Narrative review ties Lp(a)'s pro-inflammatory and prothrombotic biology to higher peripheral arterial disease incidence and restenosis risk (Vasc Health Risk Manag 2025)

Lipoprotein (a) (Lp[a]) is an independent risk factor for cardiovascular disease (CVD). Structurally like low-density lipoprotein, Lp(a) is distinguished by the covalent attachment of apolipoprotein(a) to apolipoprotein B-100. Although its physiological role remains incompletely understood, evidence suggests that Lp(a) may facilitate wound healing and inhibit cancer growth and metastasis. In contrast, Lp(a) exhibits proatherogenic properties; it transports proinflammatory oxidized phospholipids, induces the secretion of proinflammatory cytokines, increases endothelial permeability, promotes smooth muscle cell migration and proliferation, and upregulates adhesion molecules that facilitate monocyte recruitment and retention. In addition, Lp(a) exerts prothrombotic activity by enhancing platelet aggregation, suppressing plasminogen activation, and inhibiting fibrinolysis. Although its clinical relevance in CVD is well established, the role of Lp(a) in peripheral arterial disease (PAD) remains unclear. This narrative review aimed to synthesize and critically examine the current evidence on the biological role of Lp(a) in PAD pathogenesis and identify knowledge gaps in PAD-specific outcomes. This review summarizes the epidemiology, pathophysiology, and management of elevated Lp(a) levels in patients with PAD and examines their association with post-treatment clinical outcomes. Elevated Lp(a) levels are associated with an increased PAD incidence and a higher risk of restenosis post-revascularization. Understanding the mechanisms by which Lp(a) contributes to PAD pathogenesis is essential for developing effective targeted therapeutic approaches and improving the identification and management of high-risk patients.