TITLE: Does short-term whole-body vibration training affect arterial stiffness in
chronic stroke? A preliminary study

  ABSTRACT:
[Purpose] Previous studies have shown that stroke is associated with increased arterial
stiffness that can be diminished by a program of physical activity. A novel exercise
intervention, whole-body vibration (WBV), is reported to significantly improve arterial
stiffness in healthy men and older sedentary adults. However, little is known about its
efficacy in reducing arterial stiffness in chronic stroke. [Subjects and Methods] Six
participants with chronic stroke were randomly assigned to 4 weeks of WBV training or
control followed by cross-over after a 2-week washout period. WBV intervention consisted
of 3 sessions of 5 min intermittent WBV per week for 4 weeks. Arterial stiffness (carotid
arterial stiffness, pulse wave velocity [PWV], pulse and wave analysis [PWA]) were
measured before/after each intervention. [Results] No significant improvements were
reported with respect to carotid arterial stiffness, PWV, and PWA between WBV and control.
However, carotid arterial stiffness showed a decrease over time following WBV compared to
control, but this was not significant. [Conclusion] Three days/week for 4 weeks of WBV
seems too short to elicit appropriate changes in arterial stiffness in chronic stroke.
However, no adverse effects were reported, indicating that WBV is a safe and acceptable
exercise modality for people with chronic stroke.

BODY.INTRODUCTION:
Post-stroke survivors face the problem of being predisposed to a sedentary lifestyle that
restricts their ability to undertake physical activity resulting in further deconditioning,
which can significantly increase stroke reoccurrence and cardiovascular disease1). To overcome the potential for
cardiovascular disease, physical activity and exercise programs are often implemented.
However, for stroke survivors there are numerous challenges to undertaking an exercise
regime, such as time, convenience, compliance, ambulation, and postural control. Thus,
traditional exercise may not be always feasible. Alternatively, whole-body vibration (WBV)
is seen as an attractive and efficient treatment modality to complement other forms of
exercise to improve muscle function, force, and power in healthy, compromised, and sporting
individuals2).  WBV is a rhythmic activity where body-weight static and/or dynamic exercises are performed
on an oscillating plate that elicits rapid stretch-reflexes3) involving the tonic vibration reflex4), which causes changes in muscle fiber length5). Consequently, small changes in oxygen uptake occur,
suggesting that muscle energy exists6),
that may benefit cardiovascular indices. Acute WBV has been shown to significantly augment
leg blood flow7), although heart rate (HR)
and brachial blood pressure (BP) have been reported to cause only small increases8) or no changes7, 9).  Increased brachial-ankle pulse wave velocity (PWV) and arterial stiffness (PWV) are
independent predictors of stroke. Other indices of pulse wave analysis of aortic blood
pressure (BP) and augmentation index (AIx) are regarded to be more sensitive predictors of
cardiovascular events than brachial BP10).
AIx is considered an indicator of left ventricular afterload and can increase due to
arterial stiffening where wave reflection from peripheral to central arteries rise. It has
been reported that following an acute intermittent WBV protocol, brachial-ankle PWV, leg
PWV, and AIx were significantly reduced in healthy young men9, 11). Similarly, 10 min of
continuous passive vibration, which was defined by lying supine and placing both legs on a
vibrating platform, decreased brachial-ankle PWV, leg PWV, and AIx in healthy
participants10). In stroke survivors,
leg PWV and brachial-ankle PWV were significantly reduced by acute passive vibration (10
min), but it had no effect on HR, brachial BP, and aortic PWV12).  Aerobic exercise has the capability to improve arterial stiffness and cardiovascular risk
factors13). Thirty min (2×/week, 6
months) of moderate-high intensity aerobic exercise reduces BP and arterial stiffness13). However, as previously stated,
traditional exercise such as aerobic conditioning may not be appropriate for certain
patients. Thus, WBV may provide an alternative to traditional exercise as it provides an
easy and efficient modality, as shown by its improving of health parameters in less time per
session compared to resistance training11). Acute WBV has been shown to decrease arterial stiffness in healthy
individuals9, 11). Similarly, long-term (3 months) WBV training has been reported to
reduce arterial stiffness in middle-aged/older adults14). WBV is similar to mechanical compression, which produces
oscillations to elicit muscle contractions15) and causes arterial vasodilation16). The propagation of the vibration stimulus has the ability to
transmit mechanical energy to the upper-body and head17) that can enhance upper-body muscular performance18). Thus, WBV may reduce arterial stiffness
through the propagation of mechanical stimuli capable of stimulating lower and upper-body
arteries. However, to our knowledge, no study has investigated the efficacy of short-term
WBV training in post-stroke individuals. Therefore, the aim of this study was to examine the
effects of short-term WBV training on carotid arterial stiffness in chronic stroke
survivors. We hypothesized that 4 weeks of WBV training would significantly reduce arterial
stiffness.

