Real-world prediagnosis lipid management in parents identified through child-initiated reverse cascade screening for familial hypercholesterolaemia
R Tani, K Matsunaga, T Inoue, K Tanimoto, K Nishioka, M Tani, S Kondo, K Koyano, T Iwase, T Kusaka, T MinaminoAbstract
Background
Paediatric universal lipid screening can enable early identification of familial hypercholesterolaemia (FH) and facilitate prevention of atherosclerotic cardiovascular disease. Reverse cascade screening initiated by a child with FH can identify high-risk parents who are often undiagnosed and undertreated. In a school-based paediatric universal lipid screening programme, approximately 8,000 children aged 9–10 years are screened annually to identify elevated low-density lipoprotein cholesterol (LDL-C). Integrating reverse cascade screening with universal screening can enhance early detection of FH—enabling earlier treatment of affected children before atherosclerosis begins and timely intervention in parents before atherosclerotic cardiovascular disease events occur. However, real-world prediagnosis lipid management in parents identified through child-initiated reverse cascade screening for FH remains unclear.
Purpose
To clarify prediagnosis lipid-lowering therapy use and LDL-C target attainment among parents identified through child-initiated reverse cascade screening for FH.
Methods
This single-centre retrospective observational study included children aged <15 years with LDL-C ≥140 mg/dL who underwent genetic testing between January 2018 and February 2026. Child-initiated reverse cascade screening was performed for children diagnosed with FH to evaluate eligible parents. For cascade analyses, children with missing family history data and parents with a known FH diagnosis before study initiation were excluded. Clinical FH diagnosis in children and parents followed established national criteria. Prediagnosis lipid-lowering therapy use and LDL-C target attainment were assessed; LDL-C target attainment was defined using a European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guideline-based threshold of LDL-C <70 mg/dL.
Results
Among 152 children who underwent genetic testing, 80 were diagnosed with FH, and 72 did not meet FH diagnostic criteria. Of the 80 children with FH, 23 were excluded due to missing family history data or pre-existing parental FH diagnosis. The final parent cohort comprised 52 individuals; the paediatric FH cohort included 5 siblings. Before FH diagnosis, 57.7% (30/52) were receiving lipid-lowering therapy; among treated parents, 3.3% (1/30) achieved the LDL-C target. There were no significant differences in lipid-lowering therapy use by sex, age, or body mass index.
Conclusion
In parents identified through child-initiated reverse cascade screening, a substantial proportion received lipid-lowering therapy before FH diagnosis, but LDL-C target attainment was rare. These findings highlight a major unmet need for more effective lipid management in this high-risk group.Abstract Picture