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Previous work has shown lowered casual blood pressure after just six weeks of inspiratory muscle strength training (IMST), suggesting IMST as a potential therapeutic in the prevention/treatment of hypertension. In this study, we assessed the effects of IMST on cardiovascular parameters in older, overweight adults diagnosed with moderate and severe obstructive sleep apnea (OSA). Subjects were randomly assigned to one of two interventions i) high intensity IMST (n=15, 75% maximal inspiratory pressure) or ii) a control intervention (n=10, 15% maximum inspiratory pressure). Subjects in both groups trained at home completing 30 training breaths/day, 5 days/week for 6 weeks. Pre- and post- training measures included maximal inspiratory pressure, casual and ambulatory blood pressures, spontaneous cardiac baroreflex sensitivity, and muscle sympathetic nerve activity. Men and women in the high intensity IMST group exhibited reductions in casual systolic, diastolic and mean arterial blood pressures (SBP: -8.82 ± 4.98 mmHg; DBP: -4.69 ± 2.81 mmHg; MAP: -6.06 ± 1.03 mmHg; p<0.002), and nighttime SBP (pre: -12.00 ± 8.20 mmHg; (p<0.01). Muscle sympathetic nerve activities also were lower (-6.97 ± 2.29 bursts/min-1; p=0.01 and -9.55 ± 2.42 bursts per 100 heartbeats; p=0.002) by Week 6. Conversely, subjects allocated to the control group showed no change in casual blood pressure or muscle sympathetic nerve activity and a trend toward higher overnight blood pressures. A short course of high intensity IMST may offer significant respiratory and cardiovascular benefits for older, overweight adults with OSA. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Identifier: NCT02709941
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RESEARCH ARTICLE
Inspiratory muscle strength training lowers blood pressure and sympathetic
activity in older adults with OSA: a randomized controlled pilot trial
Guadalupe Elizabeth Ramos-Barrera, Claire M. DeLucia, and XE. Fiona Bailey
Department of Physiology, University of Arizona College of Medicine, Tucson, Arizona
Submitted 9 January 2020; accepted in final form 27 July 2020
Ramos-Barrera GE, DeLucia CM, Bailey EF. Inspiratory muscle
strength training lowers blood pressure and sympathetic activity in
older adults with OSA: a randomized controlled pilot trial. J Appl
Physiol 129: 449 458, 2020. First published July 30, 2020; doi:
10.1152/japplphysiol.00024.2020.—Previous work has shown low-
ered casual blood pressure after just 6 wk of inspiratory muscle
strength training (IMST), suggesting IMST as a potential therapeutic
in the prevention/treatment of hypertension. In this study, we assessed
the effects of IMST on cardiovascular parameters in older, overweight
adults diagnosed with moderate and severe obstructive sleep apnea
(OSA). Subjects were randomly assigned to one of two interventions
1) high-intensity IMST (n15, 75% maximal inspiratory pressure),
or 2) a control intervention (n10, 15% maximum inspiratory
pressure). Subjects in both groups trained at home completing 30
training breaths/day, 5 days/wk for 6 wk. Pre- and posttraining
measures included maximal inspiratory pressure, casual and ambula-
tory blood pressures, spontaneous cardiac baroreflex sensitivity, and
muscle sympathetic nerve activity. Men and women in the high-intensity
IMST group exhibited reductions in casual systolic (SBP), diastolic
(DBP), and mean arterial blood pressures (MAP) [SBP: 8.82 4.98
mmHg; DBP: 4.69 2.81 mmHg; and MAP: 6.06 1.03 mmHg;
P0.002] and nighttime SBP (pre: 12.00 8.20 mmHg; P0.01).
Muscle sympathetic nerve activities also were lower (6.97 2.29
bursts/min
1
;P0.01 and 9.55 2.42 bursts/100 heartbeats; P
0.002) by week 6. Conversely, subjects allocated to the control group
showed no change in casual blood pressure or muscle sympathetic nerve
activity and a trend toward higher overnight blood pressures. A short
course of high-intensity IMST may offer significant respiratory and
cardiovascular benefits for older, overweight adults with OSA. For
Clinical Trial Registration, see https://www.clinicaltrials.gov (Identifier:
NCT02709941).
NEW & NOTEWORTHY Older, obese adults with moderate-severe
obstructive sleep apnea who perform 5 min/day high-intensity inspira-
tory muscle strength training (IMST) exhibit lowered casual and
nighttime systolic blood pressure and sympathetic nervous outflow. In
contrast, adults assigned to a control (low-intensity) intervention
exhibit no change in casual blood pressure or muscle sympathetic
nerve activity and a trend toward increased overnight blood pressure.
Remarkably, adherence to IMST even among sleep-deprived and
exercise-intolerant adults is high (96%).
obstructive sleep apnea; respiratory training; sympathetic activation
INTRODUCTION
Obstructive sleep apnea (OSA) is characterized by repeated
airflow obstruction (apnea) and airflow limitation (hypopnea)
that result in sleep disruption and chronic intermittent hypox-
emia (CIH). CIH has been linked to increases in reactive
oxygen species and oxidative stress that contribute to sympa-
thetic nervous system (SNS) hyperactivity (10, 35, 48, 65) and
hypertension in an estimated 30 –70% of OSA adults (1). The
standard of care for OSA worldwide is continuous positive
airway pressure (CPAP), which delivers a steady stream of
pressurized air via a (nasal/oral) mask to stent the upper airway
and stabilize breathing and blood oxygenation. Among adults
with OSA and hypertension, nightly CPAP use improves
spontaneous baroreflex sensitivity (BRS) (36, 67) and overall
sympathetic nervous system activity (27, 39). However, these
favorable outcomes are offset by uniformly low adherence, i.e.,
4.4 h/night (18, 33, 38, 43), which continues to limit CPAP-
related improvements in cardiovascular health (43).
Aerobic exercise is a first-line treatment for all stages of
hypertension (74) and has well-documented benefits for blood
pressure. Indeed, 2017 guidelines issued by the American
Heart Association and American Cardiology Association ad-
vocate 150 min/week of aerobic exercise among the first-line
treatments for all stages of hypertension (74) to lower blood
pressure. Although traditional forms of aerobic exercise may
improve BRS and lower blood pressure in OSA, the salient
features of OSA including obesity [body mass index (BMI)
30] (19, 61, 75), lethargy (62, 66), and/or exercise intoler-
ance (2, 6, 9, 26), often preclude sustained exertion (16, 41).
In recent years, a novel form of exercise known as inspira-
tory muscle strength training (IMST) has yielded surprising
results including improvements in blood pressure and auto-
nomic balance in patients with hypertension (23, 39) or OSA
(70) and reductions in systemic vascular resistance in healthy
young adults (17, 69). These outcomes are of interest and
importance because in each case they were attained within 6
wk and with a training requirement of just 5 min/day for 5
days/wk or 25 min/wk total training time (70).
Whereas there is evidence that IMST performed daily lowers
casual (resting) blood pressure and plasma catecholamines in
adults with OSA and elevated or stage 1 hypertension (70), it
is unclear what effect it may have on 24-h blood pressure, a
better predictor of blood pressure related end-organ damage
(25, 44). Accordingly, in the current study we obtained mea-
sures of casual and continuous, noninvasive ambulatory blood
pressure monitoring in a cohort of older (60 80 yr), predom-
inantly obese (i.e., BMI 30) adults with moderate-severe
OSA [apnea hypopnea index (AHI) 15] pre-post 6-wk IMST.
Because OSA is a recognized cause of secondary hypertension
and sympathetic nervous system activity plays a fundamental
role in raising blood pressure in this population (11), we also
performed microneurography to quantitate sympathetic neural
Correspondence: E. F. Bailey (ebailey@arizona.edu).
J Appl Physiol 129: 449–458, 2020.
First published July 30, 2020; doi:10.1152/japplphysiol.00024.2020.
8750-7587/20 Copyright ©2020 the American Physiological Societyhttp://www.jap.org 449
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activity directed to vascular smooth muscle [i.e., muscle sym-
pathetic nerve activity (MSNA)]. Last, whereas in a previous
IMST study CPAP users had been excluded, the current study
permitted inclusion of participants identified as adherent to
CPAP or mandibular advancement devices (4 h nightly use).
METHODS
This prospective, randomized double-blind controlled pilot clinical
trial was conducted on adults with OSA who were recruited from the
general population via advertisements placed in regional publications.
Details about how the trial was conducted, reporting enrollment,
allocation, follow-up, and analysis of subjects involved in the clinical
trial are presented in a Consolidated Standards of Reporting Trials
(CONSORT) flow chart (see Fig. 1) (21, 58). Exclusion criteria
included asthma, history of respiratory disease, neurological impair-
ment, head/neck or thoracic surgery, hypothyroidism, immune or
nervous system impairments, recent history of infection, body mass
index (BMI) 40 kg/m
2
, apnea hypopnea index 15.0 events/hour
sleep, majority mixed sleep apnea (i.e., obstructive and central ap-
neas), majority central sleep apnea, anticoagulant medication, chronic
heart failure, unstable angina, myocardial infarction, smoking, hyp-
notic or immunosuppressive medication, or cognitive disorders. Ex-
clusion criteria for systolic blood pressure (SBP) was 150 and for
diastolic blood pressure (DBP) 100. The upper limit for SBP is
based on previous observations in OSA adults that show a propensity
for slight increases in BP in some subjects during the first training
week. In view of this possibility, we adopted a somewhat conservative
cutoff for purposes of the pilot trial.
In accordance with the training device manufacturer guidelines
(http://www.powerbreathe-usa.com/), subjects with presence/history
of dyspnea, ruptured eardrum or other middle ear condition, history of
rib fracture, and marked elevated left ventricular end-diastolic volume
and/or pressure also were excluded from participation. Note that
Analysis
Analyzed (n=9)
Analysis
Failed MSNA
Randomized (n=25)
Assessed for eligibility (n=136)
Excluded (n=111)
Not meeting inclusion criteria (n=62)
oAHI < 15 events/hour; mixed or
central apneas (n=34)
o< 4.0 hours HSAT or overnight
AMBP monitoring (n=28)
Declined/unavailable to participate (n=26)
Other reasons (n=23)
Home Sleep Apnea Testing
Casual Blood Pressure
Spirometry
Plmax
BRS
MSNA
24 HR Ambulatory BP monitoring
Plasma catecholamines
Excluded from analysis (n=5)
< 4.0 hours HSAT or overnight
AMBP monitoring
Analyzed (n=6)
Allocated to interventionAllocated to intervention
Control (n=10)
High Intensity IMST (n=15)
Discontinued intervention Discontinued intervention
Withdrew (n=0)
Withdrew (n=1)
Home Sleep Apnea Testing
Casual Blood Pressure
Spirometry
Plmax
BRS
MSNA
24 HR Ambulatory BP monitoring
Plasma catecholamines
Excluded from analysis (n=4)
< 4.0 hours HSAT or overnight
AMBP monitoring
Failed MSNA
Fig. 1. Consolidated Standards of Reporting
Trials (CONSORT) flow chart. AHI, apnea
hypopnea index; HSAT, home sleep apnea
testing; IMST, inspiratory muscle strength
training; AMBP, ambulatory blood pressure
monitoring; BP, blood pressure; BRS, baro-
reflex sensitivity; PI
max
, maximal inspira-
tory pressure.
