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Concordance of a High Lipoprotein(a) Concentration Among Relatives
Laurens F Reeskamp1,2, Tycho R Tromp1, Aniruddh P Patel2,3,4
1Department of Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.
Insights
Cascade screening of first-degree relatives identifies high Lipoprotein(a) (Lp[a]) concentrations in over 40% of cases. This supports recommendations for screening family members to identify individuals at risk for atherosclerotic cardiovascular disease (ASCVD).
Area of Science:
- Cardiology
- Genetics
- Public Health
Background:
- Lipoprotein(a) (Lp[a]) is a heritable risk factor for atherosclerotic cardiovascular disease (ASCVD).
- Current guidelines recommend screening relatives of individuals with high Lp(a), but population-level yield data are limited.
Purpose of the Study:
- To determine the prevalence of elevated Lp(a) concentrations in first- and second-degree relatives of individuals with high Lp(a).
- To compare this prevalence with that of unrelated individuals.
Main Methods:
- Cross-sectional analysis of UK Biobank data, comparing Lp(a) levels in first-degree (n=19,899) and second-degree (n=9,715) relatives with high Lp(a) against unrelated pairs (n=184,764).
- High Lp(a) defined as ≥125 nmol/L.
Main Results:
- Lp(a) levels showed significant correlation between first-degree relatives (Spearman ρ=0.45) and second-degree relatives (Spearman ρ=0.22).
- 47.0% of first-degree and 31.8% of second-degree relatives of index cases had high Lp(a), compared to 16.4% of unrelated individuals.
- First-degree relatives had 7.4 times higher odds, and second-degree relatives 3.0 times higher odds, of having high Lp(a) if their index relative did.
Conclusions:
- Cascade screening of first-degree relatives yields high Lp(a) levels in over 40% of individuals.
- These findings validate current recommendations for familial Lp(a) screening to identify individuals at increased ASCVD risk.
Importance:
Lipoprotein(a) (Lp[a]) concentrations are a highly heritable and potential causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Recent consensus statements by the European Atherosclerosis Society and American Heart Association recommend screening of relatives of individuals with high Lp(a) concentrations, but the expected yield of this approach has not been quantified in large populations.
Objective:
To measure the prevalence of high Lp(a) concentrations among first- and second-degree relatives of individuals with high Lp(a) concentrations compared with unrelated participants.
Design, Setting, And Participants:
In this cross-sectional analysis, pairs of first-degree (n = 19 899) and second-degree (n = 9715) relatives with measured Lp(a) levels from the UK Biobank study and random pairs of unrelated individuals (n = 184 764) were compared. Data for this study were collected from March 2006 to August 2010 and analyzed from December 2021 to August 2023.
Exposure:
Serum Lp(a) levels, with a high Lp(a) level defined as at least 125 nmol/L.
Main Outcome And Measure:
Concordance of clinically relevant high Lp(a) levels in first- and second-degree relatives of index participants with high Lp(a) levels.
Results:
A total of 52 418 participants were included in the analysis (mean [SD] age, 57.3 [8.0] years; 29 825 [56.9%] women). Levels of Lp(a) were correlated among pairs of first-degree (Spearman ρ = 0.45; P < .001) and second-degree (Spearman ρ = 0.22; P < .001) relatives. A total of 1607 of 3420 (47.0% [95% CI, 45.3%-48.7%]) first-degree and 514 of 1614 (31.8% [95% CI, 29.6%-34.2%]) second-degree relatives of index participants with high Lp(a) levels also had elevated concentrations compared with 4974 of 30 258 (16.4% [95% CI, 16.0%-16.9%]) pairs of unrelated individuals. The concordance in high Lp(a) levels was generally consistent among subgroups (eg, those with prior ASCVD, postmenopausal women, and statin users). The odds ratios for relatives to have high Lp(a) levels if their index relative had a high Lp(a) level compared with those whose index relatives did not have high Lp(a) levels were 7.4 (95% CI, 6.8-8.1) for first-degree relatives and 3.0 (95% CI, 2.7-3.4) for second-degree relatives.
Conclusions And Relevance:
The findings of this cross-sectional study suggest that the yield of cascade screening of first-degree relatives of individuals with high Lp(a) levels is over 40%. These findings support recent recommendations to use this approach to identify additional individuals at ASCVD risk based on Lp(a) concentrations.
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