Rational Pharmacotherapy in Cardiology

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Aim. To estimate influence of thrombosis associated genetic factors on cardiovascular complications (CVC) occurrence in patients with stable ischemic heart disease (IHD) on the base of 5-year prospective survey. Material and methods. A total of 503 patients with the mean age of 59.4 years were enrolled into the study. The follow-up period was 5.4 years. Composite endpoint included the following cases of fatal and nonfatal CVC: death, acute coronary syndrome, ischemic stroke/transient ischemic attack, peripheral arterial thrombosis and revascularization of affected vascular system. We determined prevalence and prognostic value of mutations and polymorphisms in genes that encode blood clotting factors (factor V Leiden G1691A, prothrombin G20210A, ß-fibrinogen 455G> A), platelet GPIIIa receptor (C1565T) and enzymes involved in homocysteine metabolism (methylentetrahydrofolate reductase  (C667 T MTHFR) and A1298C, methionine synthase (MTR) A2756G, methionine synthase-reductase (MTRR) A66G and transcobalamin (TCN) C776G). Results. Overall incidence rate of vascular events made up 31.0%. MTHFR and TCN polymorphisms proved to be significant in regard to cardiovascular risk among all studied genetic indices. Carriage of at least C667 T one MTHFR polymorphic allele increased risk of CVC 1.64 times (95% confidence interval (CI) 1.2-2.3, p=0.003). Homozygous carriage of MTHFR 1298 AА and TCN 776 СС “wild” genotypes increased risk of CVC 1.63 times (95% CI 1.2-2.3, р=0.006) and 1.37 times (95% CI 1.001-1.89, р=0.04), respectively. Such genetic variants as MTHFR C667 T/СТ and 1298 AА impacted prognosis only given concomitant decrease in plasma folate level, which was observed in 56.1% of the patients. Conclusion. It can be recommended to test the presence of MTHFR C667 T, MTHFR 1298 AА and TCN 776 СС, and to simultaneously assess folate level in IHD patients in order to clarify risk of unfavorable cardiovascular events.

About the Authors

A. L. Komarov
Russian Cardiology Research and Production Complex
Russian Federation
PhD., MD, Senior research associate

O. O. Shahmatova
Russian Cardiology Research and Production Complex
Russian Federation
PhD, MD, Junior research associate

D. V. Rebrikov
«DNA-Technology» Research and Production Company General Genetics Institute named after N.I. Vavilov
Russian Federation

PhD, R&D Director of “DNA-T echnology” Research and Production Company; Head of “Genetic Polymorphism” center of General Genetics Institute named after Vavilov N.I.

D. Yu. Trophimov
«DNA-Technology» Research and Production Company
Russian Federation

T. I. Kotkina
Russian Cardiology Research and Production Complex
Russian Federation
MD, Head of the clinical-diagnostic laboratory

T. A. Ilyushenko
Russian Cardiology Research and Production Complex
Russian Federation
MD, Postgraduate student

A. D. Deev
State Research Center for Preventive Medicine
Russian Federation
PhD, Head of the biostatistics laboratory

E. P. Panchenko
Russian Cardiology Research and Production Complex
Russian Federation

PhD, MD, Professor , Head of the atherothrombosis clinical problems laboratory


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For citation:

Komarov A.L., Shahmatova O.O., Rebrikov D.V., Trophimov D.Y., Kotkina T.I., Ilyushenko T.A., Deev A.D., Panchenko E.P. PROTHROMBOTIC POLYMORPHISMS AND LONG-TERM PROGNOSIS OF PATIENTS WITH STABLE ISCHEMIC HEART DISEASE. Rational Pharmacotherapy in Cardiology. 2011;7(4):409-425. (In Russ.)

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