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individuals who were regular users of continuous positive airway
pressure (CPAP) (or a related pressure therapy) or users of mandibular
advancement dental devices were eligible to participate, as were
subjects with elevated, stage 1, or stage 2 hypertension. The Univer-
sity of Arizona’s Human Subjects Protection Program approved the
study procedures, and all subjects provided written informed consent
before being enrolled. Some 200 adults responded to advertisements
placed in a local newsletter, 136/200 adults completed the online
screening questionnaire and were deemed eligible to complete the
preassessments outlined below.
Spirometry
Assessments of lung function comprising assessments of forced
expiratory volume in 1.0 s (FEV
1.0
), forced vital capacity (FVC),
forced inspiratory volume in 1.0 s (FIV
1.0
), forced inspiratory capacity
(FIVC), FEV
1.0
/FVC, FIV
1.0
/FVC, FIV
1.0
/FIVC, peak expiratory
flow (PEF), and peak inspiratory flow (PIF) (WinspiroPRO, Medical
International Research, New Berlin, WI) in accordance with the
guidelines of the American Thoracic Society (45). To determine
maximal inspiratory pressure (PI
max
), subjects generated a maximal
inspiration from residual lung volume using the POWERbreathe
training device in TEST mode. The average of the three trials defined
the individual’s PI
max
(8, 31).
Home Sleep Apnea Testing
We used home sleep apnea testing (HSAT) to reliably identify
those adults in our sample with moderate and severe OSA (50 –52).
The type 3 portable testing device (ApneaLink, ResMed, Bella Vista,
Sydney, Australia) is validated for use in adults with moderate and
severe OSA (20, 24, 46, 56) and captures blood oxygenation, nasal
airflow, and thoraco-abdominal movement and yields estimates of the
severity of sleep-disordered breathing based on monitoring time.
These results are referred to as the respiratory event index (REI).
Home sleep apnea testing also permitted exclusion of other forms of
sleep disordered breathing (e.g., obesity hypoventilation syndrome or
Cheyne Stokes Respiration) on the basis of nasal airflow disturbance,
awake resting, and overnight oximetry measurement. Sleep quality,
sleep duration, sleep efficacy, sleep latency, sleep disturbance, and
impact on daily function using the Pittsburgh Sleep Quality Index
(PSQI) (53) also were recorded.
Ambulatory Blood Pressure Monitoring
Eligible adults, who passed lung function assessments and had an
AHI 15, completed a period of 24-h ambulatory BP monitoring
(SOMNOmedics, Randersacker, Germany). Given the propensity for
sleep disturbance and arousal reactions to contribute to perturbations in
SBP, we obtained continuous measures of SBP and DBP using a Food
and Drug Administration-approved and European Society of Hyperten-
sion-validated SOMNO-touch noninvasive ambulatory blood pressure
monitor (7). The device includes a small control unit worn on the wrist to
measure pulse transit time (PTT), three-channel electrocardiogram (ECG)
leads placed on the chest, and an oxygen monitor fitted to the finger that
obviates the need for arm cuff inflations that may interfere with sleep
quality (4).
After fitting each subject, the device was calibrated via a manual
blood pressure measurement. Subjects were asked to refrain from any
strenuous physical activity while wearing the device and to report
back to the laboratory 24 h later for data download. For ambulatory
recordings exceeding 4.0-h continuous recording overnight, beat-to-
beat measures of blood pressure (BP) were averaged over the entire
recording period and compared for consistency with repeated mea-
sures over shorter, i.e., 10 min, representative intervals (42).
In-Laboratory Procedures
Subjects initially underwent an in-laboratory blood draw and on a
separate day underwent in-laboratory assessments of resting blood
pressure, resting muscle sympathetic nerve activity (MSNA), and
cardiorespiratory measures (see details below). Subjects were asked to
refrain from caffeine and alcohol for 12 h and instructed not to eat for
at least 4 h before their visit. Each of the measures was repeated at the
6-wk time point after completion of training.
Plasma catecholamines. Subjects underwent a fasting blood draw
and were instructed to refrain from eating or drinking (anything other
than water) and from taking over-the-counter pain or allergy medica-
tions for the 12 h leading up the draw. Venous blood samples were
collected between the hours of 0700 and 1000 from the antecubital
region following 30 min of supine rest in a quiet, temperature-
controlled room. Samples were placed on ice in lithium-heparin-
coated tubes (BD Vacutainer, Franklin Lakes, NJ) and immediately
centrifuged (4°C, 1,500 rpm, 15 min), and the plasma frozen was at
80°C. Plasma samples were analyzed via quantitative high-perfor-
mance liquid chromatography (Associated Regional and University
Pathologists–ARUP Laboratories, Salt Lake City, UT).
Resting blood pressure. In-laboratory measures of resting (seated)
blood pressure were obtained at intake and study close and once
weekly throughout the 6-wk intervention. Measures were taken in
accordance with American Heart Association guidelines (55) with an
automated oscillometric sphygmomanometer (SunTech CT40, Sun-
Tech Medical). Three measures, taken on alternate arms, were aver-
aged to obtain systolic (SBP) and diastolic (DBP) blood pressures and
to determine mean arterial pressure (MAP) using the equation:
(MAP DBP 1/3[SBP – DBP]). Measures were obtained at the
same time of day and on the same day each week for 6 wk.
Resting spontaneous cardiac baroreflex sensitivity. While subjects
were semirecumbent and after a 20-min rest, we recorded lead II-EKG
continuously (0.3–1.0 kHz) via Ag-AgCl surface electrodes placed on
the chest (2.0 kHz) and beat-to-beat changes in systolic and diastolic
blood pressures (SBP and DBP) at 1-min intervals via automated
finger cuff pressure transducer (400 Hz) (ccNexfin; Bmeye, Amster-
dam, The Netherlands). Data were recorded online using a PowerLab
(ADInstruments, Colorado Springs, CO) interface and LabChart 8.0
software. Moment-to-moment changes in the R-R interval (RRI)
coincident with fluctuations in SBP were used to obtain estimates of
cardiac BRS (28, 29, 54) using proprietary software to identify “up”
and “down” sequences (Cardioseries V2.4, Brazil). Sequences greater
than or equal to cardiac cycles that showed in beat-to-beat increases in
SBP (1 mmHg) and lengthening of the R-R interval (6 ms) for
each beat in the series or with beat-to-beat decreases in systolic blood
pressure (1 mmHg), and shortening of the R-R interval (6 ms) for
each beat in the series were included in this analysis (54, 63).
Consecutive R-R intervals were plotted against SBP (mmHg) values
in the preceding cycle to obtain regression lines and correlation values
for each sequence. Correlation coefficients 0.85 were averaged to
obtain individual subject estimates of spontaneous cardiac baroreflex
sensitivity (ms/mmHg) (54). MSNA and beat-to-beat changes in
(systolic and diastolic) blood pressure were recorded over 20 min of
undisturbed rest. Data in the final 10 min of each recording were
subject to analysis. Respiration-related motions of the chest wall (100
Hz) were recorded using respiratory belt transducers (ADInstruments,
Colorado Springs, CO) placed around the chest and abdomen. All data
were recorded continuously throughout ~20 min of undisturbed rest.
Resting muscle sympathetic nerve activity. Concurrent with ECG
recordings, sympathetic nerve traffic was recorded from the common
peroneal nerve using tungsten microelectrodes (200 m: 25– 40 mm;
impedance: 5 M) (FHC, Bowdoin, ME) inserted percutaneously
immediately posterior to the fibular head. Subjects rested semirecum-
bent in the dental chair with the right knee and foot supported by
positioning pillows (VersaForm
,
Performance Health, Warrenville,
IL). Microelectrode placement was confirmed via electrical stimula-
tion (0.02 mA, 1 Hz) as described previously (40). A second micro-
electrode, inserted just below the skin surface ~1.0 cm from the first,
served as a reference electrode. Neural activity was amplified (gain
210
4
) and filtered (500 Hz–2.0 kHz) using a preamplifier (Neuro-
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Amp Ex; ADInstruments, Colorado Springs, CO) and signals were
full wave rectified (0.1-s moving window) and stored (10-kHz sam-
pling) using a computer-based data acquisition and analysis system
(LabChart 8.0 software, ADInstruments, Colorado Springs, CO).
Electrode position in muscle fascicles was confirmed by pulse syn-
chronous bursts of activity, elicitation of afferent nerve activity by
mild muscle stretch and absence of response to startle (40).
Negative deflecting cardiac-related sympathetic action potentials
were identified using both unprocessed and root mean squared MSNA
signals and quantitated as the number of bursts per 100 heartbeats,
number of bursts per minute, and total activity (mean burst area/min)
obtained from the root mean square (RMS) processed (moving aver-
age time constant or 200 ms) signal (47, 49, 60, 68, 71, 72). The
recording period was started no earlier than 15 min after insertion of
the electrode and was continuous throughout ~20 min of undisturbed
rest.
6-wk Intervention
Twenty-five adults (17 men, 8 women) were prospectively as-
signed, via stratified block randomization to high-intensity IMST (n
15) or to the control condition (n10), outlined below. All subjects
were unfamiliar with IMST, and all were blinded to their assigned
training group.
Subjects in both groups trained independently at home completing
30 breaths, i.e., 5 sets of 6 breaths with a ~1- to 2-min rest between
each set, 5 days/wk for 6 wk on the POWERbreathe device (K3
Series, Warwickshire, UK). Training was performed at the same time
each day, and data from each day’s training were stored on the device
and uploaded in the laboratory at the end of each training week.
Subjects were instructed first to exhale to residual volume and then
inhaled via the device mouthpiece to their target pressure. As previ-
ously, target pressures for the control group were set to 15% of the
PI
max
, and those for the high-intensity IMST group were set to 75%
of the PI
max
(17, 69, 70). Neither group encountered resistance to
expiration. Because IMST improves inspiratory muscle strength and
subjects in both groups typically show improvement in PI
max
test
performance, target pressures for both groups (i.e., 15% or 75%
PI
max
) were reassessed at the end of each training week.
Statistical Analysis
A per protocol, two-way repeated-measures mixed model ANOVA
was used to test the main effects of treatment (IMST vs. control) and
time point (week 1 vs. week 6). Statistical significance was set at P
0.05. If the ANOVA revealed significance, planned post hoc within-
group and between-group comparisons were performed using paired
Table 1. Average values for age, body mass index, neck
circumference, respiratory disturbance index, Pittsburgh
Sleep Quality Index, obstructive sleep apnea therapy type,
cardiovascular risk category, blood pressure medication/s,
and level of physical activity reported by participants in the
control group and high-intensity IMST group at study intake
Parameters Intervention Group
Control (n10) High-Intensity
IMST (n15)
Subjects 6 men, 4 women 11 men, 4 women
Age 69.7 6.7 65.9 6.0
BMI, kg/m
2
31.3 6.5 30.7 6.2
Neck circumference, cm 41.0 3.9 41.6 5.2
RDI 26.2 13.5 22.9 11.0
PSQI 9.0 5.0 8.6 4.0
OSA therapies
Continuous positive airway pressure 3 3
Mandibular advancement device 1 0
No device 6 2
Cardiovascular risk category
Normal (systolic) BP (120 mmHg) 2 4
Elevated systolic BP (120–129 mmHg) 1 4
Stage 1 hypertension (130–139 mmHg) 2 1
Stage 2 hypertension (140 mmHg) 5 6
BP medications
Beta-blocker 1 3
Angiotensin receptor blocker 1 3
Calcium channel blocker 0 3
ACE inhibitor 3 0
No BP medication 5 6
Physical activity levels
Minimally active (0–2 h exercise/wk) 2 5
Moderately active (3–4 h exercise/wk) 4 7
Vigorously active no. (5 h exercise/wk) 4 3
Average values SD for age, body mass index (BMI), neck circumference,
respiratory disturbance index (RDI), Pittsburgh Sleep Quality Index (PSQI),
obstructive sleep apnea (OSA) therapy type, cardiovascular risk category,
blood pressure (BP) medication/s and level of physical activity reported by
participants in the control group (n10) and high-intensity inspiratory muscle
strength training (IMST) group (n15) at study intake. BMI, body mass
index; ACE, angiotensin-converting enzyme.
