251-OR: Cardiac Autoantibodies (AB) Predict Cardiovascular Disease (CVD) in T1D and Are Associated with Cytokine Signatures Linked to CVD Risk

CVD is the leading cause of mortality in T1D; however, only ∼50% of this risk is explained by traditional risk factors. Recent studies show that subjects with T1D in the DCCT developed cardiac autoimmunity, defined by the presence of ≥2 Ab. We tested the hypothesis that some of the unexplained CVD risk in T1D is mediated by Ab-linked cytokine pathways. We measured Ab in serum from 892 post-DCCT EDIC subjects (mean age 49 and T1D duration 28 years), with no CVD events at baseline (Figure). Cumulative incidence of a first CVD event in subjects with 0, 1, and >2 Ab was 2.0%, 8.9%, and 43%, respectively, over 4-year median follow-up. In Cox regression models, ≥2 Ab predicted CVD events with minimal attenuation by known risk factors. Using a 42-plex array to measure baseline serum cytokines in subjects with ≥2 Ab and matched controls without Ab, the ≥2 Ab group showed 3.4-fold odds (95% CI, 1.6-6.1; P In conclusion, in this cohort with longstanding T1D, cardiac Ab identified subjects at high risk for CVD events, potentially through Ab-linked cytokine pathways. These findings raise the possibility to immunologically predict and prevent CVD in T1D. Disclosure G.R. Sousa: None. M. Niewczas: None. M.A. Lipes: None. Funding National Institutes of Health (DK1036909)