Abstract Body (Do not enter title and authors here): Background: Antiphospholipid syndrome (APS) predisposes patients to thrombosis and cardiac valve lesions (e.g., Libman-Sacks endocarditis). These vegetations, though sterile, may serve as a nidus for infection. The risk of infective endocarditis (IE) and other serious infections in APS patients within large populations remains poorly quantified, representing a key knowledge gap.
Research Questions/Hypothesis: To quantify the risk of the primary outcome, IE, and secondary outcomes of MRSA sepsis and MSSA sepsis, associated with APS using a large, nationally representative inpatient database.

Methods/Approach: This retrospective cross-sectional study utilized the Nationwide Inpatient Sample (NIS) database from 2016 to 2020. Hospitalized patients aged 18-75 with APS were compared to those without APS. Patients with major pre-existing risks for IE or significant confounders (e.g., prosthetic valves, specific congenital/rheumatic heart diseases, ESRD) were excluded. Multivariable logistic regression was used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs), adjusting for age, sex, race/ethnicity, hospital region, primary payer, median household income, and Systemic Lupus Erythematosus (SLE) status.
Results/Data: A total of 297,459 patients met inclusion criteria; 223 hospitalizations (0.075%) had an APS diagnosis. APS patients were significantly younger (mean age 46.9 ± 14.4 vs. 50.8 ± 14.6 years, p<0.001) and more often female (72.6% vs. 40.0%, p<0.001). Unadjusted analyses revealed higher IE prevalence in APS (8.5% vs. 4.3%, p = 0.002), MRSA sepsis (14.3% vs. 8.9%, p = 0.004), and MSSA sepsis (15.2% vs. 9.6%, p = 0.004). In multivariable analysis, APS was significantly associated with over double the odds of IE (aOR 2.03; 95% CI 1.22–3.37; p = 0.007). APS also conferred increased risks of MRSA sepsis (aOR 1.75; 95% CI 1.18–2.58; p=0.005) and MSSA sepsis (aOR 1.86; 95% CI 1.28–2.70; p=0.001). In-hospital mortality within the IE cohort was not significantly different (0.2% vs. 0.1%, p = 0.543).

Conclusion(s): APS emerged as a significant independent risk factor for IE, MRSA, and MSSA sepsis in this nationwide analysis. These findings suggest a broader vulnerability to infection in APS, highlighting the critical need for increased clinical suspicion, vigilant monitoring, and potentially tailored prophylactic or treatment approaches for severe infections in these patients.