Evidence map›Paper›PMID 29020353›Full record

SynthesisEuropean heart journal2018

Differential effects of PCSK9 variants on risk of coronary disease and ischaemic stroke.

Jemma C Hopewell, Rainer Malik, Elsa Valdés-Márquez, Bradford B Worrall, Rory Collins, METASTROKE Collaboration of the ISGC

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in European heart journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 2 pooled it
5.7field-weighted citation impact, top 3% 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.

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

29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 84 citations in OpenAlex.

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  3. Large-Scale Phenome-Wide Association Study ofCirculation. Genomic and precision medicine · 2018
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 3 countries.

Jemma C HopewellClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, BHF Centre for Research Excellence, Big Data Institute, Old Road Campus, Roosevelt Drive, Oxford OX3?7LF, UK.
Rainer MalikInstitute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Feodor-Lynen-Straße 17, 81377 Munich, Germany.
Elsa Valdés-MárquezClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, BHF Centre for Research Excellence, Big Data Institute, Old Road Campus, Roosevelt Drive, Oxford OX3?7LF, UK.
Bradford B WorrallDepartment of Neurology, University of Virginia Health System, McKim Hall, Hospital Drive, Charlottesville, VA 22908, USA.
Rory CollinsClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, BHF Centre for Research Excellence, Big Data Institute, Old Road Campus, Roosevelt Drive, Oxford OX3?7LF, UK.
METASTROKE Collaboration of the ISGC
University of Oxford · GBLudwig-Maximilians-Universität München · DEUniversity of Virginia Health System · US

Funding

British Heart Foundation FS/14/55/30806Wellcome Trust
6 · The paper itself

Abstract

Aims: PCSK9 genetic variants that have large effects on low-density lipoprotein cholesterol (LDL-C) and coronary heart disease (CHD) have prompted the development of therapeutic PCSK9-inhibition. However, there is limited evidence that PCSK9 variants are associated with ischaemic stroke (IS). Methods and results: Associations of the loss-of-function PCSK9 genetic variant (rs11591147; R46L), and five additional PCSK9 variants, with IS and IS subtypes (cardioembolic, large vessel, and small vessel) were estimated in a meta-analysis involving 10 307 IS cases and 19 326 controls of European ancestry. They were then compared with the associations of these variants with LDL-C levels (in up to 172 970 individuals) and CHD (in up to 60 801 CHD cases and 123 504 controls). The rs11591147 T allele was associated with 0.5 mmol/L lower LDL-C level (P = 9 × 10-143) and 23% lower CHD risk [odds ratio (OR): 0.77, 95% confidence interval (CI): 0.69-0.87, P = 7 × 10-6]. However, it was not associated with risk of IS (OR: 1.04, 95% CI: 0.84-1.28, P = 0.74) or IS subtypes. Information from additional PCSK9 variants also indicated consistently weaker effects on IS than on CHD. Conclusion: PCSK9 genetic variants that confer life-long lower PCSK9 and LDL-C levels appear to have significantly weaker, if any, associations with risk of IS than with risk of CHD. By contrast, similar proportional reductions in risks of IS and CHD have been observed in randomized trials of therapeutic PCSK9-inhibition. These findings have implications for our understanding of when Mendelian randomization can be relied upon to predict the effects of therapeutic interventions.

Indexed as

Brain IschemiaCoronary DiseaseStrokeCholesterol, LDLGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansProprotein Convertase 9Cholesterol, LDLPCSK9 protein, humanProprotein Convertase 9Cardiovascular therapiesCoronary diseaseGeneticsLDL-cholesterolPCSK9Stroke

Identifiers

PMID29020353
PMCPMC5837489
OpenAlexW2766392615

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.