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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2022-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-23260-3
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author 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
author_facet 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
author_sort B. M. M. Kremers
collection DOAJ
description 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.
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spelling doaj.art-bd28060179a54b96bcf1f45168168df32022-12-22T04:38:25ZengNature PortfolioScientific Reports2045-23222022-11-011211710.1038/s41598-022-23260-3Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery diseaseB. M. M. Kremers0J. N. Posma1S. Heitmeier2J. Glunz3H. ten Cate4A. Pallares Robles5J. H. C. Daemen6A. J. ten Cate-Hoek7B. M. E. Mees8H. M. H. Spronk9Laboratory for Clinical Thrombosis and Hemostasis, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht UniversityLaboratory for Clinical Thrombosis and Hemostasis, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht UniversityBayer AGBayer AGLaboratory for Clinical Thrombosis and Hemostasis, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht UniversityCenter for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-UniversityDepartment of Vascular Surgery, Maastricht University Medical CenterLaboratory for Clinical Thrombosis and Hemostasis, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht UniversityDepartment of Vascular Surgery, Maastricht University Medical CenterLaboratory for Clinical Thrombosis and Hemostasis, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht UniversityAbstract 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.https://doi.org/10.1038/s41598-022-23260-3
spellingShingle 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
Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease
Scientific Reports
title Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease
title_full Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease
title_fullStr Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease
title_full_unstemmed Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease
title_short Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease
title_sort discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease
url https://doi.org/10.1038/s41598-022-23260-3
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