Hypertension and epigenetic aging: socio-biological pathways of health disparity.

Abstract

Hypertension incidence increases with age, with its highest burden in elderly African Americans (AAs). But socio-biological aging pathways underlying this difference are not well characterized, with a substantial paucity of epigenetic studies on hypertension-related racial disparity in the elderly. We primarily examined epigenetic aging acceleration (aging accel) in the prospective development of hypertension and secondarily investigated the extent to which adverse social exposures mediated AAs' greater aging accel and, jointly with increased aging accel, explained their greater risk of hypertension outcomes. We obtained global-level DNA methylation and clinical data, social determinants of health (SDOH), and physiological data from > 1,500 postmenopausal women in the Women's Health Initiative. Hypertension outcomes were followed for 3-year short-term and a mean of 17-year longer-term periods. Levine's aging accel was estimated, and mediation analyses were performed with SDOH and aging accel via Sobel and Multiple Mediation Analysis. Greater epigenetic aging was associated with hypertension outcomes during the short-term follow-up. While the lower level of SDOH was related to greater aging accel, its influence on greater aging accel in AAs than whites varied by SDOH type and, in combination, was partial (range, 1-26%). Finally, a group of SDOH and aging accel, both separately and jointly, mediated AAs' greater incidence of hypertension to a limited extent during both short-term and longer-term follow-up periods. Our study contributes to better understanding of socio-biological hypertensive pathways shared by aging processes, which may inform risk stratification in the elderly in hypertension prevention and racial disparity.