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Cascade testing for elevated lipoprotein(a) in relatives of probands with familial hypercholesterolaemia and elevated
Anindita Chakraborty1, Jing Pang1, Dick C Chan1
1Medical School, University of Western Australia, Perth, Western Australia, Australia.
Insights
Cascade testing for familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] in relatives effectively identifies new cases of both inherited conditions. This dual approach is crucial for cardiovascular disease prevention.
Area of Science:
- Genetics and Cardiovascular Medicine
- Inherited Lipid Disorders
- Preventive Cardiology
Background:
- Familial hypercholesterolemia (FH) and elevated plasma lipoprotein(a) [Lp(a)] are independent inherited risk factors for atherosclerotic cardiovascular disease.
- Early identification and management of these conditions are critical for reducing cardiovascular events.
Purpose of the Study:
- To investigate the effectiveness of cascade testing for detecting new cases of elevated Lp(a) in relatives of FH probands.
- To assess the prevalence of FH and elevated Lp(a) in a family-based cohort.
Main Methods:
- Genetic testing for FH and immunoassay for Lp(a) were performed on 162 relatives from 62 FH probands.
- Prevalence, yield of new cases, and association between proband Lp(a) levels and relative detection rates were analyzed.
Main Results:
- Among relatives, FH prevalence was 60.5% and elevated Lp(a) was 41.4%.
- Cascade testing identified new cases of FH, elevated Lp(a), and both conditions.
- Detection of elevated Lp(a) was higher in relatives of probands with Lp(a) ≥100 mg/dL (53%) compared to 50-99 mg/dL (34%).
Conclusions:
- Dual cascade testing for FH and elevated Lp(a) is effective in identifying affected individuals.
- The findings support the independent and co-dominant inheritance of FH and Lp(a).
- This strategy enhances the detection of individuals at high risk for cardiovascular disease.
Background And Aims:
Familial hypercholesterolaemia (FH) and elevated plasma lipoprotein(a) [Lp(a)] are inherited conditions independently associated with atherosclerotic cardiovascular disease. This study investigated the detection of new cases of elevated Lp(a) during cascade testing of relatives of probands with a definite diagnosis of FH and elevated Lp(a) (≥50 mg/dL).
Methods:
Relatives from 62 adult probands were tested for FH genetically and for elevated Lp(a) using an immunoassay. The prevalence and yield of new cases of FH with or without elevated Lp(a) among relatives and the association between the detection of elevated Lp(a) and the Lp(a) concentration of the probands were assessed.
Results:
Among 162 relatives tested (136 adults and 26 children), the prevalence of FH and elevated Lp(a) was 60.5% and 41.4%, respectively: FH alone was detected in 31.5%, elevated Lp(a) alone in 12.3%, FH with elevated Lp(a) in 29.0%, and neither disorder in 27.2% of the relatives. Cascade testing detected a new case of FH, elevated Lp(a) and FH with elevated Lp(a) for every 1.5, 2.1 and 3.0 relatives tested, respectively. The proportion of relatives detected with elevated Lp(a) was significantly higher when tested from probands with Lp(a) ≥100 mg/dL compared with those from probands with Lp(a) between 50 and 99 mg/dL (53% vs 34%, p = 0.018). The concordance between the detection of FH and elevated Lp(a) was 56.2% (kappa statistic 0.154), indicating a poor agreement.
Conclusions:
A dual approach to cascade testing families for FH and high Lp(a) from appropriate probands can effectively identify not only new cases of FH, but also new cases of elevated Lp(a) with or without FH. The findings accord with the co-dominant and independent heritability of FH and Lp(a).
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