Biomarkers Associated with Atrial Fibrillation in Patients with Ischemic Stroke: A Pilot Study from the NOR-FIB Study

Autor: Barbara Ratajczak-Tretel, Dan Atar, Anna Tancin Lambert, Huseyin Firat, Matthieu Coq, Eric Schordan, Xiang Yi Kong, David Russell, Karolina Skagen, Bente Halvorsen, Anne Hege Aamodt, Vigdis Bjerkeli, Mona Skjelland
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
lcsh:Diseases of the circulatory (Cardiovascular) system
Pilot Projects
Disease
030204 cardiovascular system & hematology
Logistic regression
Brain Ischemia
0302 clinical medicine
Risk Factors
atrial fibrillation
Aged
80 and over

Norway
Incidence
Atrial fibrillation
PTX3
Middle Aged
Stroke
Serum Amyloid P-Component
C-Reactive Protein
Neurology
Ischemic Attack
Transient

Cardiology
cryptogenic stroke
Biomarker (medicine)
Female
Inflammation Mediators
Cardiology and Cardiovascular Medicine
medicine.medical_specialty
Growth Differentiation Factor 15
Risk Assessment
03 medical and health sciences
Predictive Value of Tests
Internal medicine
medicine
ischemic stroke
Humans
Aged
Original Paper
Receiver operating characteristic
Interleukin-6
business.industry
biomarkers
Odds ratio
medicine.disease
Stenosis
inflammation
lcsh:RC666-701
Case-Control Studies
Neurology (clinical)
business
030217 neurology & neurosurgery
Zdroj: Cerebrovascular Diseases Extra, Vol 10, Iss 1, Pp 11-20 (2020)
Cerebrovascular Diseases Extra
ISSN: 1664-5456
Popis: Background and Purpose: 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: 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: 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: 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.
Databáze: OpenAIRE