Observational and Genetic Associations of Modifiable Risk Factors with Aortic Valve Stenosis: A Prospective Cohort Study of 0.5 Million Participants

Figures

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  Figure 1. The Aortic Valve Stenosis Diagram. A normal tricuspid valve, known as the aortic valve, can open or close, depending on blood volume. An abnormal aortic valve that does not open properly can block blood flow and result in systemic ischemia. The procession of one-sample Mendelian randomization analysis. The three main steps of Mendelian randomization: Firstly, the genetic tool and the corresponding phenotype perform regression, which can only be carried out in the next step under significant circumstances; Secondly, the predicted value of phenotype was predicted using the regression results. Third, regression was performed using the predicted phenotypes and outcomes, and the statistically significant condition and direction of risk (consistent with the first step) were examined.

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  Figure 2. The hazard ratio of modifiable risk factors and AVS incident patients. Adjusted by age, sex, family history of cardiovascular disease, family history of diabetes, education, household income, and Townsend deprivation index. * p-value less than 0.05 (p < 0.05); ** p-value less than 0.0018 (p < 0.05/28) for Bonferroni correction. The models adjusted for gender, age, education, income, Townsend deprivation index, family history of cardiovascular disease and diabetes, metabolic equivalent of physical activity, alcohol daily consumption, smoking status, and systolic blood pressure. Biochemical indices were further adjusted by cholesterol-lowering medication.

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  Figure 3. Adjusted HRs for risk of AVS by fifths of BMI, BF, TG, LDL, TC, and CPD in observational analysis and Mendelian randomization analysis. Cox regression was used to estimate the HRs and 95% CIs for AVS (n = 1602) by fifths of BMI, BF, TG, LDL, TC, and CPD in observational analysis (A) and Mendelian randomization analysis (B). Each square has an area inversely proportional to the variance of the log risk in a specific group. The number below each square is the AVS case number of these factors. The line represents the slope from a weighted linear regression with the weights based on the inverse variance of the log HR.

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  Figure 4. Mendelian randomization analysis between 28 modifiable risk GRS and AVS phenotypes. The MR analysis was adjusted by sex, age, the first 10 genetic principal components, and genotyping chip. The Cox model was used in patients with incident AVS, and the logistic model was used in patients with the incident and prevalent AVS patients. The weighted GRSs used for prediction. * p-value less than 0.0018 (after adjusted by Bonferroni correction).