The aim was to study the contribution of the novel markers to the prediction of thromboembolic complications (TE) in patients with non-valvular atrial fibrillation (AF).
Material and methods. The objects of the cohort prospective study were 102 patients with non-valvular AF and 0-2 additional clinical risk factors, except female gender (CHA2DS2-VASc score ≤2 in men and ≤ 3 in women). Special methods of investigation included the genotyping of the polymorphisms: G(-455)A of the fibrinogen B gene (FBG), G10976A – the factor VII gene (FVII), the C807T – the integrin α2 gene (ITGα2), the T1565C – the integrin β3 gene (ITGβ3) and the C3550T – the glycoprotein gene Ibα (GPIbα), determination of plasma concentration of VII and XII coagulation factors and plasma fibrinogen level. The follow-up period was 36 months. Endpoints were ischemic stroke, transient ischemic attack, or systemic TE.
Results. Endpoints were registered in 14 (13,7%) patients: ischemic stroke – in 13 (92,9%) cases, transient ischemic attack – in one patient (7,1%). Three (21,4%) adverse events occurred during the first year, 5 (35,7%) – during the second year and 6 (42,9%) – during the third year of follow-up. In patients with one additional risk factor (RF) while being enrolled into the study, the actual frequency of TE complications during the follow-up period exceeded the expected frequency by 3,1 times, in patients with two RF – by 3,7 times.
Patients of the combined group of GA+AA genotype of the FGB gene were more likely to reach endpoints than patients with the GG genotype (64,2% vs. 35,7%, χ2=9,5, p=0,006, OR 4,3 (95% CI 1,6–11,8)). Patients with genotypes TT and CT+TT of the ITGα2 gene reached endpoints more often than homozygous carriers of the wild allele. The plasma level of fibrinogen was significantly higher in patients of the combined group of GA+AA genotypes than in GG group of FGB gene (2,8 (2,4–2,9) g/l vs. 2,5 (2,3–2,6) g/l, p=0,002). Besides, there was a trend to a higher plasma fibrinogen concentration in the group of patients with adverse events in comparison with those without (2,7 (2,45–3,03) g/l vs. 2,51 (2,3–2,8) g/l, p=0,087).
According to the results of a three-year observation, a prognostic model including a number of novel predictors (atrial fibrillation duration, the presence of coronary heart disease, the size of the left atrium, the plasma level of fibrinogen and the presence of the polymorphic allele 807T of the ITGα2 gene), appeared to be highly informative and specific in prediction of TE complications in patients with non-valvular AF.
Conclusion. The allele (-455)A of the FGB gene, as well as the CT and TT genotypes of the polymorphic marker C807T of the ITGα2 gene, are associated with thromboembolic complications in patients with non-valvular atrial fibrillation. The prognostic model, developed on the basis of a complex of few clinical, laboratory and non-modifiable genetic biomarkers, demonstrated high reliability in predicting the actual number of thromboembolic complications in patients with non-valvular atrial fibrillation and 0-2 additional clinical risk factors, except female gender (CHA2DS2-VASc score ≤2 in men and ≤3 in women) during 3 years follow-up. The model seems to be promising for individualizing of the risk of thromboembolic complications and may provide improved decision support in terms of treatment and prevention strategy in patients with AF.

Keywords: coagulation factors, genetic predictors, risk prediction, ischemic stroke, atrial fibrillation