Unravelling the distinct effects of systolic and diastolic blood pressure using Mendelian randomisation

Le, N. N., Tran, T. Q. B., Lip, S., McCallum, L., McClure, J. , Dominiczak, A. F. , Gill, D. and Padmanabhan, S. (2022) Unravelling the distinct effects of systolic and diastolic blood pressure using Mendelian randomisation. Genes, 13(7), 1226. (doi: 10.3390/genes13071226) (PMID:35886009) (PMCID:PMC9323763)

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Abstract

A true discrepancy between the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on cardiovascular (CV) outcomes remains unclear. This study performed two-sample Mendelian randomization (MR) using genetic instruments that exclusively predict SBP, DBP or both to dissect the independent effect of SBP and DBP on a range of CV outcomes. Genetic predisposition to higher SBP and DBP was associated with increased risk of coronary artery disease (CAD), myocardial infarction (MI), stroke, heart failure (HF), atrial fibrillation (AF), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Genetically proxied SBP exclusively was associated with CAD (OR 1.18, 95% CI: 1.03–1.36, per 10 mmHg), stroke (1.44[1.28–1.62]), ischemic stroke (1.49[1.30–1.69]), HF (1.41[1.20–1.65]), AF (1.28[1.15–1.43]), and T2DM (1.2[1.13–1.46]). Genetically proxied DBP exclusively was associated with stroke (1.21[1.06–1.37], per 5 mmHg), ischemic stroke (1.24[1.09–1.41]), stroke small-vessel (1.35[1.10–1.65]) and CAD (1.19[1.00–1.41]). Multivariable MR using exclusive SBP and DBP instruments showed the predominant effect of SBP on CAD (1.23[1.05–1.44], per 10 mmHg), stroke (1.39[1.20–1.60]), ischemic stroke (1.44[1.25–1.67]), HF (1.42[1.18–1.71]), AF (1.26[1.10–1.43]) and T2DM (1.31[1.14–1.52]). The discrepancy between effects of SBP and DBP on outcomes warrants further studies on underpinning mechanisms which may be amenable to therapeutic targeting.

Item Type:Articles
Additional Information:S.P. is supported by the British Heart Foundation Centre of Excellence Award (RE/18/6/34217) and the UKRI Strength in Places Fund (SIPF00007/1).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McCallum, Dr Linsay and McClure, Dr John and Lip, Dr Stefanie and Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna and LE, NHU NGOC
Authors: Le, N. N., Tran, T. Q. B., Lip, S., McCallum, L., McClure, J., Dominiczak, A. F., Gill, D., and Padmanabhan, S.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Genes
Publisher:MDPI
ISSN:2073-4425
ISSN (Online):2073-4425
Published Online:09 July 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Genes 13(7):1226
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science