Sympathetic Regulation of Large Artery Stiffness in Humans with Age-Related Isolated Systolic Hypertension

年龄相关性单纯性收缩期高血压患者大动脉僵硬度的交感调节

基本信息

  • 批准号:
    10400014
  • 负责人:
  • 金额:
    $ 34.39万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-04-15 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract Stiffness of the large elastic central arteries (e.g., aorta and carotids) increases with advancing age and is a robust predictor of incident cardiovascular disease (CVD) events among older adults. The age-related increase in central artery stiffness is associated with a concomitant rise in systolic blood pressure (BP) and pulse pressure (PP) and subsequently the development of isolated systolic hypertension (ISH) in many older adults. Consequently, higher PP results in greater pulsatile pressure and flow penetrating into high blood flow organs such as the brain causing subclinical target organ damage. Sympathetic nerve activity (SNA) also increases with advancing age and is associated with cardiovascular target organ damage including left ventricular hypertrophy and intima-medial thickness (IMT) of peripheral conduit arteries, but it remains unclear whether enhanced SNA modulates the age-related increase in central artery stiffness and associated augmented carotid pressure and flow pulsatility and increased IMT. Therefore, the objectives of this application are to 1) determine the contribution of SNA to the age-related increase in aortic stiffness and reduced carotid compliance, and augmented carotid pressure and flow pulsatility and IMT among older adults with ISH, and 2) determine the effectiveness of chronic inhibition of SNA for reducing large artery stiffness, carotid pressure and flow pulsatility and IMT among older adults with ISH. In Aim 1, we will enroll 30 older (age 60-85 years) adults (50% women/50% men) with untreated stage 1 or stage 2 ISH (systolic BP 130-159 mmHg; diastolic BP <90mmHg) in a repeated measures experimental study assessing aortic stiffness (carotid-femoral pulse wave velocity, PWV) and carotid artery compliance and pressure pulsatility index at baseline and during -15 and -30 mmHg of lower body negative pressure. We hypothesize that acute experimental elevations in SNA will result in transient increases in carotid-femoral PWV and decreases in carotid compliance resulting in higher carotid pressure and flow pulsatility. In Aim 2, we will enroll 78 healthy older men and women (age 60-85 years) with untreated or treated ISH in a randomized, placebo-controlled double blind study. We hypothesize that 4 weeks of chronic SNA inhibition with oral clonidine will result in clinically meaningful decreases in aortic stiffness and increases in carotid artery compliance, causing significant reductions in carotid pressure and flow pulsatility index and IMT. The proposed research will fundamentally advance our understanding of the regulation of large elastic artery stiffness by SNA among older humans with ISH, and provide valuable insight into SNA as a novel therapeutic target among older adults with ISH for lowering CVD risk.
项目总结/摘要 大的弹性中央动脉的硬度(例如,主动脉和颈动脉)随着推进而增加 年龄,是老年人中心血管疾病(CVD)事件的可靠预测因子 成年人了与年龄相关的中央动脉僵硬度增加与伴随的 收缩压(BP)和脉压(PP)以及随后的 孤立性收缩期高血压(ISH)在许多老年人。因此,较高的PP导致 更大的脉动压力和渗透到高血流量器官如大脑的流量 导致亚临床靶器官损伤。交感神经活动(SNA)也随着 随着年龄的增长,与心血管靶器官损伤有关,包括左 心室肥厚和外周管道动脉内膜中层厚度(IMT),但它 尚不清楚SNA增强是否调节了与年龄相关的中央动脉 僵硬和相关的颈动脉压力和血流脉动性增加以及IMT增加。 因此,本应用程序的目标是:1)确定SNA对 年龄相关的主动脉僵硬度增加和颈动脉顺应性降低, 老年ISH患者的压力和血流脉动性以及IMT,以及2)确定 SNA慢性抑制对降低大动脉僵硬度、颈动脉压的有效性 以及老年ISH患者的血流脉动性和IMT。在目标1中,我们将招募30名年龄较大( 60-85岁)成人(50%女性/50%男性),患有未经治疗的1期或2期ISH(收缩压 130-159 mmHg;舒张压<90 mmHg)进行重复测量实验研究, 主动脉僵硬度(颈动脉-股动脉脉搏波速度,PWV)和颈动脉顺应性, 基线时和下体负压-15和-30 mmHg期间的压力脉动指数 压力我们假设SNA的急性实验性升高将导致短暂的 颈动脉-股动脉PWV增加,颈动脉顺应性降低, 颈动脉压力和血流脉动。在目标2中,我们将招募78名健康的老年男性和女性 (age 60-85岁),在一项随机、安慰剂对照的双盲研究中, 盲目的研究我们假设口服可乐定4周的慢性SNA抑制将导致 在临床上有意义的主动脉僵硬度降低和颈动脉顺应性增加中, 导致颈动脉压力和血流脉动指数以及IMT显著降低。的 拟议中的研究将从根本上推进我们对大型监管的理解。 SNA在ISH老年人中的弹性动脉硬度,并提供了有价值的见解, SNA是老年ISH患者降低CVD风险的新治疗靶点。

项目成果

期刊论文数量(0)
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Gary L. Pierce其他文献

