Worldwide experience of HoFH in the Lancet

Jan 31, 2022

“Homozygous familial hypercholesterolemia is a rare condition, extraordinarily difficult to treat, and without early identification and experienced care, leads to cardiac consequences early in life and often, death by age 30 years. New medications are on the horizon, but the prognosis remains grim. This paper shows that worldwide, much greater efforts are needed to help those affected.”

Dr Sam Gidding, Trustee and Chair of Scientific Advisory Committee, FH Europe

Global registry of homozygous familial hypercholesterolaemia highlights treatment inequity in less affluent countries

Worldwide, homozygous familial hypercholesterolaemia (HoFH), the most severe form of this high cholesterol disorder, is poorly managed with adverse health outcomes, especially among less affluent countries. These are the take home messages from the Homozygous Familial Hypercholesterolaemia International Clinical Collaboration (HICC) registry, the only international cohort of HoFH, which is partly funded by the European Atherosclerosis Society (EAS) FH Studies Collaboration. Published today in The Lancet, these insights from the HICC registry are crucial to driving change in healthcare policy to improve HoFH care.

HoFH affects about one in 300,000 people,1,2 and poses a substantial burden of disease. With very high levels of low-density lipoprotein cholesterol (LDL-C) from birth, early diagnosis is essential to avoid any delay in starting lipid-lowering therapy to reduce the severe cardiovascular complications of HoFH.  Treatment with a statin, ezetimibe and lipoprotein apheresis is often recommended as the standard of care.3Novel agents including PCSK9 inhibitors, lomitapide, and evinacumab further lower LDL-C levels on top of these treatments but are costly. 

The HICC registry was set up to learn about the characteristics and care of HoFH patients globally. This report was based on 751 patients (52 percent female), from 38 countries, representing all seven World Bank regions. Nearly half (47 percent) were in 18 non-high-income countries. Although diagnosed earlier than patients in high-income countries (at a median of 10 versus 16 years), patients in less affluent regions had higher untreated LDL-C levels (15.8 versus 13.5 mmol/L) and were likely to have a more severe clinical presentation.  

Management was far from optimal in both groups. However, patients in non-high-income countries fared worse; they were less likely to receive combination lipid lowering therapy (67 versus 85 percent among high-income countries), and rarely a PCSK9 inhibitor (17 versus 26 percent) or lomitapide. Almost none (3 percent) achieved LDL-C goal (<2.6 mmol/L or <1.8 mmol/L for patients with and without cardiovascular disease), compared with 21 percent in high-income countries.

Patients in non-high-income countries also experienced a first cardiovascular event, such as a heart attack, more than a decade earlier than those from high-income countries (median age at onset 24.5 versus 37 years).

Professor Frederick J. Raal from the Steering Committee of the HICC Registry (University of the Witwatersrand, Johannesburg, South Africa) commented:  ‘These new findings from the HICC registry show that there is much to do to improve the care of patients with HoFH. We need to identify patients much earlier; already about one in 10 patients worldwide had experienced a cardiovascular event by the time of diagnosis. Education to improve awareness is essential. Second, we have a long way to go to ensure that all patients, particularly those in less affluent countries, have access to newer treatments that are highly effective in lowering LDL-C on top of statin therapy. This is fundamental if we are to delay or even prevent cardiovascular complications such as heart attack, for patients with this severe and life-limiting condition.’

According to EAS President Professor Kausik K. Ray (Imperial College London, UK): ‘The key messages from this report are: more screening, earlier screening and earlier combination treatments are crucial for public health. We need to find the remaining 97 percent of cases that remain undetected, and hence untreated, who will have avoidable adverse health outcomes. Reducing detection times from the second decade to early in the first decade is essential. Access and equity of access to novel therapies globally are essential to prevent the catastrophic consequences of HoFH.’

Tromp TR, Hartgers ML, Hovingh GK, et al. Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study. The Lancet; Published Online January 28, 2022

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The HICC is an investigator-initiated project supported by funding from the academic institutions of the collaborators. The EAS provided funding to support a registry coordinator.
Further information at:


  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. 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.
  3. Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 2014;35:2146-57.

FH Europe is registered as a charity; Charity number 1170731, registered in England and Wales.

FH Europe is registered as a charity; Charity number 1170731, registered in England and Wales.

FH Europe is supported by an educational grant from Amgen Limited, Sanofi, Regeneron, Akcea Therapeutics Inc. and Amryt
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