This study aimed to evaluate the ability of selected microRNAs as biomarkers of atrial fibrillation (AF) in ischemic stroke patients in comparison with other established biochemical biomarkers. A prospective case-control study of consecutive ischemic stroke patients with AF admitted to a comprehensive stroke center was conducted. The control group consisted of patients with ischemic stroke with no AF detected on prolonged (at least 3 weeks) Holter ECG monitoring. As potential biomarkers of AF, we analyzed the plasma levels of microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) and 13 biochemical biomarkers at admission. The predictive accuracy of biomarkers was assessed by calculating the area under the receiver operating characteristic curve. The data of 117 patients were analyzed (61 with AF, 56 with no AF, 46% men, median age 73 years, median National Institutes of Health Stroke Scale 6). Biochemical biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and total triglycerides) were significantly associated with AF. NT-proBNP had the best diagnostic performance for AF with area under the receiver operating characteristic curve 0.92 (95%, CI 0.86-0.98); a cutoff value of >528 ng/L had a sensitivity of 79% and a specificity of 97%. None of the other biomarkers, including microRNAs, was associated with AF. Conventional biochemical biomarkers (NT-proBNP, high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and triglycerides), but not microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) were significantly associated with AF in our ischemic stroke cohort.

Department of Clinical Biochemistry Hematology and Immunology Na Homolce Hospital Prague Czech Republic

Department of Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Motol Prague Czech Republic

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Chugh SS, Havmoeller R, Narayanan K, et al. . Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation. 2014;129:837–47. PubMed PMC

Lin HJ, Wolf PA, Kelly-Hayes M, et al. . Stroke severity in atrial fibrillation. The Framingham Study. Stroke. 1996;27:1760–4. PubMed

Kirchhof P, Benussi S, Kotecha D, et al. . 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37:2893–962. PubMed

Sposato LA, Cipriano LE, Saposnik G, Ruíz Vargas E, Riccio PM, Hachinski V. Diagnosis of atrial fibrillation after stroke and transient ischemic attack: a systematic review and meta-analysis. Lancet Neurol. 2015;14:377–87. PubMed

Koudstaal PJ. Anticoagulants versus antiplatelet therapy for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attacks. Cochrane Database Syst Rev. 2000;2:CD000187. PubMed

Hart RG, Sharma M, Mundl H, et al. . Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378:2191–201. PubMed

Diener HC, Sacco RL, Easton JD, et al. . Dabigatran for prevention of stroke after embolic stroke of undetermined source. N Engl J Med. 2019;380:1906–17. PubMed

Sanna T, Diener HC, Passman RS, et al. . Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370:2478–86. PubMed

Gladstone DJ, Spring M, Dorian P, et al. . Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370:2467–77. PubMed

Atkinson AC, Degruttola W, Demets V, et al. . Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95. PubMed

Dogan U, Dogan EA, Tekinalp M, et al. . P-wave dispersion for predicting paroxysmal atrial fibrillation in acute ischemic stroke. Int J Med Sci. 2012;9:108–14. PubMed PMC

Kolb C, Nürnberger S, Ndrepepa G, Zrenner B, Schömig A, Schmitt C. Modes of initiation of paroxysmal atrial fibrillation from analysis of spontaneously occurring episodes using a 12-lead Holter monitoring system. Am J Cardiol. 2001;88:853–7. PubMed

Phang RS, Isserman SM, Karia D, et al. . Echocardiographic evidence of left atrial abnormality in young patients with lone paroxysmal atrial fibrillation. Am J Cardiol. 2004;94:511–3. PubMed

Sakai K, Shibazaki K, Kimura K, et al. . Brain natriuretic peptide as a predictor of cardioembolism in acute ischemic stroke patients: brain natriuretic peptide stroke prospective study. Eur Neurol. 2013;69:246–51. PubMed

Longstreth WT, Jr, Kronmal RA, Thompson JL, et al. . Amino terminal pro-B-type natriuretic peptide, secondary stroke prevention, and choice of antithrombotic therapy. Stroke. 2013;44:714–9. PubMed PMC

Beaulieu-Boire I, Leblanc N, Berger L, Boulanger JM. Troponin elevation predicts atrial fibrillation in patients with stroke or transient ischemic attack. J Stroke Cerebrovasc Dis. 2013;22:978–83. PubMed

Chung MK, Martin DO, Sprecher D, et al. . C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation. 2001;104:2886–91. PubMed

Liuba I, Ahlmroth H, Jonasson L, et al. . Source of inflammatory markers in patients with atrial fibrillation. Europace. 2008;10:848–53. PubMed

