In addition, after adjustment for patient age, sex and major IPAH prognostic factors (NYHA class, 6MWD, PVR and NT-proBNP) and NOTCH3-ECD in Cox’s multivariate regression, the risk of 3-year mortality rose by 18% per 3 ng ml−1 of serum NOTCH3-ECD above the diagnostic cutoff of 13.0 ng ml−1 (HR 1.18 (95% CI, 1.07–1.30); P < 0.001) (Fig. 4c). This evidence concerns the gene NPPB and idiopathic pulmonary arterial hypertension.