Accuracy of a pretest questionnaire in exercise test protocol selection.
运动测试方案选择中预测试问卷的准确性。
  • DOI:
  • 发表时间:
    2000
  • 期刊:
  • 影响因子:
    2.8
  • 作者:
    D. Bader;K. Mcinnis;T. E. Maguire;Gary L. Pierce;G. Balady
  • 通讯作者:
    G. Balady
309 Aspirin decreases triglycerides in the development of preeclampsia
  • DOI:
    10.1016/j.ajog.2023.11.331
  • 发表时间:
    2024-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Kelsey Blocklinger;Tarynne E. Kinghorn;Kaylee Weaver;Ashlyn S. Mulcahey;Wendy S. Hamilton;Sydney Pearl;Meghan L. Funk;Dane D. Sweezer;Alexis J. Faudel;Sophia T. Schnoebelen;Amy K. Stroud;Stephen K. Hunter;Gary L. Pierce;Heath A. Davis;Boyd Knosp;Debra S. Brandt;Mark K. Santillan;Donna A. Santillan
  • 通讯作者:
    Donna A. Santillan
Reduced cardiac baroreflex sensitivity is associated with greater aortic stiffness in middle-aged/older humans: Beneficial effect of habitual aerobic exercise
  • DOI:
    10.1016/j.artres.2014.09.022
  • 发表时间:
    2014-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Stephen A. Harris;Harald M. Stauss;Douglas R. Seals;Gary L. Pierce
  • 通讯作者:
    Gary L. Pierce
Higher aortic stiffness and carotid systolic and pulse pressure are selectively associated with lower white matter integrity in the genu and frontal cortex in older healthy adults
  • DOI:
    10.1016/j.artres.2014.09.028
  • 发表时间:
    2014-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Lyndsey E. Dubose;Timothy B. Weng;Kaitlyn Dubishar;Merry Mani;Michelle W. Voss;Gary L. Pierce
  • 通讯作者:
    Gary L. Pierce
Comparison of cardiopulmonary responses in obese women using ramp versus step treadmill protocols.
使用斜坡跑步机方案与步进跑步机方案比较肥胖女性的心肺反应。
  • DOI:
    10.1016/s0002-9149(98)00843-1
  • 发表时间:
    1999
  • 期刊:
  • 影响因子:
    0
  • 作者:
    K. Mcinnis;K. Mcinnis;D. Bader;Gary L. Pierce;G. Balady
  • 通讯作者:
    G. Balady

Gary L. Pierce的其他文献

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{{ truncateString('Gary L. Pierce', 18)}}的其他基金

Sympathetic Regulation of Large Artery Stiffness in Humans with Age-Related Isolated Systolic Hypertension
年龄相关性单纯性收缩期高血压患者大动脉僵硬度的交感调节
  • 批准号:
    10620643
  • 财政年份:
    2020
  • 资助金额:
    $ 34.39万
  • 项目类别:
Targeting Inflammation to Treat Cardiovascular Aging in Humans
针对炎症治疗人类心血管衰老
  • 批准号:
    8583104
  • 财政年份:
    2013
  • 资助金额:
    $ 34.39万
  • 项目类别:
Targeting Inflammation to Treat Cardiovascular Aging in Humans
针对炎症治疗人类心血管衰老
  • 批准号:
    8702981
  • 财政年份:
    2013
  • 资助金额:
    $ 34.39万
  • 项目类别:
MOLECULAR MECHANISMS ASSOCIATED WITH CARDIOVASCULAR AGING
与心血管衰老相关的分子机制
  • 批准号:
    7719548
  • 财政年份:
    2008
  • 资助金额:
    $ 34.39万
  • 项目类别:
HUMAN AGING, EXERCISE AND ENDOTHELIUM-DEPENDENT VASODILATION: TRANSLATIONAL PHY
人类衰老、运动和内皮依赖性血管舒张:翻译物理
  • 批准号:
    7719552
  • 财政年份:
    2008
  • 资助金额:
    $ 34.39万
  • 项目类别:
RELATION BETWEEN ENDOTHELIAL-DEPENDENT DILATION AND SYSTEMIC AND LOCAL "PRO-OXI
内皮依赖性扩张与全身和局部“PRO-OXI”之间的关系
  • 批准号:
    7719557
  • 财政年份:
    2008
  • 资助金额:
    $ 34.39万
  • 项目类别:
ROLE OF TETRAHYDROBIOPTERIN DEFICIENCY IN CARDIOVASCULAR FUNCTION WITH AGING
四氢生物蝶呤缺乏对衰老过程中心血管功能的作用
  • 批准号:
    7719547
  • 财政年份:
    2008
  • 资助金额:
    $ 34.39万
  • 项目类别:
RELATION BETWEEN ENDOTHELIAL-DEPENDENT DILATION AND SYSTEMIC AND LOCAL "PRO-OXI
内皮依赖性扩张与全身和局部“PRO-OXI”之间的关系
  • 批准号:
    7604514
  • 财政年份:
    2007
  • 资助金额:
    $ 34.39万
  • 项目类别:
ROLE OF TETRAHYDROBIOPTERIN DEFICIENCY IN CARDIOVASCULAR FUNCTION WITH AGING
四氢生物蝶呤缺乏对衰老过程中心血管功能的作用
  • 批准号:
    7604497
  • 财政年份:
    2007
  • 资助金额:
    $ 34.39万
  • 项目类别:
HUMAN AGING, EXERCISE AND ENDOTHELIUM-DEPENDENT VASODILATION: TRANSLATIONAL PHY
人类衰老、运动和内皮依赖性血管舒张:翻译物理
  • 批准号:
    7604505
  • 财政年份:
    2007
  • 资助金额:
    $ 34.39万
  • 项目类别:

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