Abstract 4145423: Antiphospholipid Antibodies and Risk of Atherosclerotic Cardiovascular Disease

Background: Antiphospholipid antibodies (aPL) trigger inflammation, vasculopathy, and thrombosis, sharing pathophysiological mechanisms with atherosclerosis. However, their association with incident cardiovascular events has not been defined and may impact predicting cardiovascular disease risk and guiding therapy intensity. Hypothesis: aPL predict the risk of all-cause mortality and cardiovascular disease in primary prevention, independent of traditional cardiovascular risk factors and their therapy. Aim: To determine the association between single-time-point measurement of aPL and atherosclerotic cardiovascular risk in a diverse population without established cardiovascular disease or antiphospholipid syndrome. Methods: This retrospective cohort study included patients from 2004 to 2024, measuring nine aPLs using solid plasma assays: anticardiolipin IgM, IgG, IgA; anti–β2-glycoprotein I IgM, IgG, IgA; and lupus anticoagulant IgM, IgG, IgA. Data were sourced from the TriNetX Global Collaborative Network, a centralized database of deidentified electronic medical records from 120 healthcare organizations. Eligible patients had aPL measurements and no history of cardiovascular disease or antiphospholipid syndrome. In accordance with the 2023 ACR/EULAR laboratory criteria, the group of interest was defined by the presence of high-positive aPL (>80 U), with individuals having negative aPL levels serving as the reference group. Associations between aPL and future cardiovascular events were assessed using Cox proportional hazards models, adjusted for known risk factors, medications, and multiple comparisons. Results: After nearest-neighbor matching for demographics, diagnoses, and medication use, there were 2,801 patients in each group. Over a median follow-up of 3.0 years, patients with high-positive aPL levels were at increased risk for the composite of all-cause mortality, cerebrovascular events, or coronary artery disease (HR 1.15 [95% CI 1.01–1.32]). These patients had higher risks for all-cause mortality (HR 1.25 [95% CI 1.03–1.51]) and cerebrovascular events (HR 1.30 [95% CI 1.02–1.65]), but not for coronary artery disease (P=0.76). The association with cerebrovascular events was primarily driven by stroke (HR 1.36 [95% CI 1.04–1.78]), but not transient ischemic attack (P=0.27). Conclusion: In this cohort study, a single measurement of high-positive aPL was an independent predictor of all-cause mortality and cardiovascular events, particularly stroke.