Long-term outcomes of coronary artery bypass grafting in patients with familial hypercholesterolemia

This systematic review aimed to evaluate long-term outcomes after CABG in patients with FH and to identify major determinants of prognosis. A systematic literature search was performed in PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library following PRISMA guidelines. Among 139 identified records, 17 studies met inclusion criteria and provided data on surgical revascularization in heterozygous and homozygous FH. Historical cohorts (Takahashi, Kawasuji and colleagues) demonstrated that the use of internal thoracic artery grafts combined with aggressive lipid lowering—including LDL apheresis—provides 10–18-year survival rates of 80–90%, with most late adverse events related to vein-graft atherosclerosis. Contemporary registries (Béliard, Iyen, HELLAS-FH) indicate that failure to achieve LDL-C targets substantially increases residual cardiovascular risk, while diabetes and socioeconomic deprivation further worsen outcomes. Modern CABG cohorts (Deconinck et al.) show that FH is associated with more than a twofold increase in MACE risk when preoperative lipid control is suboptimal. Long-term CABG outcomes in FH can be favorable when arterial conduits are used and strict LDL-C targets are achieved. Prognosis is driven not only by coronary anatomy but also by the quality of secondary prevention, accessibility of lipid-lowering therapy, and comorbid conditions. Further research is needed in the contemporary era of PCSK9 inhibitors and lipoprotein apheresis.

1. Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, 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;34(45):3478-90a. Erratum in: Eur Heart J. 2020;41(47):4517. DOI: 10.1093/eurheartj/eht273. Epub 2013 Aug 15.

2. Gidding SS, Champagne MA, de Ferranti SD, Defesche J, Ito MK, Knowles JW, et al. The Agenda for Familial Hypercholesterolemia: A Scientific Statement From the American Heart Association. Circulation. 2015;132(22):2167-2192. Erratum in: Circulation. 2015;132(25):e397. DOI: 10.1161/CIR.0000000000000297. Epub 2015 Oct 28.

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;75(20):2553-2566. DOI: 10.1016/j.jacc.2020.03.057

4. Goldstein JL, Hobbs HH, Brown MS. Familial Hypercholesterolemia. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill Education; 2019.

5. Soutar AK, Naoumova RP. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med. 2007;4(4):214-225. DOI: 10.1038/ncpcardio0836

6. Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223(2):262-268. DOI: 10.1016/j.atherosclerosis.2012.02.019

7. Thompson GR; HEART-UK LDL Apheresis Working Group. Recommendations for the use of LDL apheresis. Atherosclerosis. 2008;198(2):247-255. DOI: 10.1016/j.atherosclerosis.2008.02.009

8. Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146-2157. DOI: 10.1093/eurheartj/ehu274

9. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376(18):1713-1722. DOI: 10.1056/NEJMoa1615664

10. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372(25):2387-2397. DOI: 10.1056/NEJMoa1410489

11. Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34):3227-3337. Erratum in: Eur Heart J. 2022;43(42):4468. DOI: 10.1093/eurheartj/ehab484.

12. Khera AV, Rader DJ. Future therapeutic directions in reverse cholesterol transport. Curr Atheroscler Rep. 2010;12(1):73-81. DOI: 10.1007/s11883-009-0080-0

13. Takahashi T, Nakano S, Shimazaki Y, Kaneko M, Hirata N, Nakamura T, et al. Long-term appraisal of coronary bypass operations in familial hypercholesterolemia. Ann Thorac Surg. 1993;56(3):499-505. DOI: 10.1016/0003-4975(93)90887-n

14. Kawasuji M, Sakakibara N, Takemura H, Matsumoto Y, Mabuchi H, Watanabe Y. Coronary artery bypass grafting in familial hypercholesterolemia. J Thorac Cardiovasc Surg. 1995;109(2):364-369. DOI: 10.1016/S0022-5223(95)70398-5

15. Kawasuji M, Sakakibara N, Fujii S, Yasuda T, Watanabe Y. Coronary artery bypass surgery with arterial grafts in familial hypercholesterolemia. J Thorac Cardiovasc Surg. 2000;119(5):1008-1013; discussion 1013-1014. DOI: 10.1016/S0022-5223(00)70096-1

