The following are key points to remember from a 2023 update on the European Atherosclerosis Society (EAS) Consensus Statement on homozygous familial hypercholesterolemia (HoFH):

1. Plasma low-density lipoprotein cholesterol (LDL-C) is the critical discriminator for clinical diagnosis of homozygous familial hypercholesterolemia (HoFH). Updated criteria for the diagnosis of HoFH include clinical and genetic criteria.
   
   Clinical Criteria
   • LDL-C criteria: Untreated LDL-C >10 mmol/L (>∼400 mg/dL) is suggestive of HoFH requiring further investigation to confirm the diagnosis.
   • Additional criteria: Cutaneous or tendon xanthomas before age of 10 years and/or untreated elevated LDL-C levels consistent with heterozygous FH (HeFH) in both parents. In digenic form, one parent may have normal LDL-C levels and the other may have LDL-C levels consistent with HoFH.
   Genetic Criteria
   • Genetic confirmation of bi-allelic pathogenic/likely pathogenic variants on different chromosomes at the LDLR, APOB, PCSK9, or LDLRAP1 genes or ≥2 such variants at different loci. ABCG5, ABCG8: Genes encoding ATP-binding cassette subfamily G members 5 and 8.
2. Pediatric guidelines should include newborn lipid screening when both parents are known to have HeFH or simply hypercholesterolemia.
3. Polyvascular subclinical atherosclerosis may be present in coronary, femoral, and carotid vascular territories in HoFH. Where available and easily accessible, imaging is an important tool in HoFH management.
4. Lipid-lowering treatment should start at diagnosis using multiple treatments and/or lipid apheresis to reach LDL-C goal. The treatment pathway for HoFH in childhood includes:
   • Initiate lifestyle changes, statins, and ezetimibe from diagnosis.
   • If LDL-C >8 mmol/L (300 mg/dL), consider lipoprotein apheresis.
   • If LDL-C >3 mmol/L (115 mg/dL), consider novel therapies (PCSK9 [evolocumab or alirocumab at approved doses for HoFH], lomitapide evinacumab) if available and affordable.
   • If lipid apheresis or novel therapies are not available, consider liver transplantation.
5. A fast-track path for approval of novel treatments in children is needed to ensure their use from a young age, decreasing cumulative LDL-C exposure and improving outcomes.
6. Gene therapy and CRISPR-based gene editing are promising approaches, but clinical trials are needed to evaluate efficacy and safety.
7. Multidisciplinary management in specialist centers integrating imaging, treatment, and comprehensive support of these patients is needed.
8. Women with HoFH should receive integrated care from a multidisciplinary team, including cardiovascular assessment before, during, and after pregnancy.
9. To minimize LDL-C exposure, lipid apheresis should be offered during pregnancy, and statin plus other lipid-lowering therapy restarted from the second trimester.
10. There is a need for creation at the local (institutional), regional, and government level of management guidelines that take account of resources, including access to specialist centers and effective lipid-lowering treatments. These should address costs associated with treatment and access to care.

Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins

Keywords: Apolipoproteins B, Atherosclerosis, Cholesterol, LDL, Dyslipidemias, Gene Editing, Genetic Therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hyperlipoproteinemia Type II, Hyperlipoproteinemia Type III, Life Style, Lipids, Lipoproteins, LDL, Liver Transplantation, Patient Care Team, PCSK9 protein, human, Pediatrics, Pregnancy, Primary Prevention, Vascular Diseases, Xanthomatosis

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