Abstract Body (Do not enter title and authors here):
Background: Emerging evidence suggests that antiphospholipid antibodies (aPL) may be associated with an increased cardiovascular risk beyond the thrombotic antiphospholipid syndrome (APS). Among patients with ischemic stroke, the clinical significance of single positive aPL remains ill-defined. We aimed to assess the prevalence of aPL seropositivity in patients with stroke and the association between aPL seropositivity and stroke risk.

Methods: This analysis is part of a larger project with PROSPERO ID CRD420251047305. We conducted a systematic search of PubMed and Embase on 5/13/2025 to identify cohort or case-control studies of unselected adult patients (without APS) investigating the association between aPL seropositivity and acute ischemic stroke compared with non-stroke controls. Positivity for aPL was defined as a single positive measurement for lupus anticoagulant in clot-based assays, IgM/IgG anti-β2-glycoprotein I antibody, or IgM/IgG anticardiolipin antibody at the time of stroke. Random-effects models with inverse weights were utilized to calculate pooled odds ratios (OR) with 95% confidence intervals (CIs).

Results: Among 3,241 unique records, 43 studies (39 case-control and 4 cohort studies) were included representing a total of 6,374 patients (mean age 59.0 years, 51.1% men). The pooled prevalence of aPL seropositivity among patients with ischemic stroke was 18.1% (95% CI 17.2%-19.0%) (Figure, Panel A). Patients with ischemic stroke, compared with non-stroke controls, had a higher odds for seropositivity for aPL (OR: 2.94, 95% CI 2.31-3.74, I²=69%) (Figure, Panel B). In sensitivity analysis following removal of outlier studies, similar findings were demonstrated with overall improvement in model heterogeneity (OR: 2.58, 95% CI, 2.21-3.02, I²=20%).

Conclusion: In this analysis, seropositivity for aPL were present in nearly one in five patients with ischemic stroke, significantly more than in the general population, and were associated with an increased odds of stroke. Whether seropositivity for aPL at a single time point is a causal risk factor for stroke warrants further investigation in future prospective studies.