Статья
Гипертриглицеридемии — современное состояние вопроса. Часть II: первичные и вторичные гипертриглицеридемии, возможности терапии
Гипертриглицеридемии представляют собой гетерогенную группу патологий, отличающихся по механизмам повышения богатых триглицеридами липопротеидов, составу липопротеидов и рискам, с ними ассоциированным. В данной обзорной статье представлена информация о спектре и патогенезе различных форм первичных и вторичных гипертриглицеридемий, описаны современные возможности генетической диагностики, медикаментозной и немедикаментозной коррекции.
1. Ginsberg HN, Packard CJ, Chapman MJ, 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;42(47):4791-806. doi:10.1093/eurheartj/ehab551.
2. Kiss L, Fur G, Pisipati S, et al. Mechanisms linking hypertriglyceridemia to acute pancreatitis. Acta Physiol (Oxf). 2023;237(3):e13916. doi:10.1111/apha.13916.
3. Koopal C, Marais AD, Westerink J, Visseren FL. Autosomal dominant familial dysbetalipoproteinemia: A pathophysiological framework and practical approach to diagnosis and therapy. J Clin Lipidol. 2017;11(1):12-23.e1. doi:10.1016/j.jacl.2016.10.001.
4. Alves M, Laranjeira F, Correia-da-Silva G. Understanding Hypertriglyceridemia: Integrating Genetic Insights. Genes (Basel). 2024;15(2):190. doi:10.3390/genes15020190.
5. Dron JS, Hegele RA. Genetics of Hypertriglyceridemia. Front Endocrinol (Lausanne). 2020;11:455. doi:10.3389/fendo.2020.00455.
6. Hegele RA, Ginsberg HN, Chapman MJ, et al. European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014;2(8):655-66. doi:10.1016/S2213-8587(13)70191-8.
7. Paquette M, Bernard S. The Evolving Story of Multifactorial Chylomicronemia Syndrome. Front Cardiovasc Med. 2022;9:886266. doi:10.3389/fcvm.2022.886266.
8. Gill PK, Hegele RA. Familial combined hyperlipidemia is a polygenic trait. Curr Opin Lipidol. 2022;33(2):126-32. doi:10.1097/MOL.0000000000000796.
9. Hegele RA. Illuminating the full spectrum of APOE variation. Atherosclerosis. 2023; 385:117311. doi:10.1016/j.atherosclerosis.2023.117311.
10. Ruel IL, Couture P, Gagne C, et al. Characterization of a novel mutation causing hepatic lipase deficiency among French Canadians. J Lipid Res. 2003;44(8):1508-14. doi:10.1194/jlr.M200479-JLR200.
11. Gill PK, Dron JS, Berberich AJ, et al. Combined hyperlipidemia is genetically similar to isolated hypertriglyceridemia. J Clin Lipidol. 2021;15(1):79-87. doi:10.1016/j.jacl.2020.11.006.
12. O'Dea LSL, MacDougall J, Alexander VJ, et al. Differentiating Familial Chylomicronemia Syndrome From Multifactorial Severe Hypertriglyceridemia by Clinical Profiles. J Endocr Soc. 2019;3(12):2397-410. doi:10.1210/js.2019-00214.
13. Quispe R, Hendrani AD, Baradaran-Noveiry B, et al. Characterization of lipoprotein profiles in patients with hypertriglyceridemic Fredrickson-Levy and Lees dyslipidemia phenotypes: the Very Large Database of Lipids Studies 6 and 7. Arch Med Sci. 2019;15(5): 1195-202. doi:10.5114/aoms.2019.87207.
14. Hegele RA, Pollex RL. Hypertriglyceridemia: phenomics and genomics. Mol Cell Biochem. 2009;326(1-2):35-43. doi:10.1007/s11010-008-0005-1.
15. Brahm AJ, Hegele RA. Combined hyperlipidemia: familial but not (usually) monogenic. Curr Opin Lipidol. 2016;27(2):131-40. doi:10.1097/MOL.0000000000000270.
