PROJECT SUMMARY This randomized controlled trial will evaluate the impact of a novel race-based stress reduction program on well-being, inflammatory burden, and DNA methylation (DNAm) in older African American (AA) women at risk for cardiometabolic disease (CMD). Although the number of deaths related to CMD continues to decline, that decline has slowed recently with AAs bearing a disproportionate burden. Furthermore, women face more sex- specific risk factors for increased adiposity and AA women have the highest prevalence of obesity, hypertension, and prediabetes compared to all other racial and ethnic groups. Chronic stress is associated with low-grade inflammation and increased CMD risk. Growing evidence demonstrates that stressors such as racism and discrimination are significant contributing factors to psychological distress, low-grade chronic inflammation, and CMD health disparities among minorities, particularly among older AA women who endure the intersection of both racism and sexism across their lifespan. Resilience, Stress, and Ethnicity (RiSE) is a group-based, 8-week intervention that integrates cognitive-behavioral strategies focused on the biopsychosocial impact of racism, racial identity development, and empowerment. Based on our preliminary work, we anticipate that participation in RiSE will reduce psychological distress and inflammation. Further, our previous work demonstrated that women with high levels of perceived discrimination have a greater proinflammatory cytokine response to acute stress and decreased DNAm of genes related to inflammation and hypertension. DNAm is one type of epigenetic process that modulates gene expression by adding or removing methyl groups to DNA in response to the environment. Studies demonstrate that hyper or hypo methylation of genes due chronic stressors, including racism and discrimination are significantly associated with CMD risk. Emerging evidence demonstrates that psychobehavioral interventions may modify methylation of stress response-related genes potentially buffering the impact of psychological stress at the molecular level. However, few studies have examined the impact of a psychobehavioral intervention on changes in DNAm and none have addressed chronic stress in older AA women.Therefore, the specific aims are: (1) Determine the extent to which participation in RiSE decreases stress-related symptoms and inflammatory burden in older AA women at risk for CMD; (2) Evaluate the extent to which RiSE increases the use of adaptive coping versus maladaptive coping strategies in older AA women at risk for CMD; and (3) Determine the extent to which participation in RiSE modifies DNAm of stress response- related candidate genes in older AA women at risk for CMD from baseline to post RiSE intervention. AA women 50 to 70 years of age who are at risk for CMD will be randomized into either an 8-week RiSE program or a health education program. RiSE is an innovative intervention that addresses perceived racism and discrimination at the individual level. Further, RiSE has the potential to improve the health of minority women impacted by racism and discrimination.

PROJECT NARRATIVE Cardiometabolic disease (CMD), often a precursor to cardiovascular disease, is associated with a two-fold risk of mortality from coronary artery disease and is particularly prevalent in African American women. Chronic stress, associated with discrimination and racism, is linked to CMD. This investigation will evaluate the effectiveness of a novel 8-week, group-based empowerment-building program, Resilience, Stress, and Ethnicity (RiSE), in providing sustainable improvement in well-being, inflammation, and DNA methylation with the potential of decreasing risk for CMD in this high-risk population.