How should public health recommendations address Lp(a) measurement, a causative risk factor for cardiovascular disease (CVD)?

Catapano, Alberico L.; Daccord, Magdalena; Damato, Elaine; Humphries, Steve E.; Neely, R. D. G.; Nordestgaard, Børge G.; Pistollato, Michele; Steinhagen‐Thiessen, Elisabeth

doi:10.1016/j.atherosclerosis.2022.02.013

Cited by 17 publications

(20 citation statements)

References 37 publications

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“…Last, despite guidelines advocating the measurement of Lp(a) at least once in an individual’s lifetime, routine measurement of Lp(a) in current clinical practice remains uncommon . For example, in Germany, Lp(a) was measured in fewer than 1% of patients with known ASCVD, and in Israel only 0.1% of individuals within a health maintenance organization had their Lp(a) measured .…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

Concordance of a High Lipoprotein(a) Concentration Among Relatives

Reeskamp,

Tromp,

Patel

et al. 2023

JAMA Cardiol

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“…As lipoprotein(a) is an inherited causal risk factor for the development of cardiovascular disease, 20 elevated lipoprotein(a) levels (>50 mg/dL) will guide us to a more aggressive lipid lowering therapy in confirmed FH cases and to initiate a lipid-lowering therapy in borderline cases. 21 …”

Section: Methods and Analysismentioning

confidence: 99%

Screening for familial hypercholesterolaemia in primary school children: protocol for a cross-sectional, feasibility study in Luxembourg city (EARLIE)

Becker

Adamski

Fandel³

et al. 2022

BMJ Open

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IntroductionFamilial hypercholesterolaemia (FH) is a frequent (1:300) autosomal dominantly inherited condition which causes premature (women <60 years, men <55 years) cardio–cerebrovascular disease (CVD). Early detection and initiation of treatment can prevent the development of CVD and premature death. Our pilot study aims to investigate the prevalence of FH, the feasibility and efficacy of a screening based on a capillary blood test performed during a school medicine visit in primary school children.Methods and analysisIn this cross-sectional study, all children (n=3200) between 7 and 12 years, attending primary school in the city of Luxembourg and invited for their mandatory medical school examinations between 2021 and 2023 are invited to participate. A study nurse performs a capillary blood test to analyse the lipid profile. Families receive the result including an interpretation and invitation to seek medical advice if indicated. If FH is confirmed, a reverse cascade screening in that family will be proposed. The child will receive standard care. Primary outcome is the occurrence of confirmed FH in the study population. Secondary outcomes include the percentage of children screened, percentage of children with abnormal lipid values, percentage of families screened and percentage of families with additionally identified members suffering from hypercholesterolaemia. A health economic analysis will be performed.Ethics and disseminationEthics approval (reference number 202108/01) has been obtained from the National Research Ethics Committee (CNER (Luxembourg)) and was authorised by the ministry of health in Luxembourg. Families receive written information with an informed consent form. Participation requires an informed consent form signed by the parents. The results will be disseminated in peer-reviewed publications, conference presentations and by public media to the general public.Trial registration numberNCT05271305.

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“…Given that the LPA gene is transmitted in an autosomal codominant pattern, and an allele is inherited from each parent, cascade screening can help to identify elevated Lp(a) among close relatives of patients known to have elevated Lp(a) ( Table 3 ) [ 1 ]. One study showed that systematic testing for elevated Lp(a) in relatives of patients with FH identified one new case of elevated Lp(a) for every 2.4 relatives screened [ 41 ].…”

Section: Lp(a) Testing: the Ideal Scenariomentioning

confidence: 99%

“…Despite advances in diagnosing and treating cardiovascular disease (CVD), approximately 30 % of annual deaths worldwide remain attributable to CVD [ 1 ]. In addition to traditional risk factors, elevated lipoprotein(a) (Lp[a]) is a strong independent risk factor for the development of atherosclerotic cardiovascular disease (ASCVD) and affects approximately 1.4 billion people globally [ [2] , [3] , [4] , [5] , [6] ].…”

Section: Introductionmentioning

confidence: 99%

Lipoprotein(a): An important piece of the ASCVD risk factor puzzle across diverse populations

Ciffone,

McNeal,

McGowan

et al. 2024

American Heart Journal Plus: Cardiology Research and Practice

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How should public health recommendations address Lp(a) measurement, a causative risk factor for cardiovascular disease (CVD)?

Cited by 17 publications

References 37 publications

Concordance of a High Lipoprotein(a) Concentration Among Relatives

Concordance of a High Lipoprotein(a) Concentration Among Relatives

Screening for familial hypercholesterolaemia in primary school children: protocol for a cross-sectional, feasibility study in Luxembourg city (EARLIE)

Lipoprotein(a): An important piece of the ASCVD risk factor puzzle across diverse populations

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