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 |
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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 |
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