16. Béliard S, Boccara F, Cariou B, Carrié A, Collet X, Farnier M, et al. High burden of recurrent cardiovascular events in heterozygous familial hypercholesterolemia: The French Familial Hypercholesterolemia Registry. Atherosclerosis. 2018;277:334-340. DOI: 10.1016/j.atherosclerosis.2018.08.010

17. Iyen B, Qureshi N, Kai J, Capps N, Durrington PN, Cegla J, et al. Cardiovascular disease morbidity is associated with social deprivation in subjects with familial hypercholesterolaemia (FH): A retrospective cohort study of individuals with FH in UK primary care and the UK Simon Broome register, linked with national hospital records. Atherosclerosis. 2025;403:119142. DOI: 10.1016/j.atherosclerosis.2025.119142

18. Fukuzawa S, Ozawa S, Inagaki M, Morooka S, Inoue T. Secondary prevention with lipid lowering therapy in familial hypercholesterolemia: a correlation between new evolution of stenotic lesion and achieved cholesterol levels after revascularization procedures. Intern Med. 1999;38(4):330-335. DOI: 10.2169/internalmedicine.38.330

19. Waidner T, Franzen D, Voelker W, Ritter M, Borberg H, Hombach V, Höpp HW. The effect of LDL apheresis on progression of coronary artery disease in patients with familial hypercholesterolemia. Results of a multicenter LDL apheresis study. Clin Investig. 1994;72(11):858-863. DOI: 10.1007/BF00190741

20. Lauziere A, Brisson D, Tremblay G, Bedard S, Khoury E, Gaudet D. 25-Year Comparison of Coronary Lesions Anatomy in Two Cohorts of French Canadians with Familial Hypercholesterolemia. J Clin Med. 2025;14(2):305. DOI: 10.3390/jcm14020305

21. Rizos CV, Elisaf MS, Skoumas I, Tziomalos K, Kotsis V, Rallidis L, et al. Characteristics and management of 1093 patients with clinical diagnosis of familial hypercholesterolemia in Greece: Data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Atherosclerosis. 2018;277:308-313. DOI: 10.1016/j.atherosclerosis.2018.08.017

22. Reijman MD, Tromp TR, Hutten BA, Hovingh GK, Blom DJ, Catapano AL, et al. Cardiovascular outcomes in patients with homozygous familial hypercholesterolaemia on lipoprotein apheresis initiated during childhood: long-term follow-up of an international cohort from two registries. Lancet Child Adolesc Health. 2024;8(7):491-499. DOI: 10.1016/S2352-4642(24)00073-7

23. Deconinck OG, Sharman JE, Bishop W, Lees CF, Dare L, Hardikar A, et al. Familial Hypercholesterolemia and Cardiovascular Outcomes Amongst Younger Patients Undergoing Coronary Bypass Surgery. Heart Lung Circ. 2025;34(1):77-83. DOI: 10.1016/j.hlc.2024.08.001

24. Writing Committee; Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Covington AM, et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022;80(14):1366-1418. Erratum in: J Am Coll Cardiol. 2023;81(1):104. DOI: 10.1016/j.jacc.2022.07.006. Epub 2022 Aug 25.

25. deGoma EM, Ahmad ZS, O'Brien EC, Kindt I, Shrader P, Newman CB, et al. Treatment Gaps in Adults With Heterozygous Familial Hypercholesterolemia in the United States: Data From the CASCADE-FH Registry. Circ Cardiovasc Genet. 2016;9(3):240-249. DOI: 10.1161/CIRCGENETICS.116.001381

26. Trinder M, Francis GA, Brunham LR. Association of Monogenic vs Polygenic Hypercholesterolemia With Risk of Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2020;5(4):390-399. Erratum in: JAMA Cardiol. 2020;5(4):488. DOI: 10.1001/jamacardio.2019.5954.

27. Yezhov M.V., Bliznyuk S.A., Tmoyan N.A., Rozhkova T.A., Duplyakov D.V., Salchenko V.A., et al. Register of patients with familial hypercholesterolemia and patients of very high cardiovascular risk with lipid-lowering therapy underperformance (RENESSANS). Russian Journal of Cardiology. 2019;(5):7-13. (In Russ.) DOI: 10.15829/1560-4071-2019-5-7-13