Time-efficient inspiratory muscle strength training for improving blood pressure and vascular function in older adults with sleep-disordered breathing

省时的吸气肌力量训练可改善患有睡眠呼吸障碍的老年人的血压和血管功能

• 批准号: 10045685
• 负责人: E. FIONA BAILEY
• 金额: $ 75.34万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10045685
• 关键词: Acute; Adherence; Adult; Advocate; Aerobic Exercise; Antioxidants; Apnea; Ascorbic Acid; Biopsy; Blood Pressure; Blood Vessels; Cardiac Output; Cell Culture Techniques; Chronic; Clinical Treatment; Clinical Trials; Continuous Positive Airway Pressure; Controlled Clinical Trials; Data; Development; Diastolic blood pressure; Disease; Double-Blind Method; Elderly; Endothelial Cells; Endothelium; Event; Exercise; Fatigue; Guidelines; Health; Heart Rate; Hour; Human; Hyperactive behavior; Hypertension; Hypoxemia; Inflammation; Inflammatory; Infusion procedures; Interleukin-10; Interleukin-6; Intervention; Measures; Mediating; Methods; Modeling; Molecular; Muscle; Nerve; Nitric Oxide; Norepinephrine; Obesity; Obstructive Sleep Apnea; Overweight; Oxidative Stress; Patients; Peripheral Resistance; Physiologic pulse; Physiological; Placebos; Plasma; Population; Prevalence; Prevention strategy; Production; Randomized; Reactive Oxygen Species; Research; Rest; Safety; Serum; Signal Transduction; Sleep Apnea Syndromes; Snoring; Source; Superoxides; Sympathetic Nervous System; Time; Training; Umbilical vein; United States; Vasoconstrictor Agents; Woman; airway obstruction; arterial stiffness; base; blood pressure reduction; brachial artery; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; clinically relevant; clinically significant; endothelial dysfunction; evidence base; exercise intensity; exercise intolerance; hypertension treatment; improved; in vivo; indexing; inflammatory marker; insight; men; molecular marker; muscle strength; novel; peer; preservation; pressure; randomized placebo-controlled clinical trial; response; sedentary; strength training; tool; trial comparing; young adult

Project Summary Exercise has well-documented benefits for systolic blood pressure (SBP) and cardiovascular health. Whereas current guidelines advocate ~150 min moderate intensity exercise/week, our preliminary data show ~5 min/day of inspiratory muscle strength training (IMST) for 6 weeks lowers casual (resting) SBP by ~12 mmHg. This simple approach to lowering BP could be applied to almost any population however we propose to study IMST in older adults with obstructive sleep apnea (OSA). OSA is an ideal population to target because OSA prevalence is growing and because snoring and apneas result in chronic intermittent hypoxemia that drives sympathetic nervous system (SNS) hyperactivity, endothelial dysfunction and hypertension. These substantive risks for cardiovascular disease are compounded by poor adherence to the mainstay treatment continuous positive airway pressure (<50%), obesity, fatigue and a robust intolerance for exercise. Our findings in healthy young adults (n=50) show IMST-related reductions in BP are mediated by decreases in systemic vascular resistance, suggesting changes in vascular tone and function. Consistent with this hypothesis, our results from a pilot clinical trial in adults with OSA (n=24) show IMST-related reductions in plasma norepinephrine levels (PNE) and muscle sympathetic nerve activity (MSNA), both markers of SNS activity. Our preliminary mechanistic assessments indicate IMST may lower circulating concentrations of other vasoconstrictor factors and increase nitric oxide (NO)-mediated endothelium-dependent dilation. And, findings in a novel endothelial cell culture model, point to increases in NO and declines in reactive oxygen species (ROS) and oxidative stress. However, it is unknown if: 1) IMST lowers casual and 24-h (ambulatory) SBP in older adults with OSA; 2) the reductions in SBP are long-lasting; 3) arterial stiffness, NO-mediated endothelial dilation and/or oxidative stress are improved; and 4) if adherence in this population is high long term. We propose a randomized, double-blind, placebo-controlled, clinical trial to establish the efficacy of IMST (75% maximum inspiratory pressure, [PImax]) 5 days/week for 24 weeks vs. placebo (15%PImax) (n=61/group) for lowering SBP in adults (>50 years) with above normal BP and OSA. We hypothesize that IMST will lower SBP via reductions in SNS activity and circulating vasoconstrictor factors, improvements in vascular function, and reductions in oxidative stress/inflammation and that reductions in SBP will be sustained after IMST. Aim 1: To determine casual and 24-h ambulatory BP; before/after, and 4- and 12-weeks post-IMST/placebo training. Safety, tolerability and adherence also will be assessed. Aim 2: To measure arterial stiffness, brachial artery flow-mediated dilation (FMDBA), plasma PNE, MSNA, vasoconstrictor factors and inflammation; before/after, and 4- and 12-weeks post-IMST/placebo training. Aim 3: To evaluate superoxide related suppression of FMDBA, and markers of oxidative stress and antioxidant defense in endothelial cells from subjects before/after, and 4- and 12-weeks post-IMST/placebo training.

