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Cascade testing of children and adolescents for elevated Lp(a) in pedigrees with familial hypercholesterolaemia
Wann Jia Loh1, Jing Pang2, Anindita Chakraborty2
1School of Medicine, University of Western Australia, Perth, Australia (Drs Loh, Pang, Chakraborty, Chan, Hooper, Bell, Burnett, Watts); Department of Endocrinology, Changi General Hospital, Singapore (Dr Loh); Duke-NUS Medical School, Singapore (Dr Loh).
Insights
Elevated lipoprotein(a) [Lp(a)] screening is effective in children when done through families with high Lp(a) and familial hypercholesterolaemia (FH). This targeted approach identifies more elevated Lp(a) cases than general FH screening.
Area of Science:
- Cardiovascular Genetics
- Lipidology
- Preventive Cardiology
Background:
- Elevated plasma lipoprotein(a) [Lp(a)] is a prevalent, inherited risk factor for cardiovascular disease.
- Expert guidelines recommend opportunistic Lp(a) testing during familial hypercholesterolaemia (FH) cascade screening.
- The efficacy of this opportunistic screening in pediatric populations requires further investigation.
Purpose of the Study:
- To evaluate the effectiveness of detecting elevated Lp(a) in children and adolescents within an established FH cascade screening program.
- To compare the yield of elevated Lp(a) detection when screening is initiated from FH index cases with and without elevated Lp(a).
Main Methods:
- Assessed Lp(a) levels (≥30 mg/dL threshold) in 103 children/adolescents, first-degree relatives of 66 adult FH index cases.
- Compared detection rates of elevated Lp(a) in offspring based on parental Lp(a) status (≥50 mg/dL vs. normal).
Main Results:
- Cascade testing from FH index cases with elevated Lp(a) identified 1 new elevated Lp(a) case per 2 children screened.
- Opportunistic screening from FH index cases with normal Lp(a) identified 1 new elevated Lp(a) case per 7.5 children screened (p < 0.001).
Conclusions:
- Cascade testing for elevated Lp(a) is most effective when originating from FH index cases who also have elevated Lp(a).
- This targeted strategy significantly enhances the identification of elevated Lp(a) in pediatric relatives compared to broader screening.
Abstract:
Elevated plasma lipoprotein(a) [Lp(a)] is a common, inherited condition independently causing cardiovascular disease. Recent expert recommendations suggest opportunistically testing for elevated Lp(a) during cascade testing for familial hypercholesterolaemia (FH). We investigated the effectiveness of detecting elevated Lp(a) in 103 children and adolescents who were first-degree relatives of 66 adult index FH cases as part of an established FH cascade screening program. The yield of detection of elevated Lp(a) using a threshold of ≥30 mg/dL in children and adolescents was assessed. Cascade testing from FH index cases with elevated Lp(a) ≥50 mg/dL identified 1 case of Lp(a) ≥30 mg/dL for every 2 children or adolescents tested. In contrast, opportunistic screening from index cases with FH but normal Lp(a) levels demonstrated 1 case of Lp(a) ≥30 mg/dL for every 7.5 children or adolescents tested (p < 0.001). In conclusion, cascade testing for elevated Lp(a) from index cases with FH and elevated Lp(a) is effective in identifying new cases of elevated Lp(a).