16. Bashir B, Ho JH, Downie P, et al. Severe Hypertriglyceridaemia and Chylomicronaemia Syndrome-Causes, Clinical Presentation, and Therapeutic Options. Metabolites. 2023; 13(5):621. doi:10.3390/metabo13050621.
17. Brahm AJ, Hegele RA. Chylomicronaemia — current diagnosis and future therapies. Nat Rev Endocrinol. 2015;11(6):352-62. doi:10.1038/nrendo.2015.26.
18. Hopkins PN, Heiss G, Ellison RC, et al. Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia: a case-control comparison from the National Heart, Lung, and Blood Institute Family Heart Study. Circulation. 2003;108(5): 519-23. doi:10.1161/01.CIR.0000081777.17879.85.
19. Trinder M, Vikulova D, Pimstone S, et al. Polygenic architecture and cardiovascular risk of familial combined hyperlipidemia. Atherosclerosis. 2022;340:35-43. doi:10.1016/j.atherosclerosis.2021.11.032.
20. Bennet AM, Di Angelantonio E, Ye Z, et al. Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA. 2007;298(11):1300-11. doi:10.1001/jama.298.11.1300.
21. Paquette M, Trinder M, Guay SP, et al. Prevalence of Dysbetalipoproteinemia in the UK Biobank According to Different Diagnostic Criteria. J Clin Endocrinol Metab. 2024: dgae259. doi:10.1210/clinem/dgae259.
22. Blokhina AV, Ershova AI, Kiseleva A V, et al. Applicability of Diagnostic Criteria and High Prevalence of Familial Dysbetalipoproteinemia in Russia: A Pilot Study. Int J Mol Sci. 2023;24(17):13159. doi:10.3390/ijms241713159.
23. Wilson C, Mau T, Weisgraber KH, et al. Salt bridge relay triggers defective LDL receptor binding by a mutant apolipoprotein. Structure. 1994;2(8):713-8. doi:10.1016/s0969-2126(00)00072-1.
24. Ji ZS, Fazio S, Mahley RW. Variable heparan sulfate proteoglycan binding of apolipoprotein E variants may modulate the expression of type III hyperlipoproteinemia. J Biol Chem. 1994;269(18):13421-8.
25. Mahley RW, Huang Y, Rall SC Jr. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes. J Lipid Res. 1999;40(11): 1933-49.
26. Koopal C, van der Graaf Y, Asselbergs FW, et al. Influence of APOE-2 genotype on the relation between adiposity and plasma lipid levels in patients with vascular disease. Int J Obes (Lond). 2015;39(2):265-9. doi:10.1038/ijo.2014.105.
27. de Beer F, Stalenhoef AF, Hoogerbrugge N, et al. Expression of type III hyperlipoproteinemia in apolipoprotein E2 (Arg158!Cys) homozygotes is associated with hyperinsulinemia. Arterioscler Thromb Vasc Biol. 2002;22(2):294-9. doi:10.1161/hq0202.102919.
28. Chuang TY, Chao CL, Lin BJ, Lu SC. Gestational hyperlipidemic pancreatitis caused by type III hyperlipoproteinemia with apolipoprotein E2/E2 homozygote. Pancreas. 2009;38(6):716-7. doi:10.1097/MPA.0b013e3181ac6dc1.
29. Henneman P, van der Sman-de Beer F, Moghaddam PH, et al. The expression of type III hyperlipoproteinemia: involvement of lipolysis genes. Eur J Hum Genet. 2009;17(5): 620-8. doi:10.1038/ejhg.2008.202.
30. Balanescu L, Cardoneanu A, Stanciu G, et al. Hypertriglyceridemia Induced Acute Pancreatitis Caused by a Novel LIPC Gene Variant in a Pediatric Patient. Children (Basel). 2022;9(2):188. doi:10.3390/children9020188.
