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Published on: June 27, 2025
Metabolic Markers as Potential Risk Factors in Pulmonary Hypertension
Sarah McGarrity1,2, Pär I Johansson1,2,3, Jørn Carlsen1,3,4
1CAG Center for Endotheliomics Copenhagen University Hospital - Rigshospitalet Copenhagen Denmark.
Pulmonary Circulation
|July 28, 2026
Summary
Metabolomic patterns in pulmonary hypertension (PH) correlate with disease risk. Specific metabolites link to clinical markers like World Health Organization Functional Class (WHO-FC) and 6-min walk distance (6MWD), offering new risk assessment tools.
Area of Science:
- Biochemistry
- Cardiovascular Medicine
- Pulmonology
Background:
- Pulmonary hypertension (PH) involves complex vascular changes and requires accurate risk stratification for patient management.
- Current risk assessment combines World Health Organization Functional Classification (WHO-FC), 6-min walk distance (6MWD), and N-terminal pro-Brain Natriuretic Peptide (NT-proBNP).
- The relationship between metabolic profiles and established clinical risk factors in PH remains an area for further investigation.
Purpose of the Study:
- To investigate the association between untargeted metabolomic profiles and clinical risk stratification parameters in patients with pulmonary hypertension.
- To explore the distinct and overlapping metabolic signatures related to WHO-FC, 6MWD, and NT-proBNP.
- To assess the potential of metabolomics as a novel tool for risk assessment in PH.
Main Methods:
- Untargeted metabolomics was performed using ultra-high pressure liquid chromatography mass spectrometry (UHPLC-MS) and gas chromatography mass spectrometry (GC-MS).
- Analysis included 47 patients with suspected PH (40 diagnosed), with a verification set of 35 PH patients.
- Metabolite correlations were examined against risk strata and clinical measurements (WHO-FC, 6MWD, NT-proBNP).
Main Results:
- Metabolomic patterns demonstrated significant correlations with PH risk strata and its component clinical measurements.
- Distinct metabolic associations were observed for WHO-FC, 6MWD, and NT-proBNP, with greater overlap between WHO-FC and 6MWD.
- Identified metabolite patterns were validated in an independent cohort of PH patients.
Conclusions:
- Metabolic profiles in PH are intrinsically linked to predicted disease progression risk.
- Clinical variables used for prognostic stratification possess unique yet overlapping metabolic correlates.
- Metabolomics offers a promising avenue for refining risk stratification and understanding disease mechanisms in pulmonary hypertension.
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