Lipoprotein(a) and peripheral artery disease: contemporary evidence and therapeutic advances.

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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.