Elevated Levels of Circulating Bone Morphogenetic Protein 7 Predict Mortality in Pulmonary Arterial Hypertension

Abstract

Background: This study aimed to show whether circulating bone morphogenetic proteins (BMPs) levels are associated with increased risk of mortality in patients with pulmonary arterial hypertension (PAH).

Methods: A total of 156 patients with PAH including 43 with heritable PAH (HPAH) and 113 with idiopathic PAH (IPAH) diagnosed by gene screening were enrolled in the study. Circulating BMPs were measured by ELISA in plasma samples from patients with HPAH (n = 43) and IPAH (n = 113) and from control subjects (n = 51). Clinical characteristics at baseline and long-term survival were compared according to the different BMP levels.

Results: Patients with HPAH had significantly higher BMP7 concentrations than patients with IPAH and control subjects (20.1 [interquartile range (IQR), 9.4, 55.2] vs 6.5 [IQR, 3.5, 11.7] and 2.5 [IQR, 0.9, 6.6] pg/mL, respectively; P < .001). Elevated plasma BMP7 were associated with a higher risk of mortality after adjustment for sex, 6-minute walk distance, mean right atrial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output (HR, 1.904; 95% CI, 1.021-3.551; P = .043). Patients with IPAH with a BMP7 level > 7.85 pg/mL had a higher risk of mortality than those with a low BMP7 concentration (P = .042, log-rank test).

Conclusions: Levels of circulating BMP7 correlate with mortality in PAH, and may be a predictor of disease in patients with HPAH and IPAH.

Keywords: biomarker; bone morphogenetic protein 7; heritable pulmonary arterial hypertension; survival.