Exploratory assessment of catestatin and thrombospondin-1 as potential biomarkers of disease severity and treatment response in pulmonary arterial hypertension

PURPOSE: Pulmonary arterial hypertension (PAH) is a rare disease associated with high morbidity and mortality. This exploratory study evaluated the effects of treatment escalation on cardiac function and circulating biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), catestatin, and thrombospondin-1 (TSP-1), as potential markers of disease severity and treatment response. METHODS: Twenty-six patients with PAH were prospectively followed. Echocardiographic and biochemical parameters were assessed at baseline and after 3, 6, and 18 months. Five patients died during follow-up; longitudinal analyses included 21 patients with complete data. Patients received dual or triple combination therapy according to clinical indications. Owing to the observational design and limited sample size, all analyses were considered exploratory and hypothesis-generating. RESULTS: Patients receiving triple therapy showed a greater decline in left ventricular ejection fraction, larger increases in NT-proBNP, and higher rehospitalization rates than those receiving dual therapy. Catestatin and TSP-1 were associated with clinical stability and survival. However, treatment escalation was preferentially applied to patients with more severe disease; therefore, observed differences between treatment groups likely reflect baseline disease severity and confounding by indication rather than treatment efficacy. Observed differences between treatment groups should be interpreted cautiously because treatment escalation was preferentially applied to patients with more severe disease. CONCLUSIONS: In this exploratory single-centre study, catestatin and TSP-1 demonstrated potential associations with disease severity and clinical outcomes in PAH. These findings are preliminary and hypothesis-generating. Larger multicentre studies are required to validate their prognostic value before clinical application.