RT Journal Article
SR Electronic
T1 The angiostatic peptide endostatin enhances mortality risk prediction in pulmonary arterial hypertension
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00378-2021
DO 10.1183/23120541.00378-2021
VO 7
IS 4
A1 Catherine E. Simpson
A1 Megan Griffiths
A1 Jun Yang
A1 Melanie K. Nies
A1 R. Dhananjay Vaidya
A1 Stephanie Brandal
A1 Lisa J. Martin
A1 Michael W. Pauciulo
A1 Katie A. Lutz
A1 Anna W. Coleman
A1 Eric D. Austin
A1 D. Dunbar Ivy
A1 William C. Nichols
A1 Allen D. Everett
A1 Paul M. Hassoun
A1 Rachel L. Damico
YR 2021
UL http://openres.ersjournals.com/content/7/4/00378-2021.abstract
AB 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 haemodynamics 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, multicentre PAH cohort; and 2) the added value gained by incorporating endostatin into existing PAH risk prediction models.Endostatin ELISAs were performed on enrolment 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 European Society of Cardiology/European Respiratory Society (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 6-min walk distance (p<0.01). Mortality risk doubled for each log higher endostatin (hazard ratio 2.3, 95% CI 1.6–3.4, 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.Endostatin is a robust, easily accessible biomarker of PAH severity and mortality that is mechanistically related to PAH pathogenesis. Incorporating endostatin into commonly used risk prediction strategies for PAH improves prediction of mortality. https://bit.ly/3kzGT0w