High-resistance IMST for Improving CV Function
IMST is an alternative form of physical training that isolates the inspiratory muscles by requiring individuals to perform repeated inhalations against an external resistance while exhalation is unimpeded. IMST primarily uses the diaphragm and accessory respiratory muscles including the intercostal, scalene and sternocleidomastoid muscles (Figure 2). IMST is distinct from other forms of breathing exercises, such as respiratory muscle training that involves resistance to both inhalation and exhalation, or pursed-lip breathing where resistance is self-produced by narrowing the airway.
Training characteristics and cardiorespiratory responses to a single bout of high-resistance inspiratory muscle strength training (IMST) or moderate-intensity aerobic exercise. Maximal heart rate (HRMAX). BP, blood pressure.
Most studies investigating the CV health benefits of IMST have used low-resistance, high-repetition paradigms, in which users inspire against a resistance at or near 30% of their individual maximal inspiratory pressure (PIMAX).[18,19] A primary weakness of low-resistance, high-repetition IMST is that it requires a similar overall time commitment to that of moderate-intensity physical activity guidelines (i.e., ~150 min·wk−1). As time availability is the most cited barrier to achieving healthy lifestyle strategies,[39–41] low-resistance IMST interventions are unlikely to elicit high rates of adherence in a real-world setting. The purported CV health benefits of low-resistance IMST have been reviewed recently and, thus, will not be discussed in further detail.
Given the important role of time availability for meeting healthy lifestyle guidelines, the potential of time-efficient (i.e., ~30 min·wk−1 time commitment) interventions for promoting healthy CV aging is becoming a topic of increasing interest. High-resistance, low-repetition IMST is an emerging variation of the traditional, low-resistance IMST paradigm that can be accomplished with minimal time burden.
Although no standard definition has been established, high-resistance IMST most often refers to regimens using a level of resistance equivalent to ~75% of an individual's PIMAX. This level of intensity allows high-resistance IMST to be completed in as little as 5 min·d−1, making it a time-efficient intervention with the potential to promote adherence. IMST is performed with small, hand-held devices, which are ideal for use at home and during travel. There are consumer-available IMST devices that are relatively affordable when compared with gym memberships or other pieces of exercise equipment. Thus, high-resistance, low-repetition IMST has multiple characteristics that may help promote adherence (Figure 1). As such, high-resistance IMST for promoting healthy CV aging will be the focus of the remainder of this Perspective for Progress.
High-resistance IMST provides a physiological stimulus that is distinct from moderate-intensity aerobic exercise (Figure 2). Indeed, the level of inspiratory resistance attained during high-resistance IMST is approximately two to four times larger than those achieved during aerobic exercise, although the respiratory rate is appreciably lower during high-resistance IMST compared with aerobic exercise.[58–61] Compared with aerobic exercise, a single bout of high-resistance IMST results in a smaller increase in heart rate and a minimal change in SBP.[62–64] Therefore, high-resistance IMST is not simply mimicking the acute cardiorespiratory effects of moderate-intensity aerobic exercise but is instead a unique acute physiological stimulus and, when performed regularly, form of physical training.
High-resistance IMST for Lowering BP
The most established CV benefit of high-resistance IMST is for lowering casual (resting, seated) BP (Figure 3). Initial efficacy of high-resistance IMST for lowering BP was demonstrated by Bailey and colleagues, who demonstrated that 6 wk of high-resistance IMST, consisting of 30 breaths (~5 min) per day, 5 d·wk−1, at an intensity of 75% PIMAX, lowered casual SBP by 10 mm Hg and casual diastolic BP (DBP) by 6 mm Hg in young adults with normal BP at baseline. Importantly, in this same study, BP was unchanged in a group of young adults randomized to perform the same protocol but against a minimal inspiratory resistance. The study also demonstrated that large excursions in lung volume with low resistance, when employed with this 30 breaths·d−1 protocol, are inadequate for lowering BP. Thus, the necessity of high inspiratory resistance to facilitate the benefits of IMST in a time-efficient manner were initially established.
Summary of the changes in systolic blood pressure (SBP) and diastolic BP (DBP) in the high-resistance inspiratory muscle strength training (IMST) groups from available randomized clinical trials.
Next, the Bailey laboratory translated their 30 breaths·d−1 high-resistance IMST protocol to patients with obstructive sleep apnea. In these patients, 6 wk of high-resistance IMST (75% PIMAX, 6 d·wk−1) lowered SBP by 12 mm Hg and DBP by 5 mm Hg; no change was observed in the low-resistance (15% PIMAX) sham control group. Dr. Bailey's group has since replicated their initial findings in additional 6-wk-long interventions in separate cohorts of young healthy adults (SBP, −4 mm Hg; DBP, −4 mm Hg) and patients with obstructive sleep apnea (SBP, −9 mm Hg; DBP, −5 mm Hg).