Fig. 2. AF: individual results for in-laboratory measures of resting blood
pressure for subjects in the high-intensity inspiratory muscle strength training
(IMST; black symbols) (n14) and control (gray symbols) (n10) groups.
Individual results for casual systolic (SBP; Aand B; circles), diastolic blood
pressure (DBP; Cand D), and mean arterial blood pressure (MAP; Eand F)
measured pre (week 1)- and postintervention (week 6). *Significant differences
in the main effect of time pre vs. post (P0.05).
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and independent sample ttests, respectively, with significance ad-
justed (P0.025) according to the Bonferroni correction. Investiga-
tors were blinded to participant group assignment during data analy-
sis.
RESULTS
Twenty-five adults were randomized to high-intensity IMST
or the control intervention. One subject was disqualified from
continuing the study due to nonadherence to the training
regimen. As a result, the study retention rate was 96%. There
were no between-group differences in sex, age, neck circum-
ference, BMI, systolic and diastolic BP, respiratory disturbance
index, or PSQI scores (P0.1) at study intake. Details of
subject number, anthropomorphic data, and health status (i.e.,
sleep apnea severity, sleep apnea therapy, cardiovascular risk
category, medications and physical activity levels) for high-
intensity IMST and control groups are presented in Table 1.
Overall, key sleep indexes including awake and resting
oxygen desaturations, and sleep duration, were unchanged pre-
and postintervention for both groups (P0.1). Maximum
inspiratory pressures (PI
max
) were greater pre-post for IMST
(82.6 12.5 to 116.5 13.6 cmH
2
O) (P0.001) and control
groups (85.60 4.5 to 101.2 6.94 cmH
2
O) (P0.01), but
there was no effect of either intervention on tests of pulmonary
function: FEV
1.0
; FVC; FIV
1.0
; FEV
1.0
/FVC; FIV
1.0
/FIVC;
PEF; or PIF (P0.05) (data not shown).
Individual results for casual in-laboratory measures of systolic,
diastolic, and mean arterial blood pressures are shown in Fig. 2.
For the high-intensity IMST group, average (SD) SBP, DBP,
and MAP all declined from week 1 to week 6 (SBP: 8.82
4.98; DBP: 4.69 2.81; and MAP: 6.06 1.03); P
0.002). Heart rate and BRS were unchanged (Table 2). For the
control group, measures of blood pressure (SBP: 2.23 6.85;
Table 2. Average values for respiratory disturbance index;
systolic, diastolic; and mean arterial pressure, heart rate;
and cardiac baroreflex sensitivity for subjects in the high-
intensity IMST group, pre- and postintervention
High-Intensity IMST
Week 1
preintervention
Week 6
postintervention
Home sleep apnea assessment (n15)
Mild (RDI 15) 0 0
Moderate (RDI 15–29) 12 12
Severe (RDI 30) 3 2
Group average RDI 22.9 11.0 21.2 12.2
Cardiovascular measures (n15)
Systolic blood pressure, mmHg 140.8 17.9 132.8 14.2*
Diastolic blood pressure, mmHg 74.9 9.9 70.2 8.6
Mean arterial pressure, mmHg 95.0 11.2 89.0 10.4*
Heart rate, beats/min 59.2 5.4 59.7 5.5
BRS, ms/mmHg 10.4 3.9 10.9 5.8
Plasma norepinephrine, 80–520 pg/mL 307.1 69.1 293.8 72.4
Plasma epinephrine, 10–200 pg/mL 28.0 13.8 26.5 12.4
Average values SD for respiratory disturbance index (RDI); systolic,
diastolic, and mean arterial pressure; heart rate; and cardiac baroreflex sensi-
tivity (BRS) for subjects in the high-intensity inspiratory muscle strength
training (IMST) group (n14), pre (week 1)- and postintervention (week 6).
*Significant difference pre vs. post (P0.01).
Table 3. Average values obtained from 24-h noninvasive
blood pressure monitoring and in-laboratory measures of
resting muscle sympathetic nerve activity for subjects in the
high-intensity IMST group, pre- and postintervention
High-Intensity IMST
Cardiovascular Measures (n9)
Week 1
Preintervention
Week 6
Postintervention
Ambulatory (noninvasive) monitoring
24-h systolic blood pressure, mmHg 143.1 18.5 136.4 16.7
24-h diastolic blood pressure, mmHg 77.7 8.7 75.3 7.9
24-h heart rate, beats/min 66.1 2.7 67.1 6.8
Nighttime systolic blood pressure, mmHg 141.6 18.9 129.6 15.7*
Nighttime diastolic blood pressure, mmHg 76.6 8.5 74.1 9.2
Nighttime heart rate, betas/min 57.8 3.6 59.3 4.7
Muscle sympathetic nerve activity
Burst incidence, burst/100 beats
1
91.7 6.7 83.5 9.3*
Burst frequency, burst/min
1
53.7 7.0 46.7 8.0*
Average values SD obtained from 24-h noninvasive blood pressure
monitoring and in-laboratory measures of resting muscle sympathetic nerve
activity (MSNA) for subjects in the high-intensity inspiratory muscle strength
training (IMST) group (n9), pre (week 1)- and postintervention (week 6).
*Significant difference pre vs. post (P0.01).
Fig. 3. AF: individual results from in home, overnight noninvasive monitoring
of blood pressure for high-intensity inspiratory muscle strength training
(IMST; black symbols) (n9) and control (gray symbols) (n6) groups.
Individual results for systolic blood pressure (SBP; Aand B), diastolic blood
pressure (DBP; Cand D), and mean arterial blood pressure (MAP; Eand F)
measured pre (week 1)- and postintervention (week 6). *Significant differences
in the main effect of time pre vs. post (P0.05).
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DBP: 1.10 3.96; and MAP: 1.48 4.60), heart rate (2.2
2.4 beats/min), and BRS (0.31 1.9 ms/mmHg) were un-
changed pre vs. post (P0.1).
Ambulatory blood pressure and MSNA recordings were ob-
tained in a subset of individuals, pre- and postintervention (9
high-intensity and 6 control). Group data for high-intensity IMST
are provided in Table 3 and results for individuals in both groups
are shown in Fig. 3. Despite overall declines in nighttime BP, only
results for SBP (pre: 141.56 18.93 mmHg; post: 129.55
15.67 mmHg) attained significance (P0.01). Nighttime DBP
(pre: 76.56 8.88 mmHg; post: 74.11 9.22 mmHg) and MAP
(pre: 98.67 11.19; post: 92.78 8.73 mmHg) (Fig. 3) also
Fig. 4. Representative recordings (30 s) of muscle sympathetic nerve activity (MSNA), blood pressure (BP), electrocardiogram (EKG), and chest wall motion
traces from 4 obstructive sleep apnea (OSA) adults pre (week 1)- and post (week 6)-high-intensity inspiratory muscle strength training (IMST). RMS, root mean
squares. *Sympathetic bursts included in participant’s average burst/min count.
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declined but did not attain statistical significance (P0.10). In
the control group, average (SD) nighttime SBP (pre: 135.14
13.13; post: 144.67 19.10 mmHg), DBP (pre: 73.17 13.63;
post: 77.17 13.72 mmHg) and MAP (pre: 93.83 13.67; post:
100.33 15.67 mmHg) slightly increased postintervention (P
0.05) (Fig. 3).
Results for in-laboratory measures of resting MSNA for high-
intensity IMST are provided in Table 3 and representative record-
ings in Fig. 4. Average measures of MSNA bursts per minute
(6.97 2.29; P0.01) and bursts per 100 heartbeats
(9.55 2.42; P0.002) were lower at week 6 than in week 1
following high-intensity IMST but did not change following the
control intervention (4.87 2.80 bursts/min
1
;P0.10 and
5.527 2.96 bursts/100 heartbeats; P0.85) (Fig. 5). Neither
training protocol was associated with significant changes in plasma
norepinephrine (high-intensity IMST: pretraining 307.10 69.15 vs.
posttraining 293.82 72.37; P0.64; control: pretraining 298.71
89.43 vs. posttraining 313.29 99.04; P0.67).
DISCUSSION
OSA is characterized by repeated airway obstructions that
result in intermittent hypoxemia and arousal from sleep, which
together drive increases in nighttime sympathetic nervous ac-
tivity (64). Although previous studies confirm the benefits of
CPAP and/or daily exercise on cardiovascular health (3, 5, 22,
36, 67), adherence rates for CPAP remain low (43). Further-
more, many adults with OSA are unwilling or unable to
maintain a regular exercise program (2, 6).
Compared with traditional forms of aerobic exercise, reten-
tion rates for IMST are consistently high (92–95%) exceeding
those of comparable duration lifestyle, i.e., aerobic exercise
and/or dietary interventions (30, 37). With no treatment-emer-
gent adverse events and a 96% adherence rate (number of
prescribed training sessions completed at the target pressure),
IMST appears well tolerated by the OSA population.
Strengths and Limitations
Participants were recruited via advertisements in a regional
publication. The general recruitment call yielded two groups,
well matched in regard to key parameters of sex, age, BMI,
CPAP use, and sleep apnea severity (see Table 1); however, we
acknowledge that we were unable to obtain complete data sets
from all our subject participants and that the requirement for
pre- and post-24-h blood pressure monitoring and MSNA
recordings posed a particular challenge in this population.
While subject loss does not limit the generalizability of the
lower probability outcomes (i.e., P0.05), the variability
inherent in smaller samples may contribute false negative
outcomes, which may have affected outcomes for measures of
overnight BP.
Sleep and nighttime breathing including blood oxygen de-
saturation (32), nasal airflow, and thoraco-abdominal move-
ment were monitored using an in-home sleep apnea testing
(HSAT) validated for use in adults with moderate and severe
OSA (20, 46, 56). Importantly, the device assesses time spent
with blood oxygen desaturation 90%, nasal airflow, and
thoraco-abdominal movement and the intraclass correlation
between results obtained with this form of home sleep apnea
testing and with overnight PSG is excellent (12).
Pre- and post-HSAT showed no evidence of intervention-
related changes in apnea frequency (respiratory disturbance
index), oxygen desaturation (90%), total sleep time, and
modest improvements in subjects’ subjective assessment of
sleep quality (PSQI). The latter outcome differs from previ-
ously published findings in adults with mild-moderate OSA
(70) who reported improved sleep quality (PSQI) under the
same IMST protocol. Nevertheless, because weight, neck cir-
cumference, physical activity, medications, sleep quality, and
AHI each remained consistent throughout the study period, the
observed reductions in casual and overnight SBP and SNS
hyperactivity cannot be ascribed to change/s in the aforemen-
tioned variables.
Care was taken to exclude participants with prior knowledge
of or experience with inspiratory muscle strength training.
Whereas participants in both groups trained on the same
handheld pressure-threshold training device, followed the same
training regimen (i.e., 30 breaths day for 5 days/wk for 6 wk),
and attended weekly laboratory visits and reassessments, all
visits were coordinated to preclude participant overlap to
ensure participant blinding to high-intensity IMST versus con-
trol intervention formats.
