CardioSomaticsCardioSomaticsCardioСоматика2221-71852658-5707Eco-Vector4603410.26442/22217185.2020.1.200089Original study articlesОригинальные статьиResearch ArticleModern principles of atherogenic dyslipidemia management in special groups of patientsСовременные принципы управления атерогенной дислипидемией в особых группах больныхhttps://orcid.org/0000-0003-2250-59426733-1430BubnovaMarina G.БубноваМарина Геннадьевна
Russian Federation

D. Sci. (Med.), Prof., National Medical Research Center for Therapy and Preventive Medicine

д-р мед. наук, проф., рук. отд. реабилитации и вторичной профилактики сердечно-сосудистых заболеваний ФГБОУ НМИЦ ТПМ

mbubnova@gnicpm.ruParnesLev E.ПарнесЛев Евгеньевич
Russian Federation

doctor, Zhadkevich City Clinical Hospital

врач отд-ния сердечно-сосудистой патологии ГБУЗ «ГКБ им. М.Е. Жадкевича»

mbubnova@gnicpm.ruNational Medical Research Center for Therapy and Preventive MedicineФГБУ «Национальный медицинский исследовательский центр терапии и профилактической медицины» Минздрава РоссииZhadkevich City Clinical HospitalГБУЗ «Городская клиническая больница им. М.Е. Жадкевича» Департамента здравоохранения г. Москвы260920201116152609202026092020Copyright ©; 2020, Eco-VectorCopyright ©; 2020, ООО "Эко-Вектор"2020Eco-VectorООО "Эко-Вектор"https://creativecommons.org/licenses/by-nc-sa/4.0https://cardiosomatics.ru/2221-7185/article/view/46034

Aim. To provide modern view on atherogenic disorders in the blood lipid spectrum, the principles of lipid-lowering therapy prescription in certain groups of patients, the safety issues of statin therapy in patients with chronic liver diseases.

Materials and methods. The data of 55 scientific sources published in the Russian and foreign press in 1988–2020 were analyzed.

Results. It is known that atherogenic dyslipidemia is a key factor in pathogenesis of atherosclerotic cardiovascular diseases. Various disorders in blood lipids and lipoproteins are identified. In this regard, there are certain recommendations for the analysis of lipids and lipoproteins in certain situations. The issues of interpreting extreme deviations from normal values of the blood lipid spectrum are discussed. Patient groups with different levels of the cardiovascular risk, which determines prescription of lipid-lowering therapy, are presented. Statins are the first line of lipid-lowering therapy for both the correction of dyslipidemia and the prevention of cardiovascular complications. The article discusses the tactics of prescribing statins in special groups of patients, their safety issues. It considers promising ways for increasing statins tolerability in patients with chronic liver diseases, primarily with non-alcoholic fatty liver disease, by adding of combined hepatoprotector.

Conclusions. Generally, modern tactics of statins prescription are based on dyslipidemia characteristics and the patient’s cardiovascular risk level. Moreover, statins are clinically effective in special patient groups and have a good tolerability profile.

Цель. Осветить современные представления об атерогенных нарушениях в липидном спектре крови, принципах назначения гиполипидемической терапии в отдельных группах пациентов, вопросы безопасности терапии статинами у пациентов с хроническими заболеваниями печени.

Материалы и методы. Рассмотрены данные 55 научных источников, опубликованных в российской и зарубежной печати в 1988–2020 гг.

Результаты. Известно, что атерогенная дислипидемия – ключевой фактор развития атеросклеротических сердечно-сосудистых заболеваний. Выявляются разные нарушения в липидах и липопротеидах крови. В этой связи имеются определенные рекомендации к анализу липидов и липопротеидов в определенных ситуациях. Обсуждаются вопросы интерпретации экстремальных отклонений от нормальных значений показателей липидного спектра крови. Представлены группы пациентов с разной величиной сердечно-сосудистого риска, имеющего определяющую роль в назначении гиполипидемической терапии. Статины – первая линия гиполипидемической терапии как для коррекции дислипидемии, так и предупреждения развития сердечно-сосудистых осложнений. Уделяется внимание тактике назначения статинов в отдельных группах пациентов, вопросам их безопасности. Рассматриваются перспективные пути повышения переносимости статинов у больных с хроническими заболеваниями печени, в первую очередь с неалкогольной жировой болезнью печени, посредством дополнительного назначения комбинированного гепатопротектора.

Заключение. В целом современная тактика назначения статинов основывается на характеристике дислипидемии и уровне сердечно-сосудистого риска пациента. При этом статины проявляют клиническую эффективность в особых группах пациентов и имеют хороший профиль переносимости.

dyslipidemiaatherosclerosisstatinschronic liver diseaseshepatoprotectorsдислипидемияатеросклерозстатиныхронические заболевания печенигепатопротекторыPiepoli MF, Abreu A, Albus C et al. Update on cardiovascular prevention in clinical practice: A position paper of the European Association of Preventive Cardiology of the European Society of Cardiology. Eur J Preventive Cardiology 2020; 27 (2): 181–205. DOI: 10.1177/2047487319893035Timmis A, Townsend N, Gale CP et al. European Society of Cardiology: Cardiovascular Disease Statistics 2019. Eur Heart J 2020; 41: 12–85. DOI: 10.1093/eurheartj/ehz859Townsend N, Nichols M, Scarborough P, Rayner M. Cardiovascular disease in Europe–epidemiological update 2015. Eur Heart J 2015; 36: 2696–705.World Health Organization. Noncommunicable diseases: Campaign for action – meeting the NCD targets. https://www.who.int/beat-ncds/take-action/targets/en/Бойцов С.А., Погосова Н.В., Бубнова М.Г. и др. Кардиоваскулярная профилактика 2017. Российские национальные рекомендации. Рос. кардиол. журн. 2018; 23 (6): 7–122. DOI: 10.15829/1560-4071-2018-6-7-122 [Boitsov S.A., Pogosova N.V., Bubnova M.G. i dr. Kardiovaskuliarnaia profilaktika 2017. Rossiiskie natsional’nye rekomendatsii. Ros. kardiol. zhurn. 2018; 23 (6): 7–122. DOI: 10.15829/1560-4071-2018-6-7-122 (in Russian).]Fernandez-Friera L, Fuster V., López-Melgar B et al. Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors. J Am Coll Cardiol 2017; 70 (24): 2979–91. DOI: 10.1016/j.jacc.2017.10.024Yusuf S, Hawken S, Ounpuu S et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937–52.Bentzon JF, Binder CJ, Daemen MJ et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2020. DOI: 10.1093/eurheartj/ ehz962Mach F, Baigent C, Catapano AL et al. 2019 ESC/EAS Guidelines for themanagement of dyslipidaemias: lipid modification to reduce cardiovascular risk. The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J 2020; 41: 111–88. DOI: 10.1093/eurheartj/ehz/455Nordestgaard BG, Langlois MR., Langsted A et al, for the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Joint Consensus Initiative. Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM. Atherosclerosis 2020; 294: 46–61. doi.org/10.1016/j.atherosclerosis.2019.12.005Laufs U, Parhofer KG, Ginsberg HN, Hegele RA. Clinical review on triglycerides. Eur Heart J, 2020; 41: 99–109. DOI: 10.1093/eurheartj/ehz785Madsen CM, Varbo A, Nordestgaard BG. Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality inmen and women: two prospective cohort studies. Eur Heart J 2017; 38: 2478–86. DOI: 10.1093/eurheartj/ehx163Cholesterol Treatment Trialists Collaboration, Fulcher J, O’Connell R, Voysey M et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 2015; 385: 1397–405.Cholesterol Treatment Trialists Collaboration, Mihaylova B, Emberson J, Blackwell L et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012; 380: 581–90.Silverman MG, Ference BA, Im K et al. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions. A Systematic Review and Meta-analysis. JAMA 2016; 316 (12): 1289–97. DOI:10.1001/jama.2016.13985Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015; 372 (25): 2387–97. DOI: 10.1056/NEJMoa1410489Giugliano RP, Pedersen TR, Park J-G et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet 2017; 390: 1962–71. DOI: 10.1016/s0140-6736(17)32290-0Schwartz GG, Steg PG, Szarek M et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med 2018; 379 (22): 2097–107. DOI: 10.1056/NEJMoa1801174Арутюнов Г.П., Бойцов С.А., Воевода М.И. и др. Коррекция гипертриглицеридемии с целью снижения остаточного риска при заболеваниях, вызванных атеросклерозом. Заключение Совета экспертов Российского кардиологического общества, Российского научного медицинского общества терапевтов, Евразийской ассоциации терапевтов, Национального общества по изучению атеросклероза, Российской ассоциации эндокринологов и Национальной исследовательской лиги кардиологической генетики. Рациональная фармакотерапия в кардиологии. 2019; 15 (2): 282–8. DOI: 10.20996/1819-6446-2019-15-2-282-288 [Arutiunov G.P., Boitsov S.A., Voevoda M.I. et al. Korrektsiia gipertriglitseridemii s tsel’iu snizheniia ostatochnogo riska pri zabolevaniiakh, vyzvannykh aterosklerozom. Zakliuchenie Soveta ekspertov Rossiiskogo kardiologicheskogo obshchestva, Rossiiskogo nauchnogo meditsinskogo obshchestva terapevtov, Evraziiskoi assotsiatsii terapevtov, Natsional’nogo obshchestva po izucheniiu ateroskleroza, Rossiiskoi assotsiatsii endokrinologov i Natsional’noi issledovatel’skoi ligi kardiologicheskoi genetiki. Ratsional’naia farmakoterapiia v kardiologii. 2019; 15 (2): 282–8. DOI: 10.20996/1819-6446-2019-15-2-282-288 (in Russian).]Taylor F, Huffman MD, Macedo AF et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013; 1: CD004816Бубнова М.Г., Аронов Д.М., Деев А.Д. Терапия статинами в реальной клинической практике у пожилых пациентов с гиперлипидемией и коронарной болезнью сердца. Российская программа ЭФФОРТ. Атеросклероз и дислипидемии. 2018; 4 (1): 6–16. [Bubnova M.G., Aronov D.M., Deev A.D. Terapiia statinami v real’noi klinicheskoi praktike u pozhilykh patsientov s giperlipidemiei i koronarnoi bolezn’iu serdtsa. Rossiiskaia programma EFFORT. Ateroskleroz i dislipidemii. 2018; 4 (1): 6–16 (in Russian).]Cholesterol Treatment Trialists C. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet 2019; 393 (2): 407–15.Cholesterol Treatment Trialists’ (CTT) Collaboration. Impact of renal function on the eff ects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials. Lancet Diabetes Endocrinol 2016; 4: 829–39. DOI: 10.1016/S2213-8587(16)30156-5Cosentino F, Grant PJ, Aboyans V et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020; 41: 255–323. DOI:10.1093/eurheartj/ehz486Sabatine MS, Leiter LA, Wiviott SD et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol 2017; 5: 941–50.Ray KK, Colhoun HM, Szarek M et al; ODYSSEY OUTCOMES Committees and Investigators. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial. Lancet Diabetes Endocrinol 2019; pii: S2213-8587(19)30158-5. DOI: 10.1016/S2213-8587(19)30158-5Saha SA, Arora RR. Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus–a pooled meta-analysis of randomized placebo-controlled clinical trials. Int J Cardiol 2010; 141: 157–66.Younossi Z, Anstee QM, Marietti M et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018; 15 (1): 11–20.Singh S, Allen AM, Wang Z et al. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol 2015; 13 (4): 643–54.Nascimbenia F, Pellegrinia E, Lugari S et al. Statins and nonalcoholic fatty liver disease in the era of precision medicine: More friends than foes. Atherosclerosis 2019; 284: 66–74. doi.org/10.1016/j.atherosclerosis. 2019.02.028Pastori D, Polimeni L, Baratta F et al. The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis 2015; 47: 4–11.Browning JD. Statins and hepatic steatosis: perspectives from the Dallas heart study. Hepatology 2006; 44: 466–71.Athyros VG, Tziomalos K, Gossios TD et al. for the GREACE Study Collaborative Group. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet 2010; 376: 1916–22.Kim RG, Loomba R, Prokop LJ, Singh S. Statin use and risk of cirrhosis and related complications in patients with chronic liver diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2017; 15: 1521–30.Motamed N et al. Non-alcoholic fatty liver disease (NAFLD) and 10-year risk of cardiovascular diseases. Clin Res Hepatol Gastroenterol 2017; 41: 31–8.Simon TG, Corey KE, Cannon CP et al. The nonalcoholic fatty liver disease (NAFLD) fibrosis score, cardiovascular risk stratification and a strategy for secondary prevention with ezetimibe. Int J Cardiol 2018; 270: 245–52.Bohula EA, Giugliano RP, Cannon CP. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation 2015; 132: 1224–33.Takeshita Y, Takamura T, Honda M. The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial. Diabetologia 2014; 57: 878–90.Del Ben M, Baratta F, Polimeni L et al. Under-prescription of statins in patients with non-alcoholic fatty liver disease. Nutr Metabol Cardiovasc Dis 2017; 27: 161–7.Blais P, Lin M, Kramer JR et al. Statins are underutilized in patients with nonalcoholic fatty liver disease and dyslipidemia. Dig Dis Sci 2016; 61: 1714–20.Labenz C, Huber Y, Kalliga E et al. Predictors of advanced fibrosis in non-cirrhotic non-alcoholic fatty liver disease in Germany. Aliment Pharmacol Ther 2018; 48: 1109–16.Rzouq FS, Volk ML, Hatoum HH et al. Hepatotoxicity fears contribute to under-utilization of statin medications by primary care physicians. Am J Med Sci 2010; 340: 89–93.Ивашкин В.Т., Маевская М.В., Павлов Ч.С. и др. Клинические рекомендации по диагностике и лечению неалкогольной жировой болезни печени Российского общества по изучению печени и Российской гастроэнтерологической ассоциации. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии. 2016; 2: 24–42. [Ivashkin V.T., Maevskaia M.V., Pavlov Ch.S. et al. Klinicheskie rekomendatsii po diagnostike i lecheniiu nealkogol’noi zhirovoi bolezni pecheni Rossiiskogo obshchestva po izucheniiu pecheni i Rossiiskoi gastroenterologicheskoi assotsiatsii. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2016; 2: 24–42 (in Russian).]Gonciarz Z, Besser P, Lelek E et al. Randomised placebo-controlled doubleblind trial on essential phospholipids in the treatment of fatty liver associated with diabetes. Med Chir Dig 1988; 17 (1): 61–5.Sas E, Grinevich V, Efimov O et al Beneficial influence of polyunsaturated Phosphatidylcholine enhances functional liver condition and liver structure in patients with Nonalcoholic steatohepatitis. Results of prolonged randomized blinded prospective clinical study. J Hepatol 2013; 58: S549.Un C, Zheng X, Tan Z et al. Clinical Observation on Polyene Phosphatidyl Choline and Metformin in the Treatment of Type 2 Diabetes and Non-alcoholic Fatty Liver Disease. Clin Focus 2008; 23 (17): 1272–3.Yin Kong. Observation for curative effect of Essentiale in treatment of fatty liver caused by diabetes mellitus. Med J Q Ilu 2000; 15: 277–8.Ивашкин В.Т., Маевская М.В., Широкова Е.Н., Морозова М.А. Опыт применения препарата Эслидин® у пациентов с неалкогольной жировой болезнью печени в практике врача амбулаторного звена (Global Observation of Liver Disease treatment with Eslidin®, «GOLD»). РМЖ. 2015; 21: 1272–7. [Ivashkin V.T., Maevskaia M.V., Shirokova E.N., Morozova M.A. Opyt primeneniia preparata Eslidin® u patsientov s nealkogol’noi zhirovoi bolezn’iu pecheni v praktike vracha ambulatornogo zvena (Global Observation of Liver Disease treatment with EslidinR, «GOLD’). RMZh. 2015; 21: 1272–7 (in Russian).]Fernandez A, Matías N, Martínez L et al. Specific contribution of methionine and choline in nutritional nonalcoholic steatohepatitis: impact on mitochondrial S-adenosyl-l-methionine and glutathione. J Biol Chem 2010; 285: 18528–36.Moundras C, Rémésy C, Levrat MA, Demigné C. Methionine deficiency in rats fed soy protein induces hypercholesterolemia and potentiates lipoprotein susceptibility to peroxidation. Metabolism 1995; 44: 1146–52.Dhar I, Lysne V, Seifert R et al. Plasma methionine and risk of acute myocardial infarction: Effect modification by established risk factors. Atherosclerosis 2018; 272: 175–81. DOI: 10.1016/j.atherosclerosis. 2018.03.038Ruscica M, Ferri N, Macchi C et al. Liver fat accumulation is associated with circulating PCSK9. Ann Med 2016; 48 (5): 384–91.Wargnya M, Ducluzeau P-H, Petitd J-M et al. Circulating PCSK9 levels are not associated with the severity of hepatic steatosis and NASH in a high-risk population. Atherosclerosis 2018; 278: 82–90. DOI: 10.1016/j.atherosclerosis.2018.09.008Бубнова М.Г., Аронов Д.М., Евдаков В.А. Гиполипидемическая и гепатопротекторная эффективность фиксированной комбинации эссенциальных фосфолипидов с метионином на фоне терапии аторвастатином у больных с сердечно-сосудистыми заболеваниями и сахарным диабетом 2 типа, страдающих гиперлипидемией (исследование ОЛИМП, часть I). CardioСоматика. 2012; 3 (3): 82–93. [Bubnova M.G., Aronov D.M., Evdakov V.A. The hypolipidemic and hepatoprotective efficacies of a fixed-dose combination of essential phospholipids with methionine during atorvastatin therapy in hyperlipidemic patients with cardiovascular diseases and type 2 diabetes mellitus (OLYMP trial, Part 1). Cardiosomatics 2012; 3 (3): 82–93 (in Russian).]Бубнова М.Г., Аронов Д.М., Евдаков В.А., Выгодин В.А. Влияние аторвастатина при монотерапии и в комбинации с эссенциальными фосфолипидами на показатели углеводного обмена, функцию эндотелия и маркеры воспаления у больных с сердечно-сосудистыми заболеваниями и сахарным диабетом 2 типа в сочетании с гиперлипидемией (исследование ОЛИМП, часть II). CardioСоматика. 2012; 3 (4): 28–37. [Bubnova M.G., Aronov D.M., Evdakov V.A., Vygodin V.A. The effect of atorvastatin alone and in combination with essential phospholipids on carbohydrate metabolic parameters, endothelial function, and inflammatory markers in patients with cardiovascular diseases and type 2 diabetes mellitus concurrent with hypehyperlipidemia (OLYMP trial, Part II). Cardiosomatics. 2012; 3 (4): 28–37 (in Russian).]