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

• 批准号: 8082180
• 负责人: Gary Frank Mitchell
• 金额: $ 67.52万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 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/8082180
• 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; systolic hypertension; vascular bed; white matter; young adult

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. PUBLIC HEALTH RELEVANCE: Aortic stiffness increases markedly with advancing age and is associated with increased pulse pressure, 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 is limited. 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）：主动脉僵硬度随年龄增长而显著增加，并与CVD、卒中、认知障碍、白色脑病变和肾功能障碍相关。不幸的是，我们目前对动脉硬化和脉压（PP）升高的病理生理学的理解是有限的。我们组的最新数据表明，由于周围血流和不适当的较小主动脉直径之间的不匹配而导致的前向波振幅增加是高血压患者和社区中PP增加的主要组成部分。我们还发现年龄和关键的中枢血流动力学指标（如前向波振幅和PP）之间存在明显的非线性横截面关系。血流动力学的纵向变化是否反映了这些横截面关系尚不清楚。我们对这一建议的假设有三个方面：1）近端主动脉壁硬化和主动脉直径与血流之间的不匹配是老年人过度压力脉动的主要来源，2）脉动血流动力学应力的随之增加有助于收缩期高血压的发展和心脏、大脑和肾脏中的靶器官损伤，以及3）动脉特性的变化将预测偶发的临床事件。我们将测试这些假设与以下具体目标：目标1。在Frachial Offspring和OMNI-I受试者中检查6年期间关键中枢血流动力学指标变化的风险因素。我们将在下一次常规心脏研究检查（2011- 2014年）中对约3000名Frachial Offspring和少数Omni队列参与者进行动脉张力测定，以全面表征动脉硬度及其相对于既往检查（2005- 2008年）的变化。目标二。检查观察到的和预测的关键中心血流动力学指标的纵向变化之间的关系，以确定与纵向和横断面年龄关系差异相关的因素。目标3。将主动脉功能指标的基线和变化与靶器官损伤指标的基线和变化以及涉及心脏、脑和肾脏的偶发临床疾病相关。拟议的研究将描述动脉硬度随年龄增长的纵向变化及其对社区心血管疾病、中风、认知障碍和肾功能障碍发展的贡献。 公共卫生关系：主动脉僵硬度随着年龄的增长而显著增加，并与脉压增加、发生CVD、卒中、认知障碍、白色脑病变和肾功能障碍相关。不幸的是，我们目前对动脉硬化和脉压升高的病理生理学的理解是有限的。拟议的研究将描述动脉硬度随年龄增长的纵向变化及其对社区心血管疾病、中风和认知障碍以及肾功能障碍发展的贡献。