As described previously, training pressures for the control
group were significantly lower than for the high-intensity
group (i.e., 15%PI
max
vs. 75%PI
max
). However, the pressure
range for the control group encompassed 15.0 to 20.0
cmH
2
O exceeding pressures typical of tidal (73) or deep
breathing (34). We anticipated the control intervention may
contribute some improvement in inspiratory muscle strength;
however, the magnitude of the increase in PI
max
(~5 cmH
2
O) is
consistent with previously published findings in healthy adults
Fig. 5. In-laboratory measures of resting muscle sympathetic nerve activity
(MSNA). Individual measures of MSNA bursts/min
1
(Aand B) and MSNA
bursts/100 heartbeats (hb; Cand D), pre (week 1)- and post (week 6)-high-
intensity inspiratory muscle strength training (IMST) (black symbols) (n9)
or control (gray symbols) (n6) groups. *Significant differences in average
values pre- to postintervention (P0.05).
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(17) and consistent with “learning”-related improvements at-
tributable to repeat testing over a short time span (57, 59).
Mechanistic Insights into Improvement in Blood Pressure
The mechanisms responsible for the favorable effects of
IMST require further elucidation. As reported previously in
healthy adults, large (positive or negative) intrathoracic pres-
sures but not large lung volume excursions appear to be the
primary (respiratory) stimulus underpinning IMST-related re-
ductions in BP (69). However, we see no evidence of IMST-
related changes in baroreflex sensitivity, heart rate, or cardiac
output (17). Although cardiac output was not among the
primary or secondary end points of the current study, estimates
of cardiac output (CO) retrieved from in-laboratory continuous
monitoring of BP (ccNexfin, Bmeye, Amsterdam, The Neth-
erlands) indicate no changes in CO for either the high-intensity
(2.67 5.53%change) or control group (3.41 6.39%change)
relative to preintervention values. However, as these estimates
of cardiac output were derived from discontinuous data ob-
tained pre- and postintervention, they must be interpreted with
caution and are subject to reassessment using more traditional
(e.g., equilibration CO
2
rebreathing) approaches.
In contrast, there is evidence of IMST-related declines in
plasma catecholamines (70), peripheral resistance (17), endo-
thelial-dependent dilation (14) and sympathetic nervous out-
flow (current findings) that point to changes in vascular func-
tion (13). Specifically, a focus on peripheral artery stiffness
appears warranted given preliminary evidence of IMST-related
improvements in peripheral artery distensibility and increased
nitric oxide bioavailability in otherwise healthy older healthy
adults (15). Whether a similar vascular benefit might occur in
the context of OSA will require further study.
Summary
Our results confirm previously reported findings of IMST-
related improvements in casual blood pressure. In addition, the
current findings provide preliminary and novel support for the
potential for high-intensity IMST to reduce resting sympathetic
neurogenic activity and nighttime systolic blood pressure
among older, overweight adults with OSA with just 5 min
training/day. Given these findings we propose that high-inten-
sity IMST may be an effective intervention for lowering BP
among older adults with OSA. Whether IMST can confer
similar benefits when implemented in younger adults with
OSA and hypertension and whether the benefits aggregate over
the longer term (6 –12 mo) and diminish upon withdrawal
await further study.
ACKNOWLEDGMENTS
The authors thank Dr. Mark Borgstrom for assistance with statistical
analyses. We thank Dr. Chloe Taylor (School of Medicine, University of
Western Sydney) for providing us tools for assessment of baroreflex sensitiv-
ity. We sincerely thank Roxanne M. De Asis for assistance with subject
recruitment, screening, and data collection. We are indebted to all our subject
participants, who undertook the training with enthusiasm and gave willingly of
their time.
GRANTS
This work was supported by American Heart Association Grant in Aid
16GRNT26700007 (to E.F.B.).
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the authors.
AUTHOR CONTRIBUTIONS
E.F.B. conceived and designed research; G.E.R.-B., C.M.D., and E.F.B.
performed experiments; G.E.R.-B., C.M.D., and E.F.B. analyzed data; G.E.R.-
B., C.M.D., and E.F.B. interpreted results of experiments; G.E.R.-B., C.M.D.,
and E.F.B. prepared figures; G.E.R.-B., C.M.D., and E.F.B. drafted manu-
script; G.E.R.-B., C.M.D., and E.F.B. edited and revised manuscript; G.E.R.-
B., C.M.D., and E.F.B. approved final version of manuscript.
REFERENCES
1. Ahmad M, Makati D, Akbar S. Review of and updates on hypertension
in obstructive sleep apnea. Int J Hypertens 2017: 1848375, 2017. doi:10.
1155/2017/1848375.
2. Aihara K, Oga T, Yoshimura C, Hitomi T, Chihara Y, Harada Y,
Murase K, Toyama Y, Tanizawa K, Handa T, Tsuboi T, Mishima M,
Chin K. Measurement of dyspnea in patients with obstructive sleep apnea.
Sleep Breath 17: 753–761, 2013. doi:10.1007/s11325-012-0759-2.
3. Andrade FM, Pedrosa RP. The role of physical exercise in obstructive
sleep apnea. J Bras Pneumol 42: 457–464, 2016. doi:10.1590/s1806-
37562016000000156.
4. Asayama K, Fujiwara T, Hoshide S, Ohkubo T, Kario K, Stergiou GS,
Parati G, White WB, Weber MA, Imai Y; International Expert Group
of Nocturnal Home Blood Pressure. Nocturnal blood pressure measured
by home devices: evidence and perspective for clinical application. J
Hypertens 37: 905–916, 2019. doi:10.1097/HJH.0000000000001987.
5. Barnes M, Goldsworthy UR, Cary BA, Hill CJ. A diet and exercise
program to improve clinical outcomes in patients with obstructive sleep
apnea–a feasibility study. J Clin Sleep Med 05: 409 –415, 2009. doi:10.
5664/jcsm.27594.
6. Beitler JR, Awad KM, Bakker JP, Edwards BA, DeYoung P, Djon-
lagic I, Forman DE, Quan SF, Malhotra A. Obstructive sleep apnea is
associated with impaired exercise capacity: a cross-sectional study. J Clin
Sleep Med 10: 1199 –1204, 2014. doi:10.5664/jcsm.4200.
7. Bilo G, Zorzi C, Ochoa Munera JE, Torlasco C, Giuli V, Parati G.
Validation of the Somnotouch-NIBP noninvasive continuous blood pres-
sure monitor according to the European Society of Hypertension Interna-
tional Protocol revision 2010. Blood Press Monit 20: 291–294, 2015.
doi:10.1097/MBP.0000000000000124.
8. Black LF, Hyatt RE. Maximal respiratory pressures: normal values and
relationship to age and sex. Am Rev Respir Dis 99: 696 –702, 1969.
doi:10.1164/arrd.1969.99.5.696.
9. Burgess E, Hassmén P, Welvaert M, Pumpa KL. Behavioural treatment
strategies improve adherence to lifestyle intervention programmes in
adults with obesity: a systematic review and meta-analysis. Clin Obes 7:
105–114, 2017. doi:10.1111/cob.12180.
10. Carlson JT, Hedner J, Elam M, Ejnell H, Sellgren J, Wallin BG.
Augmented resting sympathetic activity in awake patients with obstructive
sleep apnea. Chest 103: 1763–1768, 1993. doi:10.1378/chest.103.6.1763.
11. Charkoudian N, Rabbitts JA. Sympathetic neural mechanisms in human
cardiovascular health and disease. Mayo Clin Proc 84: 822–830, 2009.
doi:10.4065/84.9.822.
12. Cho JH, Kim HJ. Validation of ApneaLink™ Plus for the diagnosis of
sleep apnea. Sleep Breath 21: 799 –807, 2017. doi:10.1007/s11325-017-
1532-3.
13. Craighead DH, Heinbockel TC, Hamilton MN, Bailey EF, MacDonald
MJ, Gibala MJ, Seals DR. Time-efficient physical training for enhancing
cardiovascular function in midlife and older adults: promise and current
research gaps. J Appl Physiol (1985) 127: 1427–1440, 2019. doi:10.1152/
japplphysiol.00381.2019.
14. Craighead DH, Heinbockel TC, Rossman MJ, Jankowski LR, Jack-
man RA, Bailey EF, Chonchol M, Seals DR. Inspiratory muscle strength
training lowers resting systolic blood pressure and improves vascular
endothelial function in middle-aged and older adults (Abstract). FASEB J
33: 541.4, 2019. doi:10.1096/fasebj.2019.33.1_supplement.541.4.
15. Craighead DH, Ziemba BP, Freeberg KA, Rossman MJ, Brown BC,
Nemkov T, Reisz JA, D’Alessandro A, Chonchol M, Bailey EF, Seals
DR. Inspiratory muscle strength training improves vascular endothelial
function in older adults by altering circulating factors that suppress
superoxide and enhance nitric oxide (Abstract). FASEB J 34: 1, 2020.
doi:10.1096/fasebj.2020.34.s1.04717
456 BREATHING TRAINING FOR SLEEP APNEA-RELATED HYPERTENSION
J Appl Physiol doi:10.1152/japplphysiol.00024.2020 www.jap.org
Downloaded from journals.physiology.org/journal/jappl by E. Fiona Bailey (064.119.034.107) on September 6, 2020.
16. de Carvalho MM, Coutinho RQ, Barros IM, Costa LO, Medeiros AK,
Lustosa TC, Medeiros CA, França MV, Couto TL, Montarroyos UR,
Somers VK, Pedrosa RP. Prevalence of obstructive sleep apnea and
obesity among middle-aged women: implications for exercise capacity. J
Clin Sleep Med 14: 1471–1475, 2018. doi:10.5664/jcsm.7316.
17. DeLucia CM, De Asis RM, Bailey EF. Daily inspiratory muscle training
lowers blood pressure and vascular resistance in healthy men and women.
Exp Physiol 103: 201–211, 2018. doi:10.1113/EP086641.
18. DeVan AE, Johnson LC, Brooks FA, Evans TD, Justice JN, Cruick-
shank-Quinn C, Reisdorph N, Bryan NS, McQueen MB, Santos-
Parker JR, Chonchol MB, Bassett CJ, Sindler AL, Giordano T, Seals
DR. Effects of sodium nitrite supplementation on vascular function and
related small metabolite signatures in middle-aged and older adults. J Appl
Physiol (1985) 120: 416 –425, 2016. doi:10.1152/japplphysiol.00879.
2015.
19. Drager LF, Brunoni AR, Jenner R, Lorenzi-Filho G, Benseñor IM,
Lotufo PA. Effects of CPAP on body weight in patients with obstructive
sleep apnoea: a meta-analysis of randomised trials. Thorax 70: 258 –264,
2015. doi:10.1136/thoraxjnl-2014-205361.
20. El Shayeb M, Topfer LA, Stafinski T, Pawluk L, Menon D. Diagnostic
accuracy of level 3 portable sleep tests versus level 1 polysomnography for
sleep-disordered breathing: a systematic review and meta-analysis. CMAJ
186: E25–E51, 2014. doi:10.1503/cmaj.130952.
21. Falci SG, Marques LS. CONSORT: when and how to use it. Dental
Press J Orthod 20: 13–15, 2015. doi:10.1590/2176-9451.20.3.013-015.
ebo.
22. Fatureto-Borges F, Lorenzi-Filho G, Drager LF. Effectiveness of
continuous positive airway pressure in lowering blood pressure in patients
with obstructive sleep apnea: a critical review of the literature. Integr
Blood Press Control 9: 43–47, 2016. doi:10.2147/IBPC.S70402.
23. Ferreira JB, Plentz RD, Stein C, Casali KR, Arena R, Lago PD.
Inspiratory muscle training reduces blood pressure and sympathetic activ-
ity in hypertensive patients: a randomized controlled trial. Int J Cardiol
166: 61–67, 2013. doi:10.1016/j.ijcard.2011.09.069.
