Inspiratory muscle strength training for lowering blood pressure and improving endothelial function in postmenopausal women: comparison with "standard of care" aerobic exercise

用于降低绝经后妇女血压和改善内皮功能的吸气肌力量训练：与“标准护理”有氧运动的比较

• 批准号: 10414050
• 负责人: DOUGLAS R SEALS
• 金额: $ 58.06万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10414050
• 关键词: Acute; Adherence; Adult; Aerobic Exercise; Age; Aging; Antioxidants; Ascorbic Acid; Back; Biological Availability; Biopsy; Blood Pressure; Cardiovascular Diseases; Cell Culture Techniques; Chronic Kidney Failure; Clinical; Clinical Trials; Devices; Diastolic blood pressure; Disease; Double-Blind Method; Dropout; Elderly; Endothelial Cells; Endothelium; Estrogens; Exhibits; Facility Accesses; Funding; Guidelines; Hand; Health; Home; Hour; Human; Hypertension; Infusion procedures; Inhalation; Lifestyle Therapy; Link; Measures; Mediating; Molecular; Nitric Oxide; Oxidative Stress; Pilot Projects; Plasma; Postmenopause; Premenopause; Prevalence; Process; Production; Public Health; Randomized; Randomized Clinical Trials; Reactive Oxygen Species; Resistance; Rest; Risk; Role; Safety; Serum; Signal Transduction; Time; Training; Translating; Travel; Umbilical vein; Vascular Endothelium; Walking; Woman; base; brachial artery; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; clinical practice; clinically relevant; comparative efficacy; design; effective intervention; evidence base; exercise program; exercise training; health goals; improved; in vivo; insight; lifestyle intervention; men; metabolomics; middle age; modifiable risk; molecular marker; muscle strength; novel; older men; older women; pilot trial; portability; post intervention; pressure; primary outcome; secondary outcome; standard of care; strength training; stress reduction; treatment duration; vascular endothelial dysfunction

PROJECT SUMMARY High blood pressure (BP), particularly systolic BP (SBP), is the major modifiable risk factor for cardiovascular diseases and related disorders of aging. SBP increases markedly with aging in women such that the prevalence of above-normal SBP (i.e., ≥120 mmHg) in postmenopausal (PM) women exceeds rates in age-matched men. This increase in SBP is associated with vascular endothelial dysfunction, mediated by excessive reactive oxygen species (ROS)-induced oxidative stress and consequent reductions in nitric oxide (NO) bioavailability. Moderate-intensity aerobic exercise (AE) of 150 min/week is a clinical guideline-based (standard-of-care) lifestyle therapy for reducing SBP. However, in estrogen-deficient PM (PME-) women, the effects of AE on SBP are modest and do not persist >4 weeks after AE cessation. AE also does not consistently enhance endothelial function and is associated with poor adherence (<30%) in this group. High-resistance inspiratory muscle strength training (IMST) is a novel lifestyle intervention involving repeated inhalations against a resistive load using a hand-held device. In a randomized, double-blind, sham- controlled, parallel group design R21-funded pilot study in midlife/older men and women (n=36 [17 PME- women]), we showed that IMST (30 breaths [5 minutes]/day at 75% of maximal inspiratory pressure, 6 days [30 minutes]/week for 6 weeks), lowered casual (resting) SBP by 9±2 mmHg (6±2 mmHg 6 weeks after cessation of IMST) and 24-hour SBP by 3±3 mmHg. IMST improved endothelial function (brachial artery flow- mediated dilation, FMDBA), by ~40%, while promoting excellent adherence (95% of prescribed sessions completed). Importantly, the effects of IMST on SBP and FMDBA in the PME- women were all ≥ those in men. Here we propose a larger, randomized clinical trial with a guideline-based treatment duration (3 months) to directly compare the efficacy of IMST vs. standard-of-care AE (150 min/week brisk walking) for decreasing SBP and improving FMDBA in PME- women with above-normal SBP (≥120 mmHg) at baseline. We hypothesize that IMST will reduce and largely sustain reductions in SBP and increase FMDBA > AE. Increases in FMDBA with IMST will be mediated by reduced ROS/oxidative stress, and serum post-IMST will decrease ROS and increase NO in endothelial cells > post-AE. Adherence, safety and tolerability will be > with IMST vs. AE. Aim 1: To measure casual SBP (primary outcome) and 24-hour (ambulatory) SBP (secondary outcome) before (baseline), after 3 months of IMST or AE, and 6 weeks following cessation of IMST or AE; Aim 2: To measure FMDBA (secondary outcome) before, after IMST or AE, and 6 weeks post-IMST or -AE; Aim 3: To determine in vivo ROS-mediated suppression of FMDBA (FMDBA ± vitamin C infusion); markers of oxidative stress and antioxidant status in biopsied endothelial cells; and endothelial cell culture NO and ROS production pre-post IMST or AE serum exposure and the identity of the plasma metabolites involved; Aim 4: To assess adherence (completed:prescribed sessions), safety and tolerability with IMST vs. AE.

