phgenomicsФармакогенетика и фармакогеномикаPharmacogenetics and Pharmacogenomics2588-05272686-8849LLC "Izdatelstvo OKI"10.37489/2588-0527-2023-1-46-55phgenomics-274Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHСравнительная оценка влияния носительства полиморфизма генов CYP2C19, CYP2C9, CYP4F2 на клинико-лабораторные особенности пациентов с острым коронарным синдромомComparative study of the CYP2C19, CYP2C9, CYP4F2 gene polymorphisms impact on the clinical and laboratory characteristics of acute coronary syndrome patientshttps://orcid.org/0000-0003-3278-2556КантемироваБ. И.KantemirovaB. I.

д. м. н., доцент, профессор кафедры фармакологии

Dr. Sci. (Med.), Associate Professor, Professor of the Department of Pharmacology

belakantemirova@rambler.ruhttps://orcid.org/0000-0001-7374-2660АбдуллаевМ. А.AbdullaevM. A.

ассистент кафедры фармакологии

assistant of the Department of Pharmacology

abdullaev-musalitdin@mail.ruhttps://orcid.org/0000-0001-8884-1178ЧернышеваЕ. Н.ChernyshevaE. N.

д. м. н., доцент, заведующая кафедрой кардиологии

Dr. Sci. (Med.), Associate Professor, Head of the Department of Cardiology

lena.chernysheva@inbox.ruhttps://orcid.org/0000-0001-8743-3658КитиашвилиИ. З.KitiashviliI. Z.

д. м. н., профессор, зав. кафедрой анестезиологии и реаниматологии, заместитель главноговрача по анестезиологии и реанимации ГБУЗ ГКБ №15 им. О.М. Филатова ДЗМ

Dr. Sci. (Med.), Associate Professor, Head of the Department of Anesthesiology and Intensive Care Medicine, Deputy Chief Physician for Anesthesiology and Intensive Care Medicine of SBHI CCH No.15 named after O.M. Filatov MHD

kitiashvili@mail.ruhttps://orcid.org/0000-0003-0852-8574ЖарковаЗ. В.ZharkovZ. V.

н. с. научно-исследовательского центра

Researcher at the Research Center

morikova21@mail.ruhttps://orcid.org/0000-0002-6564-3408РомановаА. Н.RomanovaA. N.

Аспирант кафедры фармакологии

Post graduate of the Department of Pharmacology

sasha.styles005@gmail.comhttps://orcid.org/0009-0001-6265-2800КоноваловаЕ. Р.KonovalovaE. R.

Студентка лечебного факультета

Student of the General Medicine Faculty

31012001k@gmail.comФГБОУ ВО "Астраханский государственный медицинский университет" Минздрава РоссииРоссияAstrakhan state medical universityRussian FederationФГБОУ ВО "Астраханский государственный медицинский университет" Минздрава РоссииРоссияAstrakhan state medical universityRussian FederationФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияRussian Medical Academy of Continuous Professional EducationRussian FederationМГБОУ ВО "Московский государственный медико-стоматологический университет им. А. И. Евдокимова" Минздрава РоссииРоссияA.I. Yevdokimov Moscow State University of Medicine and DentistryRussian Federation202319072023014655Copyright © Кантемирова Б.И., Абдуллаев М.А., Чернышева Е.Н., Китиашвили И.З., Жаркова З.В., Романова А.Н., Коновалова Е.Р., 20232023Кантемирова Б.И., Абдуллаев М.А., Чернышева Е.Н., Китиашвили И.З., Жаркова З.В., Романова А.Н., Коновалова Е.Р.Kantemirova B.I., Abdullaev M.A., Chernysheva E.N., Kitiashvili I.Z., Zharkov Z.V., Romanova A.N., Konovalova E.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacogenetics-pharmacogenomics.ru/jour/article/view/274