BODY.SUBJECTS AND METHODS.SUBJECTS:
Four sedentary men (mean and±standard deviation [SD], age 50.5±14.5 years; body mass
106.6±25.9 kg; height 179.3±3.8 cm) and two sedentary women (age 39±2 years; body mass
86.5±15.5 kg; height 168.0±4.0 cm) volunteered to participate in the study. The inclusion
criteria required that the participants be aged between 35–65 years and have suffered a
clinically diagnosed stroke between 6 months to 5 years prior to the commencement of the
study. The type of stroke (ischemic n = 1; hemorrhagic n
= 4; transient ischemic attack n = 1, its locality, left hemisphere
n = 2; right hemisphere n = 4) and extent of
disability were classified by the modified Rankin Scale (range 1–4). The participants had
to meet the requirement never having undertaken WBV and were classified as sedentary
according to the ACSM guidelines19).
Five participants were involved in weekly, organized activities such as boccia, aqua
jogging, and physiotherapy, but these activities did not exceed the aforementioned
parameters of a sedentary lifestyle. Exclusion criteria included uncontrolled hypertension
or hypotension, bone tumors, herniated discs, and recent fractures (<6 months). The
study was approved by the University Human Ethics Committee, and written informed consent
was obtained from all participants.

BODY.SUBJECTS AND METHODS.METHODS:
Prior to testing, every participant completed a familiarization session that included
WBV, sphygmoCor, and ultrasound. After baseline measurement, participants were randomly
assigned to 4 weeks of WBV training or control followed by cross-over after a 2-week
washout period. During the control and washout periods, the participants were instructed
to continue their normal daily activities. The WBV intervention consisted of 3 sessions of
5 min intermittent WBV per week for 4 weeks, with at least 24 hours of rest between each
WBV session. Pre- and post- (4 weeks) WBV and control measurements of arterial stiffness
and cardiovascular indices were performed for all participants. Prior to testing,
participants refrained from consuming caffeine during the preceding 12 hours, and
refrained from taking drugs with known vascular effects. Participants rested in the supine
position for 20 min prior to testing and to account for daily biorhythms, all testing was
conducted at the same time each day. During the course of the study, participants were
informed not to engage in any additional physical activity above what they were currently
performing (Table 1Table 1.WBV training protocolSessionVibration frequency (Hz)Peak-to-peak displacement (mm)Peak acceleration (ms−2)Vibration duration (min)1222.129.85 × 12242.130.25 × 13262.134.15 × 14224.348.85 × 15244.352.65 × 16264.360.75 × 17226.567.35 × 18246.574.55 × 19266.586.85 × 110266.586.87 × 111266.586.87 × 112266.586.87 × 1).  WBV was performed on a commercial machine (Galileo Sport, Novotec, Pforzheim, Germany),
which had a motorized teeterboard that produced side-alternating vertical sinusoidal
vibrations of up to 30 Hz, and maximum peak-to-peak displacement (p-p) of 12
mm. With this WBV machine, p-p was dependent on the participant's foot
position. The further the feet were from the central oscillating axis the larger the
p-p, and vice versa. Thus, a single-axis accelerometer (iMEMS®,
ADXL250, Analog Devices, Norwood, MA, USA) was fixed to the edge of the vibrating platform
to measure the p-p and determine the three different foot positions (FtP 1–3).
