Imperial College London
Alternate

DrKostasTsilidis

Faculty of Medicine, School of Public Health

Reader in Cancer Epidemiology and Prevention
 
 
 
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Contact

 

+44 (0)20 7594 2623k.tsilidis

 
 
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Location

 

School of Public HealthWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gill:2021:10.1038/s41366-021-00807-4,
author = {Gill, D and Zuber, V and Dawson, J and Pearson-Stuttard, J and Carter, AR and Sanderson, E and Karhunen, V and Levin, MG and Wootton, RE and Klarin, D and Tsao, PS and Tsilidis, KK and Damrauer, SM and Burgess, S and Elliott, P},
doi = {10.1038/s41366-021-00807-4},
journal = {International Journal of Obesity},
pages = {1428--1438},
title = {Risk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis},
url = {http://dx.doi.org/10.1038/s41366-021-00807-4},
volume = {45},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundHigher body mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits, and smoking is not fully understood.MethodsUsing consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, Mendelian randomization mediation analysis was performed to investigate the degree to which systolic blood pressure (SBP), diabetes, lipid traits, and smoking mediated an effect of BMI and WHR on the risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke.ResultsThe odds ratio of CAD per 1-standard deviation increase in genetically predicted BMI was 1.49 (95% CI 1.39 to 1.60). This attenuated to 1.34 (95% CI 1.24 to 1.45) after adjusting for genetically predicted SBP (proportion mediated 27%, 95% CI 3% to 50%), to 1.27 (95% CI 1.17 to 1.37) after adjusting for genetically predicted diabetes (41% mediated, 95% CI 18% to 63%), to 1.47 (95% CI 1.36 to 1.59) after adjusting for genetically predicted lipids (3% mediated, 95% −23% to 29%), and to 1.46 (95% CI 1.34 to 1.58) after adjusting for genetically predicted smoking (6% mediated, 95% CI −20% to 32%). Adjusting for all the mediators together, the estimate attenuated to 1.14 (95% CI 1.04 to 1.26; 66% mediated, 95% CI 42% to 91%). A similar pattern was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcome.ConclusionsMeasures to reduce obesity will lower the risk of cardiovascular disease primarily by impacting downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.
AU  - Gill,D
AU  - Zuber,V
AU  - Dawson,J
AU  - Pearson-Stuttard,J
AU  - Carter,AR
AU  - Sanderson,E
AU  - Karhunen,V
AU  - Levin,MG
AU  - Wootton,RE
AU  - Klarin,D
AU  - Tsao,PS
AU  - Tsilidis,KK
AU  - Damrauer,SM
AU  - Burgess,S
AU  - Elliott,P
DO  - 10.1038/s41366-021-00807-4
EP  - 1438
PY  - 2021///
SN  - 0307-0565
SP  - 1428
TI  - Risk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis
T2  - International Journal of Obesity
UR  - http://dx.doi.org/10.1038/s41366-021-00807-4
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000653128900007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41366-021-00807-4
UR  - http://hdl.handle.net/10044/1/89514
VL  - 45
ER  -
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