Abstract P264: Interleukin-1 β Mediation of Chronic Stress-Related Neural Activity and Trimethylamine- N-oxide - Data From the Washington DC Cardiovascular Health and Needs Assessment

Abstract

Introduction: Chronic stress is a cardiovascular disease (CVD) risk factor but the mechanisms by which it promotes CVD are unclear. Chronic stress can affect amygdalar activity (AmygA), leading to increased levels of activity. We evaluated mediators of the relationship between chronic stress-related amygdalar activity (AmygA) and trimethylamine n-oxide (TMAO), a cardiovascular risk marker. Hypothesis: IL-1 β mediates the association between amygdalar activity and TMAO. Methods: 60 African American adults (93% female, mean age 61±11 years) at risk for CVD living in the Washington DC area participated in a cross-sectional, community-focused study. Participants had a 18 FDG PET/CT to assess chronic stress-related AmygA, phenotyping, and ELISA-based techniques to measure serum cytokines and TMAO. Multivariable regression analyses adjusted for atherosclerotic cardiovascular disease (ASCVD) 10-year risk score and body mass index (BMI) identified associations between AmygA and TMAO. IL-1 β, TNF-α, IL-6, IL-8, IL-17 and IFN-γ were evaluated as mediators of indirect associations between AmygA and TMAO. Results: Multivariable regression modeling revealed significant associations between AmygA and TMAO (β=0.32, p=0.02), AmygA and IL-1 β (β=0.36, p=0.003), and IL-1 β and TMAO (β=0.39, p=<0.001) in the fully adjusted model. IL-1 β mediated the AmygA and TMAO relationship (mediation effect = 43.51%). Conclusions: Chronic stress measured by AmygA directly associates with TMAO, a CVD risk biomarker. This relationship is mediated by IL-1 β, suggesting the potential for chronic stress-related inflammation in the brain-gut axis potentially influencing CVD in underserved communities. These hypothesis-generating results should be studied further in the future by including large, diverse populations.