Original ArticleGaps in the Care of Familial Hypercholesterolaemia in Australia: First Report From the National Registry
Introduction
Familial hypercholesterolaemia (FH) is a high-risk condition characterised by elevated plasma low-density lipoprotein (LDL) cholesterol levels that predisposes individuals to premature coronary artery disease (CAD) [1]. FH has been defined by the Centers for Disease Control and Prevention as a Tier 1 genomic application [2], meaning that it is a preventable cause of premature disease and death with significant potential for a positive impact on public health [2]. FH has an estimated prevalence of 1 in 250 in the general population [3] and 1 in 20 among those with premature CAD [4]. There are an estimated 100,000 individuals with FH in Australia with the vast majority undiagnosed; thus FH is a public health priority.
In 2011, the FH Australasia Network (FHAN) of the Australian Atherosclerosis Society developed a comprehensive model of care for FH which encompasses detection of cases, diagnosis and assessment, management, cascade testing, genetic testing and clinical services for FH [5]. However, this model of care still requires extensive implementation in Australia. A crucial component of the model of care was to deploy a national web-based FH registry [6]. Registries capture real-world clinical practice data that are important not only to raise overall awareness of FH, but also for garnering information for health service planning and for clinical trials, as a means for improving the quality of patient care and outcomes [7,8].
Launched in 2015 in collaboration with FHAN, the Office of Population Health Genomics (Government of Western Australia) and the Centre for Comparative Genomics (Murdoch University) [6], the national FH registry now has an extensive network of clinical sites across Australia [9]. We aimed to describe the characteristics, detection and management patterns of adult FH patients enrolled in the national FH registry to highlight contemporary health care gaps that need to be addressed.
Section snippets
Methods
Eligibility criteria for adult entry into the registry included: a pathogenic gene variant causative of FH, a Dutch Lipid Clinic Network (DLCN) criteria score of ≥6 (Definite/Probable FH) or a DLCN criteria score of ≥3 (Possible FH) with familial elevation of lipoprotein(a) [Lp(a)], as well as all relatives identified via cascade screening with a pathogenic FH gene variant or “Likely” FH according to age and gender-specific LDL-cholesterol cut-offs [10]. The first participant enrolled was
Results
A total of 1,528 adult patients from 28 lipid clinics were included in the study (Figure 1). The demographic, clinical and biochemical characteristics of the cohort are shown in Table 1. The mean age at FH enrolment was 53.4±15.1 years (formal assessment for FH was undertaken 1.7±4.1 years earlier); 50.5% were male, 90.5% Caucasian (6.0% Asian, 2.0% Middle Eastern, 1.5% other ethnicity), 86.0% were index cases and of those that had undergone genetic testing, 61.8%% had a pathogenic FH-causing
Discussion
We provide the first report of adult FH patients in Australia from the FHAN registry. The data described the clinical and management characteristics of a contemporary cohort of FH patients, diagnosed using the DLCN criteria. The present study showed that although the majority of patients are on lipid-lowering therapies, CVD risk remains high, owing in part to a high prevalence of CVD risk factors and LDL-cholesterol targets not being reached.
Among adult FH patients in the FHAN registry, the
Conclusion
These registry data have demonstrated several management gaps in the care of FH in Australia that need to be addressed: (1) FH is detected too late in life, usually after a CAD event; (2) there is under-utilisation of genetic testing of index cases; (3) cascade testing, using cholesterol or genetic testing of family members of affected index cases is rarely employed; (4) the majority of patients do not attain guideline recommended LDL-cholesterol targets; (5) women with FH are receiving less
Funding
The registry received significant in-kind support from members of the FHAN and was also, in part, supported by grants from Amgen, MSD and Sanofi. JP was supported by a WAHTN Early Career Fellowship and the Australian Government’s Medical Research Future Fund.
Disclosures
DRS has received grants from Regeneron, Amgen, AstraZeneca, Amarin, Espirion, and Novartis, as well as personal fees from Amgen and Sanofi.
