Epidemiology of blood pressure responses to perturbations: Correlates and prognosis for vascular risk, end-organ damage, cognitive aging and preclinical Alzheimer's disease

血压对扰动反应的流行病学：血管风险、终末器官损伤、认知衰老和临床前阿尔茨海默病的相关性和预后

• 批准号: 10744554
• 负责人: Vasan S Ramachandran
• 金额: $ 62.7万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10744554
• 关键词: Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Area; Atherosclerosis; Back; Blood Pressure; Blood Vessels; Brain; Brain imaging; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Clinical; Cognition; Cognitive aging; Cohort Studies; Communities; Data; Devices; Diabetes Mellitus; Disease; Dyslipidemias; Early Diagnosis; Elderly; Enrollment; Epidemiology; Event; Exercise; Family; Formulation; Funding; Future; Generations; Health; Health Transition; Heart; Heart Diseases; Heart Rate; Heritability; Homeostasis; Hour; Human; Hypertension; Impaired cognition; Impairment; Injury; Isometric Exercise; Isotonic Exercise; Kidney; Left Ventricular Hypertrophy; Life course epidemiology; MRI Scans; Machine Learning; Magnetic Resonance Imaging; Measures; Memory; Microalbuminuria; Minority; Modification; Neurocognitive; Obesity; Organ; Orthostasis; Outcome; Participant; Pattern; Perfusion; Peripheral; Pharmaceutical Preparations; Phase; Phenotype; Physiologic Monitoring; Positioning Attribute; Positron-Emission Tomography; Postural adjustments; Prognosis; Property; Psyche structure; Race; Recovery; Reflex action; Renal function; Rest; Risk; Risk Assessment; Risk Factors; Sample Size; Smoking; Standardization; Stimulus; Stress; Stroke; Testing; Validation; Walking; absorption; adverse outcome; aging brain; arterial stiffness; brain health; cardiovascular disorder risk; cohort; endophenotype; hemodynamics; high dimensionality; indexing; men; middle age; mild cognitive impairment; neurocognitive test; neuroimaging; normal aging; outcome prediction; pathological aging; pre-clinical; predictive tools; prodromal Alzheimer' s disease; rate of change; resilience; response; sex; stressor; trait; vascular risk factor

The ability of blood pressure (BP) and heart rate (HR) to ‘bounce back’ after stimuli may indicate hemodynamic resilience, a property not reflected by resting BP or HR. Information on BP and HR resilience in humans is lacking. High-dimensional response-recovery curves (RRCs) for phasic beat-to-beat BP and HR data after perturbations can aid the formulation of dynamic indicators of resilience (DIORs). Thus, stochastic diurnal fluctuations in BP and HR may be DIORs reflecting micro-recoveries from small natural perturbations during daily activities (micro-stressors). RRCs for BP and HR after stimuli that evoke distinct hemodynamic responses (mental tasks, posture change, and exercise) may identify complementary DIORs that reflect risks of hypertension (HTN), BP-sensitive target organ damage (TOD), brain aging, impaired cognition and preclinical Alzheimer’s disease (AD), and cardiovascular disease (CVD). We hypothesize that: a. reduced hemodynamic resilience is associated with altered BP and HR responses to stressors marked by greater autocorrelation, increased variance and delayed recovery after a stimulus; b. BP and HR resilience metrics (DIORs) cluster within families and are influenced by antecedent trajectories of risk factors, arterial stiffness, prevalent target organ damage (TOD), brain aging, impaired cognition and preclinical AD, and subclinical atherosclerosis; c. DIORs of BP and HR will enhance prediction of adverse brain imaging, neurocognitive (including AD) and cardiovascular outcomes. We will test these hypotheses by measuring BP and HR responses to four standardized, graded and complementary stressors (mental stress [Stroop test], orthostasis; isotonic [handgrip] and isometric [3-minute walk] exercise) in 3374 participants in the third Generation (Gen3) and minority (Omni2) Framingham Study cohorts. Our aims are three-fold: Aim 1. Characterize the phasic beat-to-beat BP and HR responses to four optimally sequenced standardized perturbations in 3374 middle-aged Framingham Gen3/Omni2 participants at their fourth exam (2021-2024). We will plot dynamic RRCs for each stimulus and describe patterns by age, sex and cohort (white vs. minority). We will estimate DIORs, formulate age-specific reference limits and quantify their heritability. Aim 2. Evaluate the cross-sectional relations of BP and HR responses to the four standardized perturbations. We will relate RRC metrics and related DIORs, and binary BP responses to the following: CVD risk factors; renal function; longitudinal trajectories of resting BP and HR, arterial stiffness, and cardiac mass; subclinical atherosclerosis; prevalent BP-sensitive TOD including MRI brain aging indices; neurocognitive test scores, preclinical Alzheimer’s disease (AD) and related disorders, and prevalent CVD. Aim 3. Relate RRC metrics for BP and HR to incident HTN, mild cognitive impairment, pre-clinical/prodromal AD, and CVD. We will identify a parsimonious set of incrementally predictive DIORs. In summary, we will characterize hemodynamic resilience and relate DIORs to brain aging traits, preclinical AD and CVD in a well phenotyped community-based cohort.