31. Connelly PW, Hegele RA. Hepatic lipase deficiency. Crit Rev Clin Lab Sci. 1998;35(6):547-72. doi:10.1080/10408369891234273.
32. Santamarina-Fojo S, González-Navarro H, Freeman L, et al. Hepatic lipase, lipoprotein metabolism, and atherogenesis. Arterioscler Thromb Vasc Biol. 2004;24(10):1750-4. doi:10.1161/01.ATV.0000140818.00570.2d.
33. Dichek HL, Brecht W, Fan J, et al. Overexpression of hepatic lipase in transgenic mice decreases apolipoprotein B-containing and high density lipoproteins. Evidence that hepatic lipase acts as a ligand for lipoprotein uptake. J Biol Chem. 1998;273(4):1896-903. doi:10.1074/jbc.273.4.1896.
34. Blom DJ, Jones S, Marais AD. Dysbetalipoproteinemia — clinical and pathophysiological features. S Afr Med J. 2002;92(11):892-7.
35. Paquette M, Bernard S, Baass A. Dysbetalipoproteinemia Is Associated With Increased Risk of Coronary and Peripheral Vascular Disease. J Clin Endocrinol Metab. 2022;108(1):184-90. doi:10.1210/clinem/dgac503.
36. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-88. doi:10.1093/eurheartj/ehz455.
37. Блохина А. В., Ершова А. И., Мешков А. Н., Драпкина О. М. Семейная дисбеталипопротеидемия: высокоатерогенное и недостаточно диагностируемое заболевание. Кардиоваскулярная терапия и профилактика. 2021;20(6):2893. doi:10.15829/1728-8800-2021-2893.
38. Goldstein JL, Schrott HG, Hazzard WR, et al. Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest. 1973;52(7):1544-68. doi:10.1172/JCI107332.
39. Vikulova DN, Trinder M, Mancini GBJ, et al. Familial Hypercholesterolemia, Familial Combined Hyperlipidemia, and Elevated Lipoprotein(a) in Patients With Premature Coronary Artery Disease. Can J Cardiol. 2021;37(11):1733-42. doi:10.1016/j.cjca.2021.08.012.
40. Pallazola VA, Sathiyakumar V, Park J, et al. Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia). Arch Med Sci. 2019;16(5):993-1003. doi:10.5114/aoms.2019.86972.
41. Hopkins PN, Wu LL, Hunt SC, Brinton EA. Plasma triglycerides and type III hyperlipidemia are independently associated with premature familial coronary artery disease. J Am Coll Cardiol. 2005;45(7):1003-12. doi:10.1016/j.jacc.2004.11.062.
42. Hegele RA, Boren J, Ginsberg HN, et al. Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement. Lancet Diabetes Endocrinol. 2020;8(1):50-67. doi:10.1016/S2213-8587(19)30264-5.
43. Драпкина О. М.; Лимонова А. С., Гарбузова Е. В. и др. Персонализированная профилактика: возможности и ограничения оценки полигенного риска. Российский журнал персонализированной медицины. 2023;3(5):14-21. doi:10.18705/2782-3806-2023-3-5-14-21.
44. Brown EE, Sturm AC, Cuchel M, et al. Genetic testing in dyslipidemia: A scientific statement from the National Lipid Association. J Clin Lipidol. 2020;14(4):398-413. doi:10.1016/j.jacl.2020.04.011.
45. 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;39(12):2531-41. doi:10.1161/ATVBAHA.119.313401.
46. Guay SP, Paquette M, Taschereau A, et al. Acute pancreatitis risk in multifactorial chylomicronemia syndrome depends on the molecular cause of severe hypertriglyceridemia. Atherosclerosis. 2024;392:117489. doi:10.1016/j.atherosclerosis.2024.117489.
47. Boot CS, Luvai A, Neely RDG. The clinical and laboratory investigation of dysbetalipoproteinemia. Crit Rev Clin Lab Sci. 2020;57(7):458-69. doi:10.1080/10408363.2020.1745142.
