Lipoprotein(a) levels in children and adolescents: a systematic review and meta-analysis of associations with parental cardiovascular disease, familial hypercholesterolemia, and gender differences

Background Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein linked to atherosclerotic cardiovascular disease (CVD). Although well studied in adults, its familial determinants in children remain unclear. This systematic review and meta-analysis quantified Lp(a) across pediatric subgroups defined by familial cardiovascular risk, familial hypercholesterolemia (FH), sex, and ethnicity.Methods Following PRISMA 2020 guidelines, fifty-one observational studies were analyzed using random-effects models (Review Manager 5.4.1). Mean differences (MD) with 95% confidence intervals (CI) were calculated. Subgroup, sensitivity, and meta-regression analyses explored heterogeneity.Results Among children and adolescents with FH, those with a parental history of premature cardiovascular disease (pCVD) had significantly higher Lp(a) concentrations than FH children without parental pCVD (MD = 10.24 mg/dL; 95% CI 3.06–17.43; p = 0.005; I2 = 79%). In otherwise healthy children, parental pCVD was similarly associated with elevated Lp(a) levels (MD = 11.88 mg/dL; p = 0.005). When parental CVD was considered, healthy offspring of affected parents also showed significantly higher Lp(a) concentrations (MD = 7.00 mg/dL; 95% CI 4.45–9.55; p < 0.00001; I2 = 93%). Direct comparison between FH children and healthy controls demonstrated a modest but significant elevation in FH (MD = 1.31 mg/dL; 95% CI 0.19–2.44; p = 0.02; I2 = 74%). Girls exhibited slightly higher Lp(a) levels than boys (MD = −1.48 mg/dL; 95% CI − 2.52 to −0.43; p = 0.006), with minimal pubertal influence.Conclusion Elevated Lp(a) in children with parental CVD or pCVD reflects a strong heritable pattern from early life. FH was associated with modest but consistent Lp(a) elevation, indicating an independent risk-modifying role rather than a defining feature. Sex-related differences were minimal, whereas ethnic variation was prominent. These findings support targeted Lp(a) assessment in children with familial cardiovascular risk using ancestry-aware reference standards, with consideration of repeat evaluation in early adulthood in higher-risk individuals.