Ишемическая болезнь сердца (ИБС) является одной из самых распространённых причин смерти во всём мире. Фармакокинетические свойства лекарственных средств, используемых для лечения ИБС, зависят от генетических факторов, включая генотипы CYP2C19, CYP2C9 и CYP4F2. Однако, существующие исследования генетической основы ответа на лечение у пациентов с острым коронарным синдромом (ОКС), имеют противоречивые результаты, требуя более подробного исследования. Цель. В данном исследовании мы изучили распределение генотипов CYP2C19*2, CYP2C9*2 и CYP4F2*3 среди 59 пациентов с диагнозом ОКС, которые получали двойную антиагрегантную терапию. Методы. Использовался метод полимеразной цепной реакции (ПЦР) для определения генотипов CYP2C19, CYP2C9 и CYP4F2. Проведён корреляционный анализ результатов носительства генотипов и клинико-лабораторных показателей пациен- тов. Результаты. Распределение генотипов CYP2C9*2 было следующим: дикий генотип (CC) встречался с частотой 78 % (45 пациентов), гетерозиготы (CT) — 22 % (12 пациентов), гомозиготы (TT) не обнаружены. Генотип CYP4F2*3 распределился следующим образом: 56,14 % (32 пациента) имели дикий генотип (CC), 31,5 % (18 пациентов) были гетерозиготами со сниженной активностью фермента (CT), 12,36 % (7 пациентов) были гомозиготами по аллели T (TT). Распределение аллелей и генотипов CYP2C9 не соответствовало закону Харди-Вайнберга (χ2 = 21,55; р = 0,044), в то время как распределение аллелей и генотипов CYP4F2 соответствовало этому закону (χ2 = 3,61; p = 0,0574). Заключение. Настоящее исследование показало высокую распространённость генотипов CYP2C9*2 (СТ) и CYP4F2*3 (СТ и ТТ) среди пациентов с острым коронарным синдромом. Носительство полиморфизма CYP2C19*2 было значимо связано с неблагоприятными сердечно-сосудистыми событиями у пациентов. Эти результаты свидетельствуют о том, что генетическое тестирование может предоставить ценную информацию для стратификации риска и персонализированного лечения пациентов с острым коронарным синдромом.

Coronary heart disease (CHD) is one of the most common causes of death worldwide. The pharmacokinetic properties of drugs used to treat coronary heart disease depend on genetic factors, including the genotype of CYP2C19, CYP2C9 and CYP4F2. However, existing studies of the genetic basis of the response to treatment in patients with acute coronary syndrome (ACS) have contradictory results, requiring a more detailed study. Goal. In this study, we studied the distribution of the genotypes of CYP2C19*2, CYP2C9*2 and CYP4F2*3 among 59 patients diagnosed with ACS who received dual antiplatelet therapy. Methods. The polymerase chain reaction (PCR) method was used to determine the genotypes of CYP2C19, CYP2C9 and CYP4F2. A correlation analysis of the results of genotype carriage and clinical and laboratory parameters of patients was carried out. Results. The distribution of CYP2C9*2 genotypes was as follows: wild genotype (CC) was found with a frequency of 78 % (45 patients), heterozygotes (CT) — 22 % (12 patients), homozygotes (TT) were not detected. The CYP4F2*3 genotype was distributed as follows: 56.14 % (32 patients) had a wild genotype (CC), 31.5 % (18 patients) were heterozygotes with reduced enzyme activity (CT), 12.36 % (7 patients) were homozygotes for the T (TT) allele. The distribution of alleles and genotypes of CYP2C9 did not correspond to the Hardy-Weinberg equation (χ2 = 21.55; p = 0.044), while the distribution of alleles and genotypes of CYP4F2 corresponded to it (χ2 = 3.61; p = 0.0574). Conclusion. The study showed a high prevalence of the genotypes CYP2C9*2 (CT) and CYP4F2*3 (CT and TT) among patients with acute coronary syndrome. The carriage of CYP2C19*2 was significantly associated with adverse cardiovascular events in patients. These results suggest that genetic testing can provide valuable information for risk stratification and personalized treatment of patients with acute coronary syndrome