Using the protocol pioneered by Bailey and colleagues, our laboratory recently demonstrated that 6 wk of high-resistance IMST (75% PIMAX, 30 breaths·d−1, 6 d·wk−1) lowered casual SBP by 9 mm Hg and DBP by 2 mm Hg in a group of otherwise healthy midlife and older adults with an initial SBP above 120 mm Hg. Importantly, casual BP was measured 24 to 48 h after the last session of IMST, precluding acute effects from influencing our results. A unique feature of our study was that a majority of participants returned for reassessment after abstaining from IMST for 6 wk to determine if there were any persistent effects of the intervention on BP. SBP remained 7 mm Hg lower than baseline levels at this follow-up timepoint, suggesting the SBP-lowering effects of high-resistance IMST may be sustained at least for several weeks. BP tends to rise quickly after abstaining from aerobic exercise or withdrawing prescribed pharmacotherapy. Thus, if confirmed in additional studies, the persistent BP-lowering effects of high-resistance IMST may offer an additional advantage over other antihypertensive therapies as it may require only intermittent training periods, better promoting longer-term adherence.
The consistently observed reductions in casual BP across the 6-wk high-resistance IMST interventions performed by Dr. Bailey and our laboratory (Figure 3) are similar or greater in magnitude than the changes in BP that tend to be observed after aerobic exercise training.[20,21] These reductions in BP were achieved with a much smaller time burden in comparison to standard aerobic exercise. The reductions in BP are also similar to those observed after treatment with first-line antihypertensive pharmacotherapies.[69–71] Importantly, reductions in casual SBP (4–12 mm Hg) and DBP (2–6 mm Hg) observed across these studies are clinically significant, with an expected reduction in CVD risk of ~30% if sustained long-term. The ability of IMST to lower BP even in young adults with normal BP at baseline could be clinically meaningful as progressive, age-related increases in SBP begin in young adulthood and result in above-normal SBP in a majority of adults before midlife.[20,73,74] Thus, the efficacy of IMST for lowering SBP in this group could help maintain normal SBP levels into later life.
Mean 24-h, daytime and nighttime BP measured via ambulatory monitoring are additional CVD risk factors that offer insight into BP status beyond what is obtained through clinic-based casual BP measurements.[75,76] The effects of high-resistance IMST on ambulatory BP measures were assessed in two of the trials described above. First, Bailey and colleagues observed a nighttime-specific reduction in SBP of 12 mm Hg after 6 wk of high-resistance IMST in patients with obstructive sleep apnea. This patient group exhibits sleep-disordered breathing which leads to elevations in nighttime SBP. Thus, the nighttime-specific reduction in SBP in this group may reflect the influence of IMST on their unique pathophysiological state. Similarly, in our IMST pilot study in midlife/older adults, we observed a 4-mm Hg reduction in mean 24-h SBP, driven by equivalent reductions in daytime and nighttime SBP, such that 24-h SBP was significantly lower compared with the low-resistance sham control group after 6 wk of high-resistance IMST in our cohort of generally healthy midlife and older adults. Combined, these findings suggest high-resistance IMST may improve ambulatory measures of BP sampled over a 24-h period in addition to improving casual BP assessed at a single point in time.
High-resistance IMST for Improving Vascular Function
Vascular endothelial function tends to decline with aging and is associated with increased CVD risk.[77,78] To our knowledge, our pilot trial in midlife/older adults is the only trial to date to assess the influence of high-resistance IMST on endothelial function. We observed a 45% improvement in endothelial function, assessed via FMDBA, after 6 wk of high-resistance IMST, with no change in the sham control group, in our study. In contrast to AE training,[26,27,29] equivalent improvements in endothelial function were observed in the estrogen-deficient postmenopausal women and midlife/older men enrolled in our study. Although caution is warranted given the small subgroups, this finding suggests high-resistance IMST may overcome a limitation of aerobic exercise for improving vascular endothelial function in estrogen-deficient postmenopausal women, as discussed above. The magnitude of improvement in FMDBA we observed (~2.5Δ% units) is likely clinically significant, as a 1Δ% unit higher FMDBA is associated with an 8% to 13% lower risk for CVD.[78–82]
High-resistance IMST does not appear to improve large elastic artery stiffness, measured either as carotid-femoral pulse wave velocity or carotid artery compliance, in young or midlife/older adults.[68,83] However, it usually takes a treatment period of at least 3 months for healthy lifestyle strategies to change large elastic artery stiffness. Current studies have used only 4- or 6-wk intervention durations. Thus, large elastic artery stiffness should be assessed in longer duration trials of high-resistance IMST to further assess the efficacy of this intervention for improving this important measure of age-related vascular dysfunction.
