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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.

摘要