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

M Nazarzadeh,C.M Otto,Z Bidel,R.-A Solares,G.H Salimi-Khorshidi,G.D Smith,A Hassaine,A.-C Pinho-Gomes,A Dehghan,D Canoy,K Rahimi

doi:10.1093/ehjci/ehaa946.1990

Abstract

Abstract Background 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. Purpose We sought to assess the causal association between exposure to lipid levels and risk of aortic stenosis. Methods Causality of association was assessed using two-sample Mendelian Randomization (MR) framework through different statistical methods. MR approach uses instrumental variable analysis to mimic the randomization process that underpins causal inference in clinical trials. It takes advantage of the naturally-occurring random allocation of alleles inherited by offspring from their parents during the formation of the zygote. 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. Results The odds ratio (OR) for developing aortic stenosis per unit increase in lipid parameter was 1.52 (95% confidence interval [CI], 1.22 to 1.90; per 0.98 mmol/L) for low-density lipoprotein (LDL) cholesterol, 1.03 (95% CI, 0.80 to 1.31; per 0.41 mmol/L) for high-density lipoprotein (HDL) cholesterol, and 1.38 (95% CI 0.92 to 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. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Highlights

A marked shift in the epidemiology of valvular heart disease has been observed in the past century.[1]
Lifelong exposure to high low density lipoprotein (LDL)-cholesterol increases the risk of symptomatic aortic stenosis, suggesting that LDL
In the UK Biobank, we identified 1961 participants with aortic stenosis, 736 with aortic regurgitation, and 2213 with mitral regurgitation

Summary

Introduction

A marked shift in the epidemiology of valvular heart disease has been observed in the past century.[1]. Poor understanding of the underlying mechanisms and risk factors for initiation and progression of valvular heart disease has hindered the development of effective medical treatment for primary and secondary prevention. Considering the shared aetiological pathways between different types of cardiovascular disease,[6,7,8] several risk factors have been investigated, but findings for dyslipidaemia have been inconsistent. Whilst observational studies have suggested a potential association between dyslipidaemia and risk of aortic stenosis,[9] randomized controlled trials (RCTs) have not demonstrated any effect of statin therapy on progression of aortic stenosis.[10,11,12] RCTs have been based on mostly small sample sizes, relatively short follow-up, and inclusion of patients with established disease

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Conclusion