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Published on: September 15, 2018
Cholesterol-lowering therapy from childhood/adolescence and long-term outcomes in familial hypercholesterolaemia: the
Antonio J Vallejo-Vaz1,2,3, Raquel Arroyo-Olivares4, Rodrigo Alonso4,5
1Department of Medicine, Faculty of Medicine, University of Seville, Seville, Spain.
Insights
Early treatment of familial hypercholesterolaemia (FH) in children significantly lowers low-density lipoprotein cholesterol (LDL-C) burden and reduces cardiovascular risk compared to adult-onset treatment. This supports early detection and intervention for FH as a pediatric condition.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Pediatrics
Background:
- Familial hypercholesterolaemia (FH) causes lifelong high LDL-C, increasing premature cardiovascular disease risk.
- Evidence for childhood cholesterol-lowering medication (CLM) initiation in FH is limited.
- This study evaluated the long-term effects of contemporary FH management on LDL-C and cardiovascular events.
Purpose of the Study:
- To assess the long-term impact of childhood initiation of cholesterol-lowering medication (CLM) on cumulative low-density lipoprotein cholesterol (LDL-C) burden in familial hypercholesterolaemia (FH).
- To compare cardiovascular outcomes in FH patients treated from childhood versus those treated from adulthood.
- To support early detection and treatment of FH as a pediatric condition.
Main Methods:
- A prospective observational cohort study (SAFEHEART) included children/adolescents (<18 years) with genetically confirmed heterozygous FH (FH-Ch), their unaffected relatives (non-FH-Ch), and FH parents (FH-P).
- The study assessed the impact of CLM, LDL-C burden, and cardiovascular events over a median follow-up of 12.4 years.
- Participants included 348 FH-Ch, 165 non-FH-Ch, and 288 FH-P.
Main Results:
- At follow-up, 84.5% of FH-Ch and 95.1% of FH-P received CLM, starting at a median age of 14.5 years for FH-Ch versus 36.1 years for FH-P.
- Latest on-treatment LDL-C was 3.00 mmol/L in FH-Ch (a 47.4% reduction) and 2.44 mmol/L in FH-P (a 67.6% reduction).
- By age 30-40, median cumulative LDL-C burden was significantly lower in FH-Ch (5909.0 mg/dL*years) than FH-P (10,206.8 mg/dL*years). Cardiovascular event rates by age 39 were 0.3% for FH-Ch versus 5.2% for FH-P.
Conclusions:
- Treating FH from childhood/adolescence substantially reduces cumulative LDL-C burden compared to adult-onset treatment.
- Early treatment allows FH patients to achieve LDL-C levels closer to non-FH individuals, significantly lowering cardiovascular risk.
- These findings underscore the importance of early detection and pediatric management of FH.
Background And Aims:
Familial hypercholesterolaemia (FH) leads to life-long exposure to high low-density lipoprotein cholesterol (LDL-C) and increased risk of premature atherosclerotic cardiovascular disease. Evidence supporting initiation of cholesterol-lowering medication (CLM) in childhood to lower this cumulative cholesterol burden and cardiovascular sequelae is sparse. This study assessed the long-term impact of contemporary management of FH on LDL-C and cardiovascular events.
Methods:
Observational prospective cohort study (SAFEHEART) including children/adolescents (age <18 years) with genetically confirmed heterozygous FH (FH-Ch), their non-affected children and adolescents' relatives (non-FH-Ch), and FH parents (FH-P). Impact of CLM, LDL-C burden, and cardiovascular events were assessed.
Results:
Overall, 348 FH-Ch, 165 non-FH-Ch and 288 FH-P were included (49.8% female; median untreated LDL-C: 5.46, 2.63, and 7.19 mmol/L, respectively). Median follow-up was 12.4 years (interquartile range 9.6-15.3). At follow-up, 84.5% FH-Ch, 4.2% non-FH-Ch, and 95.1% FH-P were receiving CLM. FH-Ch started therapy at a median age of 14.5, vs. 36.1 years in their FH-P. Latest on-treatment LDL-C was 3.00 mmol/L in FH-Ch (median change: -2.60 mmol/L, -47.4%) and 2.44 mmol/L in FH-P (-4.72 mmol/L, -67.6%); LDL-C among non-FH-Ch (not on CLM) was 2.72 mmol/L. By age 30-40 years, median LDL-C burden over life was 5909.0 and 10 206.8 mg/dL*years among FH-Ch and FH-P, respectively. By age 39 years, rate of cardiovascular events was 0.0%, 0.3% and 5.2% among non-FH-Ch, FH-Ch, and FH-P, respectively.
Conclusions:
Treatment of FH from childhood/adolescence reduces the cumulative LDL-C burden compared with later onset treatment from adulthood in affected parents and permits attainment of LDL-C levels close to non-FH individuals; this finding was associated with the observation of a reduction in the cardiovascular risk of young FH patients. These findings support FH as a paediatric condition requiring early-life detection and treatment.
Study Registration Number:
ClinicalTrials.gov, NCT02693548.
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