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Plasma lipids and risk of aortic valve stenosis: A Mendelian randomization study

Lookup NU author(s): Dr Dexter CanoyORCiD, Dr Ali HassaineORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.Aims : Aortic valve stenosis is commonly considered a degenerative disorder with no recommended preventive intervention, with only valve replacement surgery or catheter intervention as treatment options. We sought to assess the causal association between exposure to lipid levels and risk of aortic stenosis. Methods and results : Causality of association was assessed using two-sample Mendelian randomization framework through different statistical methods. We retrieved summary estimations of 157 genetic variants that have been shown to be associated with plasma lipid levels in the Global Lipids Genetics Consortium that included 188 577 participants, mostly European ancestry, and genetic association with aortic stenosis as the main outcome from a total of 432 173 participants in the UK Biobank. Secondary negative control outcomes included aortic regurgitation and mitral regurgitation. The odds ratio for developing aortic stenosis per unit increase in lipid parameter was 1.52 [95% confidence interval (CI) 1.22-1.90; per 0.98 mmol/L] for low density lipoprotein (LDL)-cholesterol, 1.03 (95% CI 0.80-1.31; per 0.41 mmol/L) for high density lipoprotein (HDL)-cholesterol, and 1.38 (95% CI 0.92-2.07; per 1 mmol/L) for triglycerides. There was no evidence of a causal association between any of the lipid parameters and aortic or mitral regurgitation. Conclusion : Lifelong exposure to high LDL-cholesterol increases the risk of symptomatic aortic stenosis, suggesting that LDL-lowering treatment may be effective in its prevention.

Publication metadata

Author(s): Nazarzadeh M, Pinho-Gomes A-C, Bidel Z, Dehghan A, Canoy D, Hassaine A, Ayala Solares JR, Salimi-Khorshidi G, Smith GD, Otto CM, Rahimi K

Publication type: Article

Publication status: Published

Journal: European Heart Journal

Year: 2020

Volume: 41

Issue: 40

Pages: 3913-3920

Print publication date: 21/10/2020

Online publication date: 20/02/2020

Acceptance date: 29/01/2020

Date deposited: 25/11/2022

ISSN (print): 0195-668X

ISSN (electronic): 1522-9645

Publisher: Oxford University Press


DOI: 10.1093/eurheartj/ehaa070

PubMed id: 32076698


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Funder referenceFunder name
... a grant from the Oxford Martin School, as well as the PEAK Urban programme,...
... from the UKRI’s Global Challenge Research Fund Grant Ref: ES/P011055/1.
British Heart Foundation
George Davey Smith works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol MC_UU_00011/1.
Nazarzadeh (grant number: FS/19/36/34346)
Pinho-Gomes (grant number: FS/19/64/34673)
Rahimi (grant number: PG/18/65/33872)
Rahimi and Canoy are supported by the National Institute of Health Research (NIHR) Oxford Biomedical Research Centre ...