Abstract 12841: Mutations in the BMPR2 Gene Are Associated With Worse Survival in Patients With Pulmonary Arterial Hypertension
Introduction: Mutations in the BMPR2 gene are the commonest genetic cause of pulmonary arterial hypertension (PAH), however the impact of BMPR2 mutations on clinical phenotype and outcomes remains uncertain.
Methods: We collated individual participant-level data on 1550 patients with idiopathic, familial and anorexigen-associated PAH from 8 studies that had systematically tested for the presence of BMPR2 mutations. 1164 patients from 6 studies were included in the primary survival analysis. Associations of BMPR2 mutation status with risk of all cause death and death or transplant were assessed by calculating age and sex adjusted hazard ratios (95% CI) using Cox proportional-hazard regression models stratified by study.
Results: Overall, 448 (28.9%) of 1550 patients had a BMPR2 mutation. BMPR2 mutation carriers were younger at diagnosis, (mean ±SD) 35 ±15 versus 42 ±18 years, p<0.001), had a higher mean pulmonary artery pressure (61 ±14 versus 56 ±15 mmHg, p<0.001) and pulmonary vascular resistance (17 ±8 versus 13 ±8 Wood units, p<0.001) and lower cardiac index (2.1 ±0.7 versus 2.5 ±0.9 L/min/m2, p<0.001) at diagnostic right heart catheterization. Patients with BMPR2 mutations were less likely to respond to acute vasodilator testing (2.7% versus 16.6%, p<0.001). Hazard ratios for those carrying a BMPR2 mutation for all cause death and death or transplant are shown in the figure below. In a complete case analysis, the increased risk of all cause death (HR 1.50 (1.07-2.12), p=0.02) and death or transplant (HR 1.76 (1.31-2.38), p<0.001) in those aged <50 at diagnosis persisted after adjusting for right atrial pressure, pulmonary vascular resistance and NYHA functional class at diagnosis.
Conclusions: Patients with PAH and BMPR2 mutations are younger at diagnosis and present with more severe disease. Patients with BMPR2 mutations (particularly those diagnosed at a younger age) are at increased risk of death or transplantation compared with BMPR2 negative patients.
Author Disclosures: J.D. Evans: None. B. Girerd: None. D. Montani: Research Grant; Modest; Actelion, Bayer, GSK, Pfizer. Honoraria; Modest; Actelion, Bayer, GSK, BMS, Pfizer. Z. Jing: None. Y. Yan: None. X. Wang: None. N. Galiè: None. A. Manes: None. M. Palazzini: None. E.D. Austin: Research Grant; Modest; NIH (K23; R01; P01 support). Other Research Support; Modest; ATS Foundation Research Program support. L.A. Wheeler: None. G. Elliott: None. I. Nakayama: None. K. Asano: None. E. Grünig: None. C. Eichstaedt: None. K. Hinderhofer: None. M. Wolf: None. E.B. Rosenzweig: None. W.K. Chung: None. F. Soubrier: None. G. Simonneau: None. S. Gräf: None. S. Kaptoge: None. E. Di Angelantonio: None. M. Humbert: None. N.W. Morrell: None.
- © 2015 by American Heart Association, Inc.