Potential Mechanisms of High-resistance IMST for Improving CV Function
Currently, there is limited information on potential mechanisms through which high-resistance IMST improves CV function, with available evidence coming from a heterogenous group of studies. In healthy young adults, IMST reduces BP by lowering systemic vascular resistance without changing resting heart rate or cardiac output. This suggests that high-resistance IMST likely lowers BP by acting primarily on the vasculature, but additional research is needed to confirm these observations in patient groups and older adults.
We used an innovative ex vivo cell culture technique to assess the effect of high-resistance IMST on oxidative stress and NO bioavailability. Endothelial cells were cultured in serum obtained from midlife/older adults before and after 6 wk of high-resistance IMST or low-resistance sham training. Serum samples collected after IMST reduced endothelial cell superoxide production by ~25% to 35% relative to baseline and serum from the sham control group. In addition, serum obtained post-IMST increased markers of activation for the NO-producing enzyme, endothelial NO synthase, by ~75% compared with serum sampled pre-IMST. This increase in activation of endothelial NO synthase was associated with a corresponding ~10% to 15% increase in NO production in endothelial cells cultured with serum obtained after the high-resistance IMST intervention compared with preintervention and sham training. Combined, these ex vivo results from our pilot trial suggest that high-resistance IMST may improve CV function, in part, by inducing beneficial changes to factors in the circulation that decrease oxidative stress and increase NO bioavailability. These findings remain to be confirmed, and expanded upon, in subsequent trials.
Results from multiple trials suggest IMST may reduce chronic, low-grade inflammation, although findings are varied. We observed reductions in plasma CRP, a marker of systemic inflammation, after 6 wk of high-resistance IMST in our pilot trial in midlife and older adults. Similarly, moderate-intensity IMST (50% PIMAX) reduced plasma CRP and soluble TNFα receptor 2 in patients on hemodialysis.[84,85] Conversely, a similar 8-wk, moderate-intensity IMST (50% PIMAX) trial in healthy older adults observed no changes in plasma cytokine concentrations. It is likely that larger sample sizes or more sensitive measures will be needed to interrogate the effects of high-resistance IMST on low-grade inflammation.
There also are inconsistent results on the influence of high-resistance IMST on sympathetic nervous system activity, an additional mechanism linked to above-normal BP. Bailey and colleagues observed that 6 wk of high-resistance IMST was sufficient to lower sympathetic activity, measured either directly via muscle sympathetic nerve activity or indirectly using plasma concentrations of norepinephrine, in patients with obstructive sleep apnea.[65,67] However, 6 wk of high-resistance IMST did not change plasma norepinephrine concentrations in our trial in generally healthy midlife/older adults. A potential explanation for these disparate findings is that obstructive sleep apnea is associated with elevated baseline sympathetic nervous system activity.
In addition, some respiratory muscle strength training interventions (i.e., those not falling under the definition of high-resistance IMST) have reported reductions in sympathetic activity in other patient groups, such as patients with heart failure or diabetes mellitus, although these findings are inconsistent. Thus, the direct effect of IMST on the neural control of the circulation is unclear currently. It is possible that high-resistance IMST may impact only sympathetic nervous system activity in those with significantly elevated levels at baseline. Moreover, arterial baroreflex control of heart rate was unchanged after 6 wk of high-resistance IMST in young adults and patients with sleep apnea. These findings suggest high-resistance IMST does not influence cardiac baroreflex sensitivity in these select groups, although investigation in other populations is warranted.
Of note, the acute impact of a single bout of IMST or aerobic exercise on BP differ, as aerobic exercise is associated with a period of postexercise hypotension that is not observed with high-resistance IMST. This further suggests that IMST is a unique intervention with differing physiological effects from aerobic exercise. However, physical activity levels across high-resistance IMST interventions have not yet been documented. Thus, whether the benefits of IMST occur independent of changes in activity levels cannot be fully confirmed.
Overall, high-resistance IMST has shown promise for lowering casual BP and potentially improving other measures of CV function across multiple small-scale pilot trials. These encouraging early results have stimulated interest in IMST and led to the initiation of multiple larger randomized controlled trials across various populations with above-normal BP (e.g., NCT04848675, NCT05000515, NCT04932447, NCT04911491). The results from these ongoing trials will greatly increase our understanding of the efficacy and mechanisms of action of IMST for improving CV function in the context of aging and common age-related diseases.
Exerc Sport Sci Rev. 2022;50(3):107-117. © 2022 American College of Sports Medicine