Aortic Dysfunction, Pulsatile Stress and Target Organ Damage in Framingham

弗雷明汉的主动脉功能障碍、脉动应激和靶器官损伤

基本信息

批准号：
8453404
负责人：
Gary Frank Mitchell
金额：
$ 62.49万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-15 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8453404
关键词：
Accounting Affect Age Age-Years Aging Arteries Blood flow Brain Caliber Cardiovascular Diseases Clinical Communities Complex Data Development Diabetes Mellitus Disease Elderly Event Functional disorder Heart Heart Diseases Homeostasis Hypertrophy Impaired cognition Incidence Indium Individual Infarction Intervention Isolated systolic hypertension Kidney Kidney Diseases Kidney Failure Left Ventricular Hypertrophy Left Ventricular Remodeling Lesion Light Macular degeneration Measures Mechanics Microalbuminuria Microcirculation Minority Obesity Organ Participant Pathogenesis Physiology Population Prevalence Process Property Public Health Pulse Pressure Research Resistance Risk Factors Role Societies Source Stress Stroke Structure Testing Ventricular Dysfunction aortic arch arterial stiffness arterial tonometry burden of illness cohort electric impedance hemodynamics men middle age offspring older women pressure prevent public health relevance systolic hypertension vascular bed white matter young adult

项目摘要

DESCRIPTION (provided by applicant): Aortic stiffness increases markedly with advancing age and is associated with incident CVD, stroke, cognitive impairment, white matter brain lesions, and kidney dysfunction. Unfortunately, our current understanding of arterial stiffening and the pathophysiology of elevated pulse pressure (PP) is limited. Recent data from our group suggests that increased forward wave amplitude due to mismatch between ambient flow and an inappropriately smaller aortic diameter accounts for a major component of increased PP in hypertensive individuals and in the community. We have also found markedly nonlinear cross-sectional relations between age and key central hemodynamic measures such as forward wave amplitude and PP. Whether longitudinal changes in hemodynamics will mirror these cross-sectional relations is unknown. Our hypotheses for this proposal are 3 fold: 1) that proximal aortic wall stiffening and mismatch between aortic diameter and flow are major sources of excessive pressure pulsatility in older people, 2) that the consequent increase in pulsatile hemodynamic stress contributes to development of systolic hypertension and target organ damage in the heart, brain and kidneys, and 3) that change in arterial properties will predict incident clinical events. We will test these hypotheses with the following specific aims: Aim 1. To examine risk factors for change in key central hemodynamic measures across an interval of 6 years in the Framingham Offspring and OMNI-I participants. We will perform arterial tonometry in ~3000 Framingham Offspring and minority Omni cohort participants at their next routine Heart Study exam (2011- 2014) to comprehensively characterize arterial stiffness and its change from their previous examination (2005- 2008). Aim 2. To examine relations between observed and predicted longitudinal change in key central hemodynamic measures in order to identify factors associated with discrepancies in longitudinal and cross-sectional age relations. Aim 3. To relate baseline and change in measures of aortic function to baseline and change in measures of target organ damage and incident clinical disease involving the heart, brain and kidneys. The proposed research will characterize longitudinal changes in arterial stiffness with aging and its contribution to the development of cardiovascular disease, stroke and cognitive impairment and renal dysfunction in the community.

描述（由申请人提供）：随着年龄的增长，主动脉僵硬明显增加，并且与事件CVD，中风，认知障碍，白质脑损伤和肾脏功能障碍有关。不幸的是，我们目前对动脉僵硬的理解和升高脉压升高（PP）的病理生理学受到限制。我们小组的最新数据表明，由于环境流和不当较小的主动脉直径不匹配而增加的前向波幅度增加，这是高血压个体和社区中PP增加的主要组成部分。我们还发现，年龄和关键中央血液动力学测量（例如前向波幅度和PP）之间明显的非线性横截面关系。血液动力学的纵向变化是否会反映这些横截面关系是未知的。 Our hypotheses for this proposal are 3 fold: 1) that proximal aortic wall stiffening and mismatch between aortic diameter and flow are major sources of excessive pressure pulsatility in older people, 2) that the consequent increase in pulsatile hemodynamic stress contributes to development of systolic hypertension and target organ damage in the heart, brain and kidneys, and 3) that change in arterial properties will predict incident clinical events.我们将以以下特定目的检验这些假设：目标1。在弗雷明汉后代和Omni-i参与者中，在6年间进行关键中央血液动力学测量的风险因素。我们将在约3000名弗雷明汉后代和少数族裔OMNI队列参与者（2011-2014）中进行大约3000名弗雷明汉后代和少数族裔OMNI队列参与者的动脉静态测量，以全面地表征动脉僵硬及其先前检查（2005- 2008年）的变化。目的2。要检查关键中央血液动力学措施中观察到的纵向变化与预测的纵向变化，以确定与纵向和横截面年龄关系中差异相关的因素。目的3。将基线和主动脉功能的度量的变化与基线和涉及心脏，大脑和肾脏的目标器官损伤和入射临床疾病的度量的变化。拟议的研究将表征动脉僵硬的纵向变化，随着衰老的衰老及其对社区心血管疾病，中风和认知障碍和肾功能障碍的贡献。