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. 2020 Oct 21;41(40):3913-3920.
doi: 10.1093/eurheartj/ehaa070.

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

Milad Nazarzadeh  1   2   3 , Ana-Catarina Pinho-Gomes  1   2 , Zeinab Bidel  1   2   3 , Abbas Dehghan  4 , Dexter Canoy  1   2   5   6 , Abdelaali Hassaine  1   2 , Jose Roberto Ayala Solares  1   2 , Gholamreza Salimi-Khorshidi  1   2 , George Davey Smith  7 , Catherine M Otto  8 , Kazem Rahimi  1   2   5
Affiliations

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

Milad Nazarzadeh et al. Eur Heart J. .

Abstract

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.

Keywords: Blood cholesterol; Heart valve diseases; Lipid profile; Mendelian randomization analysis.

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Figures

Figure 1
Figure 1
Comparison of the total causal estimations considered heterogeneity and pleiotropic effect between plasma lipids and valvular heart disease risk using two-sample Mendelian randomization. SD, standard deviation; 1 SD is equal to 0.98 mmol/L for low density lipoprotein-cholesterol, 0.41 mmol/L for high density lipoprotein-cholesterol, 1 mmol/L for triglycerides, and 1.10 mmol/L for total cholesterol.
Figure 2
Figure 2
Comparison of the direct causal estimations between plasma lipids and valvular heart disease risk using multivariable Mendelian randomization. SD, standard deviation; 1 SD is equal to 0.98 mmol/L for low density lipoprotein-cholesterol, 0.41 mmol/L for high density lipoprotein-cholesterol, 1 mmol/L for triglycerides, and 1.10 mmol/L for total cholesterol. The multivariable Mendelian randomization was adjusted to estimate direct causal effect of each plasma lipids component, independently of any other plasma lipids variables.
Take home figure
Take home figure
Schematic overview of the Mendelian randomization framework and key findings.
None
See this image and copyright information in PMC

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