Evidence map›Paper›PMID 38938725›Full record

ArticleJACC. Advances2023

Polygenic Background Modifies Risk of Coronary Artery Disease Among Individuals With Heterozygous Familial Hypercholesterolemia.

Laurens F Reeskamp, Injeong Shim, Jacqueline S Dron, Shirin Ibrahim, Tycho R Tromp, Akl C Fahed, Aniruddh P Patel, Barbara A Hutten, Erik S G Stroes, G Kees Hovingh and 1 more

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Article in JACC. Advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Laurens F ReeskampDepartment of Vascular Medicine, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
Injeong ShimCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Jacqueline S DronCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Shirin IbrahimDepartment of Vascular Medicine, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
Tycho R TrompDepartment of Vascular Medicine, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
Akl C FahedCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Aniruddh P PatelCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Barbara A HuttenDepartment of Clinical Epidemiology and Data Science, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
Erik S G StroesDepartment of Vascular Medicine, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
G Kees HovinghDepartment of Vascular Medicine, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, the Netherlands.
Amit V KheraCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Heterozygous familial hypercholesterolemia (HeFH) is a monogenic disorder characterized by increased circulating low-density lipoprotein cholesterol and accelerated atherosclerosis. Even among this high-risk group, prior studies note considerable variability in risk of coronary artery disease (CAD). Objectives: The purpose of this study was to evaluate the cumulative impact of many common DNA variants-as quantified by a polygenic score-on incident CAD among individuals carrying a HeFH variant. Methods: We analyzed data from a prospective cohort study of 1,315 individuals who carried a HeFH variant and 1,315 matched family noncarriers derived from a nationwide screening program in the Netherlands, with subsequent replication in 151,009 participants of the UK Biobank. Results: Despite identification and lipid management within the Dutch screening program, 84 (6.4%) of HeFH variant carriers developed CAD as compared to 45 (3.4%) of matched family members (median follow-up 10.2 years, HR 1.88, 95% CI: 1.31-2.70). Among HeFH variant carriers, a polygenic score was associated with CAD with an effect size similar to low-density lipoprotein cholesterol - HR of 1.35 (95% CI: 1.07-1.70) and 1.41 (95% CI: 1.17-1.70) per standard deviation increase, respectively. When compared to noncarriers, CAD risk increased from 1.24-fold (95% CI: 0.64-2.34) to 3.37-fold (95% CI: 2.11-5.36) across quintiles of the polygenic score. A similar risk gradient, 1.36-fold (95% CI: 0.65-2.85) to 2.88-fold (95% CI: 1.59-5.20), was observed in 429 carriers in the UK Biobank. Conclusions: In 2 cohort studies involving 1,744 individuals with genetically confirmed HeFH - the largest study to date - risk of CAD varied according to polygenic background, in some cases approaching the risk observed in noncarriers.

Indexed as

coronary artery diseaseFamilial Hypercholesterolemialow-density lipoprotein cholesterolpolygenic riskUK Biobank

Identifiers

PMID38938725
PMCPMC11198615

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