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 这个项目的目标是确定中年心血管应激生理学的程度 临床前脑血管疾病的严重程度。该目标与NOT-HL-23-002和NHLBI一致 战略愿景,强调需要了解中年心血管对晚年生活的贡献 痴呆症关注中年的心血管应激生理学来自于累积的证据 这表明,具有对急性心理应激反应的表型倾向的个体, 血压相对较大的升高(应激诱发的血压反应性)有风险, 高血压和不良心血管结局,它们本身就是中年心血管风险因素 治疗脑血管疾病和老年痴呆症。应激诱发的机制途径 血压反应性可能会导致脑血管风险尚不清楚。他们在这本书中假设 包括外周血管重塑和功能障碍,表现为动脉僵硬, 内皮功能障碍和心跳间血流动力学控制受损。后者进一步 假设通过神经血管损伤底物促进临床前脑血管疾病; 也就是大脑的搏动为了测试这些尚未评估的假设的预测,3个具体目标 在538名中年人(年龄40-59岁;约60%女性,约40% 确定为非白人;最终分析N=450,预期在脱落后),无临床症状 心血管疾病和认知障碍。在2次访视方案中,志愿者将完成验证 和可靠的协议,以评估:行为,社会和生物决定因素的心血管和 脑血管健康;动脉硬度、内皮功能和逐搏血流动力学控制; 心血管应激反应性;以及,脑脉动性和临床前脑血管疾病。Aim 1测试 是否更大的应激诱发的心血管(血压,心输出量,和总外周 抵抗)反应与临床前脑血管疾病标志物(更大的脑脉动, 白色病变负荷增加、海马体积减小和脑增大 血管周围空间)的多变量结构方程模型。目标2测试了 应激诱发的心血管反应和临床前脑血管疾病标志物, 这可以通过动脉僵硬、内皮功能障碍和逐搏血流动力学控制来解释。叔 目标3探讨目标1-2的影响是否受到已知心血管风险和性别的生物学调节 变量拟议的项目旨在描述心血管应激反应的程度, 中年是脑血管疾病的一个特殊的心血管风险来源。这样,新 从这个项目中得到的信息可以确定一个潜在的可改变的和与中年压力有关的因素, 可以帮助预测和减少晚年痴呆风险的血管来源。

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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