European Primary Care Cardiovascular Society

Diagnosis and management of children and adolescents with familial hypercholesterolemia

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Literature - European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration - Lancet. 2023 Dec 12:S0140-6736(23)01842-1 [Online ahead of print]. doi: 10.1016/S0140-6736(23)01842-1

Introduction and methods

Background

For patients with familial hypercholesterolemia (FH), identification in childhood and early treatment can mitigate the risk of premature ASCVD [1-6]. However, only 2.1% of adults with FH were diagnosed in their childhood or adolescence [1].

Aim of the study

The study aim was to characterize children and adolescents with heterozygous FH (HeFH) and provide evidence-based insights that may guide future public health approaches for the detection and management of FH early in life.

Methods

For this cross-sectional study, the authors collected individual-level data of children and adolescents aged<18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between October 1, 2015, and January 31, 2021. Data in this registry were collected from 55 regional or national registries in 48 countries. Exclusion criteria were diagnoses relying on a self-reported history of FH or suspected secondary hypercholesterolemia, as well as untreated LDL-c levels ≥13.0 mmol/L. Of the 63,093 individuals in the FHSC registry, 11,848 (18.8%) were <18 years old who also had HeFH.

Outcome

The main outcome was to assess current identification and management methods for children and adolescents with FH.

Main results

Diagnosis

Clinical characteristics

Management

Conclusion

This international cross-sectional registry study covering 48 countries showed that most children and adolescents with HeFH were not index cases, which probably reflected the use of family cascade screening of affected adult relatives. As classic diagnostic features of FH (e.g., physical signs and premature CVD) were uncommon in children and adolescents, diagnosis relied on either LDL-c measurements or genetic confirmation. At registry entry, ~70% of the participants were not on lipid-lowering therapy.

Distribution of LDL-c levels by age suggested that the LDL-c concentration can be used to identify individuals with FH as early as the first year of life. However, the authors believe the LDL-c cutoffs currently used in different clinical criteria need to be adapted to avoid missing potential diagnoses in individuals ages <18 years. Their “study suggests that initial screening of LDL-c should be followed by genetic testing (where available and accessible) to support diagnosis of children and adolescents with mild phenotypes.” Furthermore, once identified, children and adolescents with FH will require “increased use of and improved lifelong adherence to high-intensity statins or combination therapies” to reach the recommended LDL-c targets, similar to adults.

References

Show references

Find this article online at Lancet.

Share this page with your colleagues and friends: