Association of lipids and lipid-lowering drugs with peripheral arterial disease: A Mendelian randomization study

It remains unclear whether lipid profiles and lipid-lowering medications are causally related to PAD. Explain whether there is a causal relationship between lipid status and lipid-lowering drugs and PAD. In this two-sample Mendelian randomization (MR) analysis, we assessed the causal relationship between lipid traits, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs), total cholesterol (TC), and LDL-associated genetic variants (), and the risk of peripheral arterial disease (PAD) using genetic variants associated with these lipid markers. The study analyzed data from 1,654,960 individuals derived from the Global Lipid Genetics Consortium and the UK Biobank, ensuring a robust and comprehensive genetic insight into the effects of lipid dysfunction on PAD. We found genetically predicted associations between HDL (: 0.83, 95% : 0.83-0.77), LDL-c (: 1.29, 95% : 1.12-1.50), TC (: 1.14, 95% : 1.01- 1.29), TG (:1.16, 95% : 1.04-1.24), (: 1.31, 95% : 1.16-1.48), and (:0.84, 95%: 0.77-0.97), and the risk of PAD. In addition, inhibition of was associated with a reduced risk of PAD (:0.68, 95% : 0.57-0.79, <0.001), while no association between the other three gene proxies of LDL inhibition including (=1.21, 95% : 0.87-1.69, =0.250), NPC1L1 (:0.77, 95% 0.44-1.33, =0.344), and APOB (:1.01, 95% :0.87-1.26, =0.890), and the risk of PAD were found. Based on genetic evidence, dyslipidemia is an important risk factor for PAD. PCSK9 inhibitors may be an effective strategy for the treatment of PAD.