAWP, PVR, and decreased CO as well as CI, compared with survivors ( p < .05). Plasma levels of RUNX2 were significantly higher in nonsurvival and survival patients with IPAH compared with controls ( p ≤ .001), and higher in nonsurvivors than in survivors ( p = .001). RUNX2 levels served as an independent predictor of survival in these patients ( p < .001). RUNX2 levels ≥41.5 ng/ml had a sensitivity of 80.0% and a specificity of 74.2% by ROC analysis. Patients with a RUNX2 level <41.5 ng/ml and/or mRAP <3.5 mmHg had a significantly better prognosis than those with a higher RUNX2 level in all subjects as well as in male or female patients ( p < .05). The level of circulating RUNX2 is an independent predictor for survival and it is correlated with the clinical severity of IPAH.