Children with parental heart disease have Lp(a) 7-10 mg/dL higher, meta-analysis of fifty-one pediatric studies (Postgrad Med 2026)

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

Postgrad Med · 1 March 2026 · 7

Dholariya S, Singh R, Joshi K, Parchwani D, Anandani G, Sonagra A

PRISMA 2020 systematic review and meta-analysis of fifty-one observational studies quantifying Lp(a) in children and adolescents by familial cardiovascular risk, familial hypercholesterolaemia (FH), sex and ethnicity. Among children with FH, those with a parental history of premature cardiovascular disease (pCVD) had higher Lp(a) than FH children without (mean difference 10.24 mg/dL, 95% CI 3.06-17.43, p=0.005); in otherwise healthy children, parental pCVD was similarly linked to higher Lp(a) (MD 11.88 mg/dL, p=0.005), and healthy offspring of parents with any CVD also had higher Lp(a) (MD 7.00 mg/dL, 95% CI 4.45-9.55, p<0.00001). FH itself was associated with a modest but significant Lp(a) elevation versus healthy controls (MD 1.31 mg/dL, 95% CI 0.19-2.44, p=0.02). Girls had slightly higher Lp(a) than boys (MD 1.48 mg/dL, 95% CI 0.43-2.52, p=0.006), with minimal pubertal influence. The authors conclude parental cardiovascular history drives a strong heritable Lp(a) pattern from early life, supporting targeted, ancestry-aware paediatric Lp(a) assessment in high-risk families.

Original abstract

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.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.