Metabolic Markers as Potential Risk Factors in Pulmonary Hypertension

Pulmonary hypertension (PH) is a condition characterized by elevated mean pulmonary arterial pressure confirmed by right heart catheterization. PH involves both structural and functional changes in the pulmonary vascular bed. Since 2022, a four-level risk stratification has been used to predict 1-year mortality at follow-up. This system is based on the World Health Organization Functional Classification (WHO-FC), 6-min walk distance, and the pro-Brain Natriuretic Peptide level combined. This study included 47 patients with suspected PH. Of these, 40 were diagnosed with PH while 7 was not, and 6 were included as similarly presenting controls. Untargeted metabolomics using ultra-high pressure liquid chromatography mass spectrometry (UHPLC-MS), and gas chromatography mass spectrometry (GC-MS) showed correlations with both risk strata and their component measurements: N-terminal pro-brain natriuretic peptide (NT-proBNP), World Health Organization Functional Class (WHO-FC), and the 6-min walk distance (6MWD). There was a greater overlap in metabolites associated with WHO-FC or 6MWD than between either of them and NT-proBNP. Several of these metabolites showed the same pattern in a verification data set of 35 PH patients. In conclusion, metabolic patterns in pulmonary hypertension (PH) are related to the predicted risk of disease progression. The clinical variables that contribute to prognostic stratification have overlapping but distinct metabolic associations. Further research is needed to verify how these patterns relate to disease progression in a longitudinal cohort. Metabolomics provides a potential new tool for defining risk in PH.