48. Cortes VA, Fernandez-Galilea M. Lipodystrophies: adipose tissue disorders with severe metabolic implications. J Physiol Biochem. 2015;71(3):471-8. doi:10.1007/s13105-015-0404-1.
49. Hussain I, Patni N, Garg A. Lipodystrophies, dyslipidaemias and atherosclerotic cardiovascular disease. Pathology. 2019;51(2):202-12. doi:10.1016/j.pathol.2018.11.004.
50. Knebel B, Muller-Wieland D, Kotzka J. Lipodystrophies-Disorders of the Fatty Tissue. Int J Mol Sci. 2020;21(22):8778. doi:10.3390/ijms21228778.
51. Chiquette E, Oral EA, Garg A, et al. Estimating the prevalence of generalized and partial lipodystrophy: findings and challenges. Diabetes Metab Syndr Obes. 2017;10:375-83. doi:10.2147/DMSO.S130810.
52. Bagias C, Xiarchou A, Bargiota A, Tigas S. Familial Partial Lipodystrophy (FPLD): Recent Insights. Diabetes Metab Syndr Obes. 2020;13:1531-44. doi:10.2147/DMSO.S206053.
53. Simha V, Garg A. Inherited lipodystrophies and hypertriglyceridemia. Curr Opin Lipidol. 2009;20(4):300-8. doi:10.1097/MOL.0b013e32832d4a33.
54. Prieur X, Le May C, Magre J, Cariou B. Congenital lipodystrophies and dyslipidemias. Curr Atheroscler Rep. 2014;16(9):437. doi:10.1007/s11883-014-0437-x.
55. Kountouri A, Korakas E, Maratou E, et al. Familial Partial Lipodystrophy: Clinical Features, Genetics and Treatment in a Greek Referral Center. Int J Mol Sci. 2023;24(15):12045. doi:10.3390/ijms241512045.
56. Virani SS, Morris PB, Agarwala A, et al. 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021;78(9):960-93. doi:10.1016/j.jacc.2021.06.011.
57. Salas-Gonzalez MD, Bermejo LM, Gonzalez-Rodriguez LG, et al. Adherence to 24-h movement guidelines in Spanish schoolchildren and its association with insulin resistance: a cross-sectional study. Front Public Health. 2023;11:1146580. doi:10.3389/fpubh.2023.1146580.
58. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595-607. doi:10.2337/diab.37.12.1595.
59. Beaupere C, Liboz A, Fève B, et al. Molecular Mechanisms of Glucocorticoid-Induced Insulin Resistance. Int J Mol Sci. 2021;22(2):623. doi:10.3390/ijms22020623.
60. Lain KY, Catalano PM. Metabolic changes in pregnancy. Clin Obstet Gynecol. 2007;50(4):938-48. doi:10.1097/GRF.0b013e31815a5494.
61. Lagathu C, Bereziat V, Gorwood J, et al. Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment. Expert Opin Drug Saf. 2019;18(9):829-40. doi:10.1080/14740338.2019.1644317.
62. Fathallah N, Slim R, Larif S, et al. Drug-Induced Hyperglycaemia and Diabetes. Drug Saf. 2015;38(12):1153-68. doi:10.1007/s40264-015-0339-z.
63. Khan MAB, Hashim MJ, King JK, et al. Epidemiology of Type 2 Diabetes — Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. 2020;10(1): 107-11. doi:10.2991/jegh.k.191028.001.
64. Noubiap JJ, Nansseu JR, Lontchi-Yimagou E, et al. Geographic distribution of metabolic syndrome and its components in the general adult population: A meta-analysis of global data from 28 million individuals. Diabetes Res Clin Pract. 2022;188:109924. doi:10.1016/j.diabres.2022.109924.
65. Taskinen MR, Boren J. New insights into the pathophysiology of dyslipidemia in type 2 diabetes. Atherosclerosis. 2015;239(2):483-95. doi:10.1016/j.atherosclerosis.2015.01.039.
