TOPLINE:

Children and adolescents with familial hypercholesterolaemia (FH) who started cholesterol-lowering medication (CLM) much earlier than their affected parents achieved low-density lipoprotein cholesterol (LDL-C) levels close to their peers without FH and had more than 15-fold lower rates of cardiovascular events than their affected parents by the age of 39 years.

METHODOLOGY:

• In a prospective observational study conducted across 26 hospitals in Spain, researchers evaluated the long-term effect of contemporary management of FH on LDL-C levels and cardiovascular event rates.
• They compared children and adolescents with genetically confirmed heterozygous FH (n = 348) with their non-affected children and adolescents' relatives (n = 165; mean age, 15 years for both) and parents with heterozygous FH (n = 288; mean age, 45 years). Nearly half of the participants in each group were females.
• Participants were followed up annually from inclusion until the end of 2024, with a median follow-up duration of 12.4 years, during which lipid levels, the use of CLM, and cardiovascular events were assessed.
• Primary outcomes included changes in LDL-C levels, cumulative LDL-C burden over time, and major cardiovascular events.

TAKEAWAY:

• At the end of follow-up, 84.5% of children and adolescents with FH and 95.1% of parents with FH were receiving CLM; 55.4% of children and adolescents with FH on CLM were on regimens expected to lower the LDL-C levels by at least 50%.
• Children and adolescents with FH started CLM much earlier than their parents with FH (median age, 16.5 vs 30.9 years), achieving an absolute median decrease in the LDL-C levels of 2.60 mmol/L at the end of follow-up, which represented a median relative reduction of 47.4% from their untreated baseline levels; the levels increased by a median of 0.10 mmol/L among peers without FH. Among parents with FH on treatment, the LDL-C levels decreased by a median of 4.72 mmol/L, corresponding to a median relative reduction of 67.6% from baseline.
• By ages of 30-40 years, the estimated LDL-C burden over life was 5909.0 mg/dL × years among children and adolescents with FH vs 10,206.8 mg/dL × years among parents with FH (P < .0001).
• At the age of 39 years, cardiovascular event rates were 0.3% in children and adolescents with FH and 5.2% in parents with FH (P < .0001).

IN PRACTICE:

"Our data support incorporating the concept of cumulative LDL-C burden when assessing FH risk and defining treatment goals," the authors of the study wrote.

SOURCE:

The study was led by Antonio J. Vallejo-Vaz, Faculty of Medicine, University of Seville, Seville, Spain. It was published online on June 15, 2026, in European Heart Journal.

LIMITATIONS:

The study was observational in nature. Participants were predominantly from a European White population followed up in specialised lipid clinics, in which management may be more optimal than in other settings. Children and adolescents with FH were still young at the end of follow-up, and at least another decade of follow-up would be needed to confirm the benefits of early LDL-C reduction.

DISCLOSURES:

This study received support through grants from Instituto de Salud Carlos III to Fundación Hipercolesterolemia Familiar and from other organisations. Some of the authors disclosed past or present participation as an investigator in research grants and receiving consultancy fees and honoraria for lectures from various sources. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.