24. Ghegan MD, Angelos PC, Stonebraker AC, Gillespie MB. Laboratory
versus portable sleep studies: a meta-analysis. Laryngoscope 116: 859 –
864, 2006. doi:10.1097/01.mlg.0000214866.32050.2e.
25. Grossman E. Ambulatory blood pressure monitoring in the diagnosis and
management of hypertension. Diabetes Care 36, Suppl 2: S307–S311,
2013. doi:10.2337/dcS13-2039.
26. Hargens TA, Guill SG, Zedalis D, Gregg JM, Nickols-Richardson SM,
Herbert WG. Attenuated heart rate recovery following exercise testing in
overweight young men with untreated obstructive sleep apnea. Sleep 31:
104 –110, 2008. doi:10.1093/sleep/31.1.104.
27. Henderson LA, Fatouleh RH, Lundblad LC, McKenzie DK, Macefield
VG. Effects of 12 Months Continuous Positive Airway Pressure on
Sympathetic Activity Related Brainstem Function and Structure in Ob-
structive Sleep Apnea. Front Neurosci 10: 90, 2016. doi:10.3389/fnins.
2016.00090.
28. Iellamo F, Legramante JM, Massaro M, Galante A, Pigozzi F, Nar-
dozi C, Santilli V. Spontaneous baroreflex modulation of heart rate and
heart rate variability during orthostatic stress in tetraplegics and healthy
subjects. J Hypertens 19: 2231–2240, 2001. doi:10.1097/00004872-
200112000-00017.
29. Iellamo F, Legramante JM, Raimondi G, Castrucci F, Massaro M,
Peruzzi G. Evaluation of reproducibility of spontaneous baroreflex sen-
sitivity at rest and during laboratory tests. J Hypertens 14: 1099 –1104,
1996. doi:10.1097/00004872-199609000-00009.
30. Jette AM, Harris BA, Sleeper L, Lachman ME, Heislein D, Giorgetti
M, Levenson C. A home-based exercise program for nondisabled older
adults. J Am Geriatr Soc 44: 644 –649, 1996. doi:10.1111/j.1532-5415.
1996.tb01825.x.
31. Kellerman BA, Martin AD, Davenport PW. Inspiratory strengthening
effect on resistive load detection and magnitude estimation. Med Sci
Sports Exerc 32: 1859 –1867, 2000. doi:10.1097/00005768-200011000-
00007.
32. Kendzerska T, Gershon AS, Hawker G, Leung RS, Tomlinson G.
Obstructive sleep apnea and risk of cardiovascular events and all-cause
mortality: a decade-long historical cohort study. PLoS Med 11: e1001599,
2014. doi:10.1371/journal.pmed.1001599.
33. Khan SU, Duran CA, Rahman H, Lekkala M, Saleem MA, Kaluski E.
A meta-analysis of continuous positive airway pressure therapy in pre-
vention of cardiovascular events in patients with obstructive sleep apnoea.
Eur Heart J 39: 2291–2297, 2018. doi:10.1093/eurheartj/ehx597.
34. Landman GW, van Hateren KJ, van Dijk PR, Logtenberg SJ, Hou-
weling ST, Groenier KH, Bilo HJ, Kleefstra N. Efficacy of device-
guided breathing for hypertension in blinded, randomized, active-con-
trolled trials: a meta-analysis of individual patient data. JAMA Intern Med
174: 1815–1821, 2014. doi:10.1001/jamainternmed.2014.4336.
35. Leuenberger U, Jacob E, Sweer L, Waravdekar N, Zwillich C, Sino-
way L. Surges of muscle sympathetic nerve activity during obstructive
apnea are linked to hypoxemia. J Appl Physiol (1985) 79: 581–588, 1995.
doi:10.1152/jappl.1995.79.2.581.
36. Logan AG, Tkacova R, Perlikowski SM, Leung RS, Tisler A, Floras
JS, Bradley TD. Refractory hypertension and sleep apnoea: effect of
CPAP on blood pressure and baroreflex. Eur Respir J 21: 241–247, 2003.
doi:10.1183/09031936.03.00035402.
37. Looney SM, Raynor HA. Behavioral lifestyle intervention in the treat-
ment of obesity. Health Serv Insights 6: 15–31, 2013. doi:10.4137/HSI.
S10474.
38. Lorenzi-Filho G, Almeida FR, Strollo PJ. Treating OSA: current and
emerging therapies beyond CPAP. Respirology 22: 1500 –1507, 2017.
doi:10.1111/resp.13144.
39. Lundblad LC, Fatouleh RH, McKenzie DK, Macefield VG, Hender-
son LA. Brain stem activity changes associated with restored sympathetic
drive following CPAP treatment in OSA subjects: a longitudinal investi-
gation. J Neurophysiol 114: 893–901, 2015. doi:10.1152/jn.00092.2015.
40. Macefield VG, Wallin BG, Vallbo AB. The discharge behaviour of
single vasoconstrictor motoneurones in human muscle nerves. J Physiol
481: 799 –809, 1994. doi:10.1113/jphysiol.1994.sp020482.
41. Marillier M, Gruet M, Baillieul S, Wuyam B, Tamisier R, Levy P,
Pepin JL, Verges S. Impaired cerebral oxygenation and exercise tolerance
in patients with severe obstructive sleep apnea syndrome. Sleep Med 51:
37–46, 2018. doi:10.1016/j.sleep.2018.06.013.
42. Marrone O, Romano S, Insalaco G, Bonsignore MR, Salvaggio A,
Bonsignore G. Influence of sampling interval on the evaluation of noc-
turnal blood pressure in subjects with and without obstructive sleep
apnoea. Eur Respir J 16: 653–658, 2000. doi:10.1034/j.1399-3003.2000.
16d15.x.
43. McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O,
Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S,
Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang
J, Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson
CS; SAVE Investigators and Coordinators. CPAP for prevention of
cardiovascular events in obstructive sleep apnea. N Engl J Med 375:
919 –931, 2016. doi:10.1056/NEJMoa1606599.
44. Mena LJ, Felix VG, Melgarejo JD, Maestre GE. 24-Hour blood
pressure variability assessed by average real variability: a systematic
review and meta-analysis. J Am Heart Assoc 6: e006895, 2017. doi:10.
1161/JAHA.117.006895.
45. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates
A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R,
Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF,
Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisa-
tion of spirometry. Eur Respir J 26: 319 –338, 2005. doi:10.1183/
09031936.05.00034805.
46. Mulgrew AT, Fox N, Ayas NT, Ryan CF. Diagnosis and initial man-
agement of obstructive sleep apnea without polysomnography: a random-
ized validation study. Ann Intern Med 146: 157–166, 2007. doi:10.7326/
0003-4819-146-3-200702060-00004.
47. Narkiewicz K, Kato M, Phillips BG, Pesek CA, Davison DE, Somers
VK. Nocturnal continuous positive airway pressure decreases daytime
sympathetic traffic in obstructive sleep apnea. Circulation 100: 2332–
2335, 1999. doi:10.1161/01.CIR.100.23.2332.
48. Narkiewicz K, Somers VK. Sympathetic nerve activity in obstructive
sleep apnoea. Acta Physiol Scand 177: 385–390, 2003. doi:10.1046/j.
1365-201X.2003.01091.x.
49. Narkiewicz K, van de Borne PJ, Cooley RL, Dyken ME, Somers VK.
Sympathetic activity in obese subjects with and without obstructive sleep
apnea. Circulation 98: 772–776, 1998. doi:10.1161/01.CIR.98.8.772.
50. Ng SS, Chan TO, To KW, Ngai J, Tung A, Ko FW, Hui DS. Validation
of a portable recording device (ApneaLink) for identifying patients with
suspected obstructive sleep apnoea syndrome. Intern Med J 39: 757–762,
2009. doi:10.1111/j.1445-5994.2008.01827.x.
51. Nigro CA, Dibur E, Malnis S, Grandval S, Nogueira F. Validation of
ApneaLink Ox™ for the diagnosis of obstructive sleep apnea. Sleep
Breath 17: 259 –266, 2013. doi:10.1007/s11325-012-0684-4.
457BREATHING TRAINING FOR SLEEP APNEA-RELATED HYPERTENSION
J Appl Physiol doi:10.1152/japplphysiol.00024.2020 www.jap.org
Downloaded from journals.physiology.org/journal/jappl by E. Fiona Bailey (064.119.034.107) on September 6, 2020.
52. Nigro CA, Serrano F, Aimaretti S, González S, Codinardo C, Rhodius
E. Utility of ApneaLink for the diagnosis of sleep apnea-hypopnea
syndrome. Medicina (B Aires) 70: 53–59, 2010.
53. Nishiyama T, Mizuno T, Kojima M, Suzuki S, Kitajima T, Ando KB,
Kuriyama S, Nakayama M. Criterion validity of the Pittsburgh Sleep
Quality Index and Epworth Sleepiness Scale for the diagnosis of sleep
disorders. Sleep Med 15: 422–429, 2014. doi:10.1016/j.sleep.2013.12.015.
54. Parati G, Di Rienzo M, Bertinieri G, Pomidossi G, Casadei R, Grop-
pelli A, Pedotti A, Zanchetti A, Mancia G. Evaluation of the barore-
ceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring
in humans. Hypertension 12: 214 –222, 1988. doi:10.1161/01.HYP.12.2.
214.
55. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN,
Jones DW, Kurtz T, Sheps SG, Roccella EJ. Recommendations for
blood pressure measurement in humans and experimental animals: part 1:
blood pressure measurement in humans: a statement for professionals from
the Subcommittee of Professional and Public Education of the American
Heart Association Council on High Blood Pressure Research. Circulation
111: 697–716, 2005. doi:10.1161/01.CIR.0000154900.76284.F6.
56. Rosen IM, Kirsch DB, Chervin RD, Carden KA, Ramar K, Aurora
RN, Kristo DA, Malhotra RK, Martin JL, Olson EJ, Rosen CL,
Rowley JA; American Academy of Sleep Medicine Board of Directors.
Clinical use of a home sleep apnea test: an American Academy of Sleep
Medicine position statement. J Clin Sleep Med 13: 1205–1207, 2017.
doi:10.5664/jcsm.6774.
57. Schermer TR, Jacobs JE, Chavannes NH, Hartman J, Folgering HT,
Bottema BJ, van Weel C. Validity of spirometric testing in a general
practice population of patients with chronic obstructive pulmonary disease
(COPD). Thorax 58: 861–866, 2003. doi:10.1136/thorax.58.10.861.
58. Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT
2010 statement: updated guidelines for reporting parallel group ran-
domised trials. PLoS Med 7: e1000251, 2010. doi:10.1371/journal.pmed.
1000251.
59. Sclauser Pessoa IM, Franco Parreira V, Fregonezi GA, Sheel AW,
Chung F, Reid WD. Reference values for maximal inspiratory pressure:
a systematic review. Can Respir J 21: 43–50, 2014. doi:10.1155/2014/
982374.
60. Seitz MJ, Brown R, Macefield VG. Inhibition of augmented muscle
vasoconstrictor drive following asphyxic apnoea in awake human subjects
is not affected by relief of chemical drive. Exp Physiol 98: 405–414, 2013.
doi:10.1113/expphysiol.2012.067421.
61. Senaratna CV, Perret JL, Lodge CJ, Lowe AJ, Campbell BE, Mathe-
son MC, Hamilton GS, Dharmage SC. Prevalence of obstructive sleep
apnea in the general population: A systematic review. Sleep Med Rev 34:
70 –81, 2017. doi:10.1016/j.smrv.2016.07.002.
