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Current opinion in endocrinology, diabetes, and obesity
Apr 01, 2025;32 (2): 75-88.

An overview of persistent chylomicronemia: much more than meets the eye.

Miriam Larouche, Gerald F Watts, Christie Ballantyne, Daniel Gaudet
Author Information
  1. Miriam Larouche: Universit�� de Montr��al, Department of Medicine, Montreal.
  2. Gerald F Watts: Departments of Cardiology and Internal Medicine, Royal Perth Hospital, School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
  3. Christie Ballantyne: Internal Medicine, Baylor College of Medicine, Houston, Texas, USA.
  4. Daniel Gaudet: Universit�� de Montr��al, Department of Medicine, Montreal.
PMID: 39927417 DOI: 10.1097/MED.0000000000000903

Abstract

PURPOSE OF REVIEW: The aim of this review is to provide an overview of severe hypertriglyceridemia presenting in the form of chylomicronemia that persists despite treatment of secondary causes and the use of conventional lipid-lowering treatment.
RECENT FINDINGS: persistent chylomicronemia is a rare syndromic disorder that affects carriers of bi-allelic combinations of pathogenic gene variants impairing lipoprotein lipase (LPL) activity, as well as a significant number of individuals who do not meet this genetic criterion. It is associated with a high risk of acute pancreatitis and other morbidities. Effective innovative treatments for severe hypertriglyceridemia are being developed and are becoming available. Patients with persistent chylomicronemia of any cause respond equally to next-generation therapies with LPL-independent mechanisms of action and do not generally respond to conventional LPL-dependent treatments.
SUMMARY: Not all individuals with persistent chylomicronemia carry a proven pathogenic combination of gene variants that impair LPL activity. Documenting the clinical characteristics of people with persistent chylomicronemia and their response to emerging therapies is essential to correctly establish their risk trajectory and ensure equitable access to personalized treatment.