фармакогенетикаантиагрегантыклопидогрелCYP2C19CYP2C9CYP4F2полиморфизмpharmacogeneticsantiplatelet agentsclopidogrelCYP2C19CYP2C9CYP4F2polymorphismНаучное исследование осуществлено за счёт средств государственного задания Министерства здравоохранения Российской Федерации «Разработка алгоритмов персонализированного назначения антиагрегантов у пациентов с острым коронарным синдромом», годы выполнения 2021–2023 гг.This scientific study was carried out with the support of the funds provided by the state assignment of the Ministry of Health of the Russian Federation "Development of algorithms for personalized prescription of antiplatelet agents in patients with acute coronary syndrome", for the period of 2021–2023.ReferencesMozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016 Jan 26;133(4):e38–60. DOI: 10.1161/CIR.0000000000000350.Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016 Jan 26;133(4):e38–60. DOI: 10.1161/CIR.0000000000000350.Giacoppo D, Matsuda Y, Fovino LN, et al. Short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. prolonged dual antiplatelet therapy after percutaneous coronary intervention with secondgeneration drug-eluting stents: a systematic review and meta-analysis of randomized clinical trials. European heartjournal. 2021 Jan 21;42(4):308–19. DOI: 10.1093/eurheartj/ehaa739Giacoppo D, Matsuda Y, Fovino LN, et al. Short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. prolonged dual antiplatelet therapy after percutaneous coronary intervention with secondgeneration drug-eluting stents: a systematic review and meta-analysis of randomized clinical trials. European heartjournal. 2021 Jan 21;42(4):308–19. DOI: 10.1093/eurheartj/ehaa739Bhatt DL, Hulot JS, Moliterno DJ, Harrington RA. Antiplatelet and anticoagulation therapy for acute coronary syndromes. Circ Res. 2014;114(12):1929–1943. DOI:10.1161/circresaha.114.302737.Bhatt DL, Hulot JS, Moliterno DJ, Harrington RA. Antiplatelet and anticoagulation therapy for acute coronary syndromes. Circ Res. 2014;114(12):1929–1943. DOI:10.1161/circresaha.114.302737.Johnson JA, Cavallari LH. Pharmacogenetics and cardiovascular disease—implications for personalized medicine. Pharmacologicalreviews. 2013 Jul 1;65(3):987–1009. DOI: 10.1124/pr.112.007252.Johnson JA, Cavallari LH. Pharmacogenetics and cardiovascular disease—implications for personalized medicine. Pharmacologicalreviews. 2013 Jul 1;65(3):987–1009. DOI: 10.1124/pr.112.007252.Федина Л.В., Мирзаев К.Б., Сычёв Д.А., и др. Влияние носительства клинически значимых аллельных вариантов генов CES1, PON1, ABCG2, CYP4F2, CYP3A4, IGTB3, P2Y12, PEAR1, B4GALT2 на антиагрегантное действие клопидогрела и клинические исходы пациентов с ОКС и фибрилляцией предсердий. Фармакогенетика и фармакогеномика. 2021;(2):19–20. [Fedina LV, Mirzoev KB, SychevDA, et al. The effect of carrying clinically significant allelic variants of the CS 1,PON1, ABCG2, CYP4F2, CYP3A4, IGTB3, P2Y12, PEAR 1, B4GALT2 genes on the antiplatelet effect of clopidogrel and clinical outcomes of patients with ACS and atrial fibrillation. Farmakogenetika i farmakogenomika = Pharmacogenetics and pharmacogenomics. 2021;(2):19–20. (In Russ.)]. DOI: 10.37489/2588-0527-2020-2-19-20.Федина Л.В., Мирзаев К.Б., Сычёв Д.