62. Sengul YS, Ozalevli S, Oztura I, Itil O, Baklan B. The effect of exercise
on obstructive sleep apnea: a randomized and controlled trial. Sleep Breath
15: 49 –56, 2011. doi:10.1007/s11325-009-0311-1.
63. Shantsila A, McIntyre DB, Lip GY, Fadel PJ, Paton JF, Pickering AE,
Fisher JP. Influence of age on respiratory modulation of muscle sympa-
thetic nerve activity, blood pressure and baroreflex function in humans.
Exp Physiol 100: 1039 –1051, 2015. doi:10.1113/EP085071.
64. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural
mechanisms in obstructive sleep apnea. J Clin Invest 96: 1897–1904,
1995. doi:10.1172/JCI118235.
65. Tamisier R, Pépin JL, Rémy J, Baguet JP, Taylor JA, Weiss JW, Lévy
P. 14 nights of intermittent hypoxia elevate daytime blood pressure and
sympathetic activity in healthy humans. Eur Respir J 37: 119 –128, 2011.
doi:10.1183/09031936.00204209.
66. Thompson PD, Franklin BA, Balady GJ, Blair SN, Corrado D, Estes
NA III, Fulton JE, Gordon NF, Haskell WL, Link MS, Maron BJ,
Mittleman MA, Pelliccia A, Wenger NK, Willich SN, Costa F; Amer-
ican Heart Association Council on Nutrition, Physical Activity, and
Metabolism; American Heart Association Council on Clinical Cardi-
ology; American College of Sports Medicine. Exercise and acute car-
diovascular events placing the risks into perspective: a scientific statement
from the American Heart Association Council on Nutrition, Physical
Activity, and Metabolism and the Council on Clinical Cardiology. Circu-
lation 115: 2358 –2368, 2007. doi:10.1161/CIRCULATIONAHA.107.
181485.
67. Tkacova R, Dajani HR, Rankin F, Fitzgerald FS, Floras JS, Bradley
TD. Continuous positive airway pressure improves nocturnal baroreflex
sensitivity of patients with heart failure and obstructive sleep apnea. J
Hypertens 18: 1257–1262, 2000. doi:10.1097/00004872-200018090-
00012.
68. Vallbo AB, Hagbarth KE, Wallin BG. Microneurography: how the
technique developed and its role in the investigation of the sympathetic
nervous system. J Appl Physiol (1985) 96: 1262–1269, 2004. doi:10.1152/
japplphysiol.00470.2003.
69. Vranish JR, Bailey EF. Daily respiratory training with large intrathoracic
pressures, but not large lung volumes, lowers blood pressure in normo-
tensive adults. Respir Physiol Neurobiol 216: 63–69, 2015. doi:10.1016/
j.resp.2015.06.002.
70. Vranish JR, Bailey EF. Inspiratory muscle training improves sleep and
mitigates cardiovascular dysfunction in obstructive sleep apnea. Sleep
(Basel) 39: 1179 –1185, 2016. doi:10.5665/sleep.5826.
71. Wallin BG, Delius W, Hagbarth KE. Comparison of sympathetic nerve
activity in normotensive and hypertensive subjects. Circ Res 33: 9 –21,
1973. doi:10.1161/01.RES.33.1.9.
72. Wallin BG, Delius W, Hagbarth KE. Sympathetic activity in peripheral
nerves of normo-and hypertensive subjects. Clin Sci Mol Med Suppl 45,
Suppl 1: 127s–130s, 1973. doi:10.1042/cs045127s.
73. Walls CE, Laine CM, Kidder IJ, Bailey EF. Human hypoglossal motor
unit activities in exercise. J Physiol 591: 3579 –3590, 2013. doi:10.1113/
jphysiol.2013.252452.
74. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ,
Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA,
Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr,
Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr,
Williamson JD, Wright JT Jr. ACC/AHA/AAPA/ABC/ACPM/AGS/
APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection,
Evaluation, and Management of High Blood Pressure in Adults: A Report
of the American College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines. J Am Coll Cardiol 71: e127–e248,
2018. doi:10.1016/jacc.2017.11.006
75. Yu J, Zhou Z, McEvoy RD, Anderson CS, Rodgers A, Perkovic V,
Neal B. Association of positive airway pressure with cardiovascular
events and death in adults with sleep apnea: a systematic review and
meta-analysis. JAMA 318: 156 –166, 2017. doi:10.1001/jama.2017.7967.
458 BREATHING TRAINING FOR SLEEP APNEA-RELATED HYPERTENSION
J Appl Physiol doi:10.1152/japplphysiol.00024.2020 www.jap.org
Downloaded from journals.physiology.org/journal/jappl by E. Fiona Bailey (064.119.034.107) on September 6, 2020.
... Of these, 12 were excluded for conference abstract, two for wrong intervention, one for wrong population, and one for wrong publication type. Ultimately, eight studies met the criteria for eligibility and were included in the review [16,17,[21][22][23][24][25][26]. The flow chart of the study selection process is shown in Figure 1. ...
... Two studies were conducted in the USA [17,26], two in Taiwan [23,25], two in Brazil [16,21], one in Egypt [22], and one in Turkey [24]. All studies were published after 2016. ...
... The characteristics of the included studies are shown in Table 1. Seven studies included IMT [16,17,[21][22][23][24]26], and one applied expiratory muscle training (EMT) [25]. ...
Article
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Background: Effective treatments for obstructive sleep apnoea (OSA) include positive pressure, weight loss, oral appliances, surgery, and exercise. Although the involvement of the respiratory muscles in OSA is evident, the effect of training them to improve clinical outcomes is not clear. We aimed to determine the effects of respiratory muscle training in patients with OSA. Methods: A systematic review was conducted in seven databases. Studies that applied respiratory muscle training in OSA patients were reviewed. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence. Results: Of the 405 reports returned by the initial search, eight articles reporting on 210 patients were included in the data synthesis. Seven included inspiratory muscle training (IMT), and one included expiratory muscle training (EMT). Regarding IMT, we found significant improvement in Epworth sleepiness scale in -4.45 points (95%CI -7.64 to -1.27 points, p = 0.006), in Pittsburgh sleep quality index of -2.79 points (95%CI -4.19 to -1.39 points, p <0.0001), and maximum inspiratory pressure of -29.56 cmH2O (95%CI -53.14 to -5.98 cmH2O, p =0.01). However, the apnoea/hypopnea index and physical capacity did not show changes. We did not perform a meta-analysis of EMT due to insufficient studies. Conclusion: IMT improves sleepiness, sleep quality and inspiratory strength in patients with OSA.
... TO THE EDITOR: The recent study by Ramos-Barrera and colleagues (5) shows impressive decrements in the blood pressure of older, overweight adults achieved by only 5 min of daily inspiratory muscle training (IMT) on blood pressure (BP). Upon closer analysis, however, we noted several issues with the data analysis and interpretation that is at odds with the original interpretation. ...
... Third, the captions of Figs. 2 and 3 in the study by Ramos-Barrera and colleagues (5) indicate that only a main effect of time was noted for laboratory and overnight BP, and results for the interactions are not given. While it is acceptable to look into planned post hoc comparisons in the absence of a main effect (4), at no point do the authors compare the responses of the different groups. ...
... In fact, a different line of breathing maneuvers, with slow breathing and low load, has been shown to be even more effective than IMT in lowering BP (6), in direct opposition to the hypothesis proposed by Ramos-Barrera and colleagues (5,7). Although authors should not be expected to be aware of 100% of existing literature in their field, important points of disagreement to the proposed theory have been left out, upselling the effects of IMT on blood pressure. ...
... More specifically, since OSA involves the collapse of the upper airways with inspiration during sleep, IMT may reduce the number and/or severity of apneas by improving upper airway muscle tone (How et al., 2007). In addition, IMT may also improve cardiovascular symptoms, since studies in normotensive adults and patients with OSA found significant reductions in BP with IMT, and improved functional capacity in people with heart failure (Ferreira et al., 2013;Bailey, 2015, 2016;Posser et al., 2016;DeLucia et al., 2018;Fernandez-Rubio et al., 2020;Ramos-Barrera et al., 2020). The mechanism of IMT effects on cardiovascular function is unknown, but may be due to either associations between respiratory and cardiovascular activity, or due to potential positive IMT-related effects on stress (Grossman et al., 2001;HajGhanbari et al., 2013;de Abreu et al., 2017;Fernandez-Rubio et al., 2020). ...
... For example, in IMT studies with older adults, parameters vary from 4 to 8 weeks of training duration, 30-80% target resistance, and between 5 and 7 weekly sessions (Seixas et al., 2020). Although one research group developed and successfully tested a protocol for people with OSA for 6 weeks, 75% of maximum target resistance performed twice daily (Vranish and Bailey, 2016;Ramos-Barrera et al., 2020), several of our participants required repeated practice sessions across several days to learn the technique, and were still unable to inhale against the 75% target resistance. Hence, they were unable to complete the exercise. ...
Article
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Background: Inspiratory muscle training (IMT) may improve respiratory and cardiovascular functions in obstructive sleep apnea (OSA) and is a potential alternative or adjunct treatment to continuous positive airway pressure (CPAP). IMT protocols were originally designed for athletes, however, we found some OSA patients could not perform the exercise, so we aimed for a more OSA-friendly protocol. Our feasibility criteria included (1) participants successfully managing the technique at home; (2) participants completing daily practice sessions and recording data logs; and (3) capturing performance plateaus to determine an optimal length of the intervention. Methods: Five sedentary OSA patients participated in this feasibility study (three men, mean age = 61.6 years, SD = 10.2). Using a digital POWERbreathe K4 or K5 device, participants performed 30 daily inhalations against a resistance set at a percentage of maximum, recalculated weekly. Participants were willing to perform one but not two daily practice sessions. Intervention parameters from common IMT protocols were adapted according to ability and subjective feedback. Some were unable to perform the typically used 75% of maximum inspiratory resistance so we lowered the target to 65%. The technique required some practice; therefore, we introduced a practice week with a 50% target. After an initial 8 weeks, the intervention was open-ended and training continued until all participants demonstrated at least one plateau of inspiratory strength (2 weeks without strength gain). Weekly email and phone reminders ensured that participants completed all daily sessions and logged data in their online surveys. Weekly measures of inspiratory resistance, strength, volume, and flow were recorded. Results: Participants successfully completed the practice and subsequent 65% IMT resistance targets daily for 13 weeks. Inspiratory strength gains showed plateaus in all subjects by the end of 10 weeks of training, suggesting 12 weeks plus practice would be sufficient to achieve and capture maximum gains. Participants reported no adverse effects. Conclusion: We developed and tested a 13-week IMT protocol in a small group of sedentary, untreated OSA patients. Relative to other IMT protocols, we successfully implemented reduced performance requirements, a practice week, and an extended timeframe. This feasibility study provides the basis for a protocol for clinical trials on IMT in OSA.
... [30][31][32] More recently, Bailey and colleagues developed a novel high-resistance paradigm of IMST that requires only 30 breaths (≈5 minutes) per session performed with an affordable and portable handheld device at home. 33,34 When performed 5 to 7 days (25-35 total minutes) per week for 6 weeks, reductions in casual (resting) BP, particularly SBP, were observed in young healthy adults, 35 • This is the first trial in healthy midlife and older adults to show that high-resistance inspiratory muscle strength training lowers blood pressure and improves endothelial function. • We provide the first evidence that inspiratory muscle strength training increases NO bioavailability by increasing endothelial NO synthase activation and decreasing oxidative stress. ...