血压（BP）和心率（HR）在刺激后“反弹”的能力可能表明血液动力学弹性，这是静息BP或HR反射的特性。缺乏有关BP和人力资源弹性在人类中的信息。在扰动之后，用于阶段性Beat-Beat BP和HR数据的高维响应回收曲线（RRC）可以帮助弹性的动态指标（DIORS）的公式。这就是BP和HR中随机的昼夜波动，可能是二极管，反映了日常活动期间小型自然扰动的微型造成的（微压力）。刺激后BP和HR的RRC引起了独特的血液动力学反应（心理​​任务，姿势变化和运动）可能会识别出反映高血压风险（HTN），BP敏感靶心器官损伤（TOD），大脑衰老，认知和临床上的阿尔兹氏病（CARTIAL ALZHEIMER病）的完整Diors（HTN）和（CARTAIMER疾病）和疾病（CARDASIBASIRAINT）和（CARDASIBASTIAL疾病（CARDASIBAST）和CARDASIBASTRIANT（CARDAIMAID）。我们假设：血液动力学弹性的降低与BP的改变和HR对压力源的改变有关，该压力源以更大的自相关，差异增加和刺激后的恢复延迟； b。 BP和HR弹性指标（DIORS）群集中在家庭中，受危险因素，动脉僵硬，普遍的靶心器官损伤（TOD），脑老化，认知和临床前AD和临床前AD以及亚周期性动脉粥样硬化的影响； c。 BP和人力资源的DIOR将增强对脑成像，神经认知（包括AD）和心血管结局的预测。我们将通过测量对四个标准化，分级和互补压力源的BP和HR响应（精神压力[Stroop测试]，正骨；等距[手夹]和等距[3分钟步行]运动）来检验这些假设。我们的目标是三个方面：目标1。在3374年中期的Framingham Gen3/Omni2参与者（2021-2024）中，对四个最佳测序的标准化扰动的阶段性BET-BP和HR响应。我们将为每种刺激绘制动态RRC，并按年龄，性别和队列描述模式（白人与少数群体）。我们将估计Diors，制定特定年龄的参考限制并量化其遗传力。 AIM 2。评估BP和HR对四个标准化扰动的响应的横截面关系。我们将联系RRC指标和相关的Diors，以及对以下二进制BP的响应：CVD风险因素；肾功能；静止BP和HR的纵向轨迹，动脉刚度和心脏质量；亚临床动脉粥样硬化；普遍的BP敏感TOD，包括MRI脑老化指数；神经认知测试评分，阿尔茨海默氏病（AD）和相关疾病以及普遍存在的CVD。 AIM 3。将BP和HR的RRC指标与入射HTN，轻度认知障碍，临床前/前驱AD和CVD相关联。我们将确定一组渐进式预测的Diors集。总而言之，我们将在一个基于良好的基于​​社区的队列中，表征对脑老化特征，临床前AD和CVD的血液动力学弹性和相关的Diors。