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

• 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
• 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' 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' 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

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 主动脉僵硬随着年龄的增长明显增加，与高血压，心力衰竭和加速有关 脑老化。左心室（LV）和主动脉之间的异常血流动力耦合有助于 目标器官损伤的发病机理。但是，LV还将机械耦合并拉伸 收缩期间的近端主动脉。与“主动脉弹簧”拉伸相关的力是相当大的 与LV压力产生所需的力相当。 “机械耦合”加载LV，但也加载 将能量存储在主动脉弹簧中，这有助于舒张期间心脏底部的后坐力， 产生促进早期舒张期填充的吸力。主动脉加强破坏这种机械耦合 并在LV长轴上施加不对称载荷，从而损害全局纵向应变（GL）和早期 舒张期填充。机械耦合受损会导致左心（LA）扩大和功能障碍，该功能障碍 增加肺动脉（PA）压力和刚度，导致异常右心（RV）-PA 血液动力学耦合，与年龄相关的PA收缩压增加。 PA的相关增加 脉压可能有助于对肺中的抗性血管进行重塑，从而导致前和合并 毛细血管后肺动脉高压。左右心脏异常限制的结合 心脏输出并有助于保留的LV射血分数（HFPEF），导致心力衰竭综合征。在 年轻，健康的成年人，符合正常导管动脉的符合主动脉界面的低阻抗， 产生阻抗不匹配和波浪反射，从而限制了过多的脉冲能量的传播 进入微循环，导致左心和靶器官之间的最佳“血液动力耦合” 例如大脑。主动脉僵硬会增加主动脉阻抗，降低阻抗不匹配，并导致 有害脉动能量增加向微循环的传播增加，导致微血管 损害，淀粉样蛋白纤维在脑实质中的积累，过早的大脑衰老和认知障碍。 我们将在老年弗雷明汉（Framingham）后代队列中使用传动和超声心动图来测试 假设主动脉刚度会损害主动脉和LV之间的机械耦合，从而减少LV GL和 损害LV舒张功能和LA功能。我们将评估RV结构和功能以及RV-PA耦合 通过超声心动图检验以下假设：LA压力增加会增加PA压力，刚度 和阻抗，会损害RV-PA耦合，并导致与年龄相关的肺动脉增加 收缩压。最后，我们将评估颈动脉输入阻抗和主动脉 - 凝聚耦合以测试 与普通颈动脉和脑血管相比，主动脉症的不成比例增加的假设 输入阻抗会降低阻抗梯度，并增加脉冲流入大脑的渗透率 循环，导致微血管组织损伤，淀粉样蛋白的积累和认知功能受损。