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Genetically Predicted Blood Pressure Across the Lifespan: Differential Effects of Mean and Pulse Pressure on Stroke Risk.

Georgakis, MK; Gill, D; Malik, R; Protogerou, AD; Webb, AJS; Dichgans, M (2020) Genetically Predicted Blood Pressure Across the Lifespan: Differential Effects of Mean and Pulse Pressure on Stroke Risk. Hypertension, 76 (3). pp. 953-961. ISSN 1524-4563 https://doi.org/10.1161/HYPERTENSIONAHA.120.15136
SGUL Authors: Gill, Dipender Preet Singh

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Abstract

Hypertension is the leading risk factor for stroke. Yet, it remains unknown whether blood pressure pulsatility (pulse pressure [PP]) causally affects stroke risk independently of the steady pressure component (mean arterial pressure [MAP]). It is further unknown how the effects of MAP and PP on stroke risk vary with age and stroke cause. Using data from UK Biobank (N=408 228; 38-71 years), we selected genetic variants as instruments for MAP and PP at age ≤55 and >55 years and across age deciles. We applied multivariable Mendelian randomization analyses to explore associations with ischemic stroke, intracerebral hemorrhage, and their subtypes. Higher genetically predicted MAP was associated with higher risk of ischemic stroke and intracerebral hemorrhage across the examined age spectrum. Independent of MAP, higher genetically predicted PP only at age >55 years was further associated with higher risk of ischemic stroke (odds ratio per-SD-increment, 1.23 [95% CI, 1.13-1.34]). Among subtypes, the effect of genetically predicted MAP on large artery stroke was attenuated, whereas the effect of genetically predicted PP was augmented with increasing age. Genetically predicted MAP, but not PP, was associated with small vessel stroke and deep intracerebral hemorrhage homogeneously across age deciles. Neither genetically predicted MAP nor PP were associated with lobar intracerebral hemorrhage. Beyond an effect of high MAP at any age on ischemic and hemorrhagic stroke, our results support an independent causal effect of high PP at older ages on large artery stroke. This finding warrants further investigation for the development of stroke preventive strategies targeting pulsatility in later life.

Item Type: Article
Additional Information: © 2020 The Authors. Hypertension is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
Keywords: Mendelian randomization analysis, arterial pressure, blood pressure, hypertension, 1103 Clinical Sciences, 1102 Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Hypertension
ISSN: 1524-4563
Language: eng
Dates:
DateEvent
September 2020Published
6 July 2020Published Online
3 June 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
203928/Z/16/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
RE/18/4/34215British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
666881Horizon 2020UNSPECIFIED
667375Horizon 2020UNSPECIFIED
390857198Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659
B3CRC 1123UNSPECIFIED
Health-F2-2013-601456Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
PubMed ID: 32623925
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112792
Publisher's version: https://doi.org/10.1161/HYPERTENSIONAHA.120.15136

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