Mechanisms
Nature Reviews Cardiology essay revisits how Lp(a) affects platelets, and why the ASPREE trial found aspirin helped genetically high-Lp(a) individuals most (Nat Rev Cardiol 2024)
Original title: Lipoprotein(a), platelet function and cardiovascular disease
This review, co-authored by Tsimikas and colleagues, re-examines Lp(a)'s relationship with platelet function despite genetic studies not showing an association between high Lp(a) and venous thromboembolism, and despite ex vivo studies finding that lowering Lp(a) does not alter plasma clotting properties in patients with very high levels. Lp(a) interacts with several platelet receptors, providing biological plausibility for a pro-aggregatory effect, and observational studies show elevated Lp(a) is linked to worse long-term outcomes after revascularisation, with those patients deriving greater benefit from prolonged dual antiplatelet therapy than patients with normal Lp(a). Notably, the ASPREE aspirin trial in healthy older adults found reduced ischaemic events, without increased bleeding, specifically in participants carrying an LPA single-nucleotide polymorphism associated with elevated Lp(a). The authors propose directions for future research to clarify the clinical relevance of Lp(a)'s effects on platelet biology.
Original abstract
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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.