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Familial Hypercholesterolemia Cover
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Open Access
|Sep 2026

References

  1. Müller C. Angina pectoris in hereditary xanthomatosis. Arch Intern Med. 1939;64:675-700. doi: 10.1001/archinte.1939.00190040016002
  2. Hu P, Dharmayat KI, Stevens CAT, et al. Prevalence of Familial Hypercholesterolemia Among the General Population and Patients With Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analysis.Circulation. 2020 Jun 2;141(22):1742-1759. doi: 10.1161/CIRCULATIONAHA.119.044795
  3. Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG. Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects. J Am Coll Cardiol. 2020 May 26;75(20):2553-2566. doi: 10.1016/j.jacc.2020.03.057
  4. Futema M, Bird M, Haeger A, et al. Frequency of familial hypercholesterolaemia-causing genetic variants in the 100 000 Genomes Project cohort: whole genome sequencing analyses of 77 260 participants. J Med Genet. 2026 Apr 20;63(5):284-290. doi: 10.1136/jmg-2025-111201
  5. Spinks C, Selvaraj MS, Robinson C, et al. Management and Consequences of Genotype-Positive Familial Hypercholesterolemia. JAMA Cardiol. 2026 Apr 1;11(4):378-382. doi: 10.1001/jamacardio.2026.0006
  6. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013 Dec;34(45):3478-3490. doi: 10.1093/eurheartj/eht273
  7. Ahmad Z, Agarwala A, Cuchel M, et al. Update on familial hypercholesterolemia: An expert clinical consensus from the National Lipid Association. J Clin Lipidol. 2026 Jan 29:S1933-2874(26)00010-3. doi: 10.1016/j.jacl.2026.01.011
  8. Ruel I, Brisson D, Aljenedil S, et al. Simplified Canadian Definition for Familial Hypercholesterolemia. Can J Cardiol. 2018 Sep;34(9):1210-1214. doi: 10.1016/j.cjca.2018.05.015
  9. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34-47. doi: 10.1126/science.3513311
  10. Humphries SE, Futema M. Genetic Determinants of the Familial Hypercholesterolaemia Phenotype. Ann Hum Genet. 2025 Sep;89(5):293-304. doi: 10.1111/ahg.12594
  11. Tabet DR, Coté AG, Lancaster MC, et al. The functional landscape of coding variation in the familial hypercholesterolemia gene LDLR. Science. 2026 Feb 19;391(6787). doi: 10.1126/science.ady7186
  12. Mach F, Koskinas KC, Roeters van Lennep JE, et al. ESC/EAS Scientific Document Group. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2025 Nov 7;46(42):4359-4378. doi: 10.1093/eurheartj/ehaf190
  13. Awan Z, Baass A, Genest J. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9): Lessons Learned from Patients with Hypercholesterolemia. Clin Chem. 2014 Nov;60(11):1380-1389. doi: 10.1373/clinchem.2014.225946
  14. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2026 May 19:87(19):2624-2757. doi: 10.1016/j.jacc.2025.11.016
  15. Zhang Y, Dron JS, Bellows BK, et al. Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals with Elevated Cholesterol. JAMA Cardiol. 2024 Mar 1;9(3):263-271. doi: 10.1001/jamacardio.2023.5366
  16. Tamehri Zadeh SS, Chan DC, Pang J, Watts GF. Canadian and French Risk Scores Are Valid in Identifying Cardiovascular Disease in Australian Patients With Familial Hypercholesterolemia. Can J Cardiol. 2025 Nov;41(11):2244-2251. doi: 10.1016/j.cjca.2025.07.042
  17. Elshorbagy A, Vallejo-Vaz AJ, Barkas F, et al. Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry. Eur Heart J. 2025 Mar 24;46(12):1127-1140. doi: 10.1093/eurheartj/ehae791
  18. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet 2006 Sep 16;368(9540):1005-1011. doi: 10.1016/S0140-6736(06)69208-8
  19. Danielsen R, Aspelund T, Harris TB, Gudnason V. The prevalence of aortic stenosis in the elderly in Iceland and predictions for the coming decades: the AGES-Reykjavík study. Int J Cardiol 2014 Oct 20;176(3):916-922. doi: 10.1016/j.ijcard.2014.08.053
  20. Benfari G, Essayagh B, Michelena HI, et al. Severe aortic stenosis: secular trends of incidence and outcomes. Eur Heart J. 2024 Jun 1;45(21):1877-1886. doi: 10.1093/eurheartj/ehad887
  21. Rämö JT, Jurgens SJ, Kany S, et al. Rare Genetic Variants in LDLR, APOB, and PCSK9 Are Associated With Aortic Stenosis. Circulation. 2024 Nov 26;150(22):1767-1780. doi: 10.1161/circulationaha.124.070982
  22. Small AM, Yang TY, Itoh S, et al. Genomic and transcriptomic analyses of aortic stenosis enhance therapeutic target discovery and disease prediction. Nat Genet. 2026 Jan;58(1):57-66. doi: 10.1038/s41588-025-02417-6
  23. Erzingatzian A, Brown L, Hales L, et al. Aortic Stenosis in Familial Hypercholesterolemia: A Meta-Analysis. Forthcoming 2026 (submitted under review).
