Psychosocial stressors have a significant adverse impact on cardiovascular health. While better medical treatments and increased emphasis on healthy lifestyle have improved cardiovascular health for many in the United States over the past 50 years, there are persistent inequities in cardiovascular disease (CVD) rates, with the highest rates among populations burdened by chronic exposure to psychosocial stressors such as discrimination and anxiety, among others. Genetic factors may interact with these stressors further influencing the rates of CVD in these populations. The purpose of this dissertation is to examine associations among psychosocial stressors and other CVD risk factors, and the influence of genetic variations on these associations in populations burdened with significant cardiovascular health inequities. Specific aims of this dissertation were to: (1) systematically review instruments measuring ethnic discrimination in Hispanic populations; (2) examine the association between psychosocial stressors and other CVD risk factors in adults with a high burden of health disparities who are at-risk for CVD; and (3) explore the moderation effect of genetic variants on the relationships between psychosocial stressors and CVD risk factors. This dissertation includes three original manuscripts. The first specific aim was addressed by the first paper which is a systematic review of psychometrically tested instruments used to measure ethnic discrimination is Hispanic adults. Six instruments were reviewed. Of these, the “Experiences of Discrimination” instrument, available in both English and Spanish, was a valid and reliable instrument that provided the most concise measure of lifetime experiences of ethnic discrimination in Hispanic adults. Specific aims two and three were addressed by the second and third papers. The second paper was a secondary analysis of data examining the association between anxiety and inflammation, and the moderation of this relationship by single nucleotide polymorphisms (SNPs) associated with systemic inflammation, including rs1205, rs1800797, and rs4129267, located on the CRP gene, IL-6 gene, and IL-6R gene, respectively. Findings revealed that only the IL-6R SNP, rs4129267, moderated the association between anxiety and inflammation. In the final paper, results are reported from a study conducted to assess whether experiences of ethnic discrimination predict depressive symptoms in Hispanic adults, and to examine if a SNP on the COMT (catechol-o-methyltransferase) gene moderated this relationship. Results revealed that experiences of ethnic discrimination and COMT genotype are independently associated with increased depressive symptoms. The findings from the studies conducted for this dissertation suggest that addressing psychosocial stressors such as experiences of discrimination and anxiety is critical to cardiovascular health promotion. Further, the results provide preliminary evidence of moderating effects of genetic variants on associations between psychosocial stressors and CVD risk. These findings fill an important gap in the body of knowledge related to CVD inequities in populations burdened by psychosocial stressors. Further research is needed to better understand the effects of such stressors as experiences of discrimination on CVD and genetic variants explore the unique experiences of these populations which may affect their CVD risk, as well as exploration into how best integrate genetics into CVD prevention efforts to maximize the impact of interventions.