Allostatic Load and Race: Implications for Cardiovascular Health in Pregnancy and Beyond

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PROJECT SUMMARY/ABSTRACT For decades, pregnant individuals who identify as Black have been considered at greatest risk for hypertensive disorders of pregnancy (HDP). HDP often follow individuals well past pregnancy, presenting as accelerated cardiovascular disease (CVD), which also disproportionately affects Black females. Mechanisms by which implications of race, a complex social structure, become biologically embedded and translate into pathophysiology remain unknown. Allostatic Load (AL) and is inclusive of race-related stress. The purpose of the proposed K99/R00 is to provide the candidate with adequate training and experience to investigate health disparities, AL and omics- based biomarkers, within the context of pregnancy and beyond. The K99 phase aims are to (1) evaluate the effect of first-trimester AL on the association between self-identified race and HDP, (2) evaluate the association between first-trimester AL index and genetic variation, and (3) investigate the effect of first-trimester DNA methylation on the association between first-trimester AL index and preeclampsia, the HDP with the greatest racial disparity. This project is ancillary to the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to- be Heart Health Study (nuMoM2b-HHS) and leverages existing data previously collected for nuMoM2b-HHS. Previously collected first-trimester clinical and GWAS data and recently generated DNA methylation data will be utilized to accomplish aims 1, 2, and 3. The proposed K99 training plan includes expert mentorship, meetings and seminars, coursework, and conferences, to achieve competency in (A) mechanisms of HDP/post-pregnancy cardiovascular health, (B) health disparities research, (C) bioinformatics and analysis of omics data, and (D) professional career development. The R00 phase extends this line of investigation to cardiovascular health at two timepoints, 2-7 and 7-12 years, following pregnancy in the same cohort. The R00 phase aims are to (1) evaluate the effect of AL index trajectories on the relationship between self-identified race and post-pregnancy cardiovascular health and (2) evaluate the association between DNA methylation trajectory and post-pregnancy cardiovascular health. As with the K99 phase, previously collected data will be utilized to execute aim 1, while aim 2 will employ existing DNA samples, data cleaning and quality control pipelines. This innovative application provides several experimental opportunities to greatly impact multiple fields of research including: AL, HDP, post-pregnancy CVD, and racial disparities of each. Findings will inform the development of evidence-based interventions that focus on reducing health disparities and improving pregnancy outcomes and cardiovascular health in females.