А., и др. Влияние носительства клинически значимых аллельных вариантов генов CES1, PON1, ABCG2, CYP4F2, CYP3A4, IGTB3, P2Y12, PEAR1, B4GALT2 на антиагрегантное действие клопидогрела и клинические исходы пациентов с ОКС и фибрилляцией предсердий. Фармакогенетика и фармакогеномика. 2021;(2):19–20. [Fedina LV, Mirzoev KB, SychevDA, et al. The effect of carrying clinically significant allelic variants of the CS 1,PON1, ABCG2, CYP4F2, CYP3A4, IGTB3, P2Y12, PEAR 1, B4GALT2 genes on the antiplatelet effect of clopidogrel and clinical outcomes of patients with ACS and atrial fibrillation. Farmakogenetika i farmakogenomika = Pharmacogenetics and pharmacogenomics. 2021;(2):19–20. (In Russ.)]. DOI: 10.37489/2588-0527-2020-2-19-20.Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. Journal of Thrombosis and Haemostasis. 2007 Dec 1;5(12):2429–36. DOI: 10.1111/j.1538-7836.2007.02775.x.Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. Journal of Thrombosis and Haemostasis. 2007 Dec 1;5(12):2429–36. DOI: 10.1111/j.1538-7836.2007.02775.x.Tatarunas V, Jankauskiene L, Kupstyte N, et al. The role of clinical parameters and of CYP2C19 G681 and CYP4F2 G1347A polymorphisms on platelet reactivity during dual antiplatelet therapy. Blood Coagulation & Fibrinolysis. 2014 Jun 1;25(4):369–74. DOI: 10.1097/MBC.0000000000000053.Tatarunas V, Jankauskiene L, Kupstyte N, et al. The role of clinical parameters and of CYP2C19 G681 and CYP4F2 G1347A polymorphisms on platelet reactivity during dual antiplatelet therapy. Blood Coagulation & Fibrinolysis. 2014 Jun 1;25(4):369–74. DOI: 10.1097/MBC.0000000000000053.Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. New England journal of medicine. 2009 Jan 22;360(4):354–62. DOI: 10.1056/nejmoa0809171.Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. New England journal of medicine. 2009 Jan 22;360(4):354–62. DOI: 10.1056/nejmoa0809171.Fritsma GA. Platelet structure and function. Clinical laboratory science. 2015 Apr 1;28(2):125. DOI: 10.29074/ascls.28.2.125.Fritsma GA. Platelet structure and function. Clinical laboratory science. 2015 Apr 1;28(2):125. DOI: 10.29074/ascls.28.2.125.Sang Y, Roest M, de Laat B, de Groot PG, Huskens D. Interplay between platelets and coagulation. Blood reviews. 2021 Mar 1;46:100733. DOI: 10.1016/j.blre.2020.100733.Sang Y, Roest M, de Laat B, de Groot PG, Huskens D. Interplay between platelets and coagulation. Blood reviews. 2021 Mar 1;46:100733. DOI: 10.1016/j.blre.2020.100733.Kumbhani DJ, Cannon CP, Beavers CJ, et al. 2020 ACC Expert Consensus Decision Pathway for Anticoagulant and Antiplatelet Therapy in Patients With Atrial Fibrillation or Venous Thromboembolism Undergoing Percutaneous Coronary Intervention or With Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021 Feb 9;77(5):629–658. DOI: 10.1016/j.jacc.2020.09.011.Kumbhani DJ, Cannon CP, Beavers CJ, et al. 2020 ACC Expert Consensus Decision Pathway for Anticoagulant and Antiplatelet Therapy in Patients With Atrial Fibrillation or Venous Thromboembolism Undergoing Percutaneous Coronary Intervention or With Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021 Feb 9;77(5):629–658. DOI: 10.1016/j.jacc.2020.09.011.Johnson JA, Caudle KE, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clin Pharmacol Ther. 2017 Sep;102(3):397–404. DOI: 10.1002/cpt.668.Johnson JA, Caudle KE, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clin Pharmacol Ther. 2017 Sep;102(3):397–404. DOI: 10.1002/cpt.668.Cannon CP, Harrington RA, James S, et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet. 2010 Jan 23;375(9711):283–93. DOI: 10.1016/S0140-6736(09)62191-7.Cannon CP, Harrington RA, James S, et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet. 2010 Jan 23;375(9711):283–93. DOI: 10.1016/S0140-6736(09)62191-7.