... sleep apnea. 33,34 The reductions in BP with IMST were associated with reductions in systemic vascular resistance in the absence of changes in heart rate, 36 suggesting adaptations in vascular function. ...
Article
Full-text available
Background High‐resistance inspiratory muscle strength training (IMST) is a novel, time‐efficient physical training modality. Methods and Results We performed a double‐blind, randomized, sham‐controlled trial to investigate whether 6 weeks of IMST (30 breaths/day, 6 days/week) improves blood pressure, endothelial function, and arterial stiffness in midlife/older adults (aged 50–79 years) with systolic blood pressure ≥120 mm Hg, while also investigating potential mechanisms and long‐lasting effects. Thirty‐six participants completed high‐resistance IMST (75% maximal inspiratory pressure, n=18) or low‐resistance sham training (15% maximal inspiratory pressure, n=18). IMST was safe, well tolerated, and had excellent adherence (≈95% of training sessions completed). Casual systolic blood pressure decreased from 135±2 mm Hg to 126±3 mm Hg (P
... An improvement of subjective quality of sleep and a reduction in neck circumference were also found in the "strengthening oropharyngeal muscles" group. In the last decade, several other studies have investigated the effect of respiratory muscle training to decrease the impact of OSA (Vranish and Bailey, 2016;Souza et al., 2018;Ramos-Barrera et al., 2020). Indeed, the resistance strengthening of the inspiratory muscles would have a positive impact on the tone of the oropharyngeal muscles (How et al., 2007). ...
Article
Full-text available
Background Obstructive sleep apnea (OSA) affects 5% of the adult population and its prevalence is up to 13 times higher in coronary artery disease (CAD) patients. However, OSA in this population is less symptomatic, leading to lower adherence to positive airway pressure (CPAP). While oropharyngeal exercise showed a significant decrease in apnea-hypopnea index (AHI) in patients with moderate OSA, there have been no studies testing the impact of specific inspiratory muscle training (IMT) for these patients. The aim of our study was to assess the effectiveness of IMT on AHI reduction in CAD patients with moderate OSA. Methods We included patients with CAD involved in a cardiac rehabilitation program and presenting an AHI between 15 and 30. Patients were randomized in a 1:1 allocation to a control group (CTL – classic training) or an IMT group (classic training + IMT). IMT consisted in 60 deep inspirations a day, 6 days a week, into a resistive load device set at 70% of the maximum inspiratory pressure (MIP). After 6 weeks, we compared AHI, neck circumference, Epworth Sleepiness Scale, Pittsburgh Sleep Quality index, and quality of life with the 12-item Short Form Survey before and after rehabilitation. Results We studied 45 patients (60 ± 9 y, BMI = 27 ± 6 kg.m ⁻² ). The IMT group ( n = 23) significantly improved MIP ( p < 0.05) and had a significant decrease in AHI by 25% (−6.5 ± 9.5, p = 0.02). In the CTL group ( n = 23), AHI decreased only by 3.5% (−0.7 ± 13.1; p = 0.29). Between groups, we found a significant improvement in MIP ( p = 0.003) and neck circumference ( p = 0.01) in favor of the IMT group. However, we did not find any significant improvement of AHI in the IMT group compared to CTL ( p = 0.09). Conclusion A specific IMT during cardiac rehabilitation contributes to reduce significantly AHI in CAD patients with moderate OSA. Magnitude of the decrease in OSA severity could be enhanced according to implementation of specific IMT in this population.
... Over the short-term (i.e., 6 weeks), high-resistance IMST has yielded improvements in SBP, sympathetic nervous system activity, and endothelial function in small groups of healthy and at-risk populations (45,(49)(50)(51)(52), including middle aged and older (MA/O) adults with OSA. However, the results for OSA adults are preliminary and require confirmation in a larger group of patients. ...
Article
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Background: Cardiovascular disease is a major global health concern and prevalence is high in adults with obstructive sleep apnea (OSA). Lowering blood pressure (BP) can greatly reduce cardiovascular disease risk and physical activity is routinely prescribed to achieve this goal. Unfortunately, many adults with OSA suffer from fatigue, daytime sleepiness, and exercise intolerance—due to poor sleep quality and nocturnal hypoxemia—and have difficulty initiating and maintaining an exercise program. High-resistance inspiratory muscle strength training (IMST) is a simple, time-efficient breathing exercise consistently reported to reduce BP in small, selective groups of both healthy and at-risk adults. Herein we present the study protocol for a randomized clinical trial to determine the long-term efficacy of IMST performed regularly for 24 weeks in middle-aged and older adults with OSA. The primary outcome is casual systolic BP. Secondary outcomes are 24-h systolic BP and circulating plasma norepinephrine concentration. Other outcomes include vascular endothelial function (endothelial-dependent and -independent dilation), aortic stiffness, casual and 24-h diastolic BP, and the influence of circulating factors on endothelial cell nitric oxide and reactive oxygen species production. Overall, this trial will establish efficacy of high-resistance IMST for lowering BP and improving cardiovascular health in middle-aged and older adults with OSA. Methods: This is a single-site, double-blind, randomized clinical trial. A minimum of 92 and maximum of 122 male and female adults aged 50–80 years with OSA and above-normal BP will be enrolled. After completion of baseline assessments, subjects will be randomized in a 1:1 ratio to participate in either high-resistance or sham (low-resistance) control IMST, performed at home, 5 min/day, 5 days/week, for 24 weeks. Repeat assessments will be taken after the 24-week intervention, and after 4 and 12 weeks of free living. Discussion: This study is designed to assess the effects of 24 weeks of IMST on BP and vascular function. The results will characterize the extent to which IMST can reduce BP when performed over longer periods (i.e., 6 months) than have been assessed previously. Additionally, this study will help to determine underlying mechanisms driving IMST-induced BP reductions that have been reported previously. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov (Registration Number: NCT04932447; Date of registration June 21, 2021).
... We have shown that young healthy adults who complete 6 weeks of this respiratory training regimen exhibit significant improvements in blood pressure, autonomic balance, and systemic vascular resistance (14,15), with similar outcomes in select patient populations (16,17). ...
Article
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High intensity, low volume inspiratory muscle strength training (IMST) has favorable effects on casual systolic blood pressure and systemic vascular resistance. However, the acute effects of IMST on heart rate (HR), blood pressure (BP) and sympathetic regulation of vascular resistance and the trajectory of post exercise recovery are not known. We recruited fourteen young adults (7 women/7 men, age: 22±2 years) to perform a single bout of high intensity IMST (inspiratory resistance set at 75% of maximal inspiratory pressure) importantly, female and male subjects were matched in regard to the target inspiratory pressure and target inspiratory muscle work per breath. We recorded HR, beat-to-beat changes in BP and postganglionic, muscle sympathetic nerve activities (MSNA) continuously throughout Baseline, a single bout of IMST (comprising five sets of 6 inspiratory efforts) and in Recovery. We show that one bout of IMST does not effect a change in BP however, it effects a significant increase in HR (68.4 ±11.7 BPM vs. 85.4 ±13.6 BPM; p<0.001) and a significant decline in MSNA (6.8 ±1.1 bursts/15s bin; p<0.001 vs. 3.6 ±0.6 bursts/15s bin) relative to Baseline. Remarkably, among men MSNA rebounded to Baseline levels within the first minute of Recovery however in women, MSNA suppression persisted for 5 minutes. We show that in healthy young adults, high intensity, low volume respiratory training results in the acute suppression of MSNA. Importantly, MSNA suppression is of greater magnitude and longer duration in women than in men.
Article
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Short sleep duration and poor sleep quality are associated with cardiovascular risk, and sympathetic nervous system (SNS) dysfunction appears to be a key contributor. The present review will characterize sympathetic function across several sleep disorders and insufficiencies in humans, including sleep deprivation, insomnia, narcolepsy, and obstructive sleep apnea (OSA). We will focus on direct assessments of sympathetic activation (e.g., plasma norepinephrine and muscle sympathetic nerve activity), but include heart rate variability (HRV) when direct assessments are lacking. The review also emphasizes sex as a key biological variable. Experimental models of total sleep deprivation and sleep restriction are converging to support epidemiological studies reporting an association between short sleep duration and hypertension, especially in women. A systemic increase of SNS activity via plasma norepinephrine is present with insomnia, and has also been confirmed with direct, regionally-specific evidence from microneurographic studies. Narcolepsy is characterized by autonomic dysfunction via both HRV and microneurographic studies, but with opposing conclusions regarding SNS activation. Robust sympathoexcitation is well documented in OSA, and is related to baroreflex and chemoreflex dysfunction. Treatment of OSA with continuous positive airway pressure results in sympathoinhibition. In summary, sleep disorders and insufficiencies are often characterized by sympathoexcitation and/or sympathetic/baroreflex dysfunction, with several studies suggesting women may be at heightened risk.
Article
Background The goal of this study was to evaluate the effects of adenotonsillectomy on heart function based on echocardiography indices in children with primary snoring (PS) and mild obstructive sleep apnea due to adenotonsillar hypertrophy (ATH). Methods 55 children (aged 7 to 11 years old) with PS and ATH who were a candidate for adenotonsillectomy from August 2018 to June 2019 evaluated. A history of Upper Respiratory Tract Obstruction was obtained, clinical examination was performed and the cases suspicious for moderate to severe degrees of Obstructive Sleep Apnea Syndrome were excluded. Echocardiography was performed one week before and 3–6 months after surgery. All data were analyzed by SPSS version 19 and P-value<0.05 was considered significant. Results From 55 enrolled cases, 42 [30 boys (71.5%) and 12 girls (28.5%)] completed the study course. Tricuspid Annular Plane Systolic Excursion (TAPSE), Ejection Fraction (EF), Right Ventricular Peak Systolic Myocardial Velocity (RVSM), Right Ventricular Fractional Area Change (RVFAC) were increased significantly and Isovolumic Contraction Time (IVCT) index was decreased significantly after surgery (P-value<0.05). The difference of indices between the two sexes was not significant after surgery (P-value>0.05). Conclusion Adenotonsillectomy can improve cardiac function indices in patients with PS due to ATH especially in terms of right ventricle (RV) function and reduction in pulmonary artery pressure. So, although “subclinical”, it is better to be considered PS not just as annoying noise for roommates before significant clinical cardiac problems happen.
Article
Cardiovascular diseases (CVD) remain the leading cause of death in developed and developing societies and aging is the primary risk factor for CVD. Much of the increased risk of CVD in midlife/older adults (i.e., adults aged 50 years and older) is due to increases in blood pressure, vascular endothelial dysfunction and stiffening of the large elastic arteries. Aerobic exercise training is an effective lifestyle intervention to improve CV function and decrease CVD risk with aging. However, <40% of midlife/older adults meet guidelines for aerobic exercise, due to time availability-related barriers and other obstacles to adherence. Therefore, there is a need for new lifestyle interventions that not only improve CV function with aging but also promote adherence. High-resistance inspiratory muscle strength training (IMST) is an emerging, time-efficient (5 min/day) lifestyle intervention. Early research suggests high-resistance IMST may promote adherence, lower blood pressure and potentially improve vascular endothelial function. However, additional investigation will be required to more definitively establish high-resistance IMST as a healthy lifestyle intervention for CV aging. This review will summarize the current evidence on high-resistance IMST for improving CV function with aging and will identify key research gaps and future directions.
