Collaboration (FHSC) highlights the challenges of care
Familial hypercholesterolemia (FH) is a common inherited condition, affecting about one in 300 people worldwide, and is characterised by elevated levels of low-density lipoprotein cholesterol (LDL-C) from birth.1-3 If untreated, this burden of lifelong high LDL-C levels predisposes to premature atherosclerotic cardiovascular disease (ASCVD), with individuals often experiencing their first myocardial infarction during middle-age.1 However, if detected early – ideally during childhood – with prompt initiation of guideline-recommended lipid lowering therapy, individuals with this condition can live a normal, healthy life.4
Over 20 years ago, the 1998 World Health Organization (WHO) Report on FH highlighted the challenge of FH care.5 It is important to note that this directive was made when data on FH prevalence suggested one in 500 individuals was affected, half that of current estimates. The 2013 EAS Consensus Panel on FH – underdiagnosed and undertreated – catalysed the first universal call to action to improve the care of this common inherited condition.1,6 Critical to this is understanding contemporary FH care. In 2015, the EAS-supported FH Studies Collaboration (FHSC) global registry was initiated by Professor Kausik K. Ray.6 The FHSC created a network of investigators across all WHO regions via the FHSC Coordinating Centre at Imperial College London with the long-term goal of providing unique insights into the prevalence, detection and management of FH, crucial to guiding public health policy.7 This initiative represents the most important global collaboration in this field since the WHO statement in 1998.
The high cardiovascular risk associated with FH has also been recognized by the 2019 European Society of Cardiology (ESC)/EAS dyslipidaemia guidelines.8 Even in the absence of ASCVD and risk factors, FH was identified as a high-risk condition, necessitating lower LDL-C goals of at least <1.8 mmol/L (<70 mg/dL). The greater problem, however, is attaining these recommended stringent LDL-C goals in clinical practice.
First data from the FHSC published recently in The Lancet 9 highlight the magnitude of this challenge. This unique global registry provided information on 42,167 adults (53.6% women) with heterozygous FH from 56 countries. About one in four FH patients already had ASCVD at the time of entry into the registry.
Delayed diagnosis was the norm; about 60% of the 30,560 patients with available data on the age of FH diagnosis were identified when over 40 years of age. Undertreatment was also problematic. Of the 59.5% of the total cohort on lipid lowering therapy at entry into the registry, most were not receiving the most potent statin regimens as recommended by guidelines. Importantly, only about one in five patients were on combination lipid lowering therapy at entry into the registry, recommended by guidelines as the standard of care for FH.9
The FHSC data also highlighted disparities in FH care between men and women. Women were diagnosed later than men, on average by ~2.5 years. Over the age of 50 years, untreated women had higher LDL-C levels, on average by 0.64 mmol/L or 25 mg/dL, than untreated men. Among FH patients on treatment, women were less likely to be on potent statin therapy (13.1% versus 16.6% of men were on the highest doses of rosuvastatin and atorvastatin, p<0.001), or on combination lipid lowering therapy (19.9% versus 22.7%, p<0.001).9
These findings from the FHSC are depressingly familiar. Detection and initiation of lipid lowering therapy for FH are generally too late, highlighting the challenge of implementing guideline recommendations in routine practice. Moreover, as most patients were enrolled in Europe, knowledge about FH prevalence and care in other regions of the world is limited.
There are, however, some positive messages. Screening family members of an FH index case (cascade screening) is a key strategy for earlier FH diagnosis. The FHSC report showed that those FH patients identified by screening were younger at diagnosis, had lower untreated LDL-C levels (by 1.55 mmol/L, or 60 mg/dL), as well as lower prevalence of other cardiovascular risk factors such as hypertension and diabetes, compared with index cases.9 These findings support the role of screening strategies to identify and treat FH earlier to reduce ASCVD risk. Such approaches also have value in targeting risk factors other than LDL-C earlier. As previously noted, screening during childhood may be the ideal to gain years of healthy life.
Why are these data from the FHSC crucial? The FHSC is a unique global registry covering all WHO regions. These baseline findings are essential to inform policy makers how FH is currently managed, and where to target policy changes to improve FH care. In 1998 the WHO first drew attention to the challenges of FH. In 2021, the FHSC provides critical new information on contemporary FH care. Now is the time to leverage these data to drive healthcare policy on FH, with the ultimate aim of gaining healthy life years in all patients.
Key take home messages
|• The FHSC is a unique global registry. This report included data from over 40,000 FH individuals worldwide.|
• The findings show that FH is poorly treated. Most patients are diagnosed late, over the age of 40 years.
• Intensification of therapy, likely including combination lipid lowering treatment, is needed to attain guideline-recommended LDL-C goals.
• The care of FH women falls behind that of men. These sex disparities have potential implications when developing public health strategies for FH detection and care.
• Family screening of index cases (cascade screening) is critical to identifying FH and initiating therapy from a young age.
• The FHSC data on contemporary FH care across the world will help to drive healthcare policy for FH, to gain healthy life years for individuals with FH.
1. 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.
2. 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 StudiesCollaboration (FHSC). Atherosclerosis 2018;277: 234-55.
3. 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: 3478-90a.
4. Wiegman A, Gidding SS, Watts GF, et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015;36: 2425–37.
5. Familial Hypercholesterolemia [FH]: Report of a WHO Consultation. World Health Organization, Human Genetics Programme, Division of Noncommunicable Diseases. WHO/HGN/FH/CONS/98.7. Geneva, 1998.
6. Vallejo-Vaz AJ, Kondapally Seshasai SR, Cole D, et al. Familial hypercholesterolaemia: A global call to arms. Atherosclerosis 2015;243: 257-9.
7. 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.
8. Mach F, Baigent C, Catapano AL, et al; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41: 111-88.
9. EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). The Lancet 2021; DOI:https://doi.org/10.1016/S0140-6736(21)01122-3.