Tao Mengjun, Zhang Yuanxiang, Li Qi, Feng Xuebing, Ping Cheng
Department of Health Management Center, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, China (Dr Tao).
School of Pharmacy, Wannan Medical College, Wuhu, 241001, China (Dr Zhang).
J Clin Lipidol. 2024 Nov-Dec;18(6):e968-e976. doi: 10.1016/j.jacl.2024.06.007. Epub 2024 Jul 5.
It remains unclear whether lipid profiles and lipid-lowering medications are causally related to peripheral arterial disease (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 cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), total cholesterol (TC), and LDL-associated genetic variants (HMGCR, NPC1L1, PCSK9, APOB), and the risk of 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-C (OR: 0.83, 95% CI: 0.83-0.77), LDL-C (OR: 1.29, 95% CI: 1.12-1.50), TC (OR: 1.14, 95% CI: 1.01- 1.29), TG (OR: 1.16, 95% CI: 1.04-1.24), APOB (OR: 1.31, 95% CI: 1.16-1.48), and APOA1 (OR: 0.84, 95% CI: 0.77-0.97), and the risk of PAD. In addition, inhibition of PCSK9 was associated with a reduced risk of PAD (OR: 0.68, 95% CI: 0.57-0.79, P<0.001), while no association between the other three gene proxies of LDL inhibition including HMGCR (OR: 1.21, 95% CI: 0.87-1.69, P=0.250), NPC1L1 (OR: 0.77, 95% CI: 0.44-1.33, P=0.344), and APOB (OR: 1.01, 95% CI: 0.87-1.26, P=0.890), and the risk of PAD were found.
Based on genetic evidence, dyslipidemia is an important risk factor for PAD. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may be an effective strategy for the treatment of PAD.
尚不清楚血脂谱和降脂药物与外周动脉疾病（PAD）之间是否存在因果关系。
解释血脂状况、降脂药物与PAD之间是否存在因果关系。
在这项两样本孟德尔随机化（MR）分析中，我们使用与这些血脂标志物相关的基因变异，评估了包括高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TGs）、总胆固醇（TC）以及与LDL相关的基因变异（HMGCR、NPC1L1、PCSK9、APOB）在内的血脂特征与PAD风险之间的因果关系。该研究分析了来自全球脂质遗传学联盟和英国生物银行的1654960名个体的数据，以确保对脂质功能障碍对PAD的影响有全面且可靠的基因见解。
我们发现基因预测的HDL-C（比值比：0.83，95%置信区间：0.83 - 0.77）、LDL-C（比值比：1.29，95%置信区间：1.12 - 1.50）、TC（比值比：1.14，95%置信区间：1.01 - 1.29）、TG（比值比：1.16，95%置信区间：1.04 - 1.24）、APOB（比值比：1.31，95%置信区间：1.16 - 1.48）和APOA1（比值比：0.84，95%置信区间：0.77 - 0.97）与PAD风险之间存在关联。此外，抑制PCSK9与PAD风险降低相关（比值比：0.68，95%置信区间：0.57 - 0.79，P<0.001），而在包括HMGCR（比值比：1.21，95%置信区间：0.87 - 1.69，P = 0.250）、NPC1L1（比值比：0.77，95%置信区间：0.44 - 1.33，P = 0.344）和APOB（比值比：1.01，95%置信区间：0.87 - 1.26，P = 0.890）在内的其他三种LDL抑制基因替代物与PAD风险之间未发现关联。
基于基因证据，血脂异常是PAD的重要危险因素。前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）抑制剂可能是治疗PAD的有效策略。
