Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study
<strong>Objective</strong> 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. <strong>Methods</strong> We...
| Главные авторы: | , , , , , , |
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| Формат: | Journal article |
| Опубликовано: |
American Academy of Neurology
2019
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| _version_ | 1826299996545220608 |
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| author | Valdes-Marque, E Parish, S Clarke, R Stari, T Worrall, B METASTROKE Consortium of the ISGC Hopewell, J |
| author_facet | Valdes-Marque, E Parish, S Clarke, R Stari, T Worrall, B METASTROKE Consortium of the ISGC Hopewell, J |
| author_sort | Valdes-Marque, E |
| collection | OXFORD |
| description | <strong>Objective</strong> 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. <strong>Methods</strong> 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. <strong>Results</strong> 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. <strong>Conclusions</strong> 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. |
| first_indexed | 2024-03-07T05:10:25Z |
| format | Journal article |
| id | oxford-uuid:db5e8d24-9576-44f0-b3fe-6cadafeb4a50 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T05:10:25Z |
| publishDate | 2019 |
| publisher | American Academy of Neurology |
| record_format | dspace |
| spelling | oxford-uuid:db5e8d24-9576-44f0-b3fe-6cadafeb4a502022-03-27T09:10:03ZRelative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:db5e8d24-9576-44f0-b3fe-6cadafeb4a50Symplectic Elements at OxfordAmerican Academy of Neurology2019Valdes-Marque, EParish, SClarke, RStari, TWorrall, BMETASTROKE Consortium of the ISGCHopewell, J<strong>Objective</strong> 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. <strong>Methods</strong> 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. <strong>Results</strong> 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. <strong>Conclusions</strong> 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. |
| spellingShingle | Valdes-Marque, E Parish, S Clarke, R Stari, T Worrall, B METASTROKE Consortium of the ISGC Hopewell, J 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 |
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