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Immune responses differ between men and women, with women at higher risk of developing chronic autoimmune diseases and having more robust immune responses to many viruses, including Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). Although immune dysregulation plays a prominent role in chronic systemic inflammation, a key driver in the development of atherosclerotic cardiovascular disease (ASCVD), standard ASCVD risk prediction scores underestimate risk in populations with immune disorders, particularly women. This review focuses on the ASCVD implications of immune dysregulation due to disorders with varying global prevalence by sex: autoimmune disorders (female-predominant), HIV (male-female equivalent), and HCV (male-predominant). Factors contributing to ASCVD in women with immune disorders, including traditional risk factors, dysregulated innate and adaptive immunity, sex hormones, and treatment modalities, are discussed. Finally, the need to develop new ASCVD risk stratification tools that incorporate variables specific to populations with chronic immune disorders, particularly in women, is emphasized.

Introduction: Arterial stiffness is a precursor for development of hypertension and premature cardiovascular disease (CVD). Physical activity has been associated with lower arterial stiffness among largely White populations, but the types of activity required and whether these findings apply to Blacks remain unknown. We examined whether physical activity levels were associated with arterial stiffness among Blacks in two independent cohorts. Methods: In the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity, 458 Black adults (age 53 ± 10, 39% male) without known CVD living in Atlanta, GA were recruited. Arterial stiffness was measured as pulse wave velocity (PWV) using applanation tonometry (Sphygmocor Inc). Total and domain specific physical activity (work, active living, household, and sport/exercise) were assessed by self-report using the Jackson Heart Study Physical Activity Questionnaire. Multiple linear regression models were used to investigate differences after adjusting for age, gender, blood pressure, diabetes, and smoking. Change in the Framingham Risk Score (FRS) was tested as a potential mediator. Findings were validated in the Emory-Morehouse Partnership to Reduce Cardiovascular Health Disparities (META-Health) --another independent cohort of Black adults (n=60, age 50 ± 10, 25% male). Results: Lower arterial stiffness was associated with higher self-reported levels of sport/exercise (Beta = -0.54 [-1.03, -0.05], p=0.03, highest versus lowest quartile), but not work, active living, household-related physical activities, or the overall physical activity scores. 26.9% of this improvement appeared to be mediated through changes in FRS factors. These findings were confirmed in an independent group of Blacks in META-Health where higher levels of sport/exercise remained associated with lower arterial stiffness (Beta = -1.46 [-2.80, -0.12], p=0.03, highest versus lowest quartile). Conclusion: Higher sport/exercise related physical activity is associated with lower arterial stiffness in Blacks, an association that is only partially attributable to a lower traditional CVD risk factor burden.