Smoking, Alcohol Consumption, and Risk of Arterial Stiffness: A Two-Sample Mendelian Randomization Study

Abstract

Background: While observational studies have demonstrated connections between cigarette smoking, alcohol consumption, and arterial stiffness, establishing a causal relationship has proven challenging because of potential confounding factors. To address this problem, we employed a two-sample Mendelian randomization approach.

Methods: We selected genetic instruments for these risk factors from genome-wide association studies encompassing 3,383,199 individuals at the genome-wide significance level (p $<$ 5 $\times$ ${\mathrm{10}}^{-9}$ ). Arterial stiffness data were acquired from the UK Biobank, which included 127,121 participants. Our primary analysis utilized the inverse variance-weighted method to explore causality. To confirm our results' robustness, we conducted sensitivity analyses using Egger regression, the weighted median method, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO).

Results: Our analysis revealed a significant association between genetic inclination to smoking initiation and an increase in the arterial stiffness index ( $\beta$ = 0.11; 95% confidence interval [CI], 0.06 to 0.16; p = 1.95 $\times$ ${\mathrm{10}}^{-5}$ ). Additionally, there was a suggestive connection between genetically predicted number of cigarettes per day and the arterial stiffness index ( $\beta$ = 0.05; 95% CI, 5.25 $\times$ ${\mathrm{10}}^{-4}$ to 0.10; p = 4.75 $\times$ ${\mathrm{10}}^{-2}$ ). No causal relationships were observed between the genetically predicted age of smoking initiation, smoking cessation, or alcohol consumption and the risk of arterial stiffness index.

Conclusions: This Mendelian randomization study indicates that smoking initiation is likely a causative risk factor for arterial stiffness. However, further research is needed to determine if the quantity of daily cigarettes directly contributes to arterial stiffness development. Regarding alcohol consumption, age of smoking initiation, and smoking cessation, there was insufficient evidence to establish causality.

Keywords: Mendelian randomization; alcohol consumption; arterial stiffness; smoking.