Abstract Body (Do not enter title and authors here):
Background: Although antiphospholipid antibodies (aPL) are classically associated with excess risk of thrombosis in antiphospholipid syndrome (APS), emerging data suggest that aPLs may confer a prognostic role in patients with cardiovascular conditions who do not fulfill traditional research criteria for APS. We aimed to investigate the prevalence of aPL seropositivity among patients with peripheral artery disease (PAD) and to assess outcomes among those with and without aPL.

Methods: In this study, as part of a larger project (PROSPERO ID CRD420251047305), we systematically searched PubMed and Embase through 3/11/2025 to determine the pooled prevalence of aPL seropositivity among patients with PAD. Despite variation in PAD severity across studies, aPL testing occurred in unselected individuals (rather than by clinical suspicion). aPL positivity was defined as at least one single positive measurement for either anticardiolipin, anti-β2 glycoprotein, or lupus anticoagulant. For studies with longitudinal data available, we assessed a composite outcome of subsequent arterial thrombosis, revascularization failure, amputations, and death stratified by aPL seropositivity. Random-effects models with inverse weights were used to calculate pooled odds ratios (ORs).

Results: Among 2,890 records, we identified 31 studies assessing aPL prevalence and 11 evaluating clinical outcomes (3,364 total patients, mean age 58.6 years, 62.3% men). Seropositivity for at least one aPL was observed in 21.1% of patients with PAD (95% CI, 19.7%-22.5%). aPL seropositivity was associated with a significantly higher odds of the primary outcome (OR: 2.49, 95% CI 1.48-4.18) (Figure). Among patients who underwent revascularization, aPL seropositivity was associated with a higher odds of a failed revascularization procedure (OR: 2.72, 95% CI 1.49-4.98).

Conclusion: aPL seropositivity is present in approximately one-in-five patients with PAD and correlates with a subsequent risk of adverse clinical events. Whether early testing can help inform management strategies and improve outcomes requires further investigation.