Smartphone app-guided inspiratory muscle strength training for lowering systolic blood pressure - PROJECT SUMMARY High blood pressure (BP), particularly systolic BP (SBP), is the major modifiable risk factor for cardiovascular diseases (CVD) and related conditions such as chronic kidney disease and cognitive decline/dementia. In fact, ~60% of adults in the United States have above-normal SBP (≥120 mmHg). Above-normal SBP is associated with vascular endothelial dysfunction, a key antecedent for developing CVD. In addition, rates of BP control continue to worsen, predicting a new epidemic of disorders driven by above-normal SBP unless innovative therapies with clinical efficacy for lowering SBP can be adopted by and translated to the public. High-resistance inspiratory muscle strength training (IMST) is a novel, low-barrier, time-efficient, lifestyle intervention involving repeated inhalations against resistance with a hand-held device. In a randomized, double-blind, sham-controlled, parallel group design, pilot study in men and women (n=36) with initial SBP ≥120 mmHg, I showed that IMST (30 breaths/day [~5 min/day] at 75% maximal inspiratory pressure [PIMAX], 6 days/week for 6 weeks) had excellent adherence (94% of prescribed training sessions completed), increased inspiratory muscle strength (~20% increase in PIMAX), lowered SBP by 9 mmHg, and improved vascular endothelial function by ~45% compared to low-resistance sham training – thus establishing the clinical efficacy of high-resistance IMST. However, this trial was performed with frequent researcher supervision and feedback. Therefore, the next step in the overall translation of IMST for improving public health is to establish a vehicle for dissemination of IMST by utilizing digital health technologies. In this R03 application, I propose to pilot-test a smartphone app that independently guides users through an IMST intervention. I will directly compare the efficacy of 6 weeks (30 breaths/day, 6 days/week, 75% PIMAX) of at-home, app-guided IMST vs. an established clinic-based, investigator-supervised IMST program. I hypothesize that at-home IMST with a smartphone app will lower SBP, improve vascular endothelial function, promote adherence and increase inspiratory muscle strength to a similar extent as clinic-based IMST. I also will utilize an innovative follow-up period in which adherence to IMST and changes in home SBP are monitored for an additional 12 months after completing the randomized controlled trial, under free-living conditions, in all study participants; this will provide invaluable real-world data to inform future trial designs. Aim 1: To determine changes in home SBP after 6 weeks of at-home or clinic-based IMST in men and women with above-normal SBP at baseline. Safety and tolerability also will be assessed. Aim 2: To measure a) adherence; b) the change in PIMAX; and c) the change in vascular endothelial function after 6 weeks of at-home or clinic-based IMST. Aim 3: To monitor adherence to IMST and changes in home SBP during a 12-month free-living follow-up period in which all participants are given unrestricted access to the IMST smartphone app and training device.