CIRCADIAN PATTERN OF REST-ACTIVITY RHYTHMS AND BLOOD PRESSURE AND THE UNDERLYING

休息活动节律和血压的昼夜节律模式及其基础

• 批准号: 10552581
• 负责人: Nour Makarem
• 金额: $ 23.78万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10552581
• 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; Life; Life Style; Link; Measures; Mediating; Mentors; Methods; Modeling; Modernization; 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; Research; Research Activity; Research Priority; Rest; Risk; Risk Factors; Scientist; Sex Differences; Sleep; Societies; Statistical Methods; Strategic vision; Training; Training Activity; Variant; Woman; Work; Writing; age related; apprenticeship; awake; cardiovascular disorder risk; cardiovascular risk factor; career; career development; circadian; design; epidemiology study; epigenome; ethnic difference; ethnic disparity; ethnic minority; hypertension prevention; improved; insight; interdisciplinary approach; methylation pattern; mortality; novel; prognostic significance; prospective; racial difference; racial minority; risk prediction; 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.

项目摘要： 美国近一半的成年人出现了HTN，这是心血管疾病（CVD）最强的危险因素之一 以及CVD死亡率的主要原因。血压（BP）表现出昼夜节律，异常 昼夜BP的变化与CVD的发病率和死亡率有关。新兴证据表明昼夜节律 在24小时内行为因素的节奏性可以改变BP水平及其自然变异模式。 有趣的是，令人震惊的HTN患病率与从白天的转变到 延迟的生活方式，夜间饮食和活动受到限制。干预研究建议 昼夜节律破坏对BP的影响在幅度上相似，但在方向上与 饮食中停止高血压（DASH）饮食和某些抗高血压药物的方法。但是，这些 研究不能反映在现实生活中的行为习惯模式，不要捕获长期的健康影响 在人群中高度普遍的温和昼夜节律的未对准且尚未阐明基础 机制。该K99/R00奖的研究目标是评估昼夜节律活动的关联 节奏（crar）是自由生活环境中昼夜节律的量度，具有HTN风险和昼夜BP 变异和研究表观遗传途径是一种基本机制。我正在寻找通往 独立奖，以获得实现我长期职业目标所需的额外培训：成为一个 跨学科独立科学家专门研究行为风险因素，昼夜节律 关系心血管风险的节奏和表观遗传学。该项目的培训部分将提供 专业知识：1）昼夜节律概念和方法，2）人类表观遗传学的设计和分析（DNA 甲基化）研究，3）高级统计方法，4）卧床BP的收集和解释 监视（ABPM）数据。这将通过正式的课程，定向阅读和教学来实现 教学，研究学徒制，学术研讨会和会议的出席以及指导职业 开发活动，包括赠款写作。该项目的研究组成部分将利用目标 来自动脉粥样硬化（MESA）多民族研究的睡眠和活动数据并使用非参数 估计休息活性模式的昼夜节律的方法。在AIM 1中，我们将调查 具有HTN患病率和发病率并阐明潜在的性别和种族/种族差异的crar。在AIM 2中， 我们将检查crar，表观遗传年龄（基于DNA的生物衰老的度量）之间的关系 甲基化模式）和BP，并确定表观遗传年龄加速度是否介导 带有HTN的crar。为了延长这项工作以准备R01，对于AIM 3，我们将进行试点研究 检查crar，表观遗传年龄和24小时ABPM测度之间的关联。培训和 研究活动将导致科学演示，出版物和初步数据，并为我做好准备 在R00阶段成功竞争R01资金。