Hemostatic Gene Polymorphisms in Acute Coronary Syndrome with Nonobstructive Coronary Atherosclerosis

Purpose: to study distribution of genes of the coagulation system, unfavorable in relation to the risk of thrombosis, and their influence on serum parameters ofthe hemostasis system in patients with nonobstructive coronary atherosclerosis (NCA) and acute coronary syndrome (ACS).

Materials and methods. We included in this nonrandomized open study patients with ACS older than 18 years with intact coronary arteries or confirmed at coronary angiography stenosis <50%. Genotypes of these patients were analyzed by 8 polymorphic variants of the hemostatic system genes which previously were found to be associated with the thrombophilia risk: F2 (20210 G>A) rs1799963, F5 (1691 G>A) rs6025, F7 (10976G>A) rs6046, F13 (163 G>T) rs5985, F1 (-455G>A) rs1800790, GP Ia - Ila (807C>t) rs1126643, GP Ilb-IIIa (1565 T>C) rs5918, PAI-I (-6755G>4G) rs1799889. Activities of protein C, Von Willebrand factor, plasminogen, and antithrombin III were also determined.

Results. Of 913 patients with ACS in 30 (3.3%) with mean age 54±11 years we detected NCA. Acute myocardial infarction (AMI) was diagnosed in 24 (80%), unstable angina - in 6 (20%) patients. Only in 1 patient we found no carriage of thrombosis associated genotypes. The frequency of occurrence of the heterozygous genotype of the factor V gene was 1 (3%). Heterozygous genotype of the factor XIII was registered significantly more often in patients with present atherosclerotic lesion compared with those with intact coronary arteries. Mean activity of protein C was 103% [90; 110], antithrombin III - 96% [88; 103], Von Willebrand factor - 137% [114; 162], plasminogen - 109% [102; 112]. At admission lowering of antithrombin III and protein C activities was detected in 4 cases (13%). In dynamics level of these parameters was restored. Elevation of Von Willebrand factor activity at admission was detected in 14 cases (14%) and remained elevated one year after the index event. There was no association between of fibrinogen level, protein C activity, rs1800790 and rs6025 gene polymorphisms, respectively. One-year mortality was 7% (n=2). For one year occurred 1 AIM recurrence (3%), heart failure developed in 15 patients (50%), 11 patients (37%) were repetitively hospitalized due to all causes. No association was revealed between activity of studied blood serum markers and 1 -year outcomes (death, re-AIM, rehospitalization).

Conclusion. Among ACS patients 3.3% had NCA, what corresponded to the literature data. Carriage of at least 1 polymorphic variant of 8 thrombosis associated genes of the coagulation system was found in 97 % of patients with ACS and NCA. Distribution of these variants was like that in the European population and in patients with AIM at the background of stenosing atherosclerosis. Level of serum markers did not depend on distribution of polymorphic variants of the coagulation system genes, and presence of atherosclerotic coronary artery lesions. There was no association between hospital and long-term outcomes and distribution of polymorphic variants of thrombosis associated coagulation system genes, as well as levels of blood serum markers.

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