503 Stress and Discrimination Predict Cardiovascular Disease in a Population-Based Cohort with Systemic Lupus Erythematosus

Background/Purpose Stress is known to contribute to the development of atherosclerosis in the general population. African American (AA) people are more likely to experience psychosocial and environmental stressors and are three times more likely to develop systemic lupus erythematosus (SLE) than White people. Cardiovascular disease (CVD) is a leading cause of SLE morbidity and mortality. However, the increased CVD risk is not completely attributable to disease activity and traditional risk factors. We examined if psychosocial stress predicts CVD in SLE. Methods Georgians Organized Against Lupus (GOAL) is a population-based cohort of validated SLE patients in Atlanta, Georgia supported by the Centers for Disease Control and Prevention. Sociodemographic information, disease factors, CVD risk factors and social determinants of health measures were collected at baseline in 2016. Potential CVD events were identified by participant report and by matching with the Georgia Hospital Discharge Database for CVD-related codes. Associated medical records were reviewed by study physicians and adjudicated for CVD events (myocardial infarction, angina, transient ischemic attack, thrombotic stroke, and/or peripheral vascular disease) using validated algorithms. After participants with prevalent CVD events through 2016 were identified, CVD-naïve participants were surveilled for incident CVD events from 2017-2021. We analyzed 2 validated measures of psychosocial stress, Perceived Stress Scale (PSS) and Everyday Discrimination Scale (EDS). Univariate and multivariate Cox regression analyses were used to evaluate the ability of PSS or EDS to predict incident CVD. Results Out of 780 participants, 179 (23%) were adjudicated as having had prevalent CVD events through 2016. Two individuals died before reaching 2017. The majority of the remaining 599 CVD-naïve participants were AA (472, 78.8%) or White (115, 19.2%). From 2017-2021, 113 (18.9%) participants were adjudicated as having had an incident CVD event, with a mean time to event of 27.6 months (SD 16.9, range 0.7-60). The proportion of African American participants with incident CVD (94/472) was 19.9% compared to 15.7% in White participants (18/115), though not statistically significant. Those with incident CVD were older, had longer duration of SLE, were less employed, and had more federal insurance than those without CVD. They also had more SLE activity and organ damage, longer glucocorticoid use, and more traditional CVD risk factors. There were no differences in race, ethnicity, and poverty status. Multivariate Cox regression analyses showed the PSS and EDS (table 3. Models 1 and 2) were independent predictors of incident CVD events. Race, glucocorticoid duration, and hydroxychloroquine did not predict incident CVD in either model. Conclusions The burden of CVD remains very high in this SLE cohort. This is the first study in SLE to find that psychosocial stressors (perceived stress and discrimination) independently predict incident CVD events controlling for race/ethnicity, traditional CVD risk factors, and other sociodemographic and disease- related factors. High stress is known to contribute to the development of atherosclerosis in the general population. The disproportionate burden of negative social determinants of health in communities of color may be a significant driver of CVD and other disparities described in SLE. Further research into related causal pathways, mitigating factors, and biologic mechanisms is needed. Lay Summary The burden of cardiovascular disease (CVD) remains very high in this systemic lupus erythematosus (SLE) cohort. This is the first study in SLE to find that psychosocial stressors (perceived stress and discrimination) independently predict incident CVD events controlling for race/ethnicity, traditional CVD risk factors, and other sociodemographic and disease-related factors. High stress is known to contribute to the development of atherosclerosis in the general population. The disproportionate burden of negative social determinants of health in communities of color may be a significant driver of CVD and other disparities described in SLE. Further research into related causal pathways, mitigating factors, and biologic mechanisms is needed.