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Genetically determined blood pressure, antihypertensive drug classes and risk of stroke subtypes

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Title: Genetically determined blood pressure, antihypertensive drug classes and risk of stroke subtypes
Authors: Georgakis, MK
Gill, D
Webb, AJS
Evangelou, E
Elliott, P
Sudlow, CLM
Dehghan, A
Malik, R
Tzoulaki, I
Dichgans, M
Item Type: Journal Article
Abstract: Objective: We employed Mendelian Randomization to explore whether the effects of blood pressure (BP) and BP lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology. Methods: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from a GWAS on 757,601 individuals. Applying two-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of WMH. Results: Genetic predisposition to higher systolic and diastolic BP was associated with higher risk of any stroke, ischemic stroke, and ICH. We found associations between genetically determined BP and all ischemic stroke subtypes with a higher risk of large artery and small vessel stroke compared to cardioembolic stroke, as well as associations with deep, but not lobar ICH. Genetic proxies for calcium channel blockers, but not beta blockers, were associated with lower risk of any stroke and ischemic stroke. Proxies for CCBs showed particularly strong associations with small vessel stroke and the related radiological phenotype of WMH. Conclusions: This study supports a causal role of hypertension in all major stroke subtypes except lobar ICH. We find differences in the effects of BP and BP lowering through antihypertensive drug classes between stroke subtypes and identify calcium channel blockade as a promising strategy for preventing manifestations of cerebral small vessel disease.
Issue Date: 28-Jul-2020
Date of Acceptance: 5-Jan-2020
URI: http://hdl.handle.net/10044/1/76811
DOI: 10.1212/WNL.0000000000009814
ISSN: 0028-3878
Publisher: American Academy of Neurology
Start Page: e353
End Page: 361
Journal / Book Title: Neurology
Volume: 95
Issue: 4
Copyright Statement: © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium,provided the original work is properly cited.
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Health Data Research Uk
Medical Research Council (MRC)
UK DRI Ltd
Funder's Grant Number: RDF03
Health Data Research UK
MR/L01341X/1
4050641385
Keywords: 1103 Clinical Sciences
1109 Neurosciences
1702 Cognitive Sciences
Neurology & Neurosurgery
Publication Status: Published
Online Publication Date: 2020-07-01
Appears in Collections:Faculty of Medicine
School of Public Health



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