Management and clinical outcomes of patients with homozygous familial hypercholesteremia in Saudi Arabia

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Submitted: December 5, 2022
Accepted: December 26, 2022
Published: February 2, 2023
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We report the incidence, patient characteristic with clinical outcomes in patients with homozygous familial hypercholesterolemia (HoFH) in Saudi Arabia. This is a retrospective and prospective, single center study which included 37 patients 14 years and older enrolled and followed up between 2018-2021 for three years. 46% were females, 78% were offspring of consanguineous marriage. LDLR mutation was in 78% and LDL-C/LDLRAP in 3% of patients. Mean LDL-C at the first presentation was 14.2±3.7 mmol/L, average Dutch lipid score was 20.9±6.24. LDL apheresis was performed on 70% of patients. Most patients were on ezetimibe (92%), high-dose statins ( 84%) and  PCSK9 inhibitors (32%). 48.6% had aortic stenosis, out of which 30% had severe aortic stenosis. Ten underwent aortic valve surgery (5 mechanical valve, 3 Ross procedure, 1 aortic valve repair, 1 bioprosthetic valve) and one had transcatheter aortic valve implantation (TAVI). Coronary artery bypass surgery (CABG) was performed on 32% and percutaneous intervention (PCI) on 11% of patients. HoFH patients have complex diseases with high morbidity and mortality, and benefit from a highly specialized multidisciplinary clinic to address their clinical needs. Although there are several therapeutic agents on the horizon, early diagnosis, and treatment of HoFH remain critical to optimize patient outcomes. 



