Currently available noninvasive markers for assessing disease severity and mortality risk in pulmonary arterial hypertension (PAH) are unrelated to fundamental disease biology. Endostatin, an angiostatic peptide known to inhibit pulmonary artery endothelial cell migration, proliferation, and survival in vitro, has been linked to adverse hemodynamics and shortened survival in small PAH cohorts. This observational cohort study sought to assess 1) the prognostic performance of circulating endostatin levels in a large, multicenter PAH cohort, and 2) the added value gained by incorporating endostatin into existing PAH risk prediction models.Endostatin ELISAs were performed on enrollment samples collected from 2017 PAH subjects with detailed clinical data, including survival times. Endostatin associations with clinical variables, including survival, were examined using multivariable regression and Cox proportional hazards models. Extended survival models including endostatin were compared to null models based on the REVEAL risk prediction tool and ESC/ERS low risk criteria using likelihood ratio tests, Akaike and Bayesian information criteria, and C-statistics.Higher endostatin was associated with higher right atrial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance and with shorter six-minute walk distance (p<0.01). Mortality risk doubled for each log-higher endostatin (hazard ratio 2.3, 95% confidence interval 1.6 to 3.4, p<0.001). Endostatin remained an independent predictor of survival when incorporated into existing risk prediction models. Adding endostatin to REVEAL-based and ESC/ERS criteria-based risk assessment strategies improved mortality risk prediction.Endostatin is a robust, independent predictor of mortality in PAH. Adding endostatin to existing PAH risk prediction strategies improves PAH risk assessment.
A STANDARDIZED APPROACH TO GUIDELINE ADHERENCE THROUGH A SINGLE MORTALITY RISK ASSESSMENT TOOL IN PULMONARY ARTERIAL HYPERTENSION BY QUALITY IMPROVEMENT METHODS