Biomarkers in Carotid and Peripheral Artery Disease: Unravelling pieces of the complex atherosclerotic puzzle

Joost Mekke

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)

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Abstract

This dissertation investigates the relationship between biomarkers and cardiovascular event risks after vascular surgeries on the carotid and femoral arteries. It aims to identify plaque-, plasma-, and extracellular vesicle-based biomarkers linked to increased MACE (Major Adverse Cardiovascular Events) or MALE (Major Adverse Limb Events) risk to improve future risk stratification.

Part I focuses on atherosclerotic plaques. Mast cell density was highest in “culprit” lesions and linked to vulnerability. Red blood cell accumulation in plaques was associated with instability, particularly in men, and related to neurological symptoms before CEA. Accumulation was also linked to plaque hemorrhages, suggesting a role in instability.

Part II examines biomarkers in CEA patients. Extracellular vesicle biomarkers had stronger associations with MACE than plasma or plaque counterparts. Plasma LPL showed a time-dependent risk association: higher risk in the first 30 days but lower risk from 30 days to 3 years. Blood cell features like RDW, MCV, and neutrophil size were independently linked to MACE and are measurable with routine clinical tools.

Part III explores PAD patients undergoing FEA. Both MACE and MALE risks were assessed, with CD14, Serpin G1, and lipoprotein(a) identified as key markers. CD14 and Serpin G1 were linked to MACE, while Serpin G1 and lipoprotein(a) were associated with MALE. These findings highlight potential biomarkers for tailored treatment and risk stratification in PAD patients.
Original languageEnglish
Awarding Institution
  • University Medical Center (UMC) Utrecht
Supervisors/Advisors
  • de Borst, Gert Jan, Supervisor
  • de Kleijn, Dominique, Supervisor
  • van der Laan, Sander, Co-supervisor
  • Haitjema, Saskia, Co-supervisor
Award date6 Feb 2025
Publisher
Print ISBNs978-94-6506-758-2
DOIs
Publication statusPublished - 6 Feb 2025

Keywords

  • biomarkers
  • atherosclerosis
  • plaque
  • plasma
  • cardiovascular disease
  • carotid artery disease
  • peripheral artery disease
  • endarterectomy

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