Lipoprotein(a) levels in children with genetically confirmed heterozygous familial hypercholesterolaemia

Background Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder characterized by elevated LDL-cholesterol (LDL-C) levels from childhood. Increased lipoprotein(a)[Lp(a)] levels, a genetically determined risk factor for atherosclerotic events, may influence the clinical presentation of FH. However, limited data exist regarding the distribution of Lp(a) levels and their association with other lipid and clinical characteristics in pediatric HeFH populations. Purpose to describe Lp(a) levels and their association with lipid, clinical characteristics and family history of coronary artery disease (CAD) in a cohort of genetically confirmed pediatric HeFH patients. Methods This retrospective cohort study utilized data from a specialized lipid clinic database. Patients under 19 years of age with a genetically confirmed diagnosis of HeFH, at least one clinical consultation and biochemical assessment, including Lp(a) measurement were eligible for inclusion. Participants were stratified based on a clinically relevant Lp(a) threshold (< 50 mg/dL vs. ≥ 50 mg/dL). Additional analyses were performed across five predefined Lp(a) categories:0–29 mg/dL, 30–49 mg/dL, 50–69 mg/dL, 70–89 mg/dL, and ≥ 90 mg/dL. Results Among 188 individuals identified with a pathogenic HeFH-related genetic variant, 106 met the inclusion criteria. Mean age was 7.9 years(±3.7), with 52% being male, and a median follow-up of 83.4 months (Table 1). Most patients had Lp(a) levels < 50 mg/dL(68.9%), but nearly one-third had Lp(a) levels ≥ 50 mg/dL(31.1%), and 9.4% had extremely high Lp(a) concentrations(≥ 90 mg/dL)(Figure 1). Despite significant differences in median Lp(a) levels between the< 50 mg/dL and ≥50 mg/dL categories[15.7(9.0–26.9) vs.74.2(59.2–114), respectively;p< 0.001], baseline LDL-C levels, as well as other lipid, glycemic, and inflammatory parameters, were not significantly different between the group. A family history of CAD, whether premature or not, and in first-degree or overall relatives, was similarly distributed across both Lp(a) groups. Median LDL-C levels at the last visit [150(122–194) mg/dL] exceeded the recommended goal (< 130 mg/dL) in the entire cohort, despite 67% receiving lipid-lowering therapy, with no difference between Lp(a) groups. Conclusions In this study, nearly one in three children had elevated Lp(a) levels (≥ 50 mg/dL), a prevalence higher than in the general population, indicating potentially very high future cardiovascular risk if not managed appropriately. This high prevalence of elevated Lp(a) underscores the importance of measuring Lp(a) in children with FH, as it may identify those at greater cardiovascular risk and guide more tailored management strategies. Although no differences were observed in baseline or final LDL-C levels or family history of CAD across Lp(a) categories, further research is needed to clarify the clinical impact of elevated Lp(a) levels in this population.