Distribution of Lipoprotein(a) concentrations in children and young people with Familial Hypercholesterolemia (FH) compared to those without FH: A systematic review and narrative synthesis

BACKGROUND: Elevated Lipoprotein(a) [Lp(a)] is an established independent risk factor for Atherosclerotic Cardiovascular Disease (ASCVD) in adults, largely determined by genetic variation and present from birth. Despite increasing recognition of its contribution to cardiovascular risk, the clinical significance of elevated Lp(a) in children with familial Hypercholesterolaemia (FH) remains incompletely understood. The coexistence of elevated LDL cholesterol and elevated Lp(a) may compound lifetime atherosclerotic burden from an early age. Clarifying the distribution of Lp(a) in paediatric FH compared with non-FH populations is therefore important to inform screening strategies and improve early cardiovascular risk stratification. AIM: To systematically review and synthesise evidence comparing Lp(a) concentrations in FH versus non-FH paediatric cohorts and identify implications for clinical practice. METHODS: This review followed PRISMA guidelines and was prospectively registered on PROSPERO. Multiple electronic databases were searched for studies reporting Lp(a) concentrations in children with FH and their non-FH comparators. Data extraction was conducted using Covidence. Heterogeneity in assay methods, units of measurement, and reporting formats precluded quantitative meta-analysis; therefore, a structured narrative synthesis was performed. RESULTS: Across non-FH cohorts, most children had Lp(a) concentrations below adult risk thresholds. In contrast, paediatric FH cohorts consistently demonstrated higher Lp(a) distributions, with approximately 20-40% exceeding adult high-risk thresholds, indicating a notable difference in cardiovascular risk burden from early life. CONCLUSION: Elevated Lp(a) is substantially more prevalent in paediatric FH cohorts than in non-FH populations, highlighting the potential value of targeted Lp(a) screening to improve early cardiovascular risk assessment and inform preventive strategies. Further research is needed to define paediatric risk thresholds for raised Lp(a) and with the advent of emerging novel Lp(a) lowering therapy, prospective randomised trials will establish the prognostic role of lowering Lp(a) in children.