Relationship between blood pressure and incident cardiovascular disease. Linear and non-linear Mendelian randomization analyses
File(s)
Published version
Supplementary information
Author(s)
Type
Journal Article
Abstract
Observational studies exploring whether there is a nonlinear effect of blood pressure on cardiovascular disease (CVD) risk are hindered by confounding. This limitation can be overcome by leveraging randomly allocated genetic variants in nonlinear Mendelian randomization analyses. Based on their association with blood pressure traits in a genome-wide association study of 299 024 European ancestry individuals, we selected 253 genetic variants to proxy the effect of modifying systolic and diastolic blood pressure. Considering the outcomes of incident coronary artery disease, stroke and the combined outcome of CVD, linear and nonlinear Mendelian randomization analyses were performed on 255 714 European ancestry participants without a history of CVD or antihypertensive medication use. There was no evidence favoring nonlinear relationships of genetically proxied systolic and diastolic blood pressure with the cardiovascular outcomes over linear relationships. For every 10-mm Hg increase in genetically proxied systolic blood pressure, risk of incident CVD increased by 49% (hazard ratio, 1.49 [95% CI, 1.38–1.61]), with similar estimates obtained for coronary artery disease (hazard ratio, 1.50 [95% CI, 1.38–1.63]) and stroke (hazard ratio, 1.44 [95% CI, 1.22–1.70]). Genetically proxied blood pressure had a similar relationship with CVD in men and women. These findings provide evidence to support that even for individuals who do not have elevated blood pressure, public health interventions achieving persistent blood pressure reduction will be of considerable benefit in the primary prevention of CVD.
Date Issued
2021-06-01
Date Acceptance
2021-02-15
Citation
Hypertension, 2021, 77 (6), pp.2004-2013
ISSN
0194-911X
Publisher
American Heart Association
Start Page
2004
End Page
2013
Journal / Book Title
Hypertension
Volume
77
Issue
6
Copyright Statement
© 2021 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.
License URL
Sponsor
British Heart Foundation
UK DRI Ltd
Grant Number
RE/18/4/34215
4050641385
Subjects
blood pressure
coronary artery disease
hypertension
primary prevention
stroke
1102 Cardiorespiratory Medicine and Haematology
1103 Clinical Sciences
1117 Public Health and Health Services
Cardiovascular System & Hematology
Publication Status
Published
Date Publish Online
2021-04-05