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Reference: Hopewell, JC, Parish, S, Offer, A et al., (2013). Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study. European heart journal, 34 (13), 982-992.Citable link to this page:

 

Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.

Abstract: Aims Statins reduce LDL cholesterol (LDL-C) and the risk of vascular events, but it remains uncertain whether there is clinically relevant genetic variation in their efficacy. This study of 18 705 individuals aims to identify genetic variants related to the lipid response to simvastatin and assess their impact on vascular risk response.Methods and results A genome-wide study of the LDL-C and apolipoprotein B (ApoB) response to 40 mg simvastatin daily was performed in 3895 participants in the Heart Protection Study, and the nine strongest associations were tested in 14 810 additional participants. Selected candidate genes were also tested in up to 18 705 individuals. There was 90% power to detect differences of 2.5% in LDL-C response (e.g. 42.5 vs. 40% reduction) in the genome-wide study and of 1% in the candidate gene study. None of the associations from the genome-wide study was replicated, and nor were significant associations found for 26 of 36 candidates tested. Novel lipid response associations with variants in LPA, CELSR2/PSRC1/SORT1, and ABCC2 were found, as well as confirmatory evidence for published associations in LPA, APOE, and SLCO1B1. The largest and most significant effects were with LPA and APOE, but were only 2–3% per allele. Reductions in the risk of major vascular events during 5 years of statin therapy among 18 705 high-risk patients did not differ significantly across genotypes associated with the lipid response.Conclusions Common genetic variants do not appear to alter the lipid response to statin therapy by more than a few per cent, and there were similar large reductions in vascular risk with simvastatin irrespective of genotypes associated with the lipid response to simvastatin. Consequently, their value for informing clinical decisions related to maximizing statin efficacy appears to be limited.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Merck   Funder: Medical Research Council   Funder: British Heart Foundation   Funder: Roche Vitamins Ltd   Notes:Copyright © 2012 Hopewell et al. Published by Oxford University Press on behalf of European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions[at]oup.com.

Bibliographic Details

Publisher: Oxford University Press

Publisher Website: http://global.oup.com/

Journal: European heart journalsee more from them

Publication Website: http://eurheartj.oxfordjournals.org/

Issue Date: 2013-4

pages:982-992Identifiers

Urn: uuid:b7d20a03-6de4-4c70-9176-2b36c9aa6f66

Source identifier: 358301

Eissn: 1522-9645

Doi: https://doi.org/10.1093/eurheartj/ehs344

Issn: 0195-668X Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: MRC/BHF Heart Protection Study Collaborative Group Humans Cardiovascular Diseases Hypercholesterolemia Simvastatin Lipoprotein(a) Apolipoproteins B Anticholesteremic Agents Genotype Polymorphism, Single Nucleotide Adult Aged Aged, 80 and over Middle Aged Female Male Cholesterol, LDL Genome-Wide Association Study Genetic Loci Tiny URL: pubs:358301

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Autor: Hopewell, JC - institutionUniversity of Oxford Oxford, MSD, Clinical Medicine, Clinical Trial Service Unit grantNumberRE-08-004 f

Fuente: https://ora.ox.ac.uk/objects/uuid:b7d20a03-6de4-4c70-9176-2b36c9aa6f66



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