Cascade testing for elevated lipoprotein(a) in relatives of probands with high lipoprotein(a)

Chakraborty, Anindita; Chan, Dick C.; Ellis, Katrina L.; Pang, Jing; Barnett, Wendy; Woodward, Alan; Vorster, Mary; Norman, Richard; Moses, Eric K.; Watts, Gerald F.

doi:10.1016/j.ajpc.2022.100343

Cited by 9 publications

(9 citation statements)

References 32 publications

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“…CAC scoring can be considered to further risk stratify [ 20 , 22 ]. Cascade Lp(a) testing may be recommended for family members [ 104 , 105 ]. With regards to therapy, a healthy lifestyle should be recommended to all patients [ 19 , 106 ].…”

Section: Figurementioning

confidence: 99%

Lipoprotein(a): Evidence for Role as a Causal Risk Factor in Cardiovascular Disease and Emerging Therapies

Bhatia

2022

JCM

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Lipoprotein(a) (Lp(a)) is an established risk factor for multiple cardiovascular diseases. Several lines of evidence including mechanistic, epidemiologic, and genetic studies support the role of Lp(a) as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis/calcific aortic valve disease (AS/CAVD). Limited therapies currently exist for the management of risk associated with elevated Lp(a), but several targeted therapies are currently in various stages of clinical development. In this review, we detail evidence supporting Lp(a) as a causal risk factor for ASCVD and AS/CAVD, and discuss approaches to managing Lp(a)-associated risk.

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Section: Figurementioning

confidence: 99%

Lipoprotein(a): Evidence for Role as a Causal Risk Factor in Cardiovascular Disease and Emerging Therapies

Bhatia

2022

JCM

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“…In a recent study of 83 probands with severe hyper-Lp(a) [Lp(a) 100 mg/dl] and common hyperlipidaemia (without FH), the yield of detection for hyper-Lp(a) [Lp(a) 50 mg/dl] was 1 in 1.5 relatives tested, while for severe hyper-Lp(a) [Lp(a) 100 mg/dl], the yield of detection was 1 in 2.8 relatives tested [44]. These studies illustrate that the yield of detection is higher when cascade testing is carried out from probands or index cases with very elevated Lp(a) levels [42][43][44]. Cascade testing for Lp(a) from probands with particularly high Lp(a) levels (>100 mg/dl) is encouraged, but there are practical issues to consider, such as whether this should be centrally coordinated, as has been recommended for FH.…”

Section: Key Pointsmentioning

confidence: 99%

“…heritability [42,43]. In a recent study of 83 probands with severe hyper-Lp(a) [Lp(a) 100 mg/dl] and common hyperlipidaemia (without FH), the yield of detection for hyper-Lp(a) [Lp(a) 50 mg/dl] was 1 in 1.5 relatives tested, while for severe hyper-Lp(a) [Lp(a) 100 mg/dl], the yield of detection was 1 in 2.8 relatives tested [44]. These studies illustrate that the yield of detection is higher when cascade testing is carried out from probands or index cases with very elevated Lp(a) levels [42][43][44].…”

Section: Key Pointsmentioning

confidence: 99%

“…Studies in patients with FH showed that integrating Lp(a) measurement during cascade testing for FH is valuable, with a yield of detection of hyper-Lp(a) in every one in two relatives tested when the proband has hyper-Lp(a), consistent with co-dominance heritability [42,43]. In a recent study of 83 probands with severe hyper-Lp(a) [Lp(a) ≥100 mg/dl] and common hyperlipidaemia (without FH), the yield of detection for hyper-Lp(a) [Lp(a) ≥50 mg/dl] was 1 in 1.5 relatives tested, while for severe hyper-Lp(a) [Lp(a) ≥100 mg/dl], the yield of detection was 1 in 2.8 relatives tested [44]. These studies illustrate that the yield of detection is higher when cascade testing is carried out from probands or index cases with very elevated Lp(a) levels [42–44].…”

Section: Cascade Testingmentioning

confidence: 99%

“…A recent Danish study showed that neonatal or cord blood levels of Lp(a) at least 90th percentile was associated with elevated Lp(a) levels at 15 months and parental level of Lp(a) [48]. Preliminary estimations suggest that cascade testing of severe hyper-Lp(a) in patients with common dyslipidaemia may be cost-effective [44]. However, the benefit of forward and reverse cascade testing of hyper-Lp(a) involving children requires further investigation.…”

Section: Cascade Testingmentioning

confidence: 99%

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Detection strategies for elevated lipoprotein(a): will implementation let the genie out of the bottle?

Loh

Watts

2022

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of reviewElevated Lp(a) level is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD), principally coronary artery disease. Selective testing for Lp(a) is highly recommended in patients at intermediate and high risk for ASCVD. Lp(a) levels are predominantly genetically determined, and this has implications for cascade testing.Recent findingsRecent studies show that cascade testing is effective in identifying elevated Lp(a) in close relatives of probands with high Lp(a). Apart from selective testing and cascade testing as detection strategies, some recent guidelines recommend testing of Lp(a) in all adults at least once in their lifetime and various implementation strategies have been suggested.SummaryHyper-Lp(a) is an important global health problem that can be easily detected. Hyper-Lp(a) meets all the criteria for universal screening except that there is not yet supportive evidence from clinical interventional trials showing a reduction of ASCVD events. The cost-effectiveness of the various detection and implementation strategies need to be further evaluated.

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Concordance of a High Lipoprotein(a) Concentration Among Relatives

Reeskamp,

Tromp,

Patel

et al. 2023

JAMA Cardiol

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ImportanceLipoprotein(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.ObjectiveTo 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 ParticipantsIn 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.ExposureSerum Lp(a) levels, with a high Lp(a) level defined as at least 125 nmol/L.Main Outcome and MeasureConcordance of clinically relevant high Lp(a) levels in first- and second-degree relatives of index participants with high Lp(a) levels.ResultsA 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 &lt; .001) and second-degree (Spearman ρ = 0.22; P &lt; .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 RelevanceThe 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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Cascade testing for elevated lipoprotein(a) in relatives of probands with high lipoprotein(a)

Cited by 9 publications

References 32 publications

Lipoprotein(a): Evidence for Role as a Causal Risk Factor in Cardiovascular Disease and Emerging Therapies

Lipoprotein(a): Evidence for Role as a Causal Risk Factor in Cardiovascular Disease and Emerging Therapies

Detection strategies for elevated lipoprotein(a): will implementation let the genie out of the bottle?

Concordance of a High Lipoprotein(a) Concentration Among Relatives

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