Abstract
BackgroundAtrial fibrillation (AF) is associated with a 5-fold increased risk of thromboembolic stroke. Extracellular vesicles (EVs) convey pathophysiological information and are possible biomarkers for risk of stroke. MethodsEVs were measured in 836 patients with AF (of which 280 were stroke cases) selected from the ARISTOTLE trial and in a cohort of unselected 70 year old individuals (n = 1007, reference material). EVs from platelets, leukocytes, erythrocytes and inflammatory endothelial cells were measured using flow cytometry and a solid-phase proximity ligation assay. ResultsConcentrations of EVs were higher in the ARISTOTLE patients than in the PIVUS cohort for all the EV groups except EVs from endothelial cells (p < 0.0001). The distributions of the concentrations of the EVs were similar among the control group and the stroke cases for all of the sources of EVs in the ARISTOTLE study. EVs were modestly correlated with the levels of NT-ProBNP, Cystatin C, GDF-15 and D-dimer. Stronger correlations were found for platelet EVs as well as phosphatidyl serine positive EVs that were correlated with CD40 ligand in the ARISTOTLE study. Leukocyte EVs were correlated with IL-6 in both the ARISTOTLE and the PIVUS study, implicating them in different physiological processes. ConclusionsHigher levels of EVs were found in anticoagulated patients with AF and a higher risk of stroke than in a general population of similar age, possibly due to the high disease burden in AF patients. Our data with EVs representing a broad repertoire of activated blood cells in AF patients suggest that EVs are likely not a key mediator of occurrence of stroke in this population.
Highlights
Atrial fibrillation (AF), the most common clinical cardiac arrhythmia, is a growing condition in elderly globally [1,2,3]
Since Extracellular vesicles (EVs) are known to be pro-coagulant and previous studies have demonstrated platelet derived-EVs and endothelial derived-EVs to be elevated in AF and stroke [13,14,20], we hypothesized that EVs could be associated with stroke in patients anticoagulated for AF
Our results from the ARISTOTLE study with data from 818 individuals show, that EVs in the populations studied are not associated with thrombotic events in patients with AF during treatment with anticoagulation, and that EVs appear not be key mediators of the pathophysiology of stroke in patients with AF on anticoagulant treatment
Summary
Atrial fibrillation (AF), the most common clinical cardiac arrhythmia, is a growing condition in elderly globally [1,2,3]. Extracellular vesicles (EVs) have been associated with AF in several studies [13,14] and elevated levels of TFbearing EVs have been found in AF-patients [15]. AF-patients with left atrial thrombi had increased levels of PS + EVs compared to AF patients with no thrombi [16] Due to their inflammatory and thrombogenic properties, EVs have been proposed to contribute to the pathogenic process and the increased thrombotic risk characterizing AF [15,16,17,18,19]. Results: Concentrations of EVs were higher in the ARISTOTLE patients than in the PIVUS cohort for all the EV groups except EVs from endothelial cells (p < 0.0001). Our data with EVs representing a broad repertoire of activated blood cells in AF patients suggest that EVs are likely not a key mediator of occurrence of stroke in this population
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