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1H Nuclear Magnetic Resonance Spectroscopy Reveals Changes in Metabolic Phenotype Associated with Disease Stage in Patients with Chronic Venous Disease
Journal article   Open access   Peer reviewed

1H Nuclear Magnetic Resonance Spectroscopy Reveals Changes in Metabolic Phenotype Associated with Disease Stage in Patients with Chronic Venous Disease

Sarah Onida, Hannah J. Lees, Richmond Bergner, Joseph Shalhoub, Elaine Holmes and Alun H. Davies
European journal of vascular and endovascular surgery, Vol.69(2), pp.325-333
2025
PMID: 39303804
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Open Access CC BY V4.0

Abstract

Cardiovascular System & Cardiology Life Sciences & Biomedicine Peripheral Vascular Disease Science & Technology Surgery
Objective Chronic venous disease (CVD) is a condition presenting a great burden to patients and society, with poorly characterised pathophysiology. Metabolic phenotyping can elucidate mechanisms of disease and identify candidate biomarkers. The aim of this study was to determine differences in the metabolic signature between symptomatic patients with CVD and asymptomatic volunteers using proton nuclear magnetic resonance spectroscopy (H-1-NMR). Methods This was a prospective case control study of consecutive patients with symptomatic CVD and asymptomatic volunteers recruited from a single centre. Participants underwent clinical assessment, venous duplex ultrasound, and blood and urine sampling. Disease stage was defined according to the Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification. H-1-NMR experiments were performed, with data analysed via multivariable statistical techniques. Results A total of 622 participants were recruited, including 517 symptomatic patients with CVD (telangiectasia [C1] 0.6%, varicose veins [C2] 48.5%, swelling [C3] 12.0%, skin changes [C4] 27.7%, healed or active ulceration [C5/6] 11.2%) and 105 asymptomatic participants (no disease [C0] 69.5%, telangiectasia [C1] 29.6%). Multivariable analysis revealed differences between the metabolic profile of the symptomatic CVD and asymptomatic groups, and between CEAP clinical classes in the CVD group. Serum aromatic amino acids positively correlated with increasing CEAP clinical class (p < .001). Urinary formate, creatinine, glycine, citrate, succinate, pyruvate, and 2-hydroxyisobutyrate negatively correlated with increasing CEAP clinical class (p < .001). These metabolites are involved in the tricarboxylic acid cycle, hypoxia inducible factor pathway, and one carbon metabolism. Conclusion Untargeted biofluid analysis via H-1-NMR has detected metabolites associated with the presence and severity of CVD, highlighting biological pathways of relevance and providing candidate biomarkers to explore in future research.

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