Ventricular-vascular coupling in the elderly: lifecourse determinants, trajectories and prognostic significance

老年人的心室-血管耦合：生命历程的决定因素、轨迹和预后意义

基本信息

批准号：
10352456
负责人：
Susan Cheng
金额：
$ 20.89万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10352456
关键词：
Activities of Daily Living Adult Age Aging Alzheimer&apos s Disease Amyloid Amyloid Fibrils Aorta Arteries Blood Vessels Blood capillaries Brain Brain Injuries Cardiac Cardiac Output Cardiovascular system Carotid Arteries Cerebrovascular Circulation Cerebrovascular system Cerebrum Coupled Coupling Data Collection Dementia Deposition Development Diastole EFRAC Echocardiography Elderly Endothelium Evolution Frequencies Functional disorder Funding Generations Heart Heart Abnormalities Heart Atrium Heart Diseases Heart failure Homeostasis Hypertension Hypertrophy Impaired cognition Impairment Left Left Atrial Function Left Ventricular Remodeling Left atrial structure Left ventricular structure Lung Lung diseases Lymphatic Magnetic Resonance Imaging Measures Mechanics Mediating Memory Memory impairment Microcirculation Minority Modification Organ Orthostasis Participant Pathogenesis Penetration Positron-Emission Tomography Pulmonary Hypertension Pulmonary artery structure Pulsatile Flow Pulse Pressure Pump Research Resistance Rest Right Ventricular Function Right ventricular structure Risk Sex Differences Side Stretching Stroke Structure Suction Syndrome Systole Testing Tissues Vascular Cognitive Impairment Ventricular Woman Women&apos s Health age related aging brain arterial tonometry base brain dysfunction brain parenchyma cerebral microvasculature cerebrovascular cognitive function cohort comparative electric impedance follow-up glymphatic system hemodynamics middle age multidisciplinary neurovascular coupling offspring premature preservation pressure prevent prognostic significance prospective proteostasis pulmonary arterial pressure pulmonary arterial stiffening response sex stressor tau Proteins tonometry transmission process ultrasound vascular cognitive impairment and dementia

项目摘要

Abstract Aortic stiffness increases markedly with age and is associated with hypertension, heart failure and accelerated brain aging. Abnormal hemodynamic coupling between left ventricle (LV) and aorta contributes to pathogenesis of target organ damage. However, the LV is also mechanically coupled to and stretches the proximal aorta during systole. The force associated with stretch of the `aortic spring' is considerable, comparable to the force required for LV pressure generation. `Mechanical coupling' loads the LV but also stores energy in the aortic spring, which contributes to the recoil of the base of the heart during diastole, producing the suction that facilitates early diastolic filling. Aortic stiffening disrupts this mechanical coupling and imposes an asymmetric load on the LV long axis that impairs global longitudinal strain (GLS) and early diastolic filling. Impaired mechanical coupling contributes to left atrial (LA) enlargement and dysfunction, which increases pulmonary artery (PA) pressure and stiffness, leading to abnormal right ventricular (RV)-PA hemodynamic coupling, and an age-related increase in PA systolic pressure. An associated increase in PA pulse pressure could contribute to remodeling of resistance vessels in the lung, leading to combined pre- and post-capillary pulmonary hypertension. The resulting combination of right and left heart abnormalities limits cardiac output and contributes to the syndrome of heart failure with preserved LV ejection fraction (HFpEF). In young, healthy adults, the low impedance of a compliant aorta interfaces with normally stiff conduit arteries, creating impedance mismatch and wave reflection that limits the transmission of excessive pulsatile energy into the microcirculation, resulting in optimal `hemodynamic coupling' between the left heart and target organs, such as the brain. Aortic stiffening increases aortic impedance, reduces impedance mismatch, and results in an increased transmission of harmful pulsatile energy into the microcirculation, resulting in microvascular damage, accumulation of amyloid fibrils in brain parenchyma, premature brain aging and cognitive impairment. We will use tonometry and echocardiography in the elderly Framingham Offspring cohort to test the hypothesis that aortic stiffness impairs mechanical coupling between the aorta and LV, reduces LV GLS and impairs LV diastolic function and LA function. We will assess RV structure and function and RV-PA coupling with echocardiography to test the hypothesis that an increase in LA pressure increases PA pressure, stiffness and impedance, impairs RV-PA coupling and contributes to the age-related increase in pulmonary artery systolic pressure. Finally, we will assess carotid input impedance and aorta-carotid coupling to test the hypothesis that a disproportionate increase in aortic as compared to common carotid and cerebrovascular input impedances reduces the impedance gradient and increases penetration of pulsatile flow into the cerebral circulation, resulting in microvascular tissue damage, accumulation of amyloid and impaired cognitive function.

抽象的主动脉僵硬度随着年龄的增长而显着增加，并与高血压、心力衰竭和加速性心力衰竭有关。大脑老化。左心室 (LV) 和主动脉之间的异常血流动力学耦合导致靶器官损害的发病机制。然而，LV 也机械耦合到并拉伸收缩期的近端主动脉。与“主动脉弹簧”拉伸相关的力是相当大的，与产生 LV 压力所需的力相当。 “机械耦合”加载 LV 但也将能量储存在主动脉弹簧中，这有助于舒张期心脏底部的反冲，产生促进早期舒张期充盈的吸力。主动脉硬化破坏了这种机械耦合并对 LV 长轴施加不对称载荷，从而损害全局纵向应变 (GLS) 和早期舒张期充盈。机械耦合受损会导致左心房 (LA) 扩大和功能障碍，增加肺动脉 (PA) 压力和硬度，导致右心室 (RV)-PA 异常血流动力学耦合，以及与年龄相关的 PA 收缩压升高。 PA 相关增加脉压可能有助于肺部阻力血管的重塑，从而导致预和毛细血管后肺动脉高压。由此产生的右心和左心异常的组合限制心输出量增加，并导致左心室射血分数保留 (HFpEF) 心力衰竭综合征。在年轻、健康的成年人，顺应性主动脉与通常僵硬的导管动脉接口的低阻抗，产生阻抗失配和波反射，限制过多脉动能量的传输进入微循环，导致左心和目标器官之间的最佳“血流动力学耦合”，比如大脑。主动脉硬化增加主动脉阻抗，减少阻抗失配，并导致有害脉动能量向微循环的传输增加，导致微血管损伤损伤、脑实质中淀粉样原纤维的积累、大脑过早老化和认知障碍。我们将在老年弗雷明汉后代队列中使用张力测量和超声心动图来测试假设主动脉僵硬会损害主动脉和左心室之间的机械耦合，降低左心室 GLS 和损害左心室舒张功能和左心室功能。我们将评估 RV 结构和功能以及 RV-PA 耦合使用超声心动图来检验 LA 压力的增加会增加 PA 压力、僵硬度的假设和阻抗，损害 RV-PA 耦合并导致肺动脉随年龄增长而增加收缩压。最后，我们将评估颈动脉输入阻抗和主动脉-颈动脉耦合来测试假设与颈总动脉和脑血管相比，主动脉的增加不成比例输入阻抗降低了阻抗梯度并增加了脉动流进入大脑的渗透循环，导致微血管组织损伤、淀粉样蛋白积累和认知功能受损。