Generic placeholder image

Current Vascular Pharmacology


ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Research Article

The Gulf Familial Hypercholesterolemia Registry (Gulf FH): Design, Rationale and Preliminary Results

Author(s): Khalid Al-Rasadi *, Khalid F. Alhabib , Faisal Al-Allaf, Khalid Al-Waili, Ibrahim Al-Zakwani , Ahmad AlSarraf , Wael Almahmeed , Nasreen AlSayed , Mohammad Alghamdi , Mohammed A. Batais, Turky H. Almigbal , Fahad Alnouri, Abdulhalim Kinsara, Ashraf Hammouda , Zuhier Awan , Heba Kary , Omer A. Elamin, Fahad Zadjali , Mohammed Al-Jarallah , Abdullah Shehab , Hani Sabbour , Haitham Amin and Hani Altaradi

Volume 18, Issue 1, 2020

Page: [57 - 64] Pages: 8

DOI: 10.2174/1570161116666181005125459

open access plus


Aim: To determine the prevalence, genetic characteristics, current management and outcomes of familial hypercholesterolaemia (FH) in the Gulf region.

Methods: Adult (18-70 years) FH patients were recruited from 9 hospitals and centres across 5 Arabian Gulf countries. The study was divided into 4 phases and included patients from 3 different categories. In phase 1, suspected FH patients (category 1) were collected according to the lipid profile and clinical data obtained through hospital record systems. In phase 2, patients from category 2 (patients with a previous clinical diagnosis of FH) and category 1 were stratified into definitive, probable and possible FH according to the Dutch Lipid Clinic Network criteria. In phase 3, 500 patients with definitive and probable FH from categories 1 and 2 will undergo genetic testing for 4 common FH genes. In phase 4, these 500 patients with another 100 patients from category 3 (patients with previous genetic diagnosis of FH) will be followed for 1 year to evaluate clinical management and cardiovascular outcomes. The Gulf FH cohort was screened from a total of 34,366 patients attending out-patient clinics.

Results: The final Gulf FH cohort consisted of 3,317 patients (mean age: 47±12 years, 54% females). The number of patients with definitive FH is 203. In this initial phase of the study, the prevalence of (probable and definite) FH is 1/232.

Conclusion: The prevalence of FH in the adult population of the Arabian Gulf region is high. The Gulf FH registry, a first-of-a-kind multi-national study in the Middle East region, will help in improving underdiagnosis and undertreatment of FH in the region.

Keywords: Familial hypercholesterolemia, Middle East, registry, cardiovascular diseases, consanguinity, CHD.

