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

Daniel H Craighead, Kaitlin A Freeberg, Narissa P McCarty, Matthew J Rossman, Kerrie L Moreau, Zhiying You, Michel Chonchol, Douglas R Seals, Daniel H Craighead, Kaitlin A Freeberg, Narissa P McCarty, Matthew J Rossman, Kerrie L Moreau, Zhiying You, Michel Chonchol, Douglas R Seals

Abstract

Background: 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 women exceeds rates in age-matched men. This increase in SBP is associated with vascular endothelial dysfunction, mediated by excessive reactive oxygen species-induced oxidative stress and consequent reductions in nitric oxide bioavailability. Moderate-intensity aerobic exercise is a recommended lifestyle strategy for reducing SBP. However, adherence to aerobic exercise guidelines among postmenopausal women is low (<30%) and aerobic exercise does not consistently enhance endothelial function in estrogen-deficient postmenopausal women. High-resistance inspiratory muscle strength training (IMST) is a time-efficient, adherable lifestyle intervention that involves inhaling against resistance through a handheld device (30 breaths/day). Here, we present the protocol for a randomized controlled trial investigating the efficacy of 3 months of high-resistance IMST compared to guideline-based, "standard-of-care" aerobic exercise training for decreasing SBP and improving endothelial function in estrogen-deficient postmenopausal women with above-normal SBP (120-159 mmHg) at baseline (ClinicalTrials.gov Identifier: NCT05000515). Methods: A randomized, single-blind, parallel-group design clinical trial will be conducted in 72 (36/group) estrogen-deficient postmenopausal women with above-normal SBP. Participants will complete baseline testing and then be randomized to either 3 months of high-resistance IMST (30 breaths/day, 6 days/week, 75% maximal inspiratory pressure) or moderate-intensity aerobic exercise training (brisk walking 25 min/day, 6 days/week, 40-60% heart rate reserve). Outcome measures will be assessed after 3 months of either intervention. Following end-intervention testing, participants will abstain from their assigned intervention for 6 weeks, after which BP and endothelial function will be assessed to evaluate the potential persistent effects of the intervention on the primary and secondary outcomes. Discussion: This study is designed to compare the effectiveness of time-efficient, high-resistance IMST to guideline-based aerobic exercise training for lowering SBP and improving endothelial function, and interrogating potential mechanisms of action, in estrogen-deficient postmenopausal women. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT05000515.

Keywords: IMST; aging; cardiovascular disease; nitric oxide; oxidative stress; time-efficient.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Craighead, Freeberg, McCarty, Rossman, Moreau, You, Chonchol and Seals.

Figures

FIGURE 1
FIGURE 1
Hypothesis. Hypothesized effects of high-resistance inspiratory muscle strength training for lowering systolic blood pressure and improving endothelial function to a greater extent than guideline-based moderate-intensity aerobic exercise in estrogen-deficient postmenopausal women. E2, estrogen; BP, blood pressure; NO, nitric oxide; ROS, reactive oxygen species.
FIGURE 2
FIGURE 2
Study design. IMST, inspiratory muscle strength training; AE, aerobic exercise; PIMAX, maximal inspiratory pressure.
FIGURE 3
FIGURE 3
Expected Results. Expected results for (A) casual systolic blood pressure (SBP; primary outcome) and 24-h SBP (secondary outcome); and for (B) endothelial function measured by brachial artery flow-mediated dilation (FMDBA; secondary outcome) in the high-resistance inspiratory muscle strength training (IMST) and moderate-intensity aerobic exercise groups across the intervention. Dashed line represents expected FMDBA with supratherapeutic infusion of the potent antioxidant, vitamin C, in both subject groups.

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