Abstract Body (Do not enter title and authors here): Background: Social disadvantage, estimated by social determinants of health (SDOH) measures, is associated with subsequent incident hypertension (inc-HTN). We sought to determine whether associations between SDOH and inc-HTN may be mediated by epigenetic changes in DNA methylation represented by GrimAge acceleration (GrimAA).

Methods: The CARDIA study enrolled 5,115 Black and white men and women participants (ppts) in 1985-1986. The current analysis focused on 3,067 participants with SDOH data and without HTN at CARDIA exam year 15 (Y15) in 2000-2001. Social disadvantage was defined by variables representing the 5 domains of SDOH: difficulty paying for basics, medications, or healthcare; food insecurity; census tract poverty; residential racial segregation; and parental education. GrimAA (a summary measure of DNA methylation) at Y15 was calculated as the difference between epigenetic age and chronological age. Inc-HTN was defined as blood pressure ≥140/90 or treatment after Y15. Age-, sex-, and race-adjusted Cox regression models assessed associations between each SDOH variable with inc-HTN prior to formal mediation analysis by GrimAA.

Results: Study ppts had a mean age of 40y, 42.5% self-identified as Black, and 63.6% as female. Greater social disadvantage in every SDOH domain was associated with higher proportions of inc-HTN. Difficulty paying for basics or medications, the summed difficulty paying index, food insecurity, and parental education were each significantly associated with inc-HTN on adjusted Cox regression (Table). For example, those with food insecurity had a 34% higher hazard for inc-HTN (hazard ratio [HR] 1.34; 95% CI 1.12-1.60). Each level of parental education (e.g., completed college vs high school) was associated with 19% lower hazard for inc-HTN (HR 0.81, 95% CI 0.73-0.90). GrimAA mediated 14.6% of the food insecurity/inc-HTN association, and 34.9% of the parental education/inc-HTN association.

Conclusions: Social disadvantage measures are associated with inc-HTN. DNAm measured by GrimAA appears to statistically mediate associations of SDOH with inc-HTN, suggesting potential molecular mechanisms by which SDOH may get “under the skin” to accelerate development of HTN over the life course.