项目摘要 高血压（BP），尤其是收缩BP（SBP），是主要的可修改风险因素 衰老的心血管疾病和相关疾病。 SBP随着女性的老龄而显着增加 绝经后（PM）妇女中高于正常的SBP（即≥120mmHg）的患病率超过率 在年龄匹配的男人中。 SBP的这种增加与血管内皮功能障碍有关，由 过量的活性氧（ROS）诱导的氧化应激以及一氧化氮的降低 （否）生物利用度。中等强度有氧运动（AE）为150分钟/周是基于临床指南的 （护理标准）减少SBP的生活方式疗法。但是，在缺乏雌激素的PM（PME-）女性中 AE对SBP的影响是适度的，并且在AE停止后持续> 4周。 AE也不 始终增强内皮功能，并与该组的依从性差（<30％）有关。 高防毒的灵感肌肉力量训练（IMST）是一种新颖的生活方式干预措施，涉及 使用手持设备重复吸入电阻载荷。在随机的双盲，假手术中 受控的，平行的组设计R2​​1资助的中年/年龄较大男性和女性的试点研究（n = 36 [17 pme-- 女性]），我们表明IMST（30次呼吸[5分钟]/天，最大灵感压力的75％，6天 [30分钟]/周6周），将休闲（静止）SBP降低9±2 mmHg（6±2 mmHg 6周后6周 停止IMST）和24小时SBP> 3±3 mmHg。 IMST改善内皮功能（肱动脉流动 - 介导的字典FMDBA），约40％，同时提高出色的依从性（占方式会议的95％ 完全的）。重要的是，IMST对PME-妇女中SBP和FMDBA的影响均为男性中的所有效果。 在这里，我们提出了一项较大的随机临床试验，具有基于指南的治疗持续时间（3个月） 直接比较IMST与现有标准AE的效率（每周150分钟/周轻行走），以降低 在基线时，SBP和改善了高度SBP（≥120mmHg）的PME-FMDBA。我们假设 IMST将减少并大大减少SBP的减少并增加FMDBA> AE。 FMDBA增加 IMST将通过降低的ROS/氧化应激介导，并且IMST血清将减少ROS，并且 内皮细胞> AE的内皮细胞中不增加NO。使用IMST与AE的依从性，安全性和耐受性将为>。 目标1：测量休闲SBP（主要结果）和24小时（卧床）SBP（次要结果） 在（基线）之前，在IMST或AE 3个月后，以及在IMST或AE停止后6周； 目的2：在IMST或AE之后，IMST或-ae后6周之前测量FMDBA（次要结果）； 目标3：确定体内ROS介导的FMDBA抑制（FMDBA±维生素C输注）；标记 活检内皮细胞中的氧化应激和抗氧化状态；和内皮细胞培养号和ROS 生产前IMST或AE血清暴露以及涉及血浆代谢物的身份； AIM 4：评估依从性（已完成：规定的会话），IMST与AE的安全性和耐受性。