Меситская Д.Ф., Никитина Ю.М., Копылов Ф.Ю., и др. Клинические и фармакогенетические факторы, влияющие на резистентность к клопидогрелу у пациентов, страдающих сердечнососудистыми заболеваниями. Клиническая медицина. 2015;93(2):40–6. [Mesitskaya DF, Nikitina YuM, Kopylov FYu, et al. Clinical and pharmacological factors influencing resistance to clopidogrel in patients with cardiovascular diseases. Klin. med. 2015;93(2):40–6. (In Russ.)].Меситская Д.Ф., Никитина Ю.М., Копылов Ф.Ю., и др. Клинические и фармакогенетические факторы, влияющие на резистентность к клопидогрелу у пациентов, страдающих сердечнососудистыми заболеваниями. Клиническая медицина. 2015;93(2):40–6. [Mesitskaya DF, Nikitina YuM, Kopylov FYu, et al. Clinical and pharmacological factors influencing resistance to clopidogrel in patients with cardiovascular diseases. Klin. med. 2015;93(2):40–6. (In Russ.)].Harmsze A, van Werkum JW, Bouman HJ, et al. Besides CYP2C19*2, the variant allele CYP2C9*3 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation. Pharmacogenet Genomics. 2010 Jan;20(1):18–25. DOI: 10.1097/FPC.0b013e328333dafe.Harmsze A, van Werkum JW, Bouman HJ, et al. Besides CYP2C19*2, the variant allele CYP2C9*3 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation. Pharmacogenet Genomics. 2010 Jan;20(1):18–25. DOI: 10.1097/FPC.0b013e328333dafe.Yu C, Yan Q, Fu C, et al. CYP4F2 genetic polymorphisms are associated with coronary heart disease in a Chinese population. Lipids Health Dis. 2014 May 20;13:83. DOI: 10.1186/1476-511X-13-83.Yu C, Yan Q, Fu C, et al. CYP4F2 genetic polymorphisms are associated with coronary heart disease in a Chinese population. Lipids Health Dis. 2014 May 20;13:83. DOI: 10.1186/1476-511X-13-83.Iqbal J, Sumaya W, Tatman V, et al. Incidence and predictors of stent thrombosis: a single-centre study of 5,833 consecutive patients undergoing coronary artery stenting. Euro Intervention. 2013 May 20;9(1):62–9. DOI: 10.4244/EIJV9I1A10.Iqbal J, Sumaya W, Tatman V, et al. Incidence and predictors of stent thrombosis: a single-centre study of 5,833 consecutive patients undergoing coronary artery stenting. Euro Intervention. 2013 May 20;9(1):62–9. DOI: 10.4244/EIJV9I1A10.Voora D, Shah SH, Spasojevic I, et al. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol. 2009 Oct 20;54(17):1609–16. DOI: 10.1016/j.jacc.2009.04.053.Voora D, Shah SH, Spasojevic I, et al. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol. 2009 Oct 20;54(17):1609–16. DOI: 10.1016/j.jacc.2009.04.053.Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021 Apr 7;42(14):1289–1367. doi: 10.1093/eurheartj/ehaa575. Erratum in: Eur Heart J. 2021 May 14;42(19):1908. Erratum in: Eur Heart J. 2021 May 14;42(19):1925. Erratum in: Eur Heart J. 2021 May 13; PMID: 32860058.Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021 Apr 7;42(14):1289–1367. doi: 10.1093/eurheartj/ehaa575. Erratum in: Eur Heart J. 2021 May 14;42(19):1908. Erratum in: Eur Heart J. 2021 May 14;42(19):1925. Erratum in: Eur Heart J. 2021 May 13; PMID: 32860058.Hurst NL, Nooney VB, Raman B, et al. Clopidogrel "resistance": pre- vs post-receptor determinants. Vascul Pharmacol. 