Graphical Abstract
Goldstein JK, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: Scriver CR, Beaud, Sly WS, Valle D (Eds), The metabolic & molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001; pp. 2863-913.
Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: A Huge prevalence review. Am J Epidemiol 2004; 160: 407-20.
Civeira F. Guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia. Atherosclerosis 2004; 173: 55-68.
Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest 2003; 111: 1795-803.
Børge G, Nordestgaard M, Chapman J, Humphries SE. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: Guidance for clinicians to prevent coronary heart disease. Eur Heart J 2013; 34: 3478-90.
Huijgen R, Vissers MN, Defesche JC, Lansberg PJ, Kastelein JJ, Hutten BA. Familial hypercholesterolemia: Current treatment and advances in management. Expert Rev Cardiovasc Ther 2008; 6: 567-81.
Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis 2012; 223: 262-8.
Shawar SM, Al-Drees MA, Ramadan AR, Ali NH, Alfadhli SM. The Arabic allele: A single base pair substitution activates a 10-base downstream cryptic splice acceptor site in exon 12 of LDLR and severely decreases LDLR expression in two unrelated Arab families with familial hypercholesterolemia. Atherosclerosis 2012; 220: 429-36.
Al-Hinai AT, Al-Abri A, Al-Dhuhli H, et al. First case report of familial hypercholesterolemia in an Omani family due to novel mutation in the low-density lipoprotein receptor gene. Angiology 2013; 64: 287-92.
Al-Rasadi K, Al-Waili K, Al-Zidi WA, et al. Low-density lipoprotein receptor gene mutation analysis and structure-function correlation in an Omani Arab family with familial hypercholesterolemia. Angiology 2014; 65: 911-8.
Al-Allaf FA, Athar M, Abduljaleel Z, et al. Next generation sequencing to identify novel genetic variants causative of autosomal dominant familial hypercholesterolemia associated with increased risk of coronary heart disease. Gene 2015; 565: 76-84.
Alallaf FH, Nazar FA, Alnefaie M, et al. The spectrum of familial hypercholesterolemia (FH) in Saudi Arabia: Prime time for patient FH registry. Open Cardiovasc Med J 2017; 11: 66-75.
Al-Rasadi K, Al-Zakwani I, Alsheikh-Ali AA, et al. Prevalence, management, and outcomes of familial hypercholesterolemia in patients with acute coronary syndromes in the Arabian Gulf. J Clin Lipidol 2018; 12: 685-92.
Bamimore MA, Zaid A, Banerjee Y, et al. Familial hypercholesterolemia mutations in the Middle Eastern and North African region: A need for a national registry. J Clin Lipidol 2015; 9: 187-94.
Ruel I, Aljenedil S. Sadri I1, de Varennes É, et al. Imputation of baseline LDL cholesterol concentration in patients with familial hypercholesterolemia on statins or ezetimibe. Clin Chem 2017; 64: 355-62.
Haralambos K, Whatley SD, Edwards R, et al. Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales. Atherosclerosis 2015; 240: 190-6.
Robinson JT, Thorvaldsdóttir H, Winckler W, et al. Integrative genomics viewer. Nat Biotechnol 2011; 29: 24-6.
Wang K, Li M, Hakonarson H. ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010; 38e164
el-Hazmi MA, al-Swailem AR, Warsy AS, et al. Consanguinity among the Saudi Arabian population. J Med Genet 1995; 32: 623-6.
Heiberg A, Berg K. The inheritance of hyperlipoproteinaemia with xanthomatosis. A study of 132 kindreds. Clin Genet 1976; 9: 203-33.
Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Familial hypercholesterolemia in the Danish general population: Prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab 2012; 97: 3956-64.
Bellgard MI, Walker CE, Napier KR, et al. Design of the Familial hypercholesterolaemia australasia network registry: Creating opportunities for greater international collaboration. J Atheroscler Thromb 2017; 24: 1075-84.
Batais MA, Almigbal TH, Bin Abdulhak AA, Altaradi HB, AlHabib KF. Assessment of physicians’ awareness and knowledge of familial hypercholesterolemia in Saudi Arabia: Is there a gap? PLoS One 2017; 12e0183494
Zubaid M, Rashed WA, Almahmeed W, et al. Management and outcomes of Middle East patients admitted with acute coronary syndromes in the Gulf registry of acute coronary events (Gulf RACE). Acta Cardiol 2009; 64: 439-46.
Alhabib KF, Sulaiman K, Al-Motarreb A, et al. Baseline characteristics, management practices, and long-term outcomes of Middle Eastern patients in the second gulf registry of acute coronary events (Gulf RACE-2). Ann Saudi Med 2012; 32: 9-18.
Zubaid M, Thani KB, Rashed W, et al. Design and rationale of Gulf locals with acute coronary syndrome events (Gulf coast) registry. Open Cardiovasc Med J 2014; 8: 88-93.
Henneman L, McBride CM, Cornel MC, Duquette D, Qureshi N. Screening for Familial hypercholesterolemia in children: What can we learn from adult screening programs? Health Care 2015; 3: 1018-30.
De Backer G, Besseling J, Chapman J, et al. Prevalence and management of familial hypercholesterolaemia in coronary patients: An analysis of EUROASPIRE IV, a study of the European society of cardiology. Atherosclerosis 2015; 241: 169-75.
Nanchen D, Gencer B, Auer R, et al. Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes. Eur Heart J 2015; 36: 2438-45.
Wonderling D, Umans-Eckenhausen MA, Marks D, Defesche JC, Kastelein JJ, Thorogood M. Cost-effectiveness analysis of the genetic screening program for familial hypercholesterolemia in the Netherlands. Semin Vasc Med 2004; 4: 97-104.
Nherera L, Marks D, Minhas R, Thorogood M, Humphries SE. Probabilistic cost-effectiveness analysis of cascade screening for familial hypercholesterolaemia using alternative diagnostic and identification strategies. Heart 2011; 97: 1175-81.
Lázaro P, Pérez de Isla L, Watts GF. Cost-effectiveness of a cascade screening program for the early detection of familial hypercholesterolemia. J Clin Lipidol 2017; 11: 260-71.
Sturm AC, Knowles JW, Gidding SS, et al. Clinical genetic testing for familial hypercholesterolemia. J Am Coll Cardiol 2018; 72: 662-80.
Al Sayed N, Al Waili K, Alawadi F, et al. Consensus clinical recommendations for the management of plasma lipid disorders in the Middle East. Int J Cardiol 2016; 225: 268-83.
Al Rasadi K, Almahmeed W, AlHabib KF, et al. Dyslipidaemia in the Middle East: Current status and a call for action. Atherosclerosis 2016; 252: 182-7.
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.
Arafah M, Al-Hinai AT, Al Mahmeed W, et al. Centralized Middle East survey on the undertreatment of hypercholesterolemia: Results from the CEPHEUS study in Arabian Gulf countries. Angiology 2014; 65: 919-26.
Nordestgaard BG, Chapman MJ, Humphries SE, et al. European atherosclerosis society consensus panel 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: 3478-90.
Hamilton-Craig I, Kostner K, Colquhoun D, Woodhouse S. Combination therapy of statin and ezetimibe for the treatment of familial hypercholesterolemia. Vasc Health Risk Manag 2010; 6: 1023-37.
Cuchel M, Bruckert E, Ginsberg HN, et al. European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia 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.
Kastelein JJ, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J 2015; 36: 2996-3003.
Raal FJ, Stein EA, Dufour R, et al. RUTHERFORD-2 investigators PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): A randomised, double-blind, placebo-controlled trial. Lancet 2015; 385: 331-40.

© 2022 Bentham Science Publishers | Privacy Policy