R01AG071506

Inspiratory Muscle Strength Training for Lowering Blood Pressure and Improving Endothelial Function in Postmenopausal Women: Comparison with "Standard of Care" Aerobic Exercise - 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.

The Regents Of The University Of Colorado

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Boulder, Colorado 803090001 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Required) (PA-20-183)

Amendment Since initial award the End Date has been extended from 02/28/26 to 02/28/27 and the total obligations have increased 446% from $603,004 to $3,294,392.