Sandhu RK, Conen D, Tedrow UB, et al. . Predisposing factors associated with development of persistent compared with paroxysmal atrial fibrillation. J Am Heart Assoc. 2014;3:e000916. PubMed PMC

Lopez FL, Agarwal SK, Maclehose RF, et al. . Blood lipid levels, lipid-lowering medications, and the incidence of atrial fibrillation: the atherosclerosis risk in communities study. Circ Arrhythm Electrophysiol. 2012;5:155–62. PubMed PMC

Iguchi Y, Kimura K, Kobayashi K, et al. . Relation of atrial fibrillation to glomerular filtration rate. Am J Cardiol. 2008;102:1056–9. PubMed

Wu N, Tong S, Xiang Y, et al. . Association of hemostatic markers with atrial fibrillation: a meta-analysis and meta-regression. PLoS One. 2015;10:e0124716. PubMed PMC

Gilad S, Meiri E, Yogev Y, et al. . Serum microRNAs are promising novel biomarkers. PLoS One. 2008;3:e3148. PubMed PMC

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97. PubMed

Small EM, Frost RJ, Olson EN. MicroRNAs add a new dimension to cardiovascular disease. Circulation. 2010;121:1022–32. PubMed PMC

Liu Z, Zhou C, Liu Y, et al. . The expression levels of plasma micoRNAs in atrial fibrillation patients. PLoS One. 2012;7:e44906. PubMed PMC

McManus DD, Tanriverdi K, Lin H, et al. . Plasma microRNAs are associated with atrial fibrillation and change after catheter ablation (the miRhythm study). Heart Rhythm. 2015;12:3–10. PubMed PMC

Dawson K, Wakili R, Ordög B, et al. . MicroRNA29: a mechanistic contributor and potential biomarker in atrial fibrillation. Circulation. 2013;127:1466–75, 1475e1. PubMed

Thum T, Gross C, Fiedler J, et al. . MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456:980–4. PubMed

Ling TY, Wang XL, Chai Q, et al. . Regulation of the SK3 channel by microRNA-499—potential role in atrial fibrillation. Heart Rhythm. 2013;10:1001–9. PubMed PMC

Wang S, Min J, Yu Y, et al. . Differentially expressed miRNAs in circulating exosomes between atrial fibrillation and sinus rhythm. J Thorac Dis. 2019;11:4337–48. PubMed PMC

Adams HP, Bendixen BH, Kappelle LJ, et al. . Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke. 1993;24:35–41. PubMed

Ding M, Wennberg A, Gigante B, Walldius G, Hammar N, Modig K. Lipid levels in midlife and risk of atrial fibrillation over 3 decades-Experience from the Swedish AMORIS cohort: a cohort study. PLoS Med. 2022;19:e1004044. PubMed PMC

Chang SN, Tsai CT, Wu CK, et al. . A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation. J Intern Med. 2012;272:305–15. PubMed

Kumar P, Gehi AK. Atrial fibrillation and metabolic syndrome: understanding the connection. J Atr Fibrillation. 2012;5:647. PubMed PMC

Mukamal KJ, Tolstrup JS, Friberg J, Grønbaek M, Jensen G. Fibrinogen and albumin levels and risk of atrial fibrillation in men and women (the Copenhagen City Heart Study). Am J Cardiol. 2006;98:75–81. PubMed

Qureshi AI, Baskett WI, Huang W, et al. . Acute ischemic stroke and COVID-19: an analysis of 27 676 patients. Stroke. 2021;52:905–12. PubMed PMC

Scherrer N, Fays F, Mueller B, et al. . MicroRNA 150-5p improves risk classification for mortality within 90 days after acute ischemic stroke. J Stroke. 2017;19:323–32. PubMed PMC

Ma X, Yun HJ, Elkin K, Guo Y, Ding Y, Li G. MicroRNA-29b suppresses inflammation and protects blood-brain barrier integrity in ischemic stroke. Mediators Inflamm. 2022;2022:1755416. PubMed PMC

de Boer HC, van Solingen C, Prins J, et al. . Aspirin treatment hampers the use of plasma microRNA-126 as a biomarker for the progression of vascular disease. Eur Heart J. 2013;34:3451–7. PubMed

Oikawa S, Yuan S, Kato Y, Akimoto T. Skeletal muscle-enriched miRNAs are highly unstable in vivo and may be regulated in a Dicer-independent manner. FEBS J. 2023;290:5692–703. PubMed

Boxhammer E, Dienhart C, Rezar R, Hoppe UC, Lichtenauer M. Deciphering the role of microRNAs: unveiling clinical biomarkers and therapeutic avenues in atrial fibrillation and associated stroke-a systematic review. Int J Mol Sci. 2024;25:5568. PubMed PMC