# Metabolomische subtypen voorspellen herinterventie bij perifere arteriële ziekte

*geplaatst 2026-11-13 · Cholesterol · Journal of proteome research · doi 10.1021/acs.jproteome.6c00439 · https://hartvaat.nl/2026/11/06/metabolomische-subtypen-voorspellen-herinterventie-bij-perifere-arteriele-ziekte/*

Onderzocht werd bij 175 patiënten met perifere arteriële ziekte (PAZ) na revascularisatie of moleculaire subtypen voorspellend zijn voor herinterventie. Met behulp van ongestuurde plasma-metabolomica werden drie subtypen geïdentificeerd; het subtype 'metabolische belasting' was geassocieerd met een hoger risico op herinterventie en MACE, gekenmerkt door ophoping van acylcarnitinen en ontstekingsmediatoren. Een vijf-metabolietenscore discrimineerde beter dan bestaande klinische modellen. Deze bevindingen bieden een kader voor moleculaire subtypen bij PAZ, maar de klinische toepassing vereist nog validatie in grotere cohorts.

## English: Untargeted Plasma Metabolomics Reveals Molecular Subtypes Associated with Reintervention Risk in Peripheral Artery Disease after Revascularization.

Researchers performed untargeted plasma metabolomics in 175 patients with peripheral artery disease following revascularization to identify molecular subtypes linked to reintervention risk. Three distinct metabolic profiles emerged, with the metabolic-burden subtype showing a higher risk of reintervention and major adverse cardiovascular events, driven by acylcarnitine accumulation and inflammatory lipid mediators. A five-metabolite risk score demonstrated superior discrimination compared to conventional clinical models. While this metabolomics framework offers a promising tool for risk stratification in PAD, external validation is needed before clinical implementation.

## Abstract (original, from the publication)

Peripheral artery disease (PAD) shows substantial outcome heterogeneity after revascularization that is incompletely explained by conventional severity indicators. We performed untargeted plasma LC-MS metabolomics in 175 PAD patients undergoing revascularization and applied variability-based feature selection, unsupervised clustering, pathway and chemical-class analyses, survival modeling, and metabolite prioritization. Three metabolically defined molecular subtypes were identified: redox protective (n = 93), metabolic burden (n = 72), and renal dysfunction (n = 10). Compared to the redox-protective subtype, the metabolic-burden subtype showed higher risks of composite adverse outcomes, reintervention, and major adverse cardiovascular events, accompanied by acylcarnitine accumulation, fatty-acyl enrichment, and COX-prostaglandin-related inflammatory signaling. Secondary clustering of high-risk patients identified a subgroup with increased reintervention risk, despite no corresponding increase in Rutherford classification or ankle-brachial index severity, characterized by sphingomyelin, diglyceride, and thromboxane/leukotriene-related lipid mediator signatures. A five-metabolite score was associated with reintervention risk and showed numerically higher apparent discrimination than the original and expanded clinical models. These findings establish an untargeted metabolomics framework for molecular subtyping of PAD after revascularization and nominate metabolic phenotypes for future validation.

Auteurs: Bowen Zhang, Yifan Cao, Wenxin Zhao, Jiayin Luo, Xiaolu Li, Xihao Zhang, Zhengxi Xu, Jiyang Wang, Zuoguan Chen, Lidan Chen, Yongpeng Diao, Yongjun Li

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Bron: Journal of proteome research, https://doi.org/10.1021/acs.jproteome.6c00439. Bijgewerkt 2026-11-07T02:03:38Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.