Integrated guidance to enhance the care of children and adolescents with familial hypercholesterolaemia: Practical advice for the community clinician

Ari E Horton; Andrew C Martin; Shubha Srinivasan; Robert N Justo; Nicola K Poplawski; David Sullivan; Tom Brett; Clara K Chow; Stephen J Nicholls; Jing Pang; Gerald F Watts; FH Australasia Network Consensus Working Group

doi:10.1111/jpc.16096

Integrated guidance to enhance the care of children and adolescents with familial hypercholesterolaemia: Practical advice for the community clinician

J Paediatr Child Health. 2022 Aug;58(8):1297-1312. doi: 10.1111/jpc.16096. Epub 2022 Jul 15.

Authors

Ari E Horton^{1

2

3}, Andrew C Martin^{4

5}, Shubha Srinivasan^{6

7}, Robert N Justo^{8

9}, Nicola K Poplawski^{10

11}, David Sullivan^{12

13}, Tom Brett¹⁴, Clara K Chow^{15

16

17}, Stephen J Nicholls^{1

2}, Jing Pang¹⁸, Gerald F Watts^{18

19

20}; FH Australasia Network Consensus Working Group

Affiliations

¹ Monash Heart and Monash Children's Hospital, Monash Health, Melbourne, Victoria, Australia.
² Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Melbourne, Victoria, Australia.
³ Department of Paediatrics, Monash University, Melbourne, Victoria, Australia.
⁴ Department General Paediatrics, Perth Children's Hospital, Perth, Western Australia, Australia.
⁵ Division of Paediatrics, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.
⁶ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
⁷ Discipline of Child and Adolescent Health, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
⁸ Department of Paediatric Cardiology, Queensland Children's Hospital, Brisbane, Queensland, Australia.
⁹ School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
¹⁰ Adult Genetics Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
¹¹ Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
¹² Department of Chemical Pathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
¹³ Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
¹⁴ General Practice and Primary Health Care Research, School of Medicine, University of Notre Dame Australia, Fremantle, Western Australia, Australia.
¹⁵ Westmead Applied Research Centre, The University of Sydney, Sydney, New South Wales, Australia.
¹⁶ Department of Cardiology, Westmead Hospital, Sydney, New South Wales, Australia.
¹⁷ Cardiovascular Division, George Institute for Global Health, Sydney, New South Wales, Australia.
¹⁸ School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.
¹⁹ Lipid Disorders Clinic, Cardiometabolic Service, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia.
²⁰ Lipid Disorders Clinic, Cardiometabolic Service, Department of Internal Medicine, Royal Perth Hospital, Perth, Western Australia, Australia.

Abstract

Familial hypercholesterolaemia (FH) is a highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol (LDL-C) concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). At a prevalence of 1:250 individuals, with over 90% undiagnosed, recent estimates suggest that there are approximately 22 000 children and adolescents with FH in Australia and New Zealand. However, the overwhelming majority remain undetected and inadequately treated until adulthood or after their first cardiac event. The guidance in this paper aims to increase awareness about paediatric FH and provide practical advice for the diagnosis and management of FH in children and adolescents. Recommendations are given on the detection, diagnosis, assessment and management of FH in children and adolescents. Recommendations are also made on genetic testing, including counselling and the potential for universal screening programmes. Practical guidance on management includes treatment of non-cholesterol risk factors, and safe and appropriate use of LDL-C lowering therapies, including statins, ezetimibe, PCSK9 inhibitors and lipoprotein apheresis. Models of care for FH need to be adapted to local and regional health care needs and available resources. Targeting the detection of FH as a priority in children and young adults has the potential to alter the natural history of atherosclerotic cardiovascular disease and recognise the promise of early detection for improving long-term health outcomes. A comprehensive implementation strategy, informed by further research, including assessments of cost-benefit, will be required to ensure that this new guidance benefits all families with or at risk of FH.

Keywords: cardiovascular disease; familial hypercholesterolaemia; genetic testing; inherited cardiac disease; paediatrics.

© 2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

MeSH terms

Adolescent
Adult
Atherosclerosis* / diagnosis
Atherosclerosis* / etiology
Atherosclerosis* / therapy
Child
Cholesterol, LDL
Humans
Hyperlipoproteinemia Type II* / diagnosis
Hyperlipoproteinemia Type II* / genetics
Hyperlipoproteinemia Type II* / therapy
PCSK9 Inhibitors
Proprotein Convertase 9
Young Adult

Substances

Cholesterol, LDL
PCSK9 Inhibitors
PCSK9 protein, human
Proprotein Convertase 9