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Midlife cardiovascular stress physiology and preclinical cerebrovascular disease

中年心血管应激生理学与临床前脑血管疾病

基本信息

批准号：
10720054
负责人：
Peter J Gianaros
金额：
$ 77.06万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10720054
关键词：
Accounting Acute Adult Alzheimer&apos s Disease Baroreflex Behavioral Biological Biological Testing Blood Pressure Blood Vessels Blood flow Brain Brain imaging Cardiac Output Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cerebrovascular Disorders Cerebrum Clinical Communities Coronary heart disease Data Dementia Disease Marker Elderly Endothelium Equation Exhibits Failure Future Goals Hippocampus Hypertension Impaired cognition Impairment Individual Individual Differences Ischemic Stroke Knowledge Lesion Link Liquid substance Measures Medial Mediating Mediation Mediator Modeling National Heart, Lung, and Blood Institute Outcome Pathway interactions Penetration Peripheral Peripheral Resistance Persons Phenotype Physiologic pulse Physiology Prevention Protocols documentation Public Health Reaction Reproducibility Research Risk Robin bird Role Sampling Severities Site-Directed Mutagenesis Source Specific qualifier value Strategic vision Stress Temporal Lobe Testing Tissues Vascular Cognitive Impairment Vascular Dementia Vascular Diseases Vascular remodeling Visit Visual Woman aged arterial stiffness cardiovascular health cardiovascular risk factor cerebrovascular cerebrovascular health cohort dementia risk endothelial dysfunction hemodynamics male middle age neurovascular injury pre-clinical pressure psychological stressor reactive hyperemia risk stratification sex social stem stress reactivity stressor transmission process volunteer white matter

项目摘要

Abstract The goal of this project is to determine the extent to which cardiovascular stress physiology in midlife relates to the severity of preclinical cerebrovascular disease. This goal aligns with NOT-HL-23-002 and the NHLBI Strategic Vision, which emphasize a need to understand midlife cardiovascular contributions to later life dementias. Focusing on cardiovascular stress physiology in midlife follows from cumulative evidence indicating that individuals with a phenotypic tendency to react to acute psychological stressors with relatively large rises in blood pressure (stressor-evoked blood pressure reactivity) are at risk for hypertension and adverse cardiovascular outcomes, which themselves are midlife cardiovascular risk factors for cerebrovascular disease and later life dementias. The mechanistic pathways by which stressor-evoked blood pressure reactivity may confer cerebrovascular risk are unknown. They are hypothesized in this project to include peripheral vascular remodeling and dysfunction, manifesting as arterial stiffness, endothelial dysfunction, and impaired beat-to-beat hemodynamic control. The latter are further hypothesized to promote preclinical cerebrovascular disease via a substrate for neurovascular damage; namely, cerebral pulsatility. To test predictions from these as yet unevaluated hypotheses, 3 Specific Aims are pursued in a community cohort of 538 midlife adults (aged 40-59 years; ~60% women, ~40% identifying as nonwhite; final analytic N=450 expected after attrition) who are asymptomatic for clinical cardiovascular disease and cognitive impairment. In a 2-visit protocol, volunteers will complete validated and reliable protocols to assess: behavioral, social, and biological determinants of cardiovascular and cerebrovascular health; arterial stiffness, endothelial function, and beat-to-beat hemodynamic control; cardiovascular stress reactivity; and, cerebral pulsatility and preclinical cerebrovascular disease. Aim 1 tests whether larger stressor-evoked cardiovascular (blood pressure, cardiac output, and total peripheral resistance) reactions relate to preclinical cerebrovascular disease markers (greater cerebral pulsatility, higher white matter lesion burden, decreased hippocampal volume, and increased enlargement of brain perivascular spaces) in a multivariate structural equation model. Aim 2 tests whether associations between stressor-evoked cardiovascular reactions and preclinical cerebrovascular disease markers are partly explained by arterial stiffness, endothelial dysfunction, and beat-to-beat hemodynamic control. Tertiary Aim 3 explores whether Aim 1-2 effects are moderated by known cardiovascular risks and sex as a biological variable. The proposed project seeks to characterize the extent to which cardiovascular stress reactivity in midlife is a specific cardiovascular source of risk for cerebrovascular disease. In this way, the new information from this project may identify a potentially modifiable and stress-related factor in midlife that could aid efforts to predict and reduce vascular sources of later life dementia risk.

摘要