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New findings: What is the central question of this study? What impact does inspiratory muscle training have on systemic vascular resistance, cardiac output and baroreflex sensitivity in adult men and women? What is the main finding and its importance? Inspiratory muscle training exerts favorable effects on blood pressure, vascular resistance and perception of stress. This exercise format is well-tolerated and equally effective whether implemented in men or women. Abstract: Previous work has shown that inspiratory muscle training (IMT) lowers blood pressure after a mere 6 weeks, identifying IMT as a potential therapeutic intervention to prevent or treat hypertension. Here, we explore the effects of IMT on respiratory muscle strength and select cardiovascular parameters in recreationally active men and women. Subjects were randomly assigned to IMT (n = 12, 75% maximal inspiratory pressure) or sham training (n = 13, 15% maximal inspiratory pressure) groups and underwent a 6-week intervention comprising 30 breaths day-1 , 5 days week-1 . Pre- and post-training measures included maximal inspiratory pressure and resting measures of blood pressure, cardiac output, heart rate, spontaneous cardiac baroreflex sensitivity and systemic vascular resistance. We evaluated psychological and sleep status via administration of the Cohen-Hoberman inventory of physical symptoms and the Epworth sleepiness scale. Male and female subjects in the IMT group showed declines in systolic/diastolic blood pressures (-4.3/-3.9 mmHg, P < 0.025) and systemic vascular resistance (-3.5 mmHg min l-1 , P = 0.008) at week 6. There was no effect of IMT on cardiac output (P = 0.722), heart rate (P = 0.795) or spontaneous cardiac baroreflex sensitivity (P = 0.776). The IMT subjects also reported fewer stress-related symptoms (pre- versus post-training, 12.5 ± 8.5 versus 7.2 ± 9.7, P = 0.025). Based on these results, we suggest that a short course of IMT confers significant respiratory and cardiovascular improvements and parallel (modest) psychological benefits in healthy men and women.
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Background Although 24‐hour blood pressure (BP) variability (BPV) is predictive of cardiovascular outcomes independent of absolute BP levels, it is not regularly assessed in clinical practice. One possible limitation to routine BPV assessment is the lack of standardized methods for accurately estimating 24‐hour BPV. We conducted a systematic review to assess the predictive power of reported BPV indexes to address appropriate quantification of 24‐hour BPV, including the average real variability (ARV) index. Methods and Results Studies chosen for review were those that presented data for 24‐hour BPV in adults from meta‐analysis, longitudinal or cross‐sectional design, and examined BPV in terms of the following issues: (1) methods used to calculate and evaluate ARV; (2) assessment of 24‐hour BPV determined using noninvasive ambulatory BP monitoring; (3) multivariate analysis adjusted for covariates, including some measure of BP; (4) association of 24‐hour BPV with subclinical organ damage; and (5) the predictive value of 24‐hour BPV on target organ damage and rate of cardiovascular events. Of the 19 assessed studies, 17 reported significant associations between high ARV and the presence and progression of subclinical organ damage, as well as the incidence of hard end points, such as cardiovascular events. In all these cases, ARV remained a significant independent predictor (P<0.05) after adjustment for BP and other clinical factors. In addition, increased ARV in systolic BP was associated with risk of all cardiovascular events (hazard ratio, 1.18; 95% confidence interval, 1.09–1.27). Only 2 cross‐sectional studies did not find that high ARV was a significant risk factor. Conclusions Current evidence suggests that ARV index adds significant prognostic information to 24‐hour ambulatory BP monitoring and is a useful approach for studying the clinical value of BPV.
Article
Cardiovascular diseases (CVD) remain the leading cause of death in developed societies, and "mid-life" (50-64 years) and older (65+) men and women bear the great majority of the burden of CVD. Much of the increased risk of CVD in this population is attributable to CV dysfunction, including adverse changes in the structure and function of the heart, increased systolic blood pressure, and arterial dysfunction. The latter is characterized by increased arterial stiffness and vascular endothelial dysfunction. Conventional aerobic exercise training, as generally recommended in public health guidelines, is an effective strategy to preserve or improve CV function with aging. However, <40% of mid-life and older adults meet aerobic exercise guidelines, due in part to time availability-related barriers. As such, there is a need to develop evidence-based, time-efficient exercise interventions that promote adherence and optimize CV function in these groups. Two promising interventions that may meet these criteria are interval training and inspiratory muscle strength training (IMST). Limited research suggests these modes of training may improve CV function with time commitments of <60 min/week. This review will summarize the current evidence for interval training and IMST to improve CV function in mid-life/older adults and identify key research gaps and future directions.
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Studies using ambulatory blood pressure (BP) monitoring have shown that BP during night-time sleep is a stronger predictor of cardiovascular outcomes than daytime ambulatory or conventional office BP. However, night-time ambulatory BP recordings may interfere with sleep quality because of the device cuff inflation and frequency of measurements. Hence, there is an unmet need for obtaining high quality BP values during sleep. In the last two decades, technological development of home BP devices enabled automated BP measurements during night-time. Preliminary data suggest that nocturnal home BP measurements yield similar BP values and show good agreement in detecting nondippers when compared with ambulatory BP monitoring. Thus, nocturnal home BP measurements might be a reliable and practical alternative to ambulatory BP monitoring to evaluate BP during sleep. As the use of home BP devices is widespread, well accepted by users and has relatively low cost, it may prove to be more feasible and widely available for routine clinical assessment of nocturnal BP. At present, however, data on the prognostic relevance of nocturnal BP measured by home devices, the optimal measurement schedule, and other methodological issues are lacking and await further investigation. This article offers a systematic review of the current evidence on nocturnal home BP, highlights the remaining research questions, and provides preliminary recommendations for application of this novel approach in BP management.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
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Study objectives: The aim of the current study was to evaluate the association between obstructive sleep apnea (OSA) and exercise capacity in middle-aged women. Methods: Consecutive middle-aged female subjects without cardiovascular disease, aged 45 to 65 years, from two gynecological clinics underwent detailed clinical evaluation, portable sleep study, and treadmill exercise test. Results: We studied 232 women (age: 55.6 ± 5.2 years; body mass index [BMI]: 28.0 ± 4.8 kg/m2). OSA (apnea-hypopnea index ≥ 5 events/h) was diagnosed in 90 (39%) and obesity (BMI > 30 kg/m2) in 76 (33%) women, respectively. Participants with OSA were older, had a higher BMI, and an increased frequency of arterial hypertension compared to women without OSA. Multiple logistic regression models were used to evaluate the association between OSA and exercise capacity, controlling for traditional risk factors including BMI, age, hypertension, diabetes, and sedentary lifestyle. In multivariate analysis, the presence of obesity without OSA was associated with low exercise capacity (odds ratio [OR] 2.88, 95% confidence interval [CI] 1.02-8.11, P = .045), whereas the presence of OSA without obesity was not (OR 1.07, 95% CI 0.31-3.69, P = .912). However, the coexistence of obesity and OSA increased markedly the odds of reduction in exercise capacity (OR 9.40, CI 3.79-23.3, P < .001). Conclusions: Obesity and OSA are common conditions in middle-aged women and may interact to reduce exercise capacity. These results highlight the importance of obesity control programs among women, as well as the diagnosis of comorbid OSA in older women.
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Objective and background: Impaired cerebral blood flow and cerebrovascular reactivity to hypercapnia during wakefulness at rest as well as reduced exercise tolerance have been reported in severe obstructive sleep apnea (OSA) patients. Impaired cerebral oxygenation and hemodynamics can contribute to reduced exercise performance. We hypothesized that (i) OSA patients show impaired cerebrovascular response both during exercise and in response to hypercapnia together with reduced exercise tolerance and (ii) continuous positive airway pressure (CPAP) treatment improves these alterations in cerebral oxygenation. Methods: Fifteen OSA patients and 12 healthy matched controls performed a hypercapnic response test and a maximal cardiopulmonary exercise test before and after eight weeks of CPAP treatment or control period. Prefrontal cortex and muscle oxygenation were assessed by near-infrared spectroscopy (NIRS) during both tests. Results: Cerebrovascular reactivity to hypercapnia was impaired in OSA patients (lower increase in oxyhemoglobin [0.29 ± 0.19 vs 0.44 ± 0.14 μmol mmHg-1] and total hemoglobin [0.14 ± 0.15 vs 0.26 ± 0.09 μmol mmHg-1]) compared to controls. Reduced prefrontal cortex oxygen extraction and total blood volume (ie, lower increase in deoxyhemoglobin [1.76 ± 1.57 vs 3.43 ± 2.08 μmol] and total hemoglobin [5.36 ± 7.08 vs 8.55 ± 5.13 μmol at exhaustion], respectively) during exercise together with a reduced exercise tolerance (ie, lower peak oxygen consumption) were observed in OSA patients compared to controls. CPAP treatment did not induce any improvement in cerebrovascular response during hypercapnic response test and exercise. Conlusions: This study demonstrates that cerebrovascular response to exercise is altered in OSA and may contribute to exercise intolerance in these patients. Prefrontal cortex oxygenation and exercise tolerance are not significantly improved following eight weeks of CPAP treatment. Clinical trial registration: NCT02854280.
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Aims To assess whether continuous positive airway pressure (CPAP) therapy reduces major adverse cardiovascular events (MACE) in patients with moderate-to-severe obstructive sleep apnoea (OSA). Methods and results A total of 235 articles were recovered using MEDLINE, EMBASE and Cochrane library (inception–December 2016) and references contained in the identified articles. Seven randomized controlled trials (RCTs) were selected for final analysis. Analysis of 4268 patients demonstrated non-significant 26% relative risk reduction in MACE with CPAP [risk ratio (RR) 0.74; 95% confidence interval (CI) 0.47–1.17; P = 0.19, I2 = 48%]. A series of sensitivity analyses suggested that increased CPAP usage time yielded significant risk reduction in MACE. and stroke. Subgroup analysis revealed that CPAP adherence time ≥4 hours (h)/night reduced the risk of MACE by 57% (RR 0.43; 95% CI 0.23–0.80; P = 0.01, I2 = 0%). CPAP therapy showed no beneficial effect on myocardial infarction (MI), all-cause mortality, atrial fibrillation/flutter (AF), or heart failure (HF) (P > 0.05). CPAP had positive effect on mood and reduced the daytime sleepiness [Epworth Sleepiness Scale (ESS): mean difference (MD) −2.50, 95% CI − 3.62, −1.39; P < 0.001, I2 = 81%]. Conclusion CPAP therapy might reduce MACE and stroke among subjects with CPAP time exceeding 4 h/night. Additional randomized trials mandating adequate CPAP time adherence are required to confirm this impression.
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The diagnosis and effective treatment of obstructive sleep apnea (OSA) in adults is an urgent health priority. It is the position of the American Academy of Sleep Medicine (AASM) that only a physician can diagnose medical conditions such as OSA and primary snoring. Throughout this statement, the term "physician" refers to a medical provider who is licensed to practice medicine. A home sleep apnea test (HSAT) is an alternative to polysomnography for the diagnosis of OSA in uncomplicated adults presenting with signs and symptoms that indicate an increased risk of moderate to severe OSA. It is also the position of the AASM that: the need for, and appropriateness of, an HSAT must be based on the patient's medical history and a face-to-face examination by a physician, either in person or via telemedicine; an HSAT is a medical assessment that must be ordered by a physician to diagnose OSA or evaluate treatment efficacy; an HSAT should not be used for general screening of asymptomatic populations; diagnosis, assessment of treatment efficacy, and treatment decisions must not be based solely on automatically scored HSAT data, which could lead to sub-optimal care that jeopardizes patient health and safety; and the raw data from the HSAT device must be reviewed and interpreted by a physician who is either board-certified in sleep medicine or overseen by a board-certified sleep medicine physician.