Cytomegalovirus, midlife inflammation, and subclinical cardiovascular disease: the Study of Women's Health Across the Nation

Cytomegalovirus (CMV) is a common beta herpesvirus with over half of adults in the US infected by age 40 and higher seroprevalence among women than men. Though most acute CMV infection in immunocompetent individuals is mild or asymptomatic, following acute infection the virus remains in a latent state with the potential for reactivation across the lifecourse increasing risk of the creation of a chronic inflammatory state, a well appreciated component of accelerated biological aging. Chronic inflammation from any cause can lead to deleterious effects across all organ systems, resulting particularly in later midlife increased risk of metabolic and cardiovascular disease (CVD) in women. There has been mixed evidence implicating CMV seropositivity (CMV+) in the development of CVD and CVD-related mortality. A major limitation of many studies of CMV+ and CVD risk are that such studies do not adequately capture the critical window of physiologic and inflammatory changes that occur in women during the midlife. In the proposed K01, I will obtain the necessary training in aging and field methods to address these research gaps and pursue an independent research career. My research objectives are to a) describe the midlife prevalence of CMV+ within the SWAN cohort and relate CMV+ to subclinical cardiovascular outcomes; b) examine the effect of midlife inflammation on the relationship between CMV+ and carotid intima media thickness; and c) explore changes in IgG antibody level of multiple herpesviruses across the midlife, and to examine the relationship between individual-level change in IgG level and subclinical CVD outcomes. I hypothesize that that individuals with prior CMV infection will have worse subclinical CVD outcomes than those without CMV, particularly in the absence of other common inflammatory conditions such as morbid obesity and type 2 diabetes. To test these hypotheses, I will utilize longitudinal data and banked specimens from the Study of Women’s Health Across the Nation (SWAN), a multi-site cohort of midlife women transitioning into late adulthood. I will conduct this work at the University of Michigan School of Public Health, supported by an interdisciplinary research team that will guide my training in 1) aging and cardiovascular disease epidemiology; 2) immunology and immune-related aging; and 3) practical skills in the development and implementation of prospective data collection methods. By thoroughly evaluating the connections between CMV, midlife inflammation, and CVD we can improve preventative care by identifying those who might be at increased risk for CVD regardless of the presence of other risk factors. This research will also underscore the importance of nontraditional risk factors for cardiovascular disease in women. This grant is critical to meeting the National Institute on Aging’s strategic goal of better understand the biology of aging and its impact on the prevention, progression, and prognosis of disease, and the NIH Initiative on Women’s Health Research goal of developing personalized prevention strategies for cardiovascular disease in women. This award will help launch my independent research career evaluating the etiologic intersections of chronic and infectious disease. Project Number: 1K01AG092928-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Aleda Leis | Institution: UNIVERSITY OF MICHIGAN AT ANN ARBOR, ANN ARBOR, MI | Award Amount: $127,710 | Activity Code: K01 | Study Section: Special Emphasis Panel[ZRG1 EPH-P (90)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11299311