- Title
- Relative effects of LDL-C on ischemic stroke and coronary disease: a Mendelian randomization study
- Creator
- Valdes-Marquez, Elsa; Parish, Sarah; Clarke, Robert; Stari, Traiani; Worrall, Bradford B.; Slowik, Agnieszka; Hofman, Albert; Algra, Ale; Reiner, Alex P.; Doney, Alexander S. F.; Gschwendtner, Andreas; Ilinca, Andreea; Giese, Anne-Katrin; Lindgren, Arne; Vicente, Astrid M.; Norrving, Bo; Nordestgaard, Borge G.; Mitchell, Braxton D.; Psaty, Bruce M.; Carty, Cara L.; Cheng, Y-C; Holliday, Elizabeth G.
- Relation
- Neurology Vol. 92, Issue 11, p. E1176-E1187
- Publisher Link
- http://dx.doi.org/10.1212/WNL.0000000000007091
- Publisher
- Lippincott Williams & Wilkins
- Resource Type
- journal article
- Date
- 2019
- 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 x 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 x 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 x 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.
- Subject
- effects of LDL-C; ischemic stroke; coronary disease; cholesterol; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1445051
- Identifier
- uon:42483
- Identifier
- ISSN:0028-3878
- Language
- eng
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