项目摘要 运动对收缩压（SBP）和心血管健康具有据可查的益处。然而 当前指南提倡〜150 min中度强度练习/周，我们的初步数据显示〜5 最小的灵感肌肉力量训练（IMST）持续6周，将休闲（休息）SBP降低〜12 mmHg。 这种降低BP的简单方法可以应用于几乎所有人群，但是我们建议 在患有阻塞性睡眠呼吸暂停（OSA）的老年人中研究IMST。 OSA是目标的理想人群，因为 OSA患病率正在增长，因为打s和呼吸暂停会导致慢性间歇性低氧血症 驱动交感神经系统（SNS）多动症，内皮功能障碍和高血压。这些 心血管疾病的实质性风险因对中流tay治疗的依从性而更加复杂 连续的正气道压力（<50％），肥胖，疲劳和运动不宽容。 我们在健康的年轻人（n = 50）中的发现表明，BP中与IMST相关的减少是由 系统性血管抗性的降低，表明血管张力和功能的变化。与 这个假设是我们来自OSA成人（n = 24）的成年人的试验临床试验的结果，显示与IMST相关的减少 血浆去甲肾上腺素水平（PNE）和肌肉交感神经活动（MSNA），这两个标记 活动。我们的初步机理评估表明，IMST可能会降低其他循环浓度 血管收缩因子并增加一氧化氮（NO）介导的内皮依赖性扩张。而且，发现 在一种新型的内皮细胞培养模型中，指向NO的增加，而活性氧的下降 （ROS）和氧化应激。但是，未知是否：1）IMST降低休闲和24-H（ABSURATION）SBP 老年人患有OSA； 2）SBP的减少是长期的； 3）动脉刚度，无介导的内皮 扩张和/或氧化应激得到改善； 4）如果该人群的依从性很长。 我们提出了一项随机，双盲，安慰剂对照的临床试验，以建立IMST的功效 （75％的最大吸气压力，[PIMAX]）5天/周24周与安慰剂（15％PIMAX）（n = 61/组） 用于降低成人（> 50年）的SBP，其BP和OSA高于正常的SBP。我们假设IMST会降低 SBP通过减少SNS活性和循环血管收缩因子的减少，血管功能的改善， IMST后将维持氧化应激/炎症的减少以及SBP的减少。 目标1：确定休闲和24小时的卧床BP；在IMST/安慰剂之前/之后，以及4个周和12周 训练。安全性，耐受性和依从性也将被评估。 目标2：测量动脉刚度，臂动脉流介导的扩张（FMDBA），血浆PNE，MSNA， 血管收缩因素和炎症；在IMST/安慰剂训练之前/之后，以及4周和12周。 目标3：评估FMDBA的超氧化物相关的抑制作用，以及氧化应激和抗氧化剂的标记 在IMST/安慰剂训练后/之后/之后，对内皮细胞的防御。