66. Duez H, Lamarche B, Valéro R, et al. Both intestinal and hepatic lipoprotein production are stimulated by an acute elevation of plasma free fatty acids in humans. Circulation. 2008;117(18):2369-76. doi:10.1161/CIRCULATIONAHA.107.739888.
67. Ginsberg HN, Zhang YL, Hernandez-Ono A. Regulation of plasma triglycerides in insulin resistance and diabetes. Arch Med Res. 2005;36(3):232-40. doi:10.1016/j.arcmed.2005.01.005.
68. Blasiole DA, Davis RA, Attie AD. The physiological and molecular regulation of lipoprotein assembly and secretion. Mol Biosyst. 2007;3(9):608-19. doi:10.1039/b700706j.
69. Dash S, Xiao C, Morgantini C, Lewis GF. New Insights into the Regulation of Chylomicron Production. Annu Rev Nutr. 2015;35:265-94. doi:10.1146/annurev-nutr-071714-034338.
70. Gugliucci A. The chylomicron saga: time to focus on postprandial metabolism. Front Endocrinol (Lausanne). 2024;14:1322869. doi:10.3389/fendo.2023.1322869.
71. Stahel P, Xiao C, Nahmias A, Lewis GF. Role of the Gut in Diabetic Dyslipidemia. Front Endocrinol (Lausanne). 2020;11:116. doi:10.3389/fendo.2020.00116.
72. Hirano T. Pathophysiology of Diabetic Dyslipidemia. J Atheroscler Thromb. 2018;25(9): 771-82. doi:10.5551/jat.RV17023.
73. Stahel P, Xiao C, Hegele RA, Lewis GF. The Atherogenic Dyslipidemia Complex and Novel Approaches to Cardiovascular Disease Prevention in Diabetes. Can J Cardiol. 2018;34(5):595-604. doi:10.1016/j.cjca.2017.12.007.
74. Scott R, O'Brien R, Fulcher G, et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care. 2009;32(3):493-8. doi:10.2337/dc08-1543.
75. Nichols GA, Philip S, Reynolds K, et al. Increased Cardiovascular Risk in Hypertriglyceridemic Patients With Statin-Controlled LDL Cholesterol. J Clin Endocrinol Metab. 2018;103(8):3019-27. doi:10.1210/jc.2018-00470.
76. Raposeiras-Roubin S, Rossello X, Oliva B, et al. Triglycerides and Residual Atherosclerotic Risk. J Am Coll Cardiol. 2021;77(24):3031-41. doi:10.1016/j.jacc.2021.04.059.
77. Marston NA, Giugliano RP, Im K, et al. Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials. Circulation. 2019;140(16):1308-17. doi:10.1161/CIRCULATIONAHA.119.041998.
78. Patel RS, Pasea L, Soran H, et al. Elevated plasma triglyceride concentration and risk of adverse clinical outcomes in 1.5 million people: a CALIBER linked electronic health record study. Cardiovasc Diabetol. 2022;21(1):102. doi:10.1186/s12933-022-01525-5.
79. Gervois P, Fruchart JC, Staels B. Drug Insight: mechanisms of action and therapeutic applications for agonists of peroxisome proliferator-activated receptors. Nat Clin Pract Endocrinol Metab. 2007;3(2):145-56. doi:10.1038/ncpendmet0397.
80. Lamas Bervejillo M, Ferreira AM. Understanding Peroxisome Proliferator-Activated Receptors: From the Structure to the Regulatory Actions on Metabolism. Adv Exp Med Biol. 2019;1127:39-57. doi:10.1007/978-3-030-11488-6_3.
81. Keating GM. Fenofibrate: a review of its lipid-modifying effects in dyslipidemia and its vascular effects in type 2 diabetes mellitus. Am J Cardiovasc Drugs. 2011;11(4):227-47. doi:10.2165/11207690-000000000-00000.
82. Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20): 2292-333. doi:10.1161/CIR.0b013e3182160726.
83. Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987;317(20):1237-45. doi:10.1056/NEJM198711123172001.
84. Bloomfield Rubins H, Davenport J, Babikian V, et al.; VA-HIT Study Group. Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol: The Veterans Affairs HDL Intervention Trial (VA-HIT). Circulation. 2001;103(23):2828-33. doi:10.1161/01.cir.103.23.2828.
85. Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563-74. doi:10.1056/NEJMoa1001282.
86. Kim KS, Hong S, Han K, Park CY. Fenofibrate add-on to statin treatment is associated with low all-cause death and cardiovascular disease in the general population with high triglyceride levels. Metabolism. 2022;137:155327. doi:10.1016/j.metabol.2022.15532.
87. Kim NH, Han KH, Choi J, et al. Use of fenofibrate on cardiovascular outcomes in statin users with metabolic syndrome: propensity matched cohort study. BMJ. 2019;366:l5125. doi:10.1136/bmj.l5125.
88. Hong S, Kim KS, Han K, Park CY. Fenofibrate's impact on cardiovascular risk in patients with diabetes: a nationwide propensity-score matched cohort study. Cardiovasc Diabetol. 2024;23(1):263. doi:10.1186/s12933-024-02353-5.
89. Das Pradhan A, Glynn RJ, Fruchart JC, et al.; PROMINENT Investigators. Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk. N Engl J Med. 2022; 387(21):1923-34. doi:10.1056/NEJMoa2210645.
90. Skulas-Ray AC, Wilson PWF, Harris WS, et al. Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association. Circulation. 2019;140(12):e673-e691. doi:10.1161/CIR.0000000000000709.
91. Oscarsson J, Hurt-Camejo E. Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their mechanisms of action on apolipoprotein B-containing lipoproteins in humans: a review. Lipids Health Dis. 2017;16(1):149. doi:10.1186/s12944-017-0541-3.
92. Bhatt DL, Steg PG, Miller M, et al.; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1): 11-22. doi:10.1056/NEJMoa1812792.
93. Rodriguez D, Lavie CJ, Elagizi A, Milani RV. Update on Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Health. Nutrients. 2022;14(23):5146. doi:10.3390/nu14235146.
94. Irfan A, Haider SH, Nasir A, et al. Assessing the Efficacy of Omega-3 Fatty Acids + Statins vs. Statins Only on Cardiovascular Outcomes: A Systematic Review and MetaAnalysis of 40,991 Patients. Curr Probl Cardiol. 2024;49(2):102245. doi:10.1016/j.cpcardiol.2023.102245.
95. Roth EM, Bays HE, Forker AD, et al. Prescription omega-3 fatty acid as an adjunct to fenofibrate therapy in hypertriglyceridemic subjects. J Cardiovasc Pharmacol. 2009;54(3):196-203. doi:10.1097/FJC.0b013e3181b0cf71.
96. Moon JH, Kang SB, Park JS, et al. Up-regulation of hepatic low-density lipoprotein receptor-related protein 1: a possible novel mechanism of antiatherogenic activity of hydroxymethylglutaryl-coenzyme A reductase inhibitor Atorvastatin and hepatic LRP1 expression. Metabolism. 2011;60(7):930-40. doi:10.1016/j.metabol.2010.08.013.
97. Myerson M, Ngai C, Jones J, et al. Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia. J Lipid Res. 2005;46(12):2735-44. doi:10.1194/jlr.M500335-JLR200.
98. Gouni-Berthold I, Schwarz J, Berthold HK. Updates in Drug Treatment of Severe Hypertriglyceridemia. Curr Atheroscler Rep. 2023;25(10):701-9. doi:10.1007/s11883-023-01140-z.
99. Filtz A, Parihar S, Greenberg GS, et al. New approaches to triglyceride reduction: Is there any hope left? Am J Prev Cardiol. 2024;18:100648. doi:10.1016/j.ajpc.2024.