Apolipoprotein and peripheral artery disease: Mendelian randomization analysis

Background The prevalence of peripheral arterial disease (PAD) is on the rise globally, leading to adverse clinical outcomes. Our aim was to investigate the causal relationship between apolipoprotein and PAD, as well as the potential mediating role of smoking, diabetes, hypertension, myocardial infarction, and ischemic stroke. Methods We employed two-sample Mendelian randomization (TSMR) to assess the causal effect of apoB/A1 on the risk of PAD and potential mediators (smoking, diabetes mellitus, hypertension, myocardial infarction, and ischemic stroke), as well as the causal effect of those mediators on PAD. The use of multivariate MR (MVMR) allowed us to explore and quantify the mediating role of these factors in the causal association between apoB/A1 and the risk of PAD. Results Our MR analysis showed that each standard deviation increase in apoB/A1 increased the risk of PAD by 46% (OR = 1.460, 95% CI: 1.255–1.697, P = 8.74E-07). Hypertension, myocardial infarction, and ischemic stroke were ultimately recognized as the mediators of the causal relationship between apoB/A1 and PAD, explaining 7.5%, 19.7%, and 62.5% of the causal effect, respectively, and the proportion combined of the three together was 81%. Conclusions These studies demonstrated that elevated apoB/A1 increases the risk of developing PAD and that this association may be mediated by hypertension, myocardial infarction, and ischemic stroke.