Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG. Worldwide prevalence of familial hypercholesterolemia. J Am Coll Cardiol. 2020;75(20):2553–66.

Article  CAS  PubMed  Google Scholar 

Khera AV, Won H-H, Peloso GM, Lawson KS, Bartz TM, Deng X, et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67(22):2578–89.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Borén J, John Chapman M, Krauss RM, Packard CJ, Bentzon JF, Binder CJ, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel Translational medicine. Eur Heart J. 2020;41.

Vallejo-Vaz AJ, De Marco M, Stevens CAT, Akram A, Freiberger T, Hovingh GK, et al. Overview of the current status of familial hypercholesterolaemia care in over 60 countries - the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Atherosclerosis. 2018;277:234–55.

Article  CAS  PubMed  Google Scholar 

Vallejo-Vaz AJ, Stevens CAT, Lyons ARM, Dharmayat KI, Freiberger T, Hovingh GK, et al. Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Lancet. 2021;398(10312):1713–25. This work summarizes the results from the European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC), a global registry of 42167 adults with clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia from 56 countries. The data reveals that earlier detection and greater use of combination therapies are required to reduce the global burden of FH.

Article  CAS  Google Scholar 

Luirink IK, Wiegman A, Kusters DM, Hof MH, Groothoff JW, de Groot E, et al. 20-Year follow-up of statins in children with familial hypercholesterolemia. N Engl J Med. 2019;381(16):1547–56. This work demonstrated that the initiation of statin therapy during childhood in patients with familial hypercholesterolemia slowed the progression of carotid intima-media thickness and reduced the risk of cardiovascular disease in adulthood.

Article  CAS  PubMed  Google Scholar 

Vuorio A, Kuoppala J, Kovanen PT, Humphries SE, Tonstad S, Wiegman A, et al. Statins for children with familial hypercholesterolemia. Cochrane Database Syst Rev. 2019;2019(11).

Versmissen J, Oosterveer DM, Yazdanpanah M, Defesche JC, Basart DCG, Liem AH, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008;11:337.

Google Scholar 

Wiegman A, Gidding SS, Watts GF, Chapman MJ, Ginsberg HN, Cuchel M, et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36(36):2425–37.

Article  PubMed  PubMed Central  Google Scholar 

Sturm AC, Knowles JW, Gidding SS, Ahmad ZS, Ahmed CD, Ballantyne CM, et al. Clinical genetic testing for familial hypercholesterolemia. J Am Coll Cardiol. 2018;72(6):662–80.

Article  PubMed  Google Scholar 

Ramaswami U, Futema M, Bogsrud MP, Holven KB, Roeters van Lennep J, Wiegman A, et al. Comparison of the characteristics at diagnosis and treatment of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries. Atherosclerosis. 2020;292:178–87. This work compares the characteristics and lipid levels of 3064 children with heterozygous familial hypercholesterolaemia from 8 European countries. The data suggest that many of the FH children are not receiving the full potential benefit of early identification and appropriate lipid-lowering treatment according to recommendations.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Spencer SJ, Jones LK, Guzauskas GF, Hao J, Williams MS, Peterson JF, et al. Cost-effectiveness of population-wide genomic screening for familial hypercholesterolemia in the United States. J Clin Lipidol. 2022;16(5):667–75.

Article  PubMed  PubMed Central  Google Scholar 

Graça R, Alves AC, Zimon M, Pepperkok R, Bourbon M. Functional profiling of LDLR variants: Important evidence for variant classification: functional profiling of LDLR variants. J Clin Lipidol. 2022;16(4):516–24. This work shows the important role that functional characterization plays in variant classification for an accurate diagnosis of FH.

Article  PubMed  Google Scholar 

Qureshi N, Humphries SE, Gray H. Personalised medicine in general practice: the example of raised cholesterol. Br J Gen Pract. 2018;68(667):68.

Article  PubMed  PubMed Central  Google Scholar 

Gidding SS, Europe TF, Wiegman A, Groselj U, Freiberger T, Peretti N, et al. Paediatric familial hypercholesterolaemia screening in Europe – public policy background and recommendations. Eur J Prev Cardiol. 2022 Sep 5. This work summarizes the pediatric family screening programs in several European countries and outlines recommendations to improve identification of FH.

Paediatric screening of FH (familial hypercholesterolaemia) patients. European Commission Public Health Best Practice Portal. 2021. [Internet]. Available from: https://webgate.ec.europa.eu/dyna/bp-portal/practice.cfm?id=390. Accessed 12 Sept 2022

Groselj U, Wiegman A, Gidding SS. Screening in children for familial hypercholesterolaemia: start now. Eur Heart J. 2022;43(34):3209–12. A viewpoint on the different pediatric family screening programs in Europe and the public policy recommendations addressed at the Technical Meeting of 2021 Slovenian EU presidency.

Article  PubMed  Google Scholar 

Medeiros AM, Alves AC, Aguiar P, Bourbon M. Pediatric investigators of the Portuguese familial hypercholesterolemia study Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers to identify monogenic dyslipidemia. J Lipid Res. 2014;55(5):947–55.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mariano C, Alves AC, Medeiros AM, Chora JR, Antunes M, Futema M, et al. The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes. Clin Genet. 2020;97(3):457–66.

Article  CAS  PubMed  Google Scholar 

Zuurbier LC, Defesche JC, Wiegman A. Successful genetic screening and creating awareness of familial hypercholesterolemia and other heritable dyslipidemias in the Netherlands. Genes (Basel). 2021;12:1168.

Article  CAS  PubMed  Google Scholar 

Groselj U, Kovac J, Sustar U, Mlinaric M, Fras Z, Podkrajsek KT, et al. Universal screening for familial hypercholesterolemia in children: the Slovenian model and literature review. Atherosclerosis. 2018;277:383–91.

Article  CAS  PubMed  Google Scholar 

Kreissl A, Walleczek N, Espina PR, Hallwirth U, Greber-Platzer S. Selective screening for familial hypercholesterolemia in Austrian children - first year results. BMC Pediatr. 2019;19(1):1–7.

Article  Google Scholar 

Sanin V, Schmieder R, Ates S, Schlieben LD, Wiehler J, Sun R, et al. Population-based screening in children for early diagnosis and treatment of familial hypercholesterolemia: design of the VRONI study. Eur J Public Health. 2022;32(3):422–8.

Article  PubMed  PubMed Central  Google Scholar 

Mundal L, Veierød MB, Halvorsen T, Holven KB, Ose L, Iversen PO, et al. Cardiovascular disease in patients with genotyped familial hypercholesterolemia in Norway during 1994–2009, a registry study. Eur J Prev Cardiol. 2016;23(18):1962–9.

Article  PubMed  Google Scholar 

Vrablík M, Vaclová M, Tichý L, Soška V, Bláha V, Fajkusová L, et al. Familial hypercholesterolemia in the Czech Republic: more than 17 years of systematic screening within the MedPed PROJECT. Physiol Res. 2017;66:1–9.

Article  Google Scholar 

Perez De Isla L, Alonso R, Watts GF, Mata N, SaltijeralCerezo A, Muñiz O, et al. Attainment of LDl-cholesterol treatment goals in patients with familial hypercholesterolemia: 5-year SAFEHEART registry follow-up. J Am Coll Cardiol. 2016;67(11):1278–85.

Article  PubMed  Google Scholar 

Kerr M, Pears R, Miedzybrodzka Z, Haralambos K, Cather M, Watson M, et al. Cost effectiveness of cascade testing for familial hypercholesterolaemia, based on data from familial hypercholesterolaemia services in the UK. Eur Heart J. 2017;38(23):1832–9.

