Comparative evaluation of traditional and novel biomarkers for pulmonary hypertension across clinical subtypes.

Objectives

This study aimed to compare the auxiliary diagnostic performances of traditional biomarkers, including B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), and novel biomarkers, including N-terminal insulin-like growth factor-binding protein 4, soluble suppression of tumorigenicity 2, and growth differentiation factor 15 (GDF-15), for pulmonary hypertension (pH) and its clinical subtypes.

Methods

This retrospective single-center study included 228 patients with PH and 213 healthy controls. Patients with PH were grouped based on the four World Health Organization clinical subtypes: I (n = 101), II (n = 53), III (n = 33), and IV (n = 41). The biomarker concentrations were compared across the groups and PH subtypes. Receiver operating characteristic curve analysis was performed to assess diagnostic performance. The optimal cutoff values were determined using the Youden index, and diagnostic performance was assessed based on sensitivity, specificity, and positive and negative predictive values.

Results

All biomarker concentrations were significantly elevated in patients with PH versus healthy controls. GDF-15 and NT-proBNP showed the best overall performance (AUCs: 0.96 and 0.95), while their combination achieved an AUC of 0.99. When each PH subtype was compared separately with healthy controls, NT-proBNP and GDF-15 showed high discriminatory performance across several subtype-specific comparisons. In contrast, direct discrimination among PH subtypes was limited (all AUCs <0.85).

Conclusions

GDF-15 and NT-proBNP showed strong auxiliary discriminatory performance for PH versus healthy controls, whereas their ability to distinguish PH subtypes was limited. Subtype-oriented biomarker interpretation therefore remains exploratory and requires further validation.