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

Authors :
Valdes-Marquez E
Parish S
Clarke R
Stari T
Worrall BB
Hopewell JC
Source :
Neurology [Neurology] 2019 Mar 12; Vol. 92 (11), pp. e1176-e1187. Date of Electronic Publication: 2019 Feb 20.
Publication Year :
2019

Abstract

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.<br />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.<br />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 <superscript>-8</superscript> ). 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 <superscript>-3</superscript> ) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10 <superscript>-3</superscript> ) when compared with that for CHD.<br />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.<br /> (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Details

Language :
English
ISSN :
1526-632X
Volume :
92
Issue :
11
Database :
MEDLINE
Journal :
Neurology
Publication Type :
Academic Journal
Accession number :
30787162
Full Text :
https://doi.org/10.1212/WNL.0000000000007091