https://doi.org/10.4081/monaldi.2023.2503
Management and clinical outcomes of patients with homozygous familial hypercholesteremia in Saudi Arabia
Submitted: December 5, 2022
Accepted: December 26, 2022
Published: February 2, 2023
Accepted: December 26, 2022
Abstract Views: 2090
PDF: 491
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
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.
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: https://doi.org/10.1016/j.atherosclerosis.2019.09.015
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: https://doi.org/10.1016/j.annepidem.2014.08.001
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: https://doi.org/10.1016/j.ijcha.2020.100667
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: https://doi.org/10.1371/journal.pone.0102830
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: https://doi.org/10.1371/journal.pone.0251560
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: https://doi.org/10.2174/1570161113666150827125040
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: https://doi.org/10.1016/j.ygeno.2015.12.001
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: https://doi.org/10.1016/j.amjcard.2008.07.035
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: https://doi.org/10.1016/j.atherosclerosis.2007.12.024
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: https://doi.org/10.2174/1570161116666181005125459
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: https://doi.org/10.1093/eurheartj/ehu274
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: https://doi.org/10.1038/hgv.2014.21
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: https://doi.org/10.2174/1874192401711010066
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: https://doi.org/10.1371/journal.pone.0183494
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: https://doi.org/10.4103/jfmpc.jfmpc_285_19
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: https://doi.org/10.1186/s12944-020-01266-y
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: https://doi.org/10.1155/2011/154908
Aljenedil S, Alothman L, Bélanger AM, et al. Lomitapide for treatment of homozygous familial hypercholesterolemia: The Québec experience. Atherosclerosis 2020;310:54-63.
DOI: https://doi.org/10.1016/j.atherosclerosis.2020.07.028
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: https://doi.org/10.1016/j.jacl.2020.08.006
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: https://doi.org/10.1016/j.hfc.2021.07.008
Fahed AC, Shibbani K, Andary RR, et al. Premature valvular heart disease in homozygous familial hypercholesterolemia. Cholesterol 2017;2017:3685265.
DOI: https://doi.org/10.1155/2017/3685265
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: https://doi.org/10.1097/FJC.0000000000000890
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: https://doi.org/10.1016/j.ijcard.2016.06.316
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: https://doi.org/10.1007/s12325-022-02131-3
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: https://doi.org/10.1093/eurheartj/ehn422
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: https://doi.org/10.1515/CCLM.2008.135
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: https://doi.org/10.1161/JAHA.116.003294
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: https://doi.org/10.1016/j.atherosclerosissup.2017.05.012
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: https://doi.org/10.1016/j.atherosclerosis.2020.01.031
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: https://doi.org/10.1055/a-0630-0232
Ramunni A, Burzo M, Vernò L, Brescia P. Pleiotropic effects of LDL apheresis. Atheroscler Suppl 2009;10:53-5.
DOI: https://doi.org/10.1016/S1567-5688(09)71811-2
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: https://doi.org/10.1016/j.jacl.2016.09.001
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: https://doi.org/10.1016/j.jacc.2019.12.020
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: https://doi.org/10.1016/j.jacc.2020.05.027
Rosenson RS, Burgess LJ, Ebenbichler CF, et al. Evinacumab in patients with refractory hypercholesterolemia. N Engl J Med 2020;383:2307-19.
DOI: https://doi.org/10.1056/NEJMoa2031049
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: https://doi.org/10.1056/NEJMoa0804602
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: https://doi.org/10.1161/CIRCULATIONAHA.109.900027
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: https://doi.org/10.1016/j.ahj.2008.08.021
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: https://doi.org/10.1016/S0002-8703(99)70485-0
Nohara A, Tada H, Ogura M, et al. Homozygous familial hypercholesterolemia. J Atheroscler Thromb 2021;28:665-78.
DOI: https://doi.org/10.5551/jat.RV17050
Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis 2012;223:262-8.
DOI: https://doi.org/10.1016/j.atherosclerosis.2012.02.019
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). https://doi.org/10.4081/monaldi.2023.2503.
Copyright (c) 2023 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Lawrence Paelet, Jonathan Raskin, Richard ZuWallack, Potential downside issues with telemedicine for individuals with chronic respiratory diseases , Monaldi Archives for Chest Disease: Vol. 92 No. 4 (2022)
- Fabiola B. Sozzi, Laura Iacuzio, Marta Belmonte, Marco Schiavone, Francesca Bursi, Elisa Gherbesi, Frank Levy, Ciro Canetta, Stefano Carugo, Early diagnosis of cardiomyopathies by cardiac magnetic resonance. Overview of the main criteria , Monaldi Archives for Chest Disease: Vol. 92 No. 4 (2022)
- Francesco Perone, Pilar Zamora Auñon, Laura Rodríguez, David Vinal, Juan Caro-Codon, Ana Pertejo, Virginia Martínez Marín, Enrique Espinosa, Teresa López-Fernández, Cardiac monitoring during trastuzumab therapy in metastatic breast cancer: early incidence of cardiac dysfunction , Monaldi Archives for Chest Disease: Vol. 92 No. 4 (2022)
- Prakhar Agarwal, Kranti Garg, Varinder Saini, Isha Singh, Pulmonary rehabilitation: A novel adjunct in management of obstructive sleep apnea , Monaldi Archives for Chest Disease: Vol. 93 No. 1 (2023)
- Elisabetta Zampogna, Nicolino Ambrosino, Federico Mattia Oliva, Giovanni Sotgiu, Laura Saderi, Gioele Cremonese, Giorgio Bellelli, Antonio Spanevello, Fabio Angeli, Dina Visca, Heart rate recovery in adult individuals with asthma , Monaldi Archives for Chest Disease: Vol. 93 No. 1 (2023)
- Pietro Impellizzeri, Santi Nolasco, Raffaele Campisi, Antonino Cipolla, Alba Borgese, Stefano Alia, Nunzio Crimi, Claudia Crimi, Acute and long-term management of severe bronchiectasis with high flow nasal therapy: a case report , Monaldi Archives for Chest Disease: Vol. 93 No. 2 (2023)
- Francesca Gatta, Yama Haqzad, George Gradinariu, Pietro Giorgio Malvindi, Zubair Khalid, Rona L. Suelo-Calanao, Nader Moawad, Aladdin Bashir, Luke J. Rogers, Clinton Lloyd, Bao Nguyen, Karen Booth, Lu Wang, Nawwar Al-Attar, Neil McDowall, Stuart Watkins, Rana Sayeed, Saleh Baghdadi, Andrea D’Alessio, Maria Monteagudo-vela, Jasmina Djordjevic, Matej Goricar, Solveig Hoppe, Charlotte Bocking, Azar Hussain, Betsy Evans, Salman Arif, Christopher Malkin, Mark Field, Kully Sandhu, Amer Harky, Ahmed Torky, Mauin Uddin, Muhammad Abdulhakeem, Ayman Kenawy, John Massey, Neil Cartwright, Nathan Tyson, Niki Nicou, Kamran Baig, Mark Jones, Firas Aljanadi, Colum G. Owens, Tunde Oyebanji, Joseph Doyle, Mark S. Spence, Paul F. Brennan, Ganesh Manoharan, Taha Ramadan, Sunil Ohri, Mahmoud Loubani, Redo aortic valve replacement versus valve-in-valve trans-catheter aortic valve implantation: a UK propensity-matched analysis , Monaldi Archives for Chest Disease: Vol. 94 No. 1 (2024)
You may also start an advanced similarity search for this article.
