Circadian Pattern of Rest-Activity Rhythms and Blood Pressure and the Underlying Epigenetic Mechanisms

Nearly half of US adults present with HTN, a leading risk factor for CVD. Blood pressure (BP) displays a circadian rhythm, and abnormalities in diurnal BP variation are linked to CVD morbidity and mortality. Emerging evidence suggests that the circadian rhythmicity of behavioral factors can alter BP levels and their natural variation patterns. Intervention studies indicate that the effect of circadian disruption on BP is similar in magnitude but opposite in direction to that of the Dietary Approaches to Stop Hypertension and certain anti-HTN drugs. However, these studies do not reflect habitual patterns of behavior in a real life setting, do not capture long-term effects of milder circadian misalignment that is highly prevalent in the population, and have yet to elucidate underlying mechanisms. The research goal of this career development award is to evaluate associations of circadian rest-activity rhythms (CRAR), a measure of circadian rhythmicity in the free-living setting, with HTN risk and diurnal BP variation and examine epigenetic pathways as an underlying mechanism. I am seeking this award to gain additional training needed to accomplish my career goal: to be an interdisciplinary independent scientist who specializes in the intersection of behavioral factors, circadian rhythms, and epigenetics in relation to cardiovascular risk. The training component of this project will provide expertise in: 1) circadian concepts and methods, 2) epigenetics, and 3) ambulatory BP monitoring (ABPM) through coursework, didactic instruction, apprenticeships, seminars and conferences, and mentored career development activities including grant writing. The research component of this project will leverage objective sleep and activity data from the Multi-Ethnic Study of Atherosclerosis (MESA) to estimate circadian rhythm of rest-activity patterns. In Aim 1, we will investigate associations of CRAR with HTN prevalence and incidence in MESA and elucidate sex and racial/ethnic differences. In Aim 2, we will conduct a new study to examine the associations between CRAR and 24-h ABPM measures. In Aim 3, we will examine the relations between CRAR, epigenetic age (a measure of biological aging based on DNA methylation patterns), and BP in MESA and determine whether epigenetic age acceleration mediates associations of CRAR with HTN. The training and research activities will result in scientific presentations, publications, and prepare me to successfully compete for R01 funding. (AHA Program: Career Development Award)