Multi-level drivers of pregnancy-related cardiovascular outcomes across the life-course - PROJECT SUMMARY In the U.S., cardiovascular disease (CVD) is the number one cause of death in women, claiming the life of one in five women. Moreover, perinatal cardiovascular conditions are the leading causes of maternal mortality, accounting for 33.6% of pregnancy-related deaths. Perinatal cardiometabolic dysfunction (i.e. hypertensive disorders of pregnancy or gestational diabetes) also heightens women's CVD risk long after childbirth. The rate of these adverse outcomes has been rising in recent decades, with significant geographic and population variation that persists beyond pregnancy. Yet, underlying drivers of these patterns are severely underexplored. Pregnancy-related short- and long-term CVD risk may be shaped by the community contexts in which women grow, live, and age. Specifically, community disinvestment (i.e. geospatial clustering of limited resources) may determine the quality of neighborhood environments, the prevalence of psychosocial stressors and assets, and access to economic opportunities before, during, and long after pregnancy. Impacts compound with individuallevel stressors to exacerbate CVD risk throughout the life span. In turn, healthy coping resources may provide a protective buffer. However, the extent to which community disinvestment over the life-course influences cardiometabolic health during and long-after pregnancy, and the role of psychosocial stressors and assets remains unknown. Disentangling these multi-level pathways is key in identifying points of intervention across the life span. This project will fill critical knowledge gaps by elucidating the mechanisms by which community disinvestment across the life-course influences perinatal cardiometabolic dysfunction and short- and long-term CVD risk following pregnancy and will evaluate the moderating role of psychosocial stress and social support. The central hypothesis is that community disinvestment increases cardiometabolic dysfunction in pregnancy, which mediates its impact on CVD risk long after childbirth. This project will generate a novel multi-dimensional community disinvestment index, harmonize birth hospitalization files of >4. 7 million pregnant women from California, Louisiana, Michigan, and Massachusetts, and pool data on more than 60,000 parous women (age 45+) from two national cohort studies (REasons for Geographic and Racial Differences in Stroke study and the Women's Health Initiative). This innovative study will provide rigorous evidence illuminating multifactorial early intervention targets aimed at preventing CVD in women. It leverages the candidate's background in social epidemiology and mentors with expertise in causal inference, community-level factors, CVD, and perinatal epidemiology to build additional skills in 1) pathophysiology of cardiometabolic dysfunction in pregnancy and long-term CVD risk, 2) data harmonization, and 3) advanced causal inference methods including causal mediation and quasi-experimental approaches to better estimate causal impacts of community exposures for solution-oriented intervention strategies. The synergistic research and training will prepare the candidate for a successful independent research career that advances maternal cardiovascular health across the life-course.
