The interconnected pathophysiological pathways as inflammation, fibrosis and hypercoagulation are in pathogenesis of atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is the most commonly sustained and heterogeneous type of arrhythmia. Several prothrombotic factors have been found to be elevated in AF, indicating abnormal thrombogenesis. So, tissue factor (TF) is the principal initiator of the coagulation cascade for promotions blood coagulation. Factor XII (FXII) plays an important role in the next stages of coagulation, namely the spread and stabilization of thrombi. AF is associated with structural and functional myocardial abnormalities in particular with atrial structural changes that have mostly the inflammatory basis. There has recently been much interest in the relationship between systemic inflammations, fibrosis and coagulation cascade in patients with AF. The aim of this study is to explore the relationship between inflammation, fibrosis and the prothrombotic state in the setting of AF, including the impact of this interaction on clinical presentation in patients with AF. Methods After successful cardioversion, 183 patients (average age 68±6.6) with IHD and AH non-valular paroxysmal and persistent AF were enrolled. As a control group similar in gender and age composition 88 patients with IHD and AH without AF were examined. All participants underwent the physical examination including echocardiography and 24-hour ambulatory Holter monitoring. Levels of high sensitive C reactive protein (hs-CRP), interlekine-6 (IL-6), tumor necrosis factor-α (TNF-α), TF, FXII, as well as transforming growth factor (TGF-β1) were measured by ELISA on the analyzer "Stat Fax 303 Plus". Studies were conducted on the basis of simple randomized open-label protocols, using the universal statistical packages SPSS 13.0. Results The analysis of the data showed the significant differences between the levels of hs-CRP, IL-6, TNF-α and TGF-β1 among patients with AF and the control group (7.7±1.4 vs. 2. 2± 0.6 p = 0.002; 37.6± 7.1 vs. 15.2± 5.3 p = 0.03; 14.±3, 1 vs. 8.6±4.1 p = 0.01; 1240± 75.vs 900±43 p = 0.02 accordingly). It was found that in patients with AF compared with similar patients without AF the levels of TF and FXII were increased (1300±50.4 vs 600±11.9 p=0.026; 231.4±65.4 vs 125.4±46.4 p=0.033). It was revealed the correlations between IL-6 and LAD (r= 0.464), hs-CRP and LAV (r= 0.379), as well as between TGF-β1and LAD (r= 0.479), TF and LAV (r= 0.543) and between TGF-β1 and TF. (r= 0.423). Moreover, plasma levels of TGF-β1 and TF were higher among AF patients at "high" risk of stroke by CHA2DS2-VASc Score (p = 0.001; p = 0.003). Besides the levels of IL-6 and TGF-β1 are markedly elevated in patients with dilated left atrium (p = 0.001), poorly functioning left atrial appendage (p = 0.023) and longer duration of AF (p = 0.002). Conclusion we have demonstrated that fibrosis and inflammation together with coagulation cascade are the pathophysiological pathways in pathogenesis of AF.