References

  1. Ann Intern Med. 2019 May 7;170(9):626-634 [PMID: 31035285]
  2. Curr Opin Lipidol. 2024 Apr 1;35(2):66-77 [PMID: 38117614]
  3. N Engl J Med. 2024 Sep 12;391(10):913-925 [PMID: 38809174]
  4. J Clin Endocrinol Metab. 2012 May;97(5):1635-44 [PMID: 22438229]
  5. Lipids Health Dis. 2007 Sep 20;6:23 [PMID: 17883852]
  6. N Engl J Med. 2004 Mar 18;350(12):1220-34 [PMID: 15028826]
  7. Lipids Health Dis. 2015 Feb 18;14:8 [PMID: 25889044]
  8. J Med Econ. 2013;16(5):657-66 [PMID: 23428107]
  9. Med Clin North Am. 1982 Mar;66(2):455-68 [PMID: 7040847]
  10. J Clin Lipidol. 2024 Nov 12;: [PMID: 39537503]
  11. Expert Rev Cardiovasc Ther. 2020 Apr;18(4):231-238 [PMID: 32223345]
  12. Am J Hum Genet. 2000 May;66(5):1558-68 [PMID: 10736265]
  13. J Am Coll Cardiol. 2021 Aug 31;78(9):960-993 [PMID: 34332805]
  14. Biochim Biophys Acta. 1990 May 24;1049(1):21-6 [PMID: 1972631]
  15. Adv Intern Med. 1992;37:249-73 [PMID: 1557997]
  16. Circ Cardiovasc Genet. 2015 Jun;8(3):465-72 [PMID: 25714099]
  17. N Engl J Med. 1991 Jun 20;324(25):1761-6 [PMID: 2038366]
  18. J Nutr Metab. 2019 Feb 03;2019:7078241 [PMID: 30863636]
  19. Am J Med. 1952 Jan;12(1):3-23 [PMID: 14902850]
  20. NEJM Evid. 2023 Dec;2(12):EVIDoa2200325 [PMID: 38320498]
  21. Nat Med. 2023 Mar;29(3):729-737 [PMID: 36879129]
  22. Eur Heart J. 2024 Jul 12;45(27):2377-2379 [PMID: 37936268]
  23. Science. 2008 Dec 12;322(5908):1702-5 [PMID: 19074352]
  24. J Clin Lipidol. 2019 Jan - Feb;13(1):62-69 [PMID: 30514621]
  25. Nat Med. 2023 Jul;29(7):1782-1792 [PMID: 37355760]
  26. Laval Med. 1964 Nov;35:995-1021 [PMID: 14231949]
  27. Curr Opin Drug Discov Devel. 2004 Jan;7(1):112-7 [PMID: 14982154]
  28. J Lipid Res. 2011 Feb;52(2):189-206 [PMID: 21041806]
  29. Atherosclerosis. 2018 Aug;275:265-272 [PMID: 29980054]
  30. Nature. 1993 Sep 2;365(6441):65-9 [PMID: 8361539]
  31. Circ Cardiovasc Genet. 2011 Dec;4(6):673-80 [PMID: 21984478]
  32. Am J Med. 1959 Jan;26(1):68-75 [PMID: 13606154]
  33. Eur Heart J. 2021 Dec 14;42(47):4791-4806 [PMID: 34472586]
  34. N Engl J Med. 2020 Dec 10;383(24):2307-2319 [PMID: 33196153]
  35. Nat Genet. 2007 Dec;39(12):1483-7 [PMID: 17994020]
  36. Sci Transl Med. 2020 Jan 29;12(528): [PMID: 31996466]
  37. Clin Chim Acta. 2018 Dec;487:54-59 [PMID: 30218657]
  38. J Biol Chem. 1990 Apr 5;265(10):5910-6 [PMID: 1969408]
  39. Neth J Med. 1993 Feb;42(1-2):36-44 [PMID: 8446222]
  40. J Mol Graph Model. 2001;19(6):487-94, 587-90 [PMID: 11552677]
  41. N Engl J Med. 2015 Jul 30;373(5):438-47 [PMID: 26222559]
  42. Atherosclerosis. 1977 Jan;26(1):67-77 [PMID: 836349]
  43. J Diabetes Investig. 2023 Oct;14(10):1148-1156 [PMID: 37448184]
  44. Lancet Diabetes Endocrinol. 2021 May;9(5):264-275 [PMID: 33798466]
  45. Lancet Gastroenterol Hepatol. 2023 Feb;8(2):120-132 [PMID: 36521501]
  46. Endocr Pract. 2010 Mar-Apr;16(2):310-23 [PMID: 20061300]
  47. J Clin Lipidol. 2018 Jul - Aug;12(4):920-927.e4 [PMID: 29748148]
  48. Mol Genet Metab. 2018 Aug;124(4):254-265 [PMID: 29960856]
  49. J Clin Lipidol. 2023 Mar-Apr;17(2):272-280 [PMID: 36813655]
  50. Curr Atheroscler Rep. 2023 Dec;25(12):1101-1111 [PMID: 38095804]
  51. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2403-2407 [PMID: 29659879]
  52. Curr Opin Lipidol. 2017 Feb;28(1):11-18 [PMID: 27898581]
  53. J Clin Endocrinol Metab. 2024 Sep 06;: [PMID: 39238074]
  54. J Lipid Res. 1963 Jan;4:24-33 [PMID: 14167661]
  55. Atherosclerosis. 2022 Oct;359:13-19 [PMID: 36152419]
  56. Pharmacol Ther. 1996;70(2):101-35 [PMID: 8843465]
  57. J Clin Lipidol. 2022 Nov-Dec;16(6):833-849 [PMID: 36402670]
  58. Curr Atheroscler Rep. 2024 Nov 20;27(1):6 [PMID: 39565562]
  59. Clin Biochem. 2025 Jan;135:110873 [PMID: 39756670]
  60. Curr Opin Lipidol. 2018 Apr;29(2):133-143 [PMID: 29300201]
  61. BMJ Case Rep. 2022 Mar 15;15(3): [PMID: 35292548]
  62. N Engl J Med. 2020 Aug 20;383(8):711-720 [PMID: 32813947]
  63. N Engl J Med. 2017 Apr 27;376(17):1647-1658 [PMID: 28402248]
  64. Atherosclerosis. 2017 Dec;267:49-60 [PMID: 29100061]
  65. N Engl J Med. 2025 Jan 9;392(2):127-137 [PMID: 39225259]
  66. Clin Chim Acta. 2020 Sep;508:61-68 [PMID: 32407781]
  67. Circ Res. 2019 Feb;124(3):386-404 [PMID: 30702996]
  68. AACE Clin Case Rep. 2021 Nov 26;8(2):93-95 [PMID: 35415234]
  69. N Engl J Med. 2014 Dec 4;371(23):2200-6 [PMID: 25470695]
  70. Circ Res. 2013 May 24;112(11):1479-90 [PMID: 23542898]
  71. N Engl J Med. 1967 Jan 19;276(3):148-56 contd [PMID: 5334266]
  72. J Med Econ. 2020 Sep;23(9):978-984 [PMID: 32479143]
  73. J Clin Lipidol. 2017 Jul - Aug;11(4):964-971 [PMID: 28666713]
  74. J Exp Med. 1951 Apr 1;93(4):373-84 [PMID: 14824409]
  75. Curr Opin Lipidol. 2012 Aug;23(4):310-20 [PMID: 22691709]
  76. Clin Biochem. 2023 Apr;114:67-72 [PMID: 36780934]
  77. Nature. 2010 Aug 5;466(7307):707-13 [PMID: 20686565]
  78. N Engl J Med. 2014 Jul 3;371(1):22-31 [PMID: 24941081]
  79. Front Endocrinol (Lausanne). 2020 Jul 24;11:455 [PMID: 32793115]
  80. J Clin Med. 2024 Jul 16;13(14): [PMID: 39064199]
  81. N Engl J Med. 2024 May 16;390(19):1781-1792 [PMID: 38587247]
  82. Hum Mol Genet. 2003 Oct 1;12(19):2533-9 [PMID: 12915450]
  83. J Atheroscler Thromb. 2024 Jul 1;31(7):1106-1111 [PMID: 38462482]
  84. J Clin Invest. 1960 Dec;39:1777-90 [PMID: 13712364]
  85. Curr Opin Endocrinol Diabetes Obes. 2024 Apr 1;31(2):78-83 [PMID: 37994661]
  86. Diabetes Care. 1981 May-Jun;4(3):343-8 [PMID: 7344882]
  87. J Clin Lipidol. 2018 Jul - Aug;12(4):898-907.e2 [PMID: 29784572]
  88. Atherosclerosis. 1973 May-Jun;17(3):455-62 [PMID: 4351721]
  89. Gene Ther. 2013 Apr;20(4):361-9 [PMID: 22717743]
  90. J Lipid Res. 1992 Mar;33(3):361-7 [PMID: 1569385]
  91. N Engl J Med. 2010 Dec 2;363(23):2220-7 [PMID: 20942659]
  92. Nat Rev Cardiol. 2020 Apr;17(4):201 [PMID: 32055035]
  93. J Natl Med Assoc. 1962 Sep;54:570-5 [PMID: 13904508]
  94. J Clin Lipidol. 2019 Jan - Feb;13(1):80-88 [PMID: 30466821]
  95. N Engl J Med. 1996 Sep 19;335(12):848-54 [PMID: 8778602]
  96. Curr Opin Lipidol. 2012 Jun;23(3):206-212 [PMID: 22510806]
  97. JAMA Intern Med. 2014 Mar;174(3):443-7 [PMID: 24366202]
  98. Arch Ophthal. 1948 Nov;39(5):570-3 [PMID: 18108392]
  99. J Endocr Soc. 2019 Oct 11;3(12):2397-2410 [PMID: 31777768]
  100. JIMD Rep. 2024 Sep 17;65(6):392-400 [PMID: 39512433]
  101. Curr Opin Lipidol. 2019 Apr;30(2):71-81 [PMID: 30676533]
  102. Lancet Diabetes Endocrinol. 2020 Jan;8(1):50-67 [PMID: 31582260]
  103. Atherosclerosis. 2020 Dec;315:24-32 [PMID: 33212314]
  104. Ann Intern Med. 2020 Nov 3;173(9):764-765 [PMID: 32777186]
  105. Curr Opin Lipidol. 2024 Apr 1;35(2):58-65 [PMID: 37962908]
  106. N Engl J Med. 2019 Aug 8;381(6):531-542 [PMID: 31390500]
  107. Lipids Health Dis. 2020 Jun 2;19(1):120 [PMID: 32487261]
  108. J Clin Endocrinol Metab. 2005 Jul;90(7):3995-8 [PMID: 15840743]
  109. N Engl J Med. 1978 Jun 8;298(23):1265-73 [PMID: 565877]
  110. J Clin Lipidol. 2024 Dec 21;: [PMID: 39848842]
  111. Nat Rev Endocrinol. 2015 Jun;11(6):352-62 [PMID: 25732519]
  112. Front Endocrinol (Lausanne). 2020 Oct 23;11:593931 [PMID: 33193106]
  113. Trends Pharmacol Sci. 2015 Oct;36(10):675-687 [PMID: 26435212]
  114. JAMA Cardiol. 2024 Jul 1;9(7):620-630 [PMID: 38583092]
  115. J Exp Med. 1909 Jul 17;11(4):553-60 [PMID: 19867266]
  116. Circulation. 1965 Mar;31:321-7 [PMID: 14262568]
  117. Nutr Diabetes. 2014 Jun 16;4:e118 [PMID: 24932782]

MeSH Term

Humans
Lipoprotein Lipase
Hypertriglyceridemia
Hypolipidemic Agents
Pancreatitis

Chemicals

Lipoprotein Lipase
Hypolipidemic Agents
Journal Article Review

Word Cloud

Created with Highcharts 10.0.0chylomicronemiapersistenttreatmentoverviewseverehypertriglyceridemiaconventionalpathogenicgenevariantsLPLactivityindividualsrisktreatmentsrespondtherapiesPURPOSEOFREVIEW:aimreviewprovidepresentingformpersistsdespitesecondarycausesuselipid-loweringRECENTFINDINGS:Persistentraresyndromicdisorderaffectscarriersbi-alleliccombinationsimpairinglipoproteinlipasewellsignificantnumbermeetgeneticcriterionassociatedhighacutepancreatitismorbiditiesEffectiveinnovativedevelopedbecomingavailablePatientscauseequallynext-generationLPL-independentmechanismsactiongenerallyLPL-dependentSUMMARY:carryprovencombinationimpairDocumentingclinicalcharacteristicspeopleresponseemergingessentialcorrectlyestablishtrajectoryensureequitableaccesspersonalizedchylomicronemia:muchmeetseye

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