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

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

项目成果

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Peter J Gianaros其他文献

Peter J Gianaros的其他文献

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{{ truncateString('Peter J Gianaros', 18)}}的其他基金

Metabolic and Inflammatory Pathways of Midlife Neurocognitive Disparities
中年神经认知差异的代谢和炎症途径
  • 批准号:
    10200027
  • 财政年份:
    2017
  • 资助金额:
    $ 77.06万
  • 项目类别:
Metabolic and Inflammatory Pathways of Midlife Neurocognitive Disparities
中年神经认知差异的代谢和炎症途径
  • 批准号:
    9531344
  • 财政年份:
    2017
  • 资助金额:
    $ 77.06万
  • 项目类别:
Metabolic and Inflammatory Pathways of Midlife Neurocognitive Disparities
中年神经认知差异的代谢和炎症途径
  • 批准号:
    9975001
  • 财政年份:
    2017
  • 资助金额:
    $ 77.06万
  • 项目类别:
Metabolic and Inflammatory Pathways of Midlife Neurocognitive Disparities
中年神经认知差异的代谢和炎症途径
  • 批准号:
    9754817
  • 财政年份:
    2017
  • 资助金额:
    $ 77.06万
  • 项目类别:
Central Mechanisms for Cardioprotective Behavioral Effects of W-3 Fatty Acids
W-3 脂肪酸心脏保护行为作用的核心机制
  • 批准号:
    7861036
  • 财政年份:
    2010
  • 资助金额:
    $ 77.06万
  • 项目类别:
Central Mechanisms for Cardioprotective Behavioral Effects of W-3 Fatty Acids
W-3 脂肪酸心脏保护行为作用的核心机制
  • 批准号:
    8021782
  • 财政年份:
    2010
  • 资助金额:
    $ 77.06万
  • 项目类别:
Neural Reactivity to Stress
神经对压力的反应
  • 批准号:
    7845775
  • 财政年份:
    2009
  • 资助金额:
    $ 77.06万
  • 项目类别:
Neural Reactivity to Stress
神经对压力的反应
  • 批准号:
    7460337
  • 财政年份:
    2008
  • 资助金额:
    $ 77.06万
  • 项目类别:
Neurobiological pathways linking stress and emotion to atherosclerosis
将压力和情绪与动脉粥样硬化联系起来的神经生物学途径
  • 批准号:
    8617857
  • 财政年份:
    2008
  • 资助金额:
    $ 77.06万
  • 项目类别:
Neural Reactivity to Stress
神经对压力的反应
  • 批准号:
    7599673
  • 财政年份:
    2008
  • 资助金额:
    $ 77.06万
  • 项目类别:

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