title: Atrial fibrillation and hypercoagulability: dependent on clinical factors or/and on genetic alterations?
abstract: It is well known that atrial fibrillation is associated with high incidence of thromboembolic events, propably due to a prothrombotic or hypercoagulable state. However, it is unclear whether or not there is any difference of this prothrombotic state in the clinical subgroups of atrial fibrillation patients, that is, in those with paroxysmal, persistent or permanent atrial fibrillation. From the other side the role of the arrhythmia duration on the changes of coagulative variables in atrial fibrillation patients is not clearly enough. The contribution of genetic and functional alterations in factors of the coagulation and fibrinolytic pathways (that is hemostatic risk factors) to the development of hypercoagulation state in atrial fibrillation requires clarification. We investigated therefore (1) if there are differences in the prothrombotic state between patients with different clinical status of the arrhythmia, (2) if the arrhythmia duration per se could be an independent determinant of the prothrombotic state in all atrial fibrillation patients and (3) if coexistent genetic alterations in haemostatic risk factors in patients with atrial fibrillation could contribute to the development of prothrombotic abnormalities.
  
  
  METHODS
  Over a period of 23 months, we studied 55 patients with chronic non-valvular atrial fibrillation. We recruited 18 consecutive patients (13 men, mean age 59 +/- 10 years) with paroxysmal atrial fibrillation 17 patients (11 men, mean age 61 +/- 7 years) with persistent atrial fibrillation who underwent elective successful DC and remained in sinus rhythm at the 3 month visit and 20 patients (14 men mean age 64 +/- 9) with permanent atrial fibrillation. Blood results were compared to 17 age-sex- and race-matched controls. The prothrombotic state was quantified by measurement of plasma levels of fibrinogen, soluble P -selectin (an index of platelet activation) and von Willebrand factor (a marker of endothelial dysfunction). We assessed the frequencies of factor V Leiden and prothrombin variant G20210A to determine whether particular inherited haemostatic risk factors may have contribution to the development of prothrombotic state in atrial fibrillation patients.
  
  
  RESULTS
  Permanent atrial fibrillation was associated with significant raised levels of von Willebrand factor, fibrinogen levels and soluble P -selectin compared to matched controls (all p < 0.001) and matched patients with paroxysmal and permanent AF (all p ranged between <0.003 and <0.002). Patients with persistent atrial fibrillation had significantly elevated von Willebrand factor levels (p = 0.0064) and fibrinogen levels (p = 0.002), but not Soluble P -selectin (p = 0.509). when compared to controls. Patients with paroxysmal atrial fibrillation had significantly elevated levels of P -selectin (p = 0.005) and fibrinogen (p = 0.003), but not von Willebrand factor (p =.0.61) compared to controls. Stepwise multiple regression analyses demonstrated that the arrhythmia duration (approximately 3 years) was an independent predictor of abnormal von Willebrand factor, fibrinogen and soluble P -selectin levels. Restoration of sinus rhythm in paroxysmal atrial fibrillation subgroup and successful electrical cardioversion of patients with permanent fibrillation atrial fibrillation did not significantly alter levels of the affected factors. The frequency of factor V Leiden was 8.9 in all studied patients with atrial fibrillation, versus 2.4% in the control group (odds ratio [OR] 4.6 [95% confidence (CI) 1.4-17.5], p = 0.02). The frequency of the prothrombin variant G20210A was 6.4.% compared with control group 1.6% (OR 4.9 [95% confidence interval (CI) 1.2-2.9], p = 0.04). There was a trend towards an increased frequency of factor V Leiden and/or prothrombin variant G20210A in patients age <55 years and in patients living at a particular area of Thrace mountains.
  
  
  CONCLUSIONS
  Our results showed that there were significant differences in the prothrombotic state when patients with paroxysmal, and persistent atrial fibrillation were compared to matched that there were significant differences in the prothrombotic state when patients with paroxysmal, and persistent atrial fibrillation were compared to matched patients with permanent atrial fibrillation and controls in sinus rhythm. The duration of the arrhythmia (about 3 years) was an independent predictor of abnormal measured factors. We found for the first time that some genetic alterations in haemostatic risk factors could be coexist in atrial fibrillation patients and may be a contributor to the development of hypercoagulability in atrial fibrillation patients.
authors.affiliation: Academic Cardiology Department, Demokritious University of Thrace, Greece. kokoy@otenet.gr
authors.forename: Eleni
authors.initials: E
authors.lastname: Hatzinikolaou-Kotsakou
authors.forename: Zarifis
authors.initials: Z
authors.lastname: Kartasis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tziakas
authors.forename: Athanasios
authors.initials: A
authors.lastname: Hotidis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Stakos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tsatalas
authors.forename: Georgios
authors.initials: G
authors.lastname: Bourikas
authors.forename: Maria E
authors.initials: ME
authors.lastname: Kotsakou
authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Hatseras
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005165:Factor V; D005260:Female; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011516:Prothrombin / Q000235:genetics; D019851:Thrombophilia / Q000097:blood / Q000209:etiology* / Q000235:genetics; D013997:Time Factors
chemical_list: D015415:Biomarkers; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin