persmedРоссийский журнал персонализированной медициныRussian Journal for Personalized Medicine2782-38062782-3814ФОНД АЛМАЗОВА10.18705/2782-3806-20244-3-194-205MZSDRZpersmed-262Research ArticleКАРДИОЛОГИЯCARDIOLOGYГипертриглицеридемия: сложные вопросы диагностики, терапевтические перспективыHypertriglyceridemia: diagnostic issues, therapeutic strategiesБакалейкоВ. В.BakaleikoV. V.

Бакалейко Виктория Владимировна, младший научный сотрудник НИЛ нарушений липидного обмена и атеросклероза НЦМУ «Центр персонализированной медицины»

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

Bakaleiko Victoria V., Junior researcher of the Laboratory of Lipid Metabolism Disorders and Atherosclerosis, World-Class Research Centre for Personalized Medicine

Akkuratova str., 2, Saint Petersburg, Russia, 197341

bakaleyko_vv@almazovcentre.ruРеутоваО. В.ReutovaO. V.

Реутова Ольга Вячеславовна, научный сотрудник НИЛ нарушений липидного обмена и атеросклероза НЦМУ «Центр персонализированной медицины»

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

Reutova Olga V., Researcher of the Laboratory of Lipid Metabolism Disorders and Atherosclerosis, WorldClass Research Centre for Personalized Medicine

Akkuratova str., 2, Saint Petersburg, Russia, 197341

АлиеваМ. С.AlievaM. S.

Алиева Мадина Сайгидовна, врач анестезиолог-реаниматолог отделения анестезиологии-реанимации № 5 

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

Alieva Madina S., Anesthesiologist-intensive care specialist of the 5th Department of anesthesiology and intensive care of the University clinic

Akkuratova str., 2, Saint Petersburg, Russia, 197341

БараташвилиГ. Г.BaratashviliG. G.

Бараташвили Георгий Григорьевич, к.м.н., заведующий отделением клинической трансфузиологии 

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

Baratashvili Georgy G., Head of the Department of Clinical Transfusiology

Akkuratova str., 2, Saint Petersburg, Russia, 197341

КостареваА. А.KostarevaA. A.

Костарева Анна Александровна, д.м.н., директор Института молекулярной биологии и генетики

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

Kostareva Anna A., MD, PhD, Head of Institute of Molecular Biology and Genetics

Akkuratova str., 2, Saint Petersburg, Russia, 197341

АлиеваА. С.AlievaA. S.

Алиева Асият Сайгидовна, к.м.н., заведующий НИЛ нарушений липидного обмена и атеросклероза НЦМУ «Центр персонализированной медицины»

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

Alieva Asiyat S., MD, PhD, Head of Research Laboratory of Lipid Metabolism Disorders and Atherosclerosis, World-Class Research Centre for Personalized Medicine

Akkuratova str., 2, Saint Petersburg, Russia, 197341

Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской ФедерацииРоссияAlmazov National Medical Research CentreRussian Federation20240708202443194205Copyright © Бакалейко В.В., Реутова О.В., Алиева М.С., Бараташвили Г.Г., Костарева А.А., Алиева А.С., 20242024Бакалейко В.В., Реутова О.В., Алиева М.С., Бараташвили Г.Г., Костарева А.А., Алиева А.С.Bakaleiko V.V., Reutova O.V., Alieva M.S., Baratashvili G.G., Kostareva A.A., Alieva A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://persmed.elpub.ru/jour/article/view/262

Повышение уровня триглицеридов (ТГ) вносит вклад в формирование величины сердечно-сосудистого риска у пациентов, в том числе с целевыми значениями липопротеидов низкой плотности (ХС-ЛНП) [1]. Однако многообразие этиологических факторов и патогенетических паттернов гипертриглицеридемии, их сочетания у одного и того же пациента зачастую затрудняют предикцию рисков развития сердечно-сосудистых заболеваний (ССЗ) атеросклеротического генеза, острого панкреатита, в связи с этим и выработку оптимальной стратегии ведения данной категории пациентов.

В обзоре представлены данные эпидемиологических и генетических исследований, обсуждены сложные вопросы диагностики и ведения пациентов, включая эфферентные методы лечения, а также перспективы инновационной медикаментозной терапии.

Elevated levels of triglyceride-rich lipoproteins contribute to the residual cardiovascular risk in patients, including those with optimally controlled low-density lipoproteins. However, the variety of etiological factors, pathogenetic patterns of hypertriglyceridemia and their combinations, often bring complexity to prediction of the risks of atherosclerotic cardiovascular disease, acute pancreatitis, and therefore the optimal management. The review presents data from epidemiological and genetic studies, discusses complex issues of diagnosis and management strategies, including apheresis, as well as the prospects of innovative therapy.

аферезгенетикагипертриглицеридемиямногофакторная хиломикронемияострый панкреатитсердечно-сосудистые заболеваниясиндром семейной хиломикронемииacute pancreatitisapheresiscardio-vascular diseasesfamilial chylomicronemia syndromegeneticshypertriglyceridemiamultifactorial chylomicronemiaReferencesChapman M, Ginsberg H, Amarenco P, et al. Consensus Panel. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32:1345–1361.Chapman M, Ginsberg H, Amarenco P, et al. Consensus Panel. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32:1345–1361.Puri R, Mehta V, Iyengar S, et al. Triglycerides and atherosclerotic cardiovascular disease. J Assoc Physicians India. 2020;68:35–41.Puri R, Mehta V, Iyengar S, et al. Triglycerides and atherosclerotic cardiovascular disease. J Assoc Physicians India. 2020;68:35–41.Chait A, Ginsberg H, Vaisar T, et al. Remnants of the triglyceride-rich lipoproteins, diabetes, and cardiovascular disease. Diabetes 2020;69:508–516.Chait A, Ginsberg H, Vaisar T, et al. Remnants of the triglyceride-rich lipoproteins, diabetes, and cardiovascular disease. Diabetes 2020;69:508–516.Marcoux C, Tremblay M, Nakajima K, et al. Characterization of remnant-like particles isolated by immunoaffinity gel from the plasma of type III and type IV hyperlipoproteinemic patients. J Lipid Res 1999;40:636–647.Marcoux C, Tremblay M, Nakajima K, et al. Characterization of remnant-like particles isolated by immunoaffinity gel from the plasma of type III and type IV hyperlipoproteinemic patients. J Lipid Res 1999;40:636–647.Fan W, Philip S, Granowitz C, et al. Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey. J Clin Lipidol. 2019;13(1):100–108. PMID: 30594443Fan W, Philip S, Granowitz C, et al. Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey. J Clin Lipidol. 2019;13(1):100–108. PMID: 30594443Ежов М.В., Кухарчук В.В., Сергиенко И.В. и др. Нарушения липидного обмена. Клинические рекомендации 2023. Российский кардиологический журнал. 2023;28(5):250–297. DOI:10.15829/1560-4071-2023-5471. EDN YVZOWJEzhov MV, Kuharchuk VV, Sergienko IV, et al. Dislipidemia. Guidelines 2023. Russian cardiological journal. 2023;28(5):250–297. In Russian]. DOI:10.15829/1560-4071-2023-5471. EDN YVZOWJМетельская В.А., Шальнова С.А., Деев А.Д. и др. Анализ распространенности показателей, характеризующих атерогенность спектра липопротеидов, у жителей Российской Федерации (по данным исследования ЭССЕ-РФ). Профилактическая медицина 2016; 19(1): 15–23.Metelskaya VA, Shalnova SA, Deev AD, et al. Analysis of atherogenic dyslipidemias prevalence among population of Russian Federation (results of the ESSE-RF Study). Profilakticheskaya meditsina 2016; 19(1): 20. In RussianDron JS, Wang J, Cao H, et al. Severe hypertriglyceridemia is primarily polygenic. J Clin Lipidol. 2019;13:80–88. DOI: 10.1016/j.jacl.2018.10.006.Dron JS, Wang J, Cao H, et al. Severe hypertriglyceridemia is primarily polygenic. J Clin Lipidol. 2019;13:80–88. DOI: 10.1016/j.jacl.2018.10.006.Moulin P, Dufour R, Averna M, et al. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recommendations and proposal of an “FCS score”. Atherosclerosis. 2018;275:265–272. DOI: 10.1016/j.atherosclerosis.2018.06.814.Moulin P, Dufour R, Averna M, et al. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recommendations and proposal of an “FCS score”. Atherosclerosis. 2018;275:265–272. DOI: 10.1016/j.atherosclerosis.2018.06.814.Christian JB, Arondekar B, Buysman EK, et al. Clinical and economic benefits observed when follow-up triglyceride levels are less than 500 mg/dL in patients with severe hypertriglyceridemia. J Clin Lipidol. 2012;6:450–461. DOI: 10.1016/j.jacl.2012.08.007.Christian JB, Arondekar B, Buysman EK, et al. Clinical and economic benefits observed when follow-up triglyceride levels are less than 500 mg/dL in patients with severe hypertriglyceridemia. J Clin Lipidol. 2012;6:450–461. DOI: 10.1016/j.jacl.2012.08.007.Zafrir B, Jubran A, Hijazi R, et al. Clinical features and outcomes of severe, very severe, and extreme hypertriglyceridemia in a regional health service. J Clin Lipidol. 2018;12:928–936. DOI: 10.1016/j.jacl.2018.03.086.Zafrir B, Jubran A, Hijazi R, et al. Clinical features and outcomes of severe, very severe, and extreme hypertriglyceridemia in a regional health service. J Clin Lipidol. 2018;12:928–936. DOI: 10.1016/j.jacl.2018.03.086.Yin G, Cang X, Yu G, et al. Different clinical presentations of hyperlipidemic acute pancreatitis: A retrospective study. Pancreas (2015) 44:1105–10. DOI: 10.1097/MPA.0000000000000403.Yin G, Cang X, Yu G, et al. Different clinical presentations of hyperlipidemic acute pancreatitis: A retrospective study. Pancreas (2015) 44:1105–10. DOI: 10.1097/MPA.0000000000000403.de Pretis N, Amodio A, Frulloni L. Hypertriglyceridemic pancreatitis: Epidemiology, pathophysiology and clinical management. United Eur Gastroenterol J (2018) 6:649–55. DOI: 10.1177/2050640618755002.de Pretis N, Amodio A, Frulloni L. Hypertriglyceridemic pancreatitis: Epidemiology, pathophysiology and clinical management. United Eur Gastroenterol J (2018) 6:649–55. DOI: 10.1177/2050640618755002.Valdivielso P, Ramirez-Bueno A, Ewald N. Current knowledge of hypertriglyceridemic pancreatitis. Eur J Intern Med (2014) 25:689–94. DOI: 10.1016/j.ejim.2014.08.008.Valdivielso P, Ramirez-Bueno A, Ewald N. Current knowledge of hypertriglyceridemic pancreatitis. Eur J Intern Med (2014) 25:689–94. DOI: 10.1016/j.ejim.2014.08.008.Teslovich T, Musunuru K, Smith AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010;466: 707–13.Teslovich T, Musunuru K, Smith AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010;466: 707–13.Johansen C, Hegele R. Allelic and phenotypic spectrum of plasma triglycerides. Biochim Biophys Acta 2012; 1821: 833–42.Johansen C, Hegele R. Allelic and phenotypic spectrum of plasma triglycerides. Biochim Biophys Acta 2012; 1821: 833–42.Johansen C, Wang J, Lanktree M, et al. An increased burden of common and rare lipid-associated risk alleles contributes to the phenotypic spectrum of hypertriglyceridemia. Arterioscler Thromb Vasc Biol 2011; 31: 1916–26.Johansen C, Wang J, Lanktree M, et al. An increased burden of common and rare lipid-associated risk alleles contributes to the phenotypic spectrum of hypertriglyceridemia. Arterioscler Thromb Vasc Biol 2011; 31: 1916–26.Hegele R, Ban M, Hsueh N, et al. A polygenic basis for four classical Fredrickson hyperlipoproteinemia phenotypes that are characterized by hypertriglyceridemia. Hum Mol Genet 2009; 18: 4189–94.Hegele R, Ban M, Hsueh N, et al. A polygenic basis for four classical Fredrickson hyperlipoproteinemia phenotypes that are characterized by hypertriglyceridemia. Hum Mol Genet 2009; 18: 4189–94.Johansen C, Wang J, McIntyre A, et al. Excess of rare variants in non-genome-wide association study candidate genes in patients with hypertriglyceridemia. Circ Cardiovasc Genet 2012; 5: 66–72.Johansen C, Wang J, McIntyre A, et al. Excess of rare variants in non-genome-wide association study candidate genes in patients with hypertriglyceridemia. Circ Cardiovasc Genet 2012; 5: 66–72.Rabacchi C, Pisciotta L, Cefalù A, et al. Spectrum of mutations of the LPL gene identified in Italy in patients with severe hypertriglyceridemia. Atherosclerosis. 2015;241:79–86. DOI: 10.1016/j.atherosclerosis.2015.04.815.Rabacchi C, Pisciotta L, Cefalù A, et al. Spectrum of mutations of the LPL gene identified in Italy in patients with severe hypertriglyceridemia. Atherosclerosis. 2015;241:79–86. DOI: 10.1016/j.atherosclerosis.2015.04.815.D’Erasmo L, Di Costanzo A, Cassandra F, et al. Spectrum of Mutations and Long-Term Clinical Outcomes in Genetic Chylomicronemia Syndromes. Arterioscler Thromb Vasc Biol. 2019 Dec;39(12):2531– 2541. DOI: 10.1161/ATVBAHA.119.313401. Epub 2019 Oct 17. PMID: 31619059.D’Erasmo L, Di Costanzo A, Cassandra F, et al. Spectrum of Mutations and Long-Term Clinical Outcomes in Genetic Chylomicronemia Syndromes. Arterioscler Thromb Vasc Biol. 2019 Dec;39(12):2531– 2541. DOI: 10.1161/ATVBAHA.119.313401. Epub 2019 Oct 17. PMID: 31619059.Jørgensen A, Frikke-Schmidt R, West A, et al. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J. 2013;34:1826–1833. DOI: 10.1093/eurheartj/ehs431.Jørgensen A, Frikke-Schmidt R, West A, et al. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J. 2013;34:1826–1833. DOI: 10.1093/eurheartj/ehs431.Hegele R, Ginsberg H, Chapman M, et al. European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014 Aug;2(8):655–66. DOI: 10.1016/S2213-8587(13)70191-8. Epub 2013 Dec 23. PMID: 24731657; PMCID: PMC4201123.Hegele R, Ginsberg H, Chapman M, et al. European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014 Aug;2(8):655–66. DOI: 10.1016/S2213-8587(13)70191-8. Epub 2013 Dec 23. PMID: 24731657; PMCID: PMC4201123.Berglund L, Brunzell J, Goldberg A, et al, and the Endocrine Society. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97: 2969–89.Berglund L, Brunzell J, Goldberg A, et al, and the Endocrine Society. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97: 2969–89.Yuan G, Al-Shali K, Hegele R. Hypertriglyceridemia: its etiology, effects and treatment. CMAJ 2007; 176: 1113–20.Yuan G, Al-Shali K, Hegele R. Hypertriglyceridemia: its etiology, effects and treatment. CMAJ 2007; 176: 1113–20.Catapano A, Reiner Z, De Backer G, et al, and the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS), and the ESC Committee for Practice Guidelines 2008–2010 and 2010–2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 2011; 217 (suppl 1): S1–44.Catapano A, Reiner Z, De Backer G, et al, and the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS), and the ESC Committee for Practice Guidelines 2008–2010 and 2010–2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 2011; 217 (suppl 1): S1–44.Varbo A, Freiberg J, Nordestgaard B, et al. Remnant cholesterol and myocardial infarction in normal weight, overweight, and obese individuals from the Copenhagen General Population Study. Clin Chem. 2018;64(1):219–230. PMID: 29021326.Varbo A, Freiberg J, Nordestgaard B, et al. Remnant cholesterol and myocardial infarction in normal weight, overweight, and obese individuals from the Copenhagen General Population Study. Clin Chem. 2018;64(1):219–230. PMID: 29021326.Nordestgaard BG, Langsted A, Mora S, et al. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cutpoints—A joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J. 2016;37(25):1944–1958. PMID: 27122601.Nordestgaard BG, Langsted A, Mora S, et al. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cutpoints—A joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J. 2016;37(25):1944–1958. PMID: 27122601.Farukhi Z, Mora S. Nonfasting lipids for all patients? Clin Chem. 2021;67(1):41–45. PMID: 33221866.Farukhi Z, Mora S. Nonfasting lipids for all patients? Clin Chem. 2021;67(1):41–45. PMID: 33221866.Nordestgaard B, Benn M, Schnohr P, et al. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298(3):299–308. PMID: 17635890.Nordestgaard B, Benn M, Schnohr P, et al. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298(3):299–308. PMID: 17635890.Langsted A, Freiberg J, Nordestgaard B. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. Circulation. 2008;118(20):2047–2056. PMID: 18955664.Langsted A, Freiberg J, Nordestgaard B. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. Circulation. 2008;118(20):2047–2056. PMID: 18955664.Hegele R. Plasma lipoproteins: genetic influences and clinical implications. Nat Rev Genet 2009; 10: 109–21.Hegele R. Plasma lipoproteins: genetic influences and clinical implications. Nat Rev Genet 2009; 10: 109–21.Soutar AK, Naoumova RP. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med. 2007; 4:214–25.Soutar AK, Naoumova RP. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med. 2007; 4:214–25.Hegele R, Ginsberg H, Chapman M, et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. The Lancet Diabetes & Endocrinology 2014; 2(8), 655–666. DOI:10.1016/s2213-8587(13)70191-8.Hegele R, Ginsberg H, Chapman M, et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. The Lancet Diabetes & Endocrinology 2014; 2(8), 655–666. DOI:10.1016/s2213-8587(13)70191-8.Skulas-Ray A, Wilson P, Harris W, et al. American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Omega-3 fatty acids for the management of hypertriglyceridemia: a Science Advisory from the American Heart Association. Circulation 2019;140: e673–e691.Skulas-Ray A, Wilson P, Harris W, et al. American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Omega-3 fatty acids for the management of hypertriglyceridemia: a Science Advisory from the American Heart Association. Circulation 2019;140: e673–e691.Bowman L, Hopewell JC, Chen F, et al. Effects of anacetrapib in patients with atherosclerotic vascular disease. HPS3/TIMI55–REVEAL Collaborative Group. N Engl J Med 2017;377:1217–1227.Bowman L, Hopewell JC, Chen F, et al. Effects of anacetrapib in patients with atherosclerotic vascular disease. HPS3/TIMI55–REVEAL Collaborative Group. N Engl J Med 2017;377:1217–1227.Lincoff A, Nicholls S, Riesmeyer J, et al. Evacetrapib and cardiovascular outcomes in high-risk vascular disease. ACCELERATE Investigators. N Engl J Med 2017; 376:1933–1942.Lincoff A, Nicholls S, Riesmeyer J, et al. Evacetrapib and cardiovascular outcomes in high-risk vascular disease. ACCELERATE Investigators. N Engl J Med 2017; 376:1933–1942.Blom D, Raal F, Santos R, et al. Lomitapide and mipomersen-inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 synthesis. Curr Atheroscler Rep 2019;21:48.Blom D, Raal F, Santos R, et al. Lomitapide and mipomersen-inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 synthesis. Curr Atheroscler Rep 2019;21:48.Parham J, Goldberg A. Mipomersen and its use in familial hypercholesterolemia. Expert Opin Pharmacother 2019;20:127–131.Parham J, Goldberg A. Mipomersen and its use in familial hypercholesterolemia. Expert Opin Pharmacother 2019;20:127–131.Stefanutti C. Lomitapide — a microsomal triglyceride transfer protein inhibitor for homozygous familial hypercholesterolemia. Curr Atheroscler Rep 2020;22:38.Stefanutti C. Lomitapide — a microsomal triglyceride transfer protein inhibitor for homozygous familial hypercholesterolemia. Curr Atheroscler Rep 2020;22:38.Zheng C, Khoo C, Furtado J, et al. Apolipoprotein C-III and the metabolic basis for hypertriglyceridemia and the dense low-density lipoprotein phenotype. Circulation. 2010;121(15):1722–1734. PMID: 20368524.Zheng C, Khoo C, Furtado J, et al. Apolipoprotein C-III and the metabolic basis for hypertriglyceridemia and the dense low-density lipoprotein phenotype. Circulation. 2010;121(15):1722–1734. PMID: 20368524.Ooi E, Barrett P, Chan D, et al. Apolipoprotein III. C-understanding an emerging cardiovascular risk factor. Clin Sci (Lond). 2008;114(10):611–624. PMID: 18399797.Ooi E, Barrett P, Chan D, et al. Apolipoprotein III. C-understanding an emerging cardiovascular risk factor. Clin Sci (Lond). 2008;114(10):611–624. PMID: 18399797.Kinnunen P, Ehnolm C. Effect of serum and C-apoproteins from very low-density lipoproteins on human postheparin plasma hepatic lipase. FEBS Lett. 1976;65(3):354–357. PMID: 182536.Kinnunen P, Ehnolm C. Effect of serum and C-apoproteins from very low-density lipoproteins on human postheparin plasma hepatic lipase. FEBS Lett. 1976;65(3):354–357. PMID: 182536.Yao Z, Wang Y. Apolipoprotein C-III and hepatic triglyceride-rich lipoprotein production. Curr Opin Lipidol. 2012;23(3):206–212. PMID: 22510806.Yao Z, Wang Y. Apolipoprotein C-III and hepatic triglyceride-rich lipoprotein production. Curr Opin Lipidol. 2012;23(3):206–212. PMID: 22510806.Gaudet D, Brisson D, Tremblay K, et al. Targeting APOC3 in the familial chylomicronemia syndrome. N Engl J Med. 2014;371(23):2200–2206. PMID: 25470695.Gaudet D, Brisson D, Tremblay K, et al. Targeting APOC3 in the familial chylomicronemia syndrome. N Engl J Med. 2014;371(23):2200–2206. PMID: 25470695.Witztum J, Gaudet D, Freedman S, et al. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome. N Engl J Med. 2019;381(6):531–542. PMID: 31390500.Witztum J, Gaudet D, Freedman S, et al. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome. N Engl J Med. 2019;381(6):531–542. PMID: 31390500.Alexander V, Xia S, Hurh E, et al. N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. Eur Heart J. 2019;40(33):2785–2796. PMID: 31329855.Alexander V, Xia S, Hurh E, et al. N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. Eur Heart J. 2019;40(33):2785–2796. PMID: 31329855.Conklin D, Gilbertson D, Taft D, et al. Identification of a mammalian angiopoietin-related protein expressed specifically in liver. Genomics. 1999;62(3):477–482. PMID: 10644446.Conklin D, Gilbertson D, Taft D, et al. Identification of a mammalian angiopoietin-related protein expressed specifically in liver. Genomics. 1999;62(3):477–482. PMID: 10644446.Gaudet D, Gipe D, Pordy R, et al. ANGPTL3 inhibition in homozygous familial hypercholesterolemia. N Engl J Med. 2017;377(3):296–297. PMID: 28723334.Gaudet D, Gipe D, Pordy R, et al. ANGPTL3 inhibition in homozygous familial hypercholesterolemia. N Engl J Med. 2017;377(3):296–297. PMID: 28723334.RaalF,RosensonR,ReeskampL,etal.Evinacumab for homozygous familial hypercholesterolemia. N Engl J Med. 2020;383(8):711–720. PMID: 32813947.RaalF,RosensonR,ReeskampL,etal.Evinacumab for homozygous familial hypercholesterolemia. N Engl J Med. 2020;383(8):711–720. PMID: 32813947.Banerjee P, Chan K, Tarabocchia M, et al. Functional analysis of LDLR (low-density lipoprotein receptor) variants in patient lymphocytes to assess the effect of evinacumab in homozygous familial hypercholesterolemia patients with a spectrum of LDLR activity. Arterioscler Thromb Vasc Biol. 2019;39(11):2248–2260. PMID: 31578082.Banerjee P, Chan K, Tarabocchia M, et al. Functional analysis of LDLR (low-density lipoprotein receptor) variants in patient lymphocytes to assess the effect of evinacumab in homozygous familial hypercholesterolemia patients with a spectrum of LDLR activity. Arterioscler Thromb Vasc Biol. 2019;39(11):2248–2260. PMID: 31578082.Graham M, Lee R, Brandt T, et al. Cardiovascular and metabolic effects of ANGPTL3 antisense oligonucleotides. N Engl J Med. 2017;377(3):222–232. PMID: 28538111.Graham M, Lee R, Brandt T, et al. Cardiovascular and metabolic effects of ANGPTL3 antisense oligonucleotides. N Engl J Med. 2017;377(3):222–232. PMID: 28538111.Adam R, Mintah I, Alexa-Braun C, et al. Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance. J Lipid Res. 2020;61(9):1271–1286. PMID: 32646941.Adam R, Mintah I, Alexa-Braun C, et al. Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance. J Lipid Res. 2020;61(9):1271–1286. PMID: 32646941.Wetterau J, Aggerbeck L, Bouma M, et al. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science. 1992;258(5084):999–1001. PMID: 1439810.Wetterau J, Aggerbeck L, Bouma M, et al. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science. 1992;258(5084):999–1001. PMID: 1439810.Cuchel M, Bloedon L, Szapary P, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007;356(2):148– 156. PMID: 17215532.Cuchel M, Bloedon L, Szapary P, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007;356(2):148– 156. PMID: 17215532.Meyers C, Tremblay K, Amer A, et al. Effect of the DGAT1 inhibitor pradigastat on triglyceride and apoB48 levels in patients with familial chylomicronemia syndrome. Lipids Health Dis. 2015;14:8. PMID: 25889044.Meyers C, Tremblay K, Amer A, et al. Effect of the DGAT1 inhibitor pradigastat on triglyceride and apoB48 levels in patients with familial chylomicronemia syndrome. Lipids Health Dis. 2015;14:8. PMID: 25889044.Gaudet D, Méthot J, Déry S, et al. Efficacy and long-term safety of alipogene tiparvovec (AAV1LPLS447X) genetherapyforlipoproteinlipasedeficiency: an open-label trial. Gene Ther. 2013;20(4):361–369. PMID: 22717743.Gaudet D, Méthot J, Déry S, et al. Efficacy and long-term safety of alipogene tiparvovec (AAV1LPLS447X) genetherapyforlipoproteinlipasedeficiency: an open-label trial. Gene Ther. 2013;20(4):361–369. PMID: 22717743.Carpentier A, Frisch F, Labbé S, et al. Effect of alipogene tiparvovec (AAV1-LPLS447X) on postprandial chylomicron metabolism in lipoprotein lipase-deficient patients. J Clin Endocrinol Metab. 2012;97(5):1635– 1644. PMID: 22438229.Carpentier A, Frisch F, Labbé S, et al. Effect of alipogene tiparvovec (AAV1-LPLS447X) on postprandial chylomicron metabolism in lipoprotein lipase-deficient patients. J Clin Endocrinol Metab. 2012;97(5):1635– 1644. PMID: 22438229.Gaudet D, Stroes E, Méthot J, et al. Long-term retrospective analysis of gene therapy with alipogene tiparvovec and its effect on lipoprotein lipase deficiencyinduced pancreatitis. Hum Gene Ther. 2016;27(11):916– 925. PMID: 27412455.Gaudet D, Stroes E, Méthot J, et al. Long-term retrospective analysis of gene therapy with alipogene tiparvovec and its effect on lipoprotein lipase deficiencyinduced pancreatitis. Hum Gene Ther. 2016;27(11):916– 925. PMID: 27412455.Gaudet D, Méthot J, Kastelein J. Gene therapy for lipoprotein lipase deficiency. Curr Opin Lipidol. 2012;23(4):310–320. PMID: 22691709.Gaudet D, Méthot J, Kastelein J. Gene therapy for lipoprotein lipase deficiency. Curr Opin Lipidol. 2012;23(4):310–320. PMID: 22691709.Kaeppel C, Beattie S, Fronza R, et al. A largely random AAV integration profile after LPLD gene therapy. Nat Med. 2013;19(7):889–891. PMID: 23770691.Kaeppel C, Beattie S, Fronza R, et al. A largely random AAV integration profile after LPLD gene therapy. Nat Med. 2013;19(7):889–891. PMID: 23770691.Chadwick A, Evitt N, Lv W, et al. Reduced blood lipid levels with in vivo CRISPR-Cas9 base editing of ANGPTL3. Circulation. 2018;137(9):975–977. PMID: 29483174.Chadwick A, Evitt N, Lv W, et al. Reduced blood lipid levels with in vivo CRISPR-Cas9 base editing of ANGPTL3. Circulation. 2018;137(9):975–977. PMID: 29483174.Malchesky P, Werynski A, Nomura H, et al. Thermofiltration in hypercholesterolemia treatment: analysis of removal and posttreatment cholesterol recovery. J Clin Apher. 1990;5(3):145–150. DOI: 10.1002/jca.2920050306. PMID: 2345162.Malchesky P, Werynski A, Nomura H, et al. Thermofiltration in hypercholesterolemia treatment: analysis of removal and posttreatment cholesterol recovery. J Clin Apher. 1990;5(3):145–150. DOI: 10.1002/jca.2920050306. PMID: 2345162.Wang J, Dron J, Ban M, et al. Polygenic versus monogenic causes of hypercholesterolemia ascertained clinically. Arterioscler Thromb Vasc Biol. 2016;36(12):2439–2445. DOI:10.1161/ATVBAHA.116.308027. PMID: 27765764.Wang J, Dron J, Ban M, et al. Polygenic versus monogenic causes of hypercholesterolemia ascertained clinically. Arterioscler Thromb Vasc Biol. 2016;36(12):2439–2445. DOI:10.1161/ATVBAHA.116.308027. PMID: 27765764.Hu P, Dharmayat K, Stevens C, et al. Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease: a systematic review and meta-analysis. Circulation. 2020;141(22):1742–1759. DOI: 10.1161/CIRCULATIONAHA.119.044795. PMID: 32468833.Hu P, Dharmayat K, Stevens C, et al. Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease: a systematic review and meta-analysis. Circulation. 2020;141(22):1742–1759. DOI: 10.1161/CIRCULATIONAHA.119.044795. PMID: 32468833.Moriarty P, Luyendyk J, Gibson C, et al. Effect of low-density lipoprotein apheresis on plasma levels of apolipoprotein e4. Am J Cardiol. 2010;105(11):1585–1587. DOI: 10.1016/j.amjcard.2010.01.018. PMID: 20494666.Moriarty P, Luyendyk J, Gibson C, et al. Effect of low-density lipoprotein apheresis on plasma levels of apolipoprotein e4. Am J Cardiol. 2010;105(11):1585–1587. DOI: 10.1016/j.amjcard.2010.01.018. PMID: 20494666.Ginsberg H, Packard C, Chapman M, et al. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. Eur Heart J. 2021 Dec 14;42(47):4791-4806. doi: 10.1093/eurheartj/ehab551. PMID: 34472586; PMCID: PMC8670783.Ginsberg H, Packard C, Chapman M, et al. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. Eur Heart J. 2021 Dec 14;42(47):4791-4806. doi: 10.1093/eurheartj/ehab551. PMID: 34472586; PMCID: PMC8670783.

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