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.

项目总结