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)
![[img]](https://eprints.gla.ac.uk/style/images/fileicons/text.png) |
Text
273654.pdf - Published Version Available under License Creative Commons Attribution. 1MB |
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: | Lip, Dr Stefanie and Mccallum, Dr Linsay and Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna and LE, NHU NGOC and McClure, Dr John |
| 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 |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information