Lipoprotein(a) levels in children with suspected familial hypercholesterolaemia identified through universal lipid screening: association with pathogenic variants

Abstract Background Elevated lipoprotein(a) Lp(a) levels are an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), and especially in patients with familial hypercholesterolaemia (FH), high Lp(a) levels have been reported to further increase the cardiovascular disease risk associated with FH. In our region, paediatric universal lipid screening for FH has been conducted each year in primary schools for children aged 9 or 10 years since 2018. This programme screens approximately 8,000 children annually, identifying those with high low-density lipoprotein (LDL) cholesterol who are referred through a three-step process to four major healthcare facilities within the county for further evaluation. Purpose To assess the distribution of Lp(a) levels and their association with pathogenic variants of FH (PVs of FH) in children with high LDL cholesterol identified through paediatric universal lipid screening. Methods This retrospective, single-centre observational study included 86 consecutive children under 15 years of age suspected of having FH who were referred from local medical facilities to a university hospital between January 2018 and December 2024. All children had an LDL cholesterol level ≥ 140 mg/dL and underwent both Lp(a) measurement and genetic testing. Lp(a) levels were measured using the latex agglutination-turbidimetric immunoassay method. The distribution of Lp(a) levels and their association with PVs of FH were analysed. Results The distribution of Lp(a) levels was right-skewed, with median levels of 15.2 6.9-23.4 mg/dL. The proportions of children with Lp(a) levels ≥ 30 mg/dL and ≥ 50 mg/dL were 18.6% and 12.8%, respectively. Genetic testing identified PVs of FH in 39 out of 86 children, with a median Lp(a) level of 18.0 7.0–23.4 mg/dL; among them, 17.9% had Lp(a) ≥ 30 mg/dL, and 12.8% had Lp(a) ≥ 50 mg/dL. Conversely, among the 47 children without PVs of FH, the median Lp(a) level was 12.5 5.9–23.5 mg/dL; 19.1% had Lp(a) ≥ 30 mg/dL, and 12.8% had Lp(a) ≥ 50 mg/dL. There were no significant differences in Lp(a) levels between children with and without PVs of FH (P = 0.376). Conclusion Our findings revealed that regardless of the presence of PVs of FH, approximately one in five children had Lp(a) levels ≥ 30 mg/dL, and one in eight had levels ≥ 50 mg/dL. Lp(a) measurement in these children may facilitate the early identification of those at an elevated risk of developing ASCVD in the future and is essential for risk stratification.