  24. Amerizadeh A, Javanmard SH, Sarrafzadegan N, Vaseghi G. Familial Hypercholesterolemia (FH) Registry Worldwide: A Systematic Review. Curr Probl Cardiol. 2022 Oct;47(10):100999. doi: 10.1016/j.cpcardiol.2021.100999
  25. Duell PB, Gidding SS, Andersen RL, et al. Longitudinal low density lipoprotein cholesterol goal achievement and cardiovascular outcomes among adult patients with familial hypercholesterolemia: The CASCADE FH registry. Atherosclerosis. 2019 Oct;289:85-93. doi: 10.1016/j.atherosclerosis.2019.08.007
  26. Geba GP, Mohammadi KA, Damask A, et al. Effect of PCSK9 Inhibition With Alirocumab in Patients With Probable Familial Hypercholesterolemia or Type III Hyperlipoproteinemia: Results From the ODYSSEY OUTCOMES Trial. J Am Heart Assoc. 2025 Sep 2;14(17):e041190. doi: 10.1161/JAHA.124.041190
  27. Vallejo-Vaz AJ, Stevens CAT, Lyons ARM, et al. Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Lancet. 2021 Nov 6;398(10312):1713-1725. doi: 10.1016/S0140-6736(21)01122-3
  28. Khattak S, Ochoa-Ferraro A, Khan N, et al. Relative Efficacy of Alirocumab, Evolocumab, Inclisiran, and Bempedoic Acid on Lipids in Patients with Cardiovascular Disease or Familial Hypercholesterolaemia. J Clin Med. 2025 Nov 10;14(22):7946. doi: 10.3390/jcm14227946
  29. Nicholls SJ, Nelson AJ, Ditmarsch M, et al. Obicetrapib in patients with heterozygous familial hypercholesterolemia: the BROOKLYN randomized clinical trial. Nat Med. 2026 Mar;32(3):1052-1060. doi: 10.1038/s41591-025-04179-4
  30. Ballantyne CM, Gellis L, Tardif JC, et al. Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial. JAMA. 2026 Jan 13;335(2):129-139. doi: 10.1001/jama.2025.20620
  31. Agarwala A, Deych E, Jones LK, et al. Sex-related differences in premature cardiovascular disease in familial hypercholesterolemia. J Clin Lipidol. 2023 Jan-Feb;17(1):150-156. doi: 10.1016/j.jacl.2022.11.009
  32. Iatan I, Akioyamen LE, Ruel I, et al. Sex differences in treatment of familial hypercholesterolaemia: a meta-analysis. Eur Heart J. 2024 Sep 14;45(35):3231-3250. doi: 10.1093/eurheartj/ehae417
  33. Christensen JJ, Holven KB, Bogsrud MP, et al. Statin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study. Eur Heart J. 2026 Jan 16;47(3):318-327. doi: 10.1093/eurheartj/ehaf592
  34. Ramanathan J, Sullivan D, Watts G, Holven K, Tiong YS. Familial hypercholesterolemia in pregnancy. Curr Opin Endocrinol Diabetes Obes. 2026 Apr 1;33(2):84-89. doi: 10.1097/MED.0000000000000954
  35. Klevmoen M, van Lennep JR, Bogsrud MP, et al. Extensive pregnancy-related off-treatment time in women with familial hypercholesterolaemia. Atherosclerosis. 2026 Feb 19;415:120668. doi: 10.1016/j.atherosclerosis.2026.120668
  36. Cuchel M, Raal FJ, Hegele RA, et al. 2023 Update on European Atherosclerosis Society consensus statement on homozygous familial hypercholesterolaemia: new treatments and clinical guidance. Eur Heart J. 2023 Jul 1;44(25):2277-2291. doi: 10.1093/eurheartj/ehad197
  37. Mulder J, Tromp TR, Al-Khnifsawi M, et al. Sex Differences in Diagnosis, Treatment, and Cardiovascular Outcomes in Homozygous Familial Hypercholesterolemia. JAMA Cardiol. 2024 Apr 1;9(4):313-322. doi: 10.1001/jamacardio.2023.5597
  38. Mulder JWCM, Reijman MD, Kusters DM, et al. Homozygous Familial Hypercholesterolemia International Clinical Collaborators. Homozygous Familial Hypercholesterolemia Is a Life-Limiting Condition: Medical Life-Trajectories in the Post-2010 Era. J Am Coll Cardiol. 2025 May 20;85(19):1898-1903. doi: 10.1016/j.jacc.2025.04.005
  39. Bélanger AM, Akioyamen L, Alothman L, Genest J. Evidence for improved survival with treatment of homozygous familial hypercholesterolemia. Curr Opin Lipidol. 2020 Aug;31(4):176-181. doi: 10.1097/MOL.0000000000000686
  40. Tromp TR, Hartgers ML, Hovingh GK, et al. Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study. Lancet. 2022 Feb 19;399(10326):719-728. doi: 10.1016/S0140-6736(21)02001-8
  41. Kramer AI, Akioyamen LE, Lee S, et al. Major adverse cardiovascular events in homozygous familial hypercholesterolaemia: a systematic review and meta-analysis. Eur J Prev Cardiol. 2022 May 5;29(5):817-828. doi: 10.1093/eurjpc/zwab224
  42. Cuchel M, Lee PC, Hudgins LC, et al. Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry. J Am Heart Assoc. 2023 May 2;12(9):e029175 doi: 10.1161/JAHA.122.029175
  43. Belanger AM, Akioyamen LE, Ruel I, Hales L, Genest J. Aortic stenosis in homozygous familial hypercholesterolaemia: a paradigm shift over a century. Eur Heart J. 2022 Sep 7;43(34):3227-3239. doi: 10.1093/eurheartj/ehac339
  44. Raal FJ, Pilcher GJ, Panz VR, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation. 2011 Nov 15;124(20):2202-2207 doi: 10.1161/CIRCULATIONAHA.111.042523
  45. Pirillo A, Catapano AL. Understanding the efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia. Eur J Prev Cardiol. 2022 May 5;29(5):829-831. doi: 10.1093/eurjpc/zwac028
  46. Moriarty PM, Wiegman A, Godin R, et al. Evinacumab with or without lipoprotein apheresis in homozygous familial hypercholesterolaemia. Eur J Prev Cardiol. 2026 Mar 27:zwag182. doi: 10.1093/eurjpc/zwag182
  47. Erzingatzian A, Al-Baldawi Z, Ruel I, et al. Aortic Stenosis in Homozygous Familial Hypercholesterolemia. JACC Adv. 2026 Feb;5(2):102505. doi: 10.1016/j.jacadv.2025.102505
  48. Thompson GR, Walji S, Cegla J. Liver transplantation for homozygous familial hypercholesterolaemia. Curr Opin Lipidol. 2025 Dec 1;36(6):310-317. doi: 10.1097/MOL.0000000000001007
  49. Gurevitz C, Bajaj A, Khera AV, et al. Gene therapy and genome editing for lipoprotein disorders. Eur Heart J. 2025 Sep 15;46(35):3420-3433. doi: 10.1093/eurheartj/ehaf411
DOI: https://doi.org/10.14797/mdcvj.1860 | Journal eISSN: 1947-6108
Language: English
Page range: 4 - 14
Submitted on: May 1, 2026
Accepted on: Jul 27, 2026
Published on: Sep 15, 2026
Published by: Houston Methodist DeBakey Heart & Vascular Center
In partnership with: Paradigm Publishing Services

© 2026 Iulia Iatan, Jacques Genest, published by Houston Methodist DeBakey Heart & Vascular Center
This work is licensed under the Creative Commons Attribution-NonCommercial 4.0 License.