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Published ahead of print on March 20, 2008, doi:10.1164/rccm.200712-1807OC
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American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 1377-1383, (2008)
© 2008 American Thoracic Society
doi: 10.1164/rccm.200712-1807OC

Original Article

Clinical Outcomes of Pulmonary Arterial Hypertension in Carriers of BMPR2 Mutation

Benjamin Sztrymf1, Florence Coulet2, Barbara Girerd1, Azzedine Yaici1, Xavier Jais1, Olivier Sitbon1, David Montani1, Rogério Souza1, Gerald Simonneau1, Florent Soubrier2 and Marc Humbert1

1 Université Paris-Sud 11, UPRES EA 2705, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Service de Pneumologie et Réanimation Respiratoire, Institut Paris-Sud Cytokines, Hôpital Antoine-Béclère, Assistance Publique des Hôpitaux de Paris, Clamart, France; and 2 Université Pierre et Marie Curie–Paris 6, Laboratoire d'Oncogénétique et Angiogénétique Moléculaire, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

Correspondence and requests for reprints should be addressed to Marc Humbert, M.D., Ph.D., Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine-Béclère, 157 rue de la Porte de Trivaux, 92140 Clamart, France. E-mail: marc.humbert{at}abc.aphp.fr

Rationale: Germline mutations in the gene encoding for bone morphogenetic protein receptor 2 (BMPR2) are a cause of pulmonary arterial hypertension (PAH).

Objectives: We conducted a study to determine the influence, if any, of a BMPR2 mutation on clinical outcome.

Methods: The French Network of Pulmonary Hypertension obtained data for 223 consecutive patients displaying idiopathic or familial PAH in whom point mutation and large size rearrangements of BMPR2 were screened for. Clinical, functional, and hemodynamic characteristics, as well as outcomes, were compared in BMPR2 mutation carriers and noncarriers.

Measurements and Main Results: Sixty-eight BMPR2 mutation carriers (28 familial and 40 idiopathic PAH) were compared with 155 noncarriers (all displaying idiopathic PAH). As compared with noncarriers, BMPR2 mutation carriers were younger at diagnosis of PAH (36.5 ± 14.5 vs. 46.0 ± 16.1 yr, P < 0.0001), had higher mean pulmonary artery pressure (64 ± 13 vs. 56 ± 13 mm Hg, P < 0.0001), lower cardiac index (2.13 ± 0.68 vs. 2.50 ± 0.73 L/min/m2, P = 0.0005), higher pulmonary vascular resistance (17.4 ± 6.1 vs. 12.7 ± 6.6 mm Hg/L/min/m2, P < 0.0001), lower mixed venous oxygen saturation (59 ± 9% vs. 63 ± 9%, P = 0.02), shorter time to death or lung transplantation (P = 0.044), and younger age at death (P = 0.002), but similar overall survival (P = 0.51).

Conclusions: BMPR2 mutation carriers with PAH present approximately 10 years earlier than noncarriers, with a more severe hemodynamic compromise at diagnosis.

Key Words: bone morphogenetic protein receptor 2 • genetics • hemodynamics • pulmonary arterial hypertension • survival


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Germline mutations in the gene encoding for bone morphogenetic protein receptor 2 (BMPR2) are a cause of pulmonary arterial hypertension. The influence, if any, of a BMPR2 mutation on clinical outcomes is currently unknown.

What This Study Adds to the Field
BMPR2 mutation carriers with pulmonary arterial hypertension present approximately 10 years earlier than noncarriers with a more severe hemodynamic compromise at diagnosis.

 

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AJRCCM 2008 177: 1300-1301. [Full Text]  



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