Two global reports provide consistent data showing that heterozygous familial hypercholesterolaemia (FH) is common in the general population, and even more so among individuals with atherosclerotic cardiovascular disease. Mapping the global prevalence of FH is critical for informing public health policy to identify and treat FH early.
Familial hypercholesterolemia: an urgent public health priority
Familial hypercholesterolemia (FH) is one of the most common inherited metabolic disorders. Data on prevalence predominantly relate to white European or North American populations(1,2). Defined by clinical and/or genetic diagnostic criteria, studies showed that heterozygous FH affects about 1 in 200-250 of these populations(1,2); however, uncertainty persists regarding the prevalence of FH across different regions. These data are critical to informing policies aimed at early detection of FH.
Two recent studies extend knowledge of the prevalence of heterozygous FH, both among the general population and in individuals with atherosclerotic cardiovascular disease (ASCVD)(3). The first report was a systematic review and meta-analysis of 42 general population studies (7,297,363 individuals/24,636 FH cases) and 20 studies in individuals with ASCVD (48,158 patients/2827 FH cases). While most of the data (>60% of studies and >80% of cases) related to Europe and the Americas, studies from the Eastern Mediterranean and Western Pacific Regions were also represented. There were, however, no data from Southeast Asia or Africa from general populations, although information among populations with founder effects were available. Diagnosis was predominantly based on clinical criteria.
Among the general population, the overall prevalence of heterozygous FH was 1:311 (95% confidence interval [CI] 1:250–1:397), the broad confidence intervals indicative of heterogeneity in diagnostic criteria across the studies. Importantly, among individuals with ASCVD the prevalence was 18-fold higher (1:17, 95% CI, 1:12–1:24), largely driven by prevalence in subjects with coronary artery disease (1:16, 95% CI, 1:12–1:23).
Overall, these findings are remarkably consistent with results from another systematic review and meta-analyses in more 11 million individuals included in 104 studies (44 in the general population, 28 and 32 in individuals with ischaemic heart disease (IHD) or premature IHD, respectively, and seven in those with severe hypercholesterolemia)(4). This report had different search criteria and included some populations with founder effects such as in South Africa, the Afrikaner and Jewish populations. Once again, however, there were large swathes of the global map for which there are no data: most of Africa, South-East Asia, and much of South America.
Based on predominantly clinical diagnostic criteria, the overall prevalence of FH in the general population was 1:313. Among those with IHD the prevalence was 10-fold higher and even higher, by 20-fold, among those with premature IHD. Once again, the authors underline the gaps in knowledge about heterozygous FH prevalence among different ethnicities and world regions.
Why are these studies important?
Heterozygous FH is common and impacts risk for premature ASCVD. Untreated, FH poses substantial burden on individuals, healthcare systems and society. Managing the cardiovascular complications of FH, not just manifestations of coronary artery disease but also ischaemic stroke, is costly. Yet if identified early, effective low-density lipoprotein (LDL) cholesterol lowering treatment, in addition to lifestyle intervention, can be initiated early to prevent ASCVD(5). There is a growing evidence-base for the efficacy and safety of lipid-lowering statin therapy in children with heterozygous FH, with no indication of any influence on growth and maturation(6). Moreover, the advent of novel highly efficacious LDL-lowering treatments offers the chance to improve LDL cholesterol lowering in more severe cases.
In 1998, the World Health Organization recognized FH as a public health priority, highlighting 11 recommendations to prevent early ASCVD in individuals with FH, ranging from diagnosis and treatment to family screening and education(7). Knowledge of FH has expanded since this time providing the impetus for global action to prevent the costly cardiovascular complications associated with the lifelong burden of elevated LDL cholesterol levels in FH.
Critical to planning public health policy is knowledge of the global prevalence of FH. These new reports highlight the gaps in current knowledge about FH prevalence, and underline the need to tailor clinical diagnostic criteria to the region, rather than adopt those derived from Western, largely white populations. Both are mandatory to the provision of good quality data to inform policy.
The previous survey of care and FH services conducted by the EAS FH Collaborative Studies Registry(8) showed much work is still needed on clinical implementation. This Registry, including 70 countries and 62,000 cases to date, has a key role in addressing the global challenge of FH. The work of the Registry, in partnership with FH Europe and the World Heart Federation, provides the impetus for action to promote early diagnosis and more effective treatment of this common albeit manageable disorder worldwide. In partnership with global collaborators, the EAS FH Collaborative Studies Registry is endeavouring to implement a global call to action(7) and advocate universal screening for cholesterol by the age of 20.
1. Benn M, Watts GF, Tybjærg-Hansen A, Nordestgaard BG. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. Eur Heart J 2016;37:1384-94.
2. de Ferranti SD, Rodday AM, Mendelson MM, et al. Prevalence of familial hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES). Circulation 2016;133:1067-72.
3. Hu P, Dharmayat KI, Stevens CAT, et al. Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease. A systematic review and meta-analysis. Circulation 2020;141:1742-59.
4. Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG. Worldwide prevalence of familial hypercholesterolemia: meta-analyses of 11 million subjects. J Am Coll Cardiol 2020;75:2553-66.
5. Wiegman A, Gidding SS, Watts GF, et al; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015;36:2425-37.
6. Wiegman A. Lipid screening, action, and follow-up in children and adolescents. Current Cardiology Reports 2018;20: 80.
7. Representatives of the Global Familial Hypercholesterolemia Community; 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; doi: 10.1001/jamacardio.2019.5173.
8. EAS Familial Hypercholesterolaemia Studies Collaboration, Vallejo-Vaz AJ, De Marco M, Stevens CAT, 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.
The EAS FH Collaborative Studies Registry (https://eas-fhsc.org/) is the first global registry of patients with FH. The mission of the EAS-FHSC is to empower the medical & global community to seek changes in their respective countries or organizations regarding how FH is detected and managed, with a view to promoting early diagnosis and more effective treatment of this condition. For further details refer to: EAS Familial Hypercholesterolaemia Studies Collaboration, Vallejo-Vaz AJ, Akram A, Kondapally Seshasai SR, et al. Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration. Atheroscler Suppl 2016;22:1-32.