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Genetically Predicted Midlife Blood Pressure and Coronary Artery Disease Risk: Mendelian Randomization Analysis.

Gill, D; Georgakis, MK; Zuber, V; Karhunen, V; Burgess, S; Malik, R; Dichgans, M (2020) Genetically Predicted Midlife Blood Pressure and Coronary Artery Disease Risk: Mendelian Randomization Analysis. J Am Heart Assoc, 9 (14). e016773. ISSN 2047-9980 https://doi.org/10.1161/JAHA.120.016773
SGUL Authors: Gill, Dipender Preet Singh

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Abstract

Background Elevated blood pressure is a major cause of cardiovascular morbidity and mortality. However, it is not known whether midlife blood pressure affects later life cardiovascular risk independent of later life blood pressure. Methods and Results Using genetic association estimates from the UK Biobank and CARDIoGRAMplusC4D consortium, univariable mendelian randomization was performed to investigate the total effect of genetically predicted mean arterial pressure (MAP) at age ≤55 years on coronary artery disease (CAD) risk, and multivariable mendelian randomization was performed to investigate the effect of genetically predicted MAP on CAD risk after adjusting for genetically predicted MAP at age >55 years. In both univariable and multivariable mendelian randomization analyses, there was consistent evidence of higher genetically predicted MAP at age ≤55 years increasing CAD risk. This association persisted after adjusting for genetically predicted MAP at age >55 years, when considering nonoverlapping populations for the derivation of MAP and CAD risk genetic association estimates, when investigating only incident CAD events after age >55 years, and when restricting the analysis to variants with most heterogeneity in their associations with MAP ≤55 and >55 years. For a 10-mm Hg increase in genetically predicted MAP at age ≤55 years, the odds ratio of later life CAD was 1.43 (95% CI, 1.16-1.77; P=0.001) after adjusting for genetically predicted MAP at age >55 years. Conclusions These mendelian randomization findings support a cumulative lifetime effect of elevated blood pressure on increasing CAD risk. Clinical and public health efforts toward cardiovascular disease reduction should optimize blood pressure control throughout life.

Item Type: Article
Additional Information: Copyright © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: age, blood pressure, coronary artery disease, mendelian randomization
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Am Heart Assoc
ISSN: 2047-9980
Language: eng
Dates:
DateEvent
21 July 2020Published
4 July 2020Published Online
1 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
204623/Z/16/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 32627641
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112762
Publisher's version: https://doi.org/10.1161/JAHA.120.016773

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