Abstract
Background: Atrial fibrillation (AF) is an important cause of stroke, for which anticoagulation provides substantial benefit. However, not all patients with AF will have a stroke. There remains uncertainty regarding factors that promote thromboembolism and stroke in patients with AF. In this study we examined differences in blood cell gene expression unique to AF in acute stroke to better understand factors important to atrial fibrillation thromboembolism in human stroke. Methods: Gene expression in blood was compared in acute stroke patients with AF to non-AF stroke and to controls without stroke. Blood was collected in PAXgene tubes, and leukocyte/platelet gene expression was measured by Affymetrix microarray. Differentially expressed genes were identified using ANOVA adjusted for age, sex and batch. Results: In the 184 patients studied, 40 were acute strokes with AF, 143 had non-AF acute stroke, and 116 were non-stroke controls. There were 43 genes unique to AF in patients with stroke, and 69 genes associated AF that were shared between AF stroke and controls (FDR<0.05, fold change>|1.5|). Functional analysis indicate acute stroke AF genes are associated with changes in the hematological system including blood cell rheology and leukocyte activation. In contrast non-stroke AF genes are associated cardiac hypertrophy and blood vessel injury. Conclusions: AF has differences in blood cell gene expression in acute stroke that may relate to risk of thromboembolism. Acute stroke patients with AF display changes in blood cell rheology and leukocyte activation; whereas non-stroke AF patients have changes in cardiac hypertrophy and vascular injury. These differences are important to understanding blood cell contribution to thrombus formation and stroke risk in patients with AF. Further study is required to assess the relationship of these gene changes to stroke risk and response to anticoagulation in patients with AF.
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