Lipoprotein(a): a unique lipoprotein at the crossroads of atherosclerosis and thrombosis.

Purpose

OF REVIEW Elevated plasma concentrations of lipoprotein(a) [Lp(a)] are a causal and independent risk factor for atherosclerotic cardiovascular disease and an emerging therapeutic target. However, despite Lp(a) being on the cusp of widespread clinical consideration, fundamental questions regarding the pathophysiology of Lp(a) remain, most notably its contribution to atherothrombosis. This review will summarize recent evidence for both indirect and direct prothrombotic roles of Lp(a). RECENT

Findings

Preclinical studies show that the proinflammatory properties of Lp(a) - largely attributable to its cargo of oxidized phospholipids - promote vulnerable plaques through effects on vascular and immune/inflammatory cells. Advanced imaging techniques show that elevated Lp(a) is associated with vulnerable plaque phenotypes in patients. Regarding thrombosis, previous assumptions that Lp(a) is antifibrinolytic have given way to an emerging picture that Lp(a) promotes a lysis-resistant clot architecture while stimulating the coagulation cascade and potentiating platelet responses. Indeed, clinical studies have demonstrated that patients with elevated Lp(a) specifically accrue clinical benefit from aspirin in the primary prevention setting. SUMMARY That elevated Lp(a) is both directly and indirectly prothrombotic remains to be proven by additional clinical and animal model studies Nonetheless, the accumulating evidence indicates that considering the prothrombotic activities of Lp(a) will impact clinical management of Lp(a) and the deployment of Lp(a)-lowering therapies.