Biomarkers Associated with Atrial Fibrillation in Patients with Ischemic Stroke: A Pilot Study from the NOR-FIB Study.
Aged
Aged, 80 and over
Atrial Fibrillation
/ blood
Biomarkers
/ blood
Brain Ischemia
/ blood
C-Reactive Protein
/ analysis
Case-Control Studies
Female
Growth Differentiation Factor 15
/ blood
Humans
Incidence
Inflammation Mediators
/ blood
Interleukin-6
/ blood
Ischemic Attack, Transient
/ blood
Male
Middle Aged
Norway
/ epidemiology
Pilot Projects
Predictive Value of Tests
Risk Assessment
Risk Factors
Serum Amyloid P-Component
/ analysis
Stroke
/ blood
Atrial fibrillation
Biomarkers
Cryptogenic stroke
Inflammation
Ischemic stroke
Journal
Cerebrovascular diseases extra
ISSN: 1664-5456
Titre abrégé: Cerebrovasc Dis Extra
Pays: Switzerland
ID NLM: 101577885
Informations de publication
Date de publication:
2020
2020
Historique:
received:
10
07
2019
accepted:
04
11
2019
pubmed:
7
2
2020
medline:
23
6
2020
entrez:
7
2
2020
Statut:
ppublish
Résumé
Cardioembolic stroke due to paroxysmal atrial fibrillation (AF) may account for 1 out of 4 cryptogenic strokes (CS) and transient ischemic attacks (TIAs). The purpose of this pilot study was to search for biomarkers potentially predicting incident AF in patients with ischemic stroke or TIA. Plasma samples were collected from patients aged 18 years and older with ischemic stroke or TIA due to AF (n = 9) and large artery atherosclerosis (LAA) with ipsilateral carotid stenosis (n = 8) and age- and sex-matched controls (n = 10). Analyses were performed with the Olink technology simultaneously measuring 184 biomarkers of cardiovascular disease. For bioinformatics, acquired data were analyzed using gene set enrichment analysis (GSEA). Selected proteins were validated using ELISA. Individual receiver operating characteristic (ROC) curves and odds ratios from logistic regression were calculated. A randomForest (RF) model with out-of-bag estimate was applied for predictive modeling. GSEA indicated enrichment of proteins related to inflammatory response in the AF group. Interleukin (IL)-6, growth differentiation factor (GDF)-15, and pentraxin-related protein PTX3 were the top biomarkers on the ranked list for the AF group compared to the LAA group and the control group. ELISA validated increased expression of all tested proteins (GDF-15, PTX3, and urokinase plasminogen activator surface receptor [U-PAR]), except for IL-6. 19 proteins had the area under the ROC curve (AUC) over 0.85 including all of the proteins with significant evolution in the logistic regression. AUCs were very discriminant in distinguishing patients with and without AF (LAA and control group together). GDF-15 alone reached AUC of 0.95. Based on RF model, all selected participants in the tested group were classified correctly, and the most important protein in the model was GDF-15. Our results demonstrate an association between inflammation and AF and that multiple proteins alone and in combination may potentially be used as indicators of AF in CS and TIA patients. However, further studies including larger samples sizes are needed to support these findings. In the ongoing NOR-FIB study, we plan further biomarker assessments in patients with CS and TIA undergoing long-term cardiac rhythm monitoring with insertable cardiac monitors.
Sections du résumé
BACKGROUND AND PURPOSE
OBJECTIVE
Cardioembolic stroke due to paroxysmal atrial fibrillation (AF) may account for 1 out of 4 cryptogenic strokes (CS) and transient ischemic attacks (TIAs). The purpose of this pilot study was to search for biomarkers potentially predicting incident AF in patients with ischemic stroke or TIA.
METHODS
METHODS
Plasma samples were collected from patients aged 18 years and older with ischemic stroke or TIA due to AF (n = 9) and large artery atherosclerosis (LAA) with ipsilateral carotid stenosis (n = 8) and age- and sex-matched controls (n = 10). Analyses were performed with the Olink technology simultaneously measuring 184 biomarkers of cardiovascular disease. For bioinformatics, acquired data were analyzed using gene set enrichment analysis (GSEA). Selected proteins were validated using ELISA. Individual receiver operating characteristic (ROC) curves and odds ratios from logistic regression were calculated. A randomForest (RF) model with out-of-bag estimate was applied for predictive modeling.
RESULTS
RESULTS
GSEA indicated enrichment of proteins related to inflammatory response in the AF group. Interleukin (IL)-6, growth differentiation factor (GDF)-15, and pentraxin-related protein PTX3 were the top biomarkers on the ranked list for the AF group compared to the LAA group and the control group. ELISA validated increased expression of all tested proteins (GDF-15, PTX3, and urokinase plasminogen activator surface receptor [U-PAR]), except for IL-6. 19 proteins had the area under the ROC curve (AUC) over 0.85 including all of the proteins with significant evolution in the logistic regression. AUCs were very discriminant in distinguishing patients with and without AF (LAA and control group together). GDF-15 alone reached AUC of 0.95. Based on RF model, all selected participants in the tested group were classified correctly, and the most important protein in the model was GDF-15.
CONCLUSIONS
CONCLUSIONS
Our results demonstrate an association between inflammation and AF and that multiple proteins alone and in combination may potentially be used as indicators of AF in CS and TIA patients. However, further studies including larger samples sizes are needed to support these findings. In the ongoing NOR-FIB study, we plan further biomarker assessments in patients with CS and TIA undergoing long-term cardiac rhythm monitoring with insertable cardiac monitors.
Identifiants
pubmed: 32028277
pii: 000504529
doi: 10.1159/000504529
pmc: PMC7036587
doi:
Substances chimiques
Biomarkers
0
GDF15 protein, human
0
Growth Differentiation Factor 15
0
IL6 protein, human
0
Inflammation Mediators
0
Interleukin-6
0
Serum Amyloid P-Component
0
PTX3 protein
148591-49-5
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11-20Informations de copyright
© 2020 The Author(s) Published by S. Karger AG, Basel.
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