Systemic lupus erythematosus (SLE) is a debilitating multisystem, chronic, inflammatory, autoimmune disease that impacts an estimated 1.5 million individuals in the United States alone. Almost 90% of those affected by SLE are women, and African-American women have rates of SLE that are 3 to 4 times higher than women from other racial/ethnic groups. Among women with SLE, premature Cardiovascular Disease (CVD) is a major cause of death and this is particularly true for African-Americans. Compared to African-American women without SLE, African-American women with SLE die from CVD-related causes almost 20 years earlier. This increased risk is not completely due to traditional CVD risk factors (e.g. blood pressure, diabetes, cholesterol, smoking), or SLE factors; thus, there remain major gaps in our understanding of why African American women with SLE bear such a strikingly high burden of early CVD. The proposed project is designed to determine whether aspects of the African-American lived experience-- i.e. social stressors, such as discrimination, financial strain, inadequate social support and early adversity—contribute to atherosclerotic progression and inflammation (markers of early CVD) among African-American women with SLE. Leveraging existing resources from a well-characterized cohort of women with SLE, we will examine the impact of social stressors on the atherosclerotic process and on molecular markers of immunity and inflammation (those linked to CVD in healthy populations and those implicated in SLE-related atherosclerosis) over a 2-year follow up. In order to determine whether these effects are unique to SLE, our sample will consist of 200 African-American women with SLE and 200 comparison women from similar environments. Because African-American women with SLE are already immune-compromised, it is hypothesized that social stressors will prove especially problematic for this group; by exacerbating the inflammatory processes associated with SLE to further increase their risk of atherosclerotic disease. Additionally, given the significant financial and social resources required to manage a chronic illness, we will examine whether certain social stressors (financial strain, inadequate social support) disproportionately impact women with (vs. those without) SLE. Finally, to determine whether some African-American women with SLE are more vulnerable to early CVD than others, we will also examine several SLE factors (e.g. age of onset, disease activity, lupus nephritis) as potential modifiers, among women with SLE only. This project will fill critical gaps in knowledge by examining several understudied, yet highly relevant risk factors for early CVD in a uniquely vulnerable, but frequently overlooked population of women. Findings from the proposed study will be used to identify targets for future intervention.