Mechanisms
Review notes Lp(a)'s stroke association is well replicated in epidemiology but only marginal in Mendelian randomisation studies (J Int Med Res 2024)
Original title: Lipoprotein (a) and cerebrovascular disease
This narrative review examines Lp(a)'s role in cerebrovascular disease from multiple angles. Numerous epidemiological studies confirm a positive correlation between elevated Lp(a) and the occurrence or recurrence of cerebrovascular events, particularly ischaemic stroke, in adults, though the authors note this correlation is marginal in Mendelian randomisation studies specifically, and its strength varies across the literature. In children, screening remains limited to those with a relevant medical history, but Lp(a) appears to play a significant role in arterial ischaemic stroke pathogenesis precisely because the environmental thrombotic and atherogenic factors present in adults are generally absent. The review anticipates that phase 3 trials of pelacarsen and olpasiran will clarify whether Lp(a)-lowering reduces stroke incidence, and calls for new screening and management guidelines in targeted populations to improve primary and secondary stroke prevention.
Original abstract
The role of lipoprotein (a) [Lp(a)] in cerebrovascular disease is a topic of importance. In this narrative review, pertinent studies have been leveraged to comprehensively examine this relationship from diverse perspectives.Lp(a) shares structural traits with low-density lipoprotein cholesterol. Lp(a) is synthesized by hepatocytes, and its plasma levels are genetically determined by the LPA gene, which produces apolipoprotein (a).Numerous epidemiological studies have confirmed the positive correlation between elevated serum Lp(a) levels and the occurrence or recurrence of cerebrovascular events, especially ischemic strokes, in adults. It should be noted that the correlation strength varies among studies and is marginal in Mendelian randomization studies.Regarding pediatric patients, screening is currently limited to those with a relevant medical history. Lp(a) seems to play a significant role in the pathogenesis of arterial ischemic stroke in children because environmental thrombotic and atherogenic factors are generally not present.Phase 3 trials of novel Lp(a) targeting agents, such as pelacarsen and olpasiran, are anticipated to demonstrate their efficacy in reducing the incidence of stroke. Given the richness of the literature, new guidelines regarding Lp(a) screening and management in targeted populations are warranted to provide more effective primary and secondary prevention.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.