Article  PubMed  PubMed Central  Google Scholar 

Lauer RM, Barness LA, Clark R, Deckelbaum RJ, Finberg L, Kwiterovich PO, et al. National Cholesterol Education Program (NCEP): Highlights of the report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics. 1992;89(3 SUPPL):495–501.

Google Scholar 

De Jesus JM. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128(SUPP. 5):S213.

Google Scholar 

de Ferranti SD, Rodday AM, Parsons SK, Cull WL, O’Connor KG, Daniels SR, et al. Cholesterol screening and treatment practices and preferences: a survey of United States pediatricians. J Pediatr. 2017;1(185):99-105.e2.

Article  Google Scholar 

Portuguese Directorate General of Health (DGS). Norma da Direção-geral da saúde n. 10/2013. Programa Nacional de Saúde Infantil e Juvenil. 2013.

Kwiterovich PO, Gidding SS. Universal screening of cholesterol in children. Clin Cardiol. 2012;35(11):662–4.

Article  PubMed  PubMed Central  Google Scholar 

Sustar U, Kordonouri O, Mlinaric M, Kovac J, Arens S, Sedej K, et al. Universal screening for familial hypercholesterolemia in 2 populations. Genet Med. 2022 Aug 1.

Wald DS, Bestwick JP, Morris JK, Whyte K, Jenkins L, Wald NJ. Child–parent familial hypercholesterolemia screening in primary care. N Engl J Med. 2016;375(17):1628–37.

Article  CAS  PubMed  Google Scholar 

Martin AC, Hooper AJ, Norman R, Nguyen LT, Burnett JR, Bell DA, et al. Pilot study of universal screening of children and child-parent cascade testing for familial hypercholesterolaemia in Australia. 2022;58(2):281–7.

Google Scholar 

McKay AJ, Hogan H, Humphries SE, Marks D, Ray KK, Miners A. Universal screening at age 1–2 years as an adjunct to cascade testing for familial hypercholesterolaemia in the UK: a cost-utility analysis. Atherosclerosis. 2018;1(275):434–43.

Article  Google Scholar 

Pirillo A, Garlaschelli K, Arca M, Averna M, Bertolini S, Calandra S, et al. Spectrum of mutations in Italian patients with familial hypercholesterolemia: new results from the LIPIGEN study. Atheroscler Suppl. 2017;29:17–24.

Article  PubMed  Google Scholar 

Bedlington N, Abifadel M, Beger B, Bourbon M, Bueno H, Ceska R, et al. The time is now: achieving FH paediatric screening across Europe - the Prague Declaration. GMS Heal Innov Technol. 2022;16:Doc04. This political document is a result of the Czech EU Presidency meeting on FH paediatric screening and addresses the barriers to the implementation of FH paediatric screening across Europe and also concrete actions needed to move forward.

Familial hypercholesterolaemia: identification and management [Internet]. Familial hypercholesterolaemia: identification and management: evidence reviews for case-finding, diagnosis and statin monotherapy. National Institute for Health and Care Excellence (NICE); 2017.

Mach F, Baigent C, Catapano AL, Koskina KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–88.

Article  PubMed  Google Scholar 

Sturm AC, Truty R, Callis TE, Aguilar S, Esplin ED, Garcia S, et al. Limited-variant screening vs comprehensive genetic testing for familial hypercholesterolemia diagnosis. JAMA Cardiol. 2021;6(8):902–9.

Article  PubMed  PubMed Central  Google Scholar 

Iacocca MA, Hegele RA. Recent advances in genetic testing for familial hypercholesterolemia. Expert Rev Mol Diagn. 2017;17(7):641–51.

Article  CAS  PubMed  Google Scholar 

Ibrahim S, Defesche JC, Kastelein JJP. Beyond the usual suspects: expanding on mutations and detection for familial hypercholesterolemia expert review of molecular diagnostics. Expert Rev Mol Diagn. 2021;21(9):887–95.

Article  CAS  PubMed  Google Scholar