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Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study

OBJECTIVE: To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. METHODS: We undertook a 2-sample Mendelian randomization, based on su...

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Autores principales: Valdes-Marquez, Elsa, Parish, Sarah, Clarke, Robert, Stari, Traiani, Worrall, Bradford B., Hopewell, Jemma C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511103/
https://www.ncbi.nlm.nih.gov/pubmed/30787162
http://dx.doi.org/10.1212/WNL.0000000000007091
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author Valdes-Marquez, Elsa
Parish, Sarah
Clarke, Robert
Stari, Traiani
Worrall, Bradford B.
Hopewell, Jemma C.
author_facet Valdes-Marquez, Elsa
Parish, Sarah
Clarke, Robert
Stari, Traiani
Worrall, Bradford B.
Hopewell, Jemma C.
author_sort Valdes-Marquez, Elsa
collection PubMed
description OBJECTIVE: To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. METHODS: We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. RESULTS: A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32−1.68, p = 1.1 × 10(−8)). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96−1.30, p = 0.14; p for heterogeneity = 2.6 × 10(−3)) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84−1.33, p = 0.64; p for heterogeneity = 8.6 × 10(−3)) when compared with that for CHD. CONCLUSIONS: In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.
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spelling pubmed-65111032019-06-12 Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study Valdes-Marquez, Elsa Parish, Sarah Clarke, Robert Stari, Traiani Worrall, Bradford B. Hopewell, Jemma C. Neurology Article OBJECTIVE: To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. METHODS: We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. RESULTS: A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32−1.68, p = 1.1 × 10(−8)). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96−1.30, p = 0.14; p for heterogeneity = 2.6 × 10(−3)) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84−1.33, p = 0.64; p for heterogeneity = 8.6 × 10(−3)) when compared with that for CHD. CONCLUSIONS: In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed. Lippincott Williams & Wilkins 2019-03-12 /pmc/articles/PMC6511103/ /pubmed/30787162 http://dx.doi.org/10.1212/WNL.0000000000007091 Text en Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Valdes-Marquez, Elsa
Parish, Sarah
Clarke, Robert
Stari, Traiani
Worrall, Bradford B.
Hopewell, Jemma C.
Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study
title Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study
title_full Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study
title_fullStr Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study
title_full_unstemmed Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study
title_short Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study
title_sort relative effects of ldl-c on ischemic stroke and coronary disease: a mendelian randomization study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511103/
https://www.ncbi.nlm.nih.gov/pubmed/30787162
http://dx.doi.org/10.1212/WNL.0000000000007091
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