kpcczКомплексные проблемы сердечно-сосудистых заболеванийComplex Issues of Cardiovascular Diseases2306-12782587-9537Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”10.17802/2306-1278-2022-11-3-17-28kpccz-1133Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ. КардиологияORIGINAL STUDIES. CardiologyВлияние полиморфизмов гена CYP2C19 на клинические исходы пациентов с инфарктом миокарда в течение 12-месячного периода наблюденияImpact of CYP2C19 gene polymorphisms on clinical outcomes in patients with myocardial infarction during 12-month follow-uphttps://orcid.org/0000-0003-3857-7705ГражданкинИ. О.GrazhdankinI. O.

Гражданкин Игорь Олегович - научный сотрудник.

ул. Речкуновская, 15, Новосибирск, 630055.

Igor O. Grazhdankin - Researcher at the Academician E.N. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation.

15, Rechkunovskaya St., Novosibirsk, 630055.

iggrazhdankin@gmail.comhttps://orcid.org/0000-0003-2883-6574БайструковВ. И.BaystrukovV. I.

Байструков Виталий Игоревич - кандидат медицинских наук врач по рентгенэндоваскулярным диагностике и лечению, научный сотрудник.

ул. Речкуновская, 15, Новосибирск, 630055.

Vitaly I. Baystrukov - PhD, Specialist in Endovascular Diagnostics and Treatment, Researcher at the Academician E.N. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation.

15, Rechkunovskaya St., Novosibirsk, 630055.

https://orcid.org/0000-0002-7109-9074КретовЕ. И.KretovE. I.

Кретов Евгений Иванович - доктор медицинских наук врач по рентгенэндоваскулярным диагностике и лечению.

ул. Пирогова, 25, Новосибирск, 630090.

Evgeny I. Kretov - PhD, Specialist in Endovascular Diagnostics and Treatment at the Central Clinical Hospital.

25, Pirogova St., Novosibirsk, 630090.

https://orcid.org/0000-0002-3247-8290ПрохорихинА. А.ProkhorikhinA. A.

Прохорихин Алексей Андреевич - кандидат медицинских наук научный сотрудник.

ул. Аккуратова, 2, Санкт-Петербург, 197341.

Alexey A. Prokhorikhin - PhD, Researcher at the V.A. Almazov National Medical Research Center of the Ministry of Health of the Russian Federation.

Akkuratova St., 2, Saint Petersburg, 197341.

https://orcid.org/0000-0001-9818-8678ЧернявскийА. М.ChernyavskyA. M.

Чернявский Александр Михайлович - член-корреспондент РАН, доктор медицинских наук, профессор, директор НМИЦ им. ак. Е.Н. Мешалкина МЗ РФ.

ул. Речкуновская, 15, Новосибирск, 630055.

Alexander M. Chernyavsky - Corresponding Member of  the Russian Academy of Sciences, PhD, Professor, Director  of the Academician E.N. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation.

15, Rechkunovskaya St., Novosibirsk, 630055.

Национальный медицинский исследовательский центр имени академика Е.Н. Мешалкина Министерства здравоохранения Российской ФедерацииРоссияMeshalkin National Medical Research Center of the Ministry of Health of Russian FederationRussian FederationГосударственное бюджетное учреждение здравоохранения Новосибирской области «Центральная клиническая больница»РоссияState Budgetary Healthcare Institution of the Novosibirsk region “Central Clinical Hospital”Russian FederationНациональный медицинский исследовательский центр имени В.А. Алмазова Министерства здравоохранения Российской ФедерацииРоссияAlmazov National Medical Research CentreRussian Federation2022080820221131728Copyright © Гражданкин И.О., Байструков В.И., Кретов Е.И., Прохорихин А.А., Чернявский А.М., 20222022Гражданкин И.О., Байструков В.И., Кретов Е.И., Прохорихин А.А., Чернявский А.М.Grazhdankin I.O., Baystrukov V.I., Kretov E.I., Prokhorikhin A.A., Chernyavsky A.M.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nii-kpssz.com/jour/article/view/1133Основные положения

Основные положения. Полиморфизмы гена CYP2C19 у пациентов с острым инфарктом встречаются часто в клинической практике. В работе оценена роль генетической предрасположенности как в развитии ишемических, так и геморрагических событий на фоне терапии аспирином и клопидогрелом в течение первых 12 мес. после реваскуляризации по поводу острого инфаркта миокарда.

Цель

Цель. Оценить влияние полиморфизмов гена CYP2C19 (аллели *1, *2, *3, *17) на клинические исходы у пациентов после успешной реваскуляризации острого инфаркта миокарда (ИМ) на фоне терапии клопидогрелом на протяжении 12-месячного периода наблюдения.

Материалы и методы

Материалы и методы. С 2011 по 2012 г. в исследование включено 363 пациента с острым ИМ, перенесшего реваскуляризацию миокарда. Всем больным проведен генетический анализ на полиморфизмы гена CYP2C19 (аллели *1, *2, *3, *17). В течение 12 мес. пациенты получали двойную антитромбоцитарную терапию, включавшую аспирин и клопидогрел, после чего оценена частота сердечно-сосудистой смерти, повторного ИМ, инсульта и кровотечения.