2013 Nov-Dec;59(5-6):152–61. DOI: 10.1016/j.vph.2013.10.002.Hurst NL, Nooney VB, Raman B, et al. Clopidogrel "resistance": pre- vs post-receptor determinants. Vascul Pharmacol. 2013 Nov-Dec;59(5-6):152–61. DOI: 10.1016/j.vph.2013.10.002.Pereira NL, Rihal CS, So DYF, et al. Clopidogrel Pharmacogenetics. Circ Cardiovasc Interv. 2019 Apr;12(4):e007811. DOI: 10.1161/CIRCINTERVENTIONS.119.007811.Pereira NL, Rihal CS, So DYF, et al. Clopidogrel Pharmacogenetics. Circ Cardiovasc Interv. 2019 Apr;12(4):e007811. DOI: 10.1161/CIRCINTERVENTIONS.119.007811.Verma SS, Bergmeijer TO, Gong L, et al. Genomewide Association Study of Platelet Reactivity and Cardiovascular Response in Patients Treated With Clopidogrel: A Study by the International Clopidogrel Pharmacogenomics Consortium. Clin Pharmacol Ther. 2020 Nov;108(5):1067– 1077. DOI: 10.1002/cpt.1911.Verma SS, Bergmeijer TO, Gong L, et al. Genomewide Association Study of Platelet Reactivity and Cardiovascular Response in Patients Treated With Clopidogrel: A Study by the International Clopidogrel Pharmacogenomics Consortium. Clin Pharmacol Ther. 2020 Nov;108(5):1067– 1077. DOI: 10.1002/cpt.1911.Gremmel T, Steiner S, Seidinger D, et al. Obesity is associated with poor response to clopidogrel and an increased susceptibility to protease activated receptor-1 mediated platelet activation. Transl Res. 2013 May;161(5):421–9. DOI: 10.1016/j.trsl.2012.12.015.Gremmel T, Steiner S, Seidinger D, et al. Obesity is associated with poor response to clopidogrel and an increased susceptibility to protease activated receptor-1 mediated platelet activation. Transl Res. 2013 May;161(5):421–9. DOI: 10.1016/j.trsl.2012.12.015.Kazi DS, Garber AM, Shah RU, et al. Cost-effectiveness of genotypeguided and dual antiplatelet therapies in acute coronary syndrome. Ann Intern Med. 2014 Feb 18;160(4):221–32. DOI: 10.7326/M13-1999.Kazi DS, Garber AM, Shah RU, et al. Cost-effectiveness of genotypeguided and dual antiplatelet therapies in acute coronary syndrome. Ann Intern Med. 2014 Feb 18;160(4):221–32. DOI: 10.7326/M13-1999.Seo SM, Choo EH, Koh YS, et al. High-density lipoprotein cholesterol as a predictor of clinical outcomes in patients achieving low-density lipoprotein cholesterol targets with statins after percutaneous coronary intervention. Heart. 2011 Dec;97(23):1943–50. DOI: 10.1136/hrt.2011.225466.Seo SM, Choo EH, Koh YS, et al. High-density lipoprotein cholesterol as a predictor of clinical outcomes in patients achieving low-density lipoprotein cholesterol targets with statins after percutaneous coronary intervention. Heart. 2011 Dec;97(23):1943–50. DOI: 10.1136/hrt.2011.225466.Niessner A, Hofmann R, Kypta A, et al. Low high-density lipoprotein cholesterol predicts cardiovascular events after carotid stenting: a long-term survey. J Thromb Haemost. 2007 May;5(5):950–4. DOI: 10.1111/j.1538-7836.2007.02451.x.Niessner A, Hofmann R, Kypta A, et al. Low high-density lipoprotein cholesterol predicts cardiovascular events after carotid stenting: a long-term survey. J Thromb Haemost. 2007 May;5(5):950–4. DOI: 10.1111/j.1538-7836.2007.02451.x.

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