Lipoprotein(a), platelet function and cardiovascular disease

Lipoprotein(a) (Lp(a)) is associated with atherothrombosis through several mechanisms, including putative antifibrinolytic properties. However, genetic association studies have not demonstrated an association between high plasma levels of Lp(a) and the risk of venous thromboembolism, and studies in patients with highly elevated Lp(a) levels have shown that Lp(a) lowering does not modify the clotting properties of plasma ex vivo. Lp(a) can interact with several platelet receptors, providing biological plausibility for a pro-aggregatory effect. Observational clinical studies suggest that elevated plasma Lp(a) concentrations are associated with worse long-term outcomes in patients undergoing revascularization. Furthermore, in these patients, those with elevated plasma Lp(a) levels derive more benefit from prolonged dual antiplatelet therapy than those with normal Lp(a) levels. The ASPREE trial in healthy older individuals treated with aspirin showed a reduction in ischaemic events in those who had a single-nucleotide polymorphism in LPA that is associated with elevated Lp(a) levels in plasma, without an increase in bleeding events. In this Review, we re-examine the role of Lp(a) in the regulation of platelet function and suggest areas of research to define further the clinical relevance to cardiovascular disease of the observed associations between Lp(a) and platelet function.