Abstract 1103: The Relationship Between PAI-1, Corticosterone, And Splenic Activity: Data From The Washington, D.C. Cardiovascular Health And Needs Assessment

Abstract

Background: Chronic psychosocial stress (CS) has been associated with cardiovascular disease (CVD) which disproportionally affects African Americans (AA) at least partially via activation of the neuro-hematopoietic axis. Prior studies suggest plasminogen activator inhibitor 1 (PAI-1) is associated with hypertension, obesity, atherosclerosis, and major adverse cardiac events. Yet, little is known about the connection between CS and PAI-1 and its potential association with the neuro-hematopoietic axis in AA. Research Question: We examined associations between measures of CS and PAI-1 in a community-based cohort of AA residing in resource-limited Washington, D.C. neighborhoods, at risk for CVD. Methods: Participants were enrolled in the Washington, D.C. CV Health and Needs Assessment (DC-CHNA). CS was evaluated using the Cohen Stress Scale questionnaire. Fasting blood samples were taken to measure circulating levels of PAI-1 as well as cortisol and corticosterone, known biomarkers of stress. Participants underwent 18 FDG PET/CT to measure metabolic activity of the amygdala, bone marrow, and spleen, indicators of the neuro-hematopoietic axis. Multivariable linear regression analyses were adjusted for BMI and ASCVD 10-year risk score. Results: The DC-CHNA consisted of AA, the majority of whom were women, (N=60, mean age: 61±10.52, mean BMI: 33±7.85) at intermediate risk for CVD. Higher CS scores associated with higher PAI-1 levels (β=0.32, p=0.02). Higher PAI-1 associated with higher corticosterone (β=0.35, p=0.01) but not cortisol. Additionally, higher corticosterone associated with splenic activity (β=0.46, p=0.03) but not amygdala or bone marrow activity. Subsequently, higher PAI-1 also associated with higher splenic activity (β=0.22, p=0.01), while bone marrow activity was shown to be trending (β=0.14, p=0.06). Conclusions: We found that chronic psychosocial stress is associated with higher PAI-1 levels, which are associated with corticosterone and splenic activity, thus providing a potential link to how CS contributes to disparate CVD risk and health outcomes. Larger longitudinal studies are needed to investigate the predictive and potential therapeutic value of PAI-1 in individuals at risk for CVD.