Allostatic Load and the DNA Methylome: Implications for Cardiovascular Health in Pregnancy and Beyond

Hypertensive disorders of pregnancy (HDP) are associated with accelerated cardiovascular disease (CVD) following pregnancy. While studies have demonstrated how psychosocial exposures contribute to the progression from HDP to accelerated CVD, the biological and molecular mechanisms by which chronic stress translates into pathophysiological changes remain uncertain. Allostatic Load (AL) is a quantitative, physiological measure of “wear and tear” from chronic stress. While the K99 phase focused upon the first trimester of pregnancy, the R00 phase extends this line of investigation to evaluate AL patterns/trajectories, DNA methylation, and post-pregnancy CVD at two timepoints following pregnancy. This project is ancillary to the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study I (HHS1; 2-7 years following index pregnancy) and Heart Health Study II (HHS2; 8-12 years following index pregnancy) and will leverage existing data and biospecimens collected during both HHS1 and HHS2. The R00 phase aims are to (1) evaluate AL trajectories and their associations with post-pregnancy cardiovascular disease, and the moderation effects of HDP; and (2) investigate the association between DNA methylation and post-pregnancy cardiovascular disease. Measures of post-pregnancy CVD include incident hypertension, observed at HHS1 and HHS2, as well carotid intima-media thickness observed at HHS2. Previously collected data will be utilized to execute Aim 1, while Aim 2 will utilize existing DNA samples, data cleaning and quality control workflows. This innovative application provides several experimental opportunities to greatly impact multiple fields of research including stress biology, HDP, and post-pregnancy CVD. Findings can inform the development of evidence-based, multi-level interventions that focus improving pregnancy outcomes and cardiovascular health.