A meta-analysis of 20,678 atrial fibrillation patients finds modestly higher Lp(a) in those with ischaemic stroke, but flags low-certainty evidence (J Clin Med 2025)

Background/Objectives: Atrial fibrillation (AF) is a significant contributor to ischemic stroke; however, existing thromboembolic risk scores exhibit only moderate predictive accuracy. Lipoprotein(a) (Lp(a)), a genetically determined lipoprotein characterized by proatherogenic and prothrombotic properties, may play a role in cardioembolic events in AF. Nonetheless, its clinical relevance in this context remains ambiguous. The goal of this systematic review and meta-analysis was to look at the differences in circulating Lp(a) levels between AF patients who had an ischemic stroke and those who did not, as well as to see if Lp(a) could help figure out who is at risk of thromboembolic events. Methods: A thorough search was performed in PubMed/MEDLINE, Embase, Scopus, Web of Science, and CENTRAL until September 2025, in accordance with PRISMA 2020 and Cochrane Handbook guidelines. Eligible studies encompassed adults with AF and accessible data on Lp(a) concentrations, contrasting individuals with and without ischemic stroke. Results: Five observational studies involving 20,678 atrial fibrillation patients (3104 with ischemic stroke) were incorporated. The pooled analysis revealed markedly elevated Lp(a) concentrations in stroke patients relative to non-stroke controls (MD = 2.42 mg/dL; 95% CI 0.68-4.16; p = 0.007). Conclusions: While Lp(a) testing is not presently endorsed in AF guidelines, our results indicate a possible correlation with ischemic stroke risk. Nonetheless, these findings must be regarded with caution owing to significant heterogeneity, the predominance of Chinese cohorts, and the exceedingly low certainty of evidence as per GRADE assessment. Additional extensive, multi-ethnic, and rigorously designed prospective studies are necessary to ascertain whether Lp(a) constitutes an independent risk factor for ischemic stroke in atrial fibrillation.