Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease

B M M Kremers*, J N Posma, S Heitmeier, J Glunz, H Ten Cate, A Pallares Robles, J H C Daemen, A J Ten Cate-Hoek, B M E Mees, H M H Spronk

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Peripheral artery disease (PAD) patients have an increased cardiovascular risk despite pharmacological treatment strategies. Biomarker research improving risk stratification only focused on known atherothrombotic pathways, but unexplored pathways might play more important roles. To explore the association between a broad cardiovascular biomarker set and cardiovascular risk in PAD. 120 PAD outpatients were enrolled in this observational cohort study. Patients were followed for one year in which the composite endpoint (myocardial infarction, coronary revascularization, stroke, acute limb ischemia and mortality) was assessed. Patient data and blood samples were collected upon inclusion, and citrated platelet-poor plasma was used to analyze 184 biomarkers in Olink Cardiovascular panel II and III using a proximity extension assay. Fifteen patients reached the composite endpoint. These patients had more prior strokes and higher serum creatinine levels. Multivariate analysis revealed increased plasma levels of protease-activated receptor 1 (PAR1), galectin-9 (Gal-9), tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) and interleukin 6 (IL-6) to be most predictive for cardiovascular events and mortality. Positive regulation of acute inflammatory responses and leukocyte chemotaxis were identified as involved biological processes. This study identified IL-6, PAR1, Gal-9, TNFRSF11A as potent predictors for cardiovascular events and mortality in PAD, and potential drug development targets.

Original languageEnglish
Article number18388
Number of pages7
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - 1 Nov 2022

Keywords

  • Humans
  • Receptor, PAR-1
  • Interleukin-6/therapeutic use
  • Risk Factors
  • Peripheral Arterial Disease
  • Stroke
  • Biomarkers
  • Treatment Outcome

Cite this