Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation.
BACKGROUND
Germline mutations in the gene encoding for bone morphogenetic protein receptor 2 (BMPR2) are a cause of pulmonary arterial hypertension (PAH).


OBJECTIVE
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.


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/m(2), P = 0.0005), higher pulmonary vascular resistance (17.4 +/- 6.1 vs. 12.7 +/- 6.6 mm Hg/L/min/m(2), 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.
Sztrymf
Benjamin
B
Université Paris-Sud 11, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine-Béclère, 157 rue de la Porte de Trivaux, 92140 Clamart, France.
Coulet
Florence
F
Girerd
Barbara
B
Yaici
Azzedine
A
Jais
Xavier
X
Sitbon
Olivier
O
Montani
David
D
Souza
Rogério
R
Simonneau
Gerald
G
Soubrier
Florent
F
Humbert
Marc
M
D000328:Adult; D017668:Age of Onset; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D017384:Sequence Deletion; D015996:Survival Rate
C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II