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

休息活动节律和血压的昼夜节律模式及其潜在的表观遗传机制

• 批准号: 9806535
• 负责人: Nour Makarem
• 金额: $ 12.94万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9806535
• 关键词: Acceleration; Address; Adult; Affect; Age; Aging; Ambulatory Blood Pressure Monitoring; Ancillary Study; Antihypertensive Agents; Award; Behavior; Behavior Therapy; Behavioral; Biological; Biological Aging; Biological Clocks; Biological Markers; Blood Pressure; Cardiovascular Diseases; Cardiovascular system; Circadian Dysregulation; Circadian Rhythms; Circadian desynchrony; Collection; Cues; DASH diet; DNA Methylation; Data; Disease; Disease susceptibility; Eating; Epigenetic Process; Etiology; Event; Frequencies; Funding; Goals; Grant; Guidelines; Health; Human; Hypertension; Incidence; Individual; Instruction; Intervention Studies; Lead; Life; Life Style; Link; Measures; Mediating; Mentors; Methods; Modeling; Modernization; Monitor; Morbidity - disease rate; Multi-Ethnic Study of Atherosclerosis; National Heart, Lung, and Blood Institute; Pathway interactions; Pattern; Periodicity; Pharmaceutical Preparations; Phase; Physiological; Pilot Projects; Population; Predisposition; Preparation; Prevalence; Prevention; Prevention Guidelines; Publications; Reading; Research; Research Activity; Research Priority; Rest; Risk; Risk Factors; Scientist; Sex Differences; Sleep; Societies; Statistical Methods; Training; Training Activity; Variant; Vision; Woman; Work; Writing; age related; apprenticeship; awake; base; cardiovascular disorder risk; cardiovascular risk factor; career; career development; circadian; design; epidemiology study; epigenome; ethnic difference; ethnic disparity; ethnic minority population; hypertension prevention; improved; insight; interdisciplinary approach; methylation pattern; mortality; novel; prognostic significance; prospective; racial and ethnic; sex; statistics; symposium

Project Summary: Nearly half of US adults present with HTN, one of the strongest risk factors for cardiovascular disease (CVD) and a leading cause of CVD mortality. 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 within the 24-h day can alter BP levels and their natural variation patterns. Interestingly, the alarming HTN prevalence rates have paralleled the shift from a predominantly daytime to a delayed lifestyle, in which eating and activity occur at night and sleep is restricted. Intervention studies suggest 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 (DASH) diet and certain anti-hypertensive drugs. However, these studies do not reflect habitual patterns of behavior in a real-life setting, do not capture long-term health effects of milder circadian misalignment that is highly prevalent in the population, and have yet to elucidate underlying mechanisms. The research goal of this K99/R00 award is to evaluate the 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 investigate epigenetic pathways as an underlying mechanism. I am seeking the Pathway to Independence Award to gain the additional training needed to accomplish my long-term career goal: to be an interdisciplinary independent scientist who specializes in the intersection of behavioral risk factors, circadian rhythms, and epigenetics in relation cardiovascular risk. The training component of this project will provide expertise in: 1) circadian concepts and methods, 2) design and analysis of human epigenetics (DNA methylation) studies, 3) advanced statistical methods, and 4) collection and interpretation of ambulatory BP monitoring (ABPM) data. This will be accomplished through formal coursework, directed readings and didactic instruction, research apprenticeships, attendance to scholarly 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) and use non-parametric methods to estimate circadian rhythm of rest-activity patterns. In Aim 1, we will investigate associations of CRAR with HTN prevalence and incidence and elucidate potential sex and racial/ethnic differences. In Aim 2, we will examine the relations between CRAR, epigenetic age (a measure of biological aging based on DNA methylation patterns), and BP and determine whether epigenetic age acceleration mediates associations of CRAR with HTN. To extend this work in preparation for an R01, for Aim 3, we will conduct a pilot study to examine the associations between CRAR, epigenetic age, and 24-h ABPM measures. The training and research activities will result in scientific presentations, publications, and preliminary data and prepare me to successfully compete for R01 funding during the R00 phase.

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