Lipoprotein(a) levels in children with hypercholesterolemia

Matej Mlinaric; Barbara Cugalj Kern; Ana Drole Torkar; Jaka Sikonja; Jan Kafol; Robert Sket; Tine Tesovnik; Jernej Kovac; Tadej Battelino; Urh Groselj

doi:10.1093/eurjpc/zwag126

Lipoprotein(a) levels in children with hypercholesterolemia

Eur J Prev Cardiol. 2026 Feb 24:zwag126. doi: 10.1093/eurjpc/zwag126. Online ahead of print.

Authors

Matej Mlinaric^{1

2}, Barbara Cugalj Kern³, Ana Drole Torkar¹, Jaka Sikonja^{2

4}, Jan Kafol^{2

5}, Robert Sket^{2

3}, Tine Tesovnik^{2

3}, Jernej Kovac^{2

3}, Tadej Battelino^{1

2}, Urh Groselj^{1

2}

Affiliations

¹ Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
² Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
³ Clinical Institute of Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
⁴ Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Division of Internal Medicine, 1000 Ljubljana, Slovenia.
⁵ Department of Vascular Diseases, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia.

PMID: 41734088
DOI: 10.1093/eurjpc/zwag126

Abstract

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.

Keywords: Cardiovascular disease; Children; Familial Hypercholesterolemia; LDL-cholesterol; Lipoprotein(a); Universal screening.

Plain language summary

Lipoprotein(a) is a cholesterol-carrying particle in the blood, similar to LDL cholesterol, that accumulates in vessel walls and contributes to atherosclerosis and cardiovascular disease. Data on Lipoprotein(a) in children is limited. Our study shows that Lipoprotein(a) is a significant cause of elevated LDL cholesterol in children: 34.9% of those suspected of Familial Hypercholesterolemia have high Lp(a), and the Lp(a) mass can account for up to 46.7% of the LDL-C mass. However screening only children with hypercholesterolemia for high Lp(a) is insufficient; universal Lp(a) measurement is essential. Additionally, modifiable risk factors like obesity are already present in children with high Lp(a), emphasizing the need for early, targeted evaluation and management.