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Wilemon KA, Patel J, Aguilar-Salinas C, et al. Reducing the clinical and public health burden of familial hypercholesterolemia: a global call to action. JAMA Cardiol 2020:5:217-29.
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;34:3478-90a.
Goldstein JL, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001. pp. 2863-2913.
Stock J. First insights from the EAS familial hypercholesterolaemia collaboration registry: FH is still underdiagnosed and undertreated. Atherosclerosis 2019;290:138-9. DOI:
Al-Nozha MM, Arafah MR, Al-Maatouq MA, et al. Hyperlipidemia in Saudi Arabia. Saudi Med J 2008;29:282-7.
Basulaiman M, El Bcheraoui C, Tuffaha M, et al. Hypercholesterolemia and its associated risk factors - Kingdom of Saudi Arabia, 2013. Ann Epidemiol 2014;24:801–8. DOI:
Alasnag M, Awan Z, Al Ghamdi A, et al. Improvement initiative in LDL-C management in Saudi Arabia: a call of action. Int J Cardiol Heart Vasc 2020;31:100667. DOI:
Alsheikh-Ali AA, Omar MI, Raal FJ, et al. Cardiovascular risk factor burden in Africa and the Middle East: the Africa Middle East Cardiovascular Epidemiological (ACE) study. PLoS One 2014;9:e102830. DOI:
Alhabib KF, Al-Rasadi K, Almigbal TH, et al. Familial hypercholesterolemia in the Arabian Gulf Region: Clinical results of the Gulf FH Registry. PLoS One 2021;16:e0251560. DOI:
Al-Ashwal A, Alnouri F, Sabbour H, et al. Identification and treatment of patients with homozygous familial hypercholesterolaemia: information and recommendations from a middle east advisory panel. Curr Vasc Pharmacol 2015;13:759-70. DOI:
Al-Allaf FA, Alashwal A, Abduljaleel Z, et al. Identification of a recurrent frameshift mutation at the LDLR exon 14 (c.2027delG, p.(G676Afs*33)) causing familial hypercholesterolemia in Saudi Arab homozygous children. Genomics 2016;107:24-32. DOI:
Kolansky DM, Cuchel M, Clark BJ, et al. Longitudinal evaluation and assessment of cardiovascular disease in patients with homozygous familial hypercholesterolemia. Am J Cardiol 2008;102:1438-43. DOI:
Alonso R, Mata N, Castillo S, et al. Spanish familial hypercholesterolaemia group cardiovascular disease in familial hypercholesterolaemia: influence of low-density lipoprotein receptor mutation type and classic risk factors. Atherosclerosis 2008;200:315-21. DOI:
Al-Rasadi K, Alhabib KF, Al-Allaf F, et al. The Gulf familial hypercholesterolemia registry (Gulf FH): design, rationale and preliminary results. Curr Vasc Pharmacol 2020;18:57-64. DOI:
Cuchel M, Bruckert E, Ginsberg HN, 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;35:2146-57. DOI:
Al-Allaf FA, Athar M, Abduljaleel Z, et al. Identification of a novel nonsense variant c.1332dup, p. (D445*) in the LDLR gene that causes familial hypercholesterolemia. Hum Genome Var 2014;1:14021. DOI:
Alallaf F, Nazar FAH, Alnefaie M, et al. The spectrum of familial hypercholesterolemia (FH) in Saudi Arabia: prime time for patient FH registry. Open Cardiovas Med J 2017;11:66-75. DOI:
Batais MA, Almigbal TH, Bin Abdulhak AA, et al. Assessment of physicians’ awareness and knowledge of familial hypercholesterolemia in Saudi Arabia: is there a gap? PLoS One 2017;12:e0183494. DOI:
Arnous MM, Alghamdi AM, Ghoraba MA. Assessment of family physicians’ awareness and knowledge of familial hypercholesterolemia in governmental hospitals in Riyadh, Saudi Arabia. J Family Med Prim Care 2019;8:1981-6. DOI:
Alzahrani SH, Bima A, Algethami MR, Awan Z. Assessment of medical intern’s knowledge, awareness and practice of familial hypercholesterolemia at academic institutes in Jeddah, Saudi Arabia. Lipids Health Dis 2020;19:101. DOI:
Palacio CH, Harring TR, Nguyen NT, et al. Homozygous familial hypercholesterolemia: case series and review of the literature. Case Rep Transplant 2011;2011:154908. DOI:
Aljenedil S, Alothman L, Bélanger AM, et al. Lomitapide for treatment of homozygous familial hypercholesterolemia: The Québec experience. Atherosclerosis 2020;310:54-63. DOI:
Underberg JA, Cannon CP, Larrey D, et al. Long-term safety and efficacy of lomitapide in patients with homozygous familial hypercholesterolemia: Five-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER). J Clin Lipidol 2020;14:807-17. DOI:
Cesaro A, Fimiani F, Gragnano F, et al. New frontiers in the treatment of homozygous familial hypercholesterolemia. Heart Fail Clin 2022;18:177-88. DOI:
Fahed AC, Shibbani K, Andary RR, et al. Premature valvular heart disease in homozygous familial hypercholesterolemia. Cholesterol 2017;2017:3685265. DOI:
Hu H, Cheng J, Lin S, et al. Calcified aortic valve disease in patients with familial hypercholesterolemia. J Cardiovasc Pharmacol 2020;76:506-13. DOI:
Sahiner L, Asil S, Kaya EB, et al. Percutaneous implantation of the self-expanding valve Prosthesis a patient with homozygous familial hypercholesterolemia severe aortic stenosis and porcelain aorta. Int J Cardiol 2016;220:661-4. DOI:
Al Dubayee M, Kayikcioglu M, van Lennep JR, et al. Is liver transplant curative in homozygous familial hypercholesterolemia? A review of nine global cases. Adv Ther 2022;39:3042-57. DOI:
Neil A, Cooper J, Betteridge J, et al. Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study. Eur Heart J 2008;29:2625-33. DOI:
Starr B, Hadfield SG, Hutten BA, et al. Development of sensitive and specific age- and gender-specific low-density lipoprotein cholesterol cutoffs for diagnosis of first-degree relatives with familial hypercholesterolaemia in cascade testing. Clin Chem Lab Med 2008;46:791-803. DOI:
Wang A, Richhariya A, Gandra SR, et al. Systematic review of low‐density lipoprotein cholesterol apheresis for the treatment of familial hypercholesterolemia. J Am Heart Assoc 2016;5:e003294. DOI:
Hohenstein B, Tselmin S, Bornstein SR, et al. How effectively will PCSK9 inhibitors allow retrieval of freedom from apheresis in cardiovascular high risk patients? - Estimates form a large single center. Atheroscler Suppl 2017;30:28-32. DOI:
Luirink IK, Hutten BA, Greber-Platzer S, et al. Practice of lipoprotein apheresis and short-term efficacy in children with homozygous familial hypercholesterolemia: Data from an international registry. Atherosclerosis 2020;299:24-31. DOI:
von Bauer R, Oikonomou D, Sulaj A, et al. Pleiotropic effect of lipoprotein-apheresis on the soluble form of activated leukocyte cell adhesion molecule (sALCAM) in familial hypercholesterolaemia. Exp Clin Endocrinol Diabetes 2019;127:276-80. DOI:
Ramunni A, Burzo M, Vernò L, Brescia P. Pleiotropic effects of LDL apheresis. Atheroscler Suppl 2009;10:53-5. DOI:
Lappegård KT, Enebakk T, Thunhaug H, et al. LDL apheresis activates the complement system and the cytokine network, whereas PCSK9 inhibition with evolocumab induces no inflammatory response. J Clin Lipidol 2016;10:1481-7. DOI:
Santos RD, Stein EA, Hovingh GK, et al. Long-term evolocumab in patients with familial hypercholesterolemia. J Am Coll Cardiol 2020;75:565-74. DOI:
Blom DJ, Harada-Shiba M, Rubba P, et al. Efficacy and safety of alirocumab in adults with homozygous familial hypercholesterolemia: The ODYSSEY HoFH trial. J Am Coll Cardiol 2020;76:131-42. DOI:
Rosenson RS, Burgess LJ, Ebenbichler CF, et al. Evinacumab in patients with refractory hypercholesterolemia. N Engl J Med 2020;383:2307-19. DOI:
Rossebø AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008;359:1343-56. DOI:
Chan KL, Teo K, Dumesnil JG, et al. Effect of lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation 2010;121:306-14. DOI:
Representatives of the Global Familial Hypercholesterolemia Community, Wilemon KA, Patel J, et al. Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action. JAMA Cardiol 2020;5:217-29. Erratum in: JAMA Cardiol 2020;5:613.
Alrasadi K, Alwaili K, Awan Z, et al. Aortic calcifications in familial hypercholesterolemia: potential role of the low-density lipoprotein receptor gene. Am Heart J 2009;157:170-6. DOI:
Kawaguchi A, Miyatake K, Yutani C, et al. Characteristic cardiovascular manifestation in homozygous and heterozygous familial hypercholesterolemia. Am Heart J 1999;137:410-8. DOI:
Nohara A, Tada H, Ogura M, et al. Homozygous familial hypercholesterolemia. J Atheroscler Thromb 2021;28:665-78. DOI:
Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis 2012;223:262-8. DOI:
Tahir I. Mohamed, Heart Center Department, King Faisal Specialist Hospital and Research Center, Riyadh

Department of Medicine, School of Medicine, Wayne State University, Detroit, MI, USA

How to Cite

Kholaif, Naji, Tahir I. Mohamed, Ibrahim S. Alharbi, Sumayah A. Aljenedil, Hind AlHumaidan, Abdullah Al-Ashwal, Abdulraof Almahfouz, Shahd Algorashi, Ali Almasood, and Omar J. Baqal. 2023. “Management and Clinical Outcomes of Patients With Homozygous Familial Hypercholesteremia in Saudi Arabia”. Monaldi Archives for Chest Disease 93 (4).