DLH has received consulting fees, educational grants, research grants or advisory board honoraria from Amgen, AstraZeneca, Boehringer-Ingelheim, Menarini, MSD, Novartis, Pfizer, Sanofi-Regeneron, Servier and Vifor.
DMC has received honoraria for advisory boards or research grants from Amgen, AstraZeneca, Abbott, Merck Sharpe & Dohme, Pfizer and Sanofi.
TRB has
Acknowledgements
The study was undertaken under the aegis of the FH Australasia Network (FHAN), the Australian Atherosclerosis Society (AAS) Inc. We thank Ms Natasha Whitwell and Ms Annette Pedrotti for their excellent assistance. We also acknowledge the other members of the FHAN registry team: Dr Edmund Brice, A/Prof Elif Ekinci, Dr Shahid Hafeez, A/Prof Christian Hamilton-Craig, Prof Leonard Kritharides, Dr Stephen Li, Dr Michael Metz (deceased), Dr Allison Morton, Dr Shubha Srinivasan and Dr Angela
References (44)
- et al.
Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation
Int J Cardiol
(2014) - et al.
Genetically confirmed familial hypercholesterolemia in patients with acute coronary syndrome
J Am Coll Cardiol
(2017) - et al.
Familial hypercholesterolaemia: a model of care for Australasia
Atherosclerosis Supp
(2011) - et al.
A web-based registry for familial hypercholesterolaemia
Heart Lung Circ
(2017) - et al.
Familial hypercholesterolaemia in 2020: a leading tier 1 genomic application
Heart Lung Circ
(2020) - et al.
Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel
Lancet Diabetes Endocrinol
(2016) - et al.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
J Am Coll Cardiol
(2019) - et al.
National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1—full report
J Clin Lipidol
(2015) - et al.
Cascade screening based on genetic testing is cost-effective: evidence for the implementation of models of care for familial hypercholesterolaemia
J Clin Lipidol
(2014) - et al.
Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands
Lancet
(2001)
Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service: an Australian experience
Atherosclerosis
Genetic analysis of familial hypercholesterolaemia in Western Australia
Atherosclerosis
Attainment of LDL-cholesterol treatment goals in patients with familial hypercholesterolemia: 5-Year SAFEHEART Registry follow-up
J Am Coll Cardiol
Health disparities among adult patients with a phenotypic diagnosis of familial hypercholesterolemia in the CASCADE-FH™ patient registry
Atherosclerosis
Coronary heart disease mortality in treated familial hypercholesterolaemia: Update of the UK Simon Broome FH register
Atherosclerosis
Elevated lipoprotein(a), hypertension and renal insufficiency as predictors of coronary artery disease in patients with genetically confirmed heterozygous familial hypercholesterolemia
Int J Cardiol
Lipoprotein (a) levels in familial hypercholesterolaemia: an important predictor for cardiovascular disease independent of the type of LDL-receptor mutation
J Am Coll Cardiol
NHLBI Working Group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis
J Am Coll Cardiol
High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study
Lancet Diabetes Endocrinol
Use of lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association
J Clin Lipidol
HEART UK Consensus Statement on lipoprotein(a) - a call to action
Atherosclerosis
Coronary heart disease mortality in severe vs. non-severe familial hypercholesterolaemia in the Simon Broome Register
Atherosclerosis
Cited by (16)
A systematic review of cost-effectiveness analysis of different screening strategies for familial hypercholesterolemia
2024, Journal of Clinical LipidologyBarriers to and Facilitators of Implementing Guidelines for Detecting Familial Hypercholesterolaemia in Australia
2023, Heart Lung and CirculationPatients with familial hypercholesterolemia and COVID-19: Efficient and ongoing cholesterol lowering is paramount for the prevention of acute myocardial infarction
2021, American Journal of Preventive CardiologySynopsis of an integrated guidance for enhancing the care of familial hypercholesterolaemia: an Australian perspective
2021, American Journal of Preventive CardiologyAdherence to pharmacotherapy: sine qua non for reducing cumulative risk of premature coronary disease in familial hypercholesterolemia
2024, Current Opinion in Endocrinology, Diabetes and Obesity