Результаты

Результаты. Через 12 мес. наблюдения событие комбинированной первичной конечной точки (сердечно-сосудистая смерть, повторный ИМ, инсульт) зарегистрировано у 18 (7%, 95% доверительный интервал (ДИ) [5; 11]) больных группы носительства «дикого» генотипа и у 12 (11%, 95% ДИ [6; 18]) пациентов в группе носительства аллелей CYP2C19*2 и CYP2C19*3. Данные события не имели статистического различия (отношение шансов (ОШ) 1,6, 95% ДИ [0,7; 3,6], p = 0,301). Носительство аллелей CYP2C19*2 или CYP2C19*3 в сравнении с «диким» типом не являлось предиктором наступления первичной конечной точки (ОШ 1,56, 95% ДИ [0,71; 3,34], p<0,253). В анализе путем построения оптимальной многофакторной модели логистической регрессии выявлено, что гомозиготный вариант CYP2C19 (*2/*2) по сравнению с «диким» (*1/*1) и гетерозиготным (*1/*2) генотипами служит предиктором комбинированных осложнений (ОШ 6,34, 95% ДИ [1,57; 22,23], p<0,005) и ИМ в течение 12 мес. наблюдения (ОШ 5,45, 95% ДИ [1,14; 19,97], p<0,016). У 14 пациентов развилось клинически значимое кровотечение. В многофакторной модели логистической регрессии уровень креатинина, возраст и гомозиготное носительство аллелей GOF CYP2C19*17 в сравнении с «диким» типом и гетерозиготным носительством увеличивает шансы развития кровотечения в течение 12 мес. после реваскуляризации (ОШ 6,47, 95% ДИ [1,27; 26,97], p<0,013).

Заключение

Заключение. Наличие гомозиготного носительства CYP2C19*2 оказывает влияние на частоту развития повторных ишемических событий у пациентов с ИМ после реваскуляризации миокарда на протяжении 12 мес. наблюдения. Гомозиготный вариант носительства CYP2C19*17 служит предиктором значимых кровотечений у лиц молодого возраста с повышенным уровнем креатинина.

 

 

Highlights

Highlights. CYP2C19 gene polymorphisms in patients with acute myocardial infarction are common in clinical practice. The article assesses the role of genetic predisposition in the development of ischemic and hemorrhagic events during dual antiplatelet therapy (aspirin and clopidogrel) within the first 12 months after revascularization for acute myocardial infarction.

Aim

Aim. To evaluate the impact of CYP2C19 gene *1, *2, *3, *17 alleles polymorphism on 12-month clinical outcomes in patients who underwent coronary revascularization due to acute myocardial infarction and took clopidogrel.

Methods

Methods. 363 patients with acute myocardial infarction undergoing percutaneous coronary intervention were enrolled in the prospectively study in 2010–2012. CYP2C19 gene *1, *2, *3, *17 alleles polymorphism analysis was performed in all study participants. Dual antiplatelet therapy, consisting of aspirin and clopidogrel, was prescribed for 12 months. The follow-up period was 12 months, the incidence   of cardiovascular death, non-fatal myocardial infarction, stroke and bleeding was assessed.

Results

Results. 12 months after inclusion in the study, the incidence of composite endpoint (defined as cardiovascular death, non-fatal myocardial infarction and stroke) was observed in 18 patients (7% [5%; 11%]; 95% CI) with wild-type CYP2C19 gene and in 12 patients (11% [6%; 18%]; 95% CI) with lost-of-function *2+*3 alleles, with no statistical difference (OR = 1.6 [0.7; 3.6], 95% CI; p = 0.301). Presence of any LOF-alleles did not predict composite endpoint events (OR = 1.56 [0.71; 3.34], 95% CI, p<0.253). Multivariable logistic regression analysis revealed that CYP2C19*2 homozygotes have higher risk of composite endpoint (OR = 6.34, 95% CI [1.57; 22.23], p<0.005) and myocardial infarction (OR = 5.45, 95% CI [1.14; 19.97], p<0.016) compared to *2 heterozygotes and wild-type carriers.    14 patients had major bleedings, required blood transfusion or hospitalization. Patient’s age, increase in creatinine level and gain-of-function (GOF) CYP2C19*17 homozygotic carriage were identified as the predictors of major bleeding during follow-up period.

Conclusion

Conclusion. In this study CYP2C19 LOF alleles polymorphism except the CYP2C19*2 homozygotic carriage demonstrated no impact on the incidence of ischemic events during 12-month follow-up in patients with acute MI who underwent successful revascularization. CYP2C19*17 homozygotes demonstrated increased risk of major bleeding only in young individuals with elevated blood creatinine levels.

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The authors declare that there are no conflicts of interest present.