Lipoprotein(a) levels in children with hypercholesterolaemia

AIMS: Lipoprotein(a) [Lp(a)] is a significant genetic risk factor for cardiovascular disease (CVD). Extremely high Lp(a) levels (153mg/dL), affecting about 1 in 100 individuals, can elevate low-density lipoprotein cholesterol (LDL-C) due to structural similarities between Lp(a) and LDL-C particles. This study assessed the role and impact of Lp(a) on LDL-C in children with hypercholesterolemia, a relationship that remains poorly understood. METHODS: The study included 1,418 children (median age: 6.34 years) with hypercholesterolemia, identified by universal or cascade familial hypercholesterolemia (FH) screening in Slovenia. Participants were categorized as: 363 (25.6%) with definite FH (pathogenic variants in LDLR/APOB/PCSK9), 1,014 (71.5%) with possible FH (no FH pathogenic variant), and 41 (2.9%) definite non-FH (siblings of definite FH cases without FH pathogenic variant). RESULTS: Elevated Lp(a) levels (>30 mg/dL) were found in 25.1% of definite FH and 34.9% of possible FH cases (p=0.003). In definite FH, 32.7% of Lp(a) levels contributed to LDL-C levels, and 18.6% of Lp(a) levels contributed to Apolipoprotein B. The Lp(a) component of LDL-C varied widely (0-49.6%) and accounted for 10.3% of LDL-C variability. After adjusting for Lp(a), elevated LDL-C (>3.5 mmol/L) still persisted in 88.4% of definite FH and 30.4% of possible FH children. CONCLUSIONS: One in four children with FH and one in three children with polygenic hypercholesterolemia have elevated Lp(a) levels, contributing notably to LDL-C levels and ApoB. Modifiable CVD risk factors (elevated LDL-C and obesity) are already present in those children, highlighting the need for early, targeted evaluation and management.