Thanigaimani Shivshankar, Kumar Maarisha, Golledge Jonathan
Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry.
Department of Vascular and Endovascular Surgery, Townsville University Hospital, Townsville, Queensland, Australia.
Curr Opin Lipidol. 2025 Oct 1;36(5):258-267. doi: 10.1097/MOL.0000000000000998. Epub 2025 May 21.
Peripheral artery disease (PAD) is a major cause of global health burden, including amputation and impaired quality of life. This review examines the evidence implicating lipoprotein(a) [Lp(a)] in PAD, which is timely as novel therapies lowering Lp(a) are currently being tested in several clinical trials.
Human observational studies demonstrate strong associations between elevated Lp(a) levels and increased risk of PAD incidence, severity of chronic limb-threatening ischemia, and major adverse limb events. Emerging therapies including small interfering RNA, antisense oligonucleotides, proprotein convertase subtilisin-kexin type 9 inhibitors and lipoprotein apheresis demonstrate significant Lp(a)-lowering effects. However, whether these treatments benefit patients with PAD is currently unknown.
Lp(a) may be involved in PAD pathogenesis. Lp(a)-lowering therapies may significantly reduce PAD-related events and improve outcomes. Future studies are needed to test Lp(a)-lowering therapies in people with PAD and to explore how the association of Lp(a) varies in different sexes and ethnicities and understand mechanisms by which Lp(a) may contribute to limb ischemia.
外周动脉疾病（PAD）是全球健康负担的主要原因，包括截肢和生活质量受损。本综述探讨了脂蛋白(a)[Lp(a)]与PAD相关的证据，鉴于目前正在多项临床试验中测试降低Lp(a)的新型疗法，这一探讨很及时。
人类观察性研究表明，Lp(a)水平升高与PAD发病率增加、慢性肢体威胁性缺血的严重程度以及主要肢体不良事件之间存在密切关联。包括小干扰RNA、反义寡核苷酸、前蛋白转化酶枯草溶菌素9型抑制剂和脂蛋白分离术在内的新兴疗法显示出显著的降低Lp(a)的效果。然而，这些治疗是否对PAD患者有益目前尚不清楚。
Lp(a)可能参与PAD的发病机制。降低Lp(a)的疗法可能会显著减少与PAD相关的事件并改善预后。未来需要开展研究，在PAD患者中测试降低Lp(a)的疗法，并探索Lp(a)的关联在不同性别和种族中如何变化，以及了解Lp(a)可能导致肢体缺血的机制。
