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Introduction: Self-reported experiences of discrimination have been associated with greater risk of incident cardiovascular events and all-cause mortality across racial/ethnic groups. However, questions remain regarding the potential mechanisms through which perceived discrimination may influence cardiovascular risk. Furthermore, the relationship between self-reported discrimination with markers of subclinical cardiovascular disease (CVD) such as atherosclerotic plaque presence, burden, and characteristics remains unclear. We hypothesized that perceived discrimination is associated with subclinical measures of carotid atherosclerosis indicative of greater CVD risk and that inflammation is a mechanism contributing to this relationship.Methods: Late peri- and postmenopausal women without clinical CVD (n=300) completed the Everyday Discrimination Scale, developed in order to assess day-to-day experiences of interpersonal mistreatment, and underwent B-mode ultrasound to assess carotid atherosclerosis. Associations between everyday discrimination and measures of carotid plaque presence, burden (total number of plaques, total plaque area), and characteristics (maximum height, grey-scale median, and calcification) were evaluated using linear and logistic regression models adjusted for demographics, as well as CVD and psychosocial risk factors. Overall circulating inflammatory burden, comprising C-reactive protein, interleukin-6, and fibrinogen was identified via exploratory factor analysis and was evaluated as a potential mediator of the relationship between everyday discrimination and subclinical CVD through the ratio of the natural indirect effect and the total effect by inverse probability weighting.Results: The sample was predominately white (72% white (n=216); 22% black (n=66)), nearly half the women (n=138) had at least one carotid plaque, and 40% (n=120) reported experiencing high levels of everyday discrimination. After adjustment, women who reported high levels of discrimination had a maximum carotid plaque height 0.29 mm higher (p=0.03) than those who reported lower levels of discrimination. Circulating inflammatory burden was identified as a partial mediator of the relationship between high discrimination and carotid plaque height explaining 31% of the relationship. There were no significant associations of plaque presence, burden, or other plaque characteristics with discrimination, and the results did not vary by race/ethnicity.Conclusions: These findings add to the growing evidence that perceived discrimination may be associated with elevated cardiovascular disease risk among women of various racial/ethnic groups. These results suggest that increased inflammatory burden may be a mechanism through which experiences of discrimination may be associated with the development of atherosclerosis in midlife women.