PAH Patients with BMPR2 Mutations Likely to Have Severe Disease Progression

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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familial PAH

Patients with pulmonary arterial hypertension (PAH) carrying mutations in the bone morphogenetic protein receptor type II (BMPR2) gene have a worse prognosis, namely decreased survival rates and higher risk for lung transplantation. The findings were in a study titled “BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis” and published in THE LANCET Respiratory Medicine journal.

Mutations in the BMPR2 gene were previously identified as a key genetic event leading to familial PAH. Current European guidelines for the management of PAH recommend that patients diagnosed with idiopathic, heritable and anorexigen-associated PAH should undergo screening for BMPR2 mutations followed by genetic counseling. While these mutations are expected to associate with a more severe disease progression, studies do not clearly show how these mutations impact patients’ long-term outcomes.

A research team analyzed individual data from 1,550 patients with idiopathic, heritable, and anorexigen-associated PAH from eight cohorts, based in six different countries, tested for BMPR2 mutations. The analysis’ primary outcome focus was patients who died or underwent lung transplantation; the secondary outcome assessed all-cause mortality.

In total, 448 out of the 1,550 patients with idiopathic, heritable, and anorexigen-associated PAH had a BMPR2 mutation (corresponding to 29 percent). These patients had a diagnosis of PAH at younger ages, around 35 years old, while non-mutation carriers were diagnosed around age 42. Patients positive for BMPR2 mutation exhibited significantly higher mean pulmonary artery pressure (60.5 versus 56.4 mm Hg) and pulmonary vascular resistance (16.6 versus 12.9 Wood units), while their cardiac index was lower (2.11 versus 2.51 L/min per m2). They were also found to be less responsive to acute vasodilator testing.

Authors also determined that a mutation in the BMPR2 gene is associated with an increased risk of death and connected to a higher probability of a required lung transplant.

In conclusion, BMPR2 mutations present at a younger age in PAH patients are associated with more severe disease and a higher risk for death and transplantation when compared to patients without BMPR2 mutations. While the mechanisms explaining this difference in survival are not clear, the authors suggested that the decreased cardiac index in BMPR2 patients is likely a significant contributor.

A Conversation With Rare Disease Advocates