Evidence map›Paper›PMID 20032323›Full record

ArticleThe New England journal of medicine2009

Genetic variants associated with Lp(a) lipoprotein level and coronary disease.

Robert Clarke, John F Peden, Jemma C Hopewell, Theodosios Kyriakou, Anuj Goel, Simon C Heath, Sarah Parish, Simona Barlera, Maria Grazia Franzosi, Stephan Rust and 14 more

4 registry-linked trialsOpen access · bronzeAbstract readMulticenter Study
PubMed Publisher
In one paragraph

Article in The New England journal of medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 713 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
713citing papers in PubMed, 3 pooled it
63.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04613167 naunknown statusstarted 2020, after this paper: background citation

Genetic, Biochemical and Functional Markers of Cardiovascular Risk in Patients With Premature Coronary Artery Disease and Treatment Options

Ran2020Enrolled70Registered outcomes3Posted comparisons0ConditionsAcute Coronary Syndrome, Genetic Polymorphisms, Inflammation, LipoproteinemiaArmsAlirocumab, Control group, Evolocumab
Open the trial in the graph
NCT02976818 completednot on this mapstarted 2017, after this paper: background citation

Relationships Between Lipoprotein(a) Levels and Aortic Valve Calcification in Patients With Heterozygous Familial Hypercholesterolemia

TypeobservationalSponsorLaval UniversityRan2017 to 2020Enrolled173ConditionsHeterozygous Familial Hypercholesterolemia
NCT04993664 nawithdrawnnot on this mapstarted 2021, after this paper: background citation

Influence of Pelacarsen on Arterial Wall Properties and Risk Factors in Patients After Myocardial Infarction With High Lp(a) Values

TypeinterventionalSponsorUniversity Medical Centre LjubljanaRan2021 to 2022Enrolled0ConditionsAcute Coronary Syndrome, Lipoproteinemia, Inflammation, Genetic PolymorphismsArmsPelacarsen (TQJ230), Placebo
NCT06698341 recruitingnot on this mapstarted 2024, after this paper: background citation

UNdeRstAnding Novel Variants in AcutE MyocardiaL Infarction in Young Adults

TypeobservationalSponsorNational Heart Centre SingaporeRan2024 to 2028Enrolled1,200ConditionsMyocardial Infarction, AcuteArmsBlood Draw
3 · Its place in the literature

Who cites it

713 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,605 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Lipoprotein(a), remote ischemic conditioning, and stroke recurrence in patients with symptomatic intracranial atherosclerotic stenosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Trial
  6. Trial
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  8. Article
  9. Lipoprotein(a) and premature myocardial infarction: Mechanistic insights and implications for PCI-era residual risk.International journal of cardiology. Cardiovascular risk and prevention · 2026
    Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
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  17. Journal of the American Heart Association · 2026
    Article
  18. Review
  19. An integrated cardiometabolic genetic testing program in a predominantly Hispanic population within a community setting.Genetics in medicine : official journal of the American College of Medical Genetics · 2026
    Article
  20. Clinical utility of polygenic risk scores in cardiovascular disorders.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article

653 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 6 institutions in 4 countries.

Robert ClarkeClinical Trial Service Unit, University of Oxford, Oxford, United Kingdom
John F Peden
Jemma C Hopewell
Theodosios Kyriakou
Anuj Goel
Simon C Heath
Sarah Parish
Simona Barlera
Maria Grazia Franzosi
Stephan Rust
Derrick Bennett
Angela Silveira
Anders Malarstig
Fiona R Green
Mark Lathrop
Bruna Gigante
Karin Leander
Ulf de Faire
Udo Seedorf
Anders Hamsten
Rory Collins
Hugh Watkins
Martin Farrall
PROCARDIS Consortium
University of Oxford · GBThrombosis and Atherosclerosis Research Institute · CACentre for Human Genetics · GBMario Negri Institute for Pharmacological Research · ITUniversity of Münster · DEUniversity of Surrey · GB

Funding

British Heart FoundationMedical Research Council MC_U137686857Wellcome Trust
6 · The paper itself

Abstract

backgroundAn increased level of Lp(a) lipoprotein has been identified as a risk factor for coronary artery disease that is highly heritable. The genetic determinants of the Lp(a) lipoprotein level and their relevance for the risk of coronary disease are incompletely understood.

methodsWe used a novel gene chip containing 48,742 single-nucleotide polymorphisms (SNPs) in 2100 candidate genes to test for associations in 3145 case subjects with coronary disease and 3352 control subjects. Replication was tested in three independent populations involving 4846 additional case subjects with coronary disease and 4594 control subjects.

resultsThree chromosomal regions (6q26-27, 9p21, and 1p13) were strongly associated with the risk of coronary disease. The LPA locus on 6q26-27 encoding Lp(a) lipoprotein had the strongest association. We identified a common variant (rs10455872) at the LPA locus with an odds ratio for coronary disease of 1.70 (95% confidence interval [CI], 1.49 to 1.95) and another independent variant (rs3798220) with an odds ratio of 1.92 (95% CI, 1.48 to 2.49). Both variants were strongly associated with an increased level of Lp(a) lipoprotein, a reduced copy number in LPA (which determines the number of kringle IV-type 2 repeats), and a small Lp(a) lipoprotein size. Replication studies confirmed the effects of both variants on the Lp(a) lipoprotein level and the risk of coronary disease. A meta-analysis showed that with a genotype score involving both LPA SNPs, the odds ratios for coronary disease were 1.51 (95% CI, 1.38 to 1.66) for one variant and 2.57 (95% CI, 1.80 to 3.67) for two or more variants. After adjustment for the Lp(a) lipoprotein level, the association between the LPA genotype score and the risk of coronary disease was abolished.

conclusionsWe identified two LPA variants that were strongly associated with both an increased level of Lp(a) lipoprotein and an increased risk of coronary disease. Our findings provide support for a causal role of Lp(a) lipoprotein in coronary disease.

Indexed as

Genetic Predisposition to DiseasePolymorphism, Single NucleotideCase-Control StudiesCoronary DiseaseGenetic MarkersGenome-Wide Association StudyGenotypeHumansKringlesLikelihood FunctionsLipoprotein(a)Myocardial InfarctionOligonucleotide Array Sequence AnalysisRegression AnalysisRisk FactorsGenetic MarkersLipoprotein(a)

Identifiers

PMID20032323
OpenAlexW2098230963

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.