To guarantee the location and identification of the different displacements, longitudinal
strips of reflective adhesive tape were applied to the WBV plate. This allowed
participants to place their second toe and heel midpoint in line with the tape. This
helped keep the feet in the correct position during each session. The researcher
constantly checked each participant's foot positioning and corrected any deviations. Over
the 12 sessions, participants placed their feet in three different positions: FtP 1 = 2.1
mm p-p; FtP 2 = 4.3 mm p-p; and FtP 3 = 6.5 mm p-p.  Participants were asked to maintain a static squat stance with 70° knee flexion attained
using a manual goniometer. Seventy-degree knee flexion was selected based on evidence that
beyond 30° of static squatting maximizes leg extensor activation20) and reduces the negative side effects of vibration being
transferred through to the head17). With
shoes on, participants were instructed to place their feet in the protocol-defined
positions, maintain an upright torso with their eyes and head facing forward, and evenly
distribute their body weight through the mid-foot of both feet. They were allowed to use
the support bar if required.  To date, there has been no scientific test of a short-term WBV training protocol for
stroke. A four-week training protocol was implemented, which was based on earlier work
that reported improved muscle force output, functional ability, and general well-being in
people with multiple sclerosis21). In
the current study, the vibration parameters of vibration frequency (Hz), p-p
(mm), peak acceleration (ms−2), and session duration (min) were periodized into
four blocks (Table 1). Each block consisted of
three WBV sessions where the vibration frequency was systematically increased by 2 Hz (22
Hz, 24 Hz, 26 Hz) and p-p was increased at the commencement of a new block of
training.  The duration remained the same during the first three blocks; five sets of 1-min bouts of
WBV with 1-min rests between each. The intermittent nature and volume of WBV exposure was
selected on the basis of the Mason, Cochrane, Denny, Firth, Stannard22) aforementioned study, which reported an improvement in
mobility parameters in multiple sclerosis. This is a common approach to increase muscular
power in healthy individuals23). To
maximize the associated benefits of overload, the fourth block of training (session 10–12)
was set at 26 Hz, 6.5 mm p-p, and seven sets of 1-min exposures with 1-min
rests (Table 1). The vibration frequency was
selected from previous research that showed 25–26 Hz to enhance muscular performance24). The vibration duration of 1-min
exposure with 1-min rest was prescribed based on previous research demonstrating positive
reductions in arterial stiffness9, 11).  PWA was performed using a SphygmoCor device (AtCor Medical, Sydney, Australia), which is
a non-invasive tool used to assessed arterial stiffness, central blood pressures, and
autonomic function. Brachial BP was recorded using an automated oscillometric device
(Nissei DS-157; Mentone Educational Centre, Carnegie, Victoria, Australia). Radial artery
waveforms were non-invasively recorded with a high-fidelity micromanometer (SPC-301;
Millar Instruments, TX, USA) from the wrist of the non-affected stroke arm using
applanation tonometry. These waveforms were calibrated against brachial systolic blood
pressure (SBP) and diastolic blood pressure (DBP) from comparable hemodynamic properties
of the upper limb arteries. A corresponding aortic pressure waveform was generated using a
validated transfer function25), from
which central SBP (cSBP), central DBP (cDBP), central pulse pressure (cPP), and AIx was
calculated using the integrated software (SCOR Px 7.1, AtCor Medical, Sydney, Australia).
AIx was normalized to a heart rate (HR) of 75 beats/min (AIx@75). HR was measured from the
time between pulse waveforms, and participants remained in the supine position for all PWA
measurements. If the first two consecutive AIx@75 values differed by more than 4% or blood
pressures of greater than 5 mmHg, a third measurement was taken and the mean of the
closest two values was recorded. Data were collected directly via a personal computer
(Toshiba, Intel® CoreTM i5, Windows 7 operating system).  PWV was measured using the SphygmoCor device. The pulse pressure wave of the common
carotid and radial arteries were recorded non-invasively using applanation tonometry as
described above. The recordings were gated using the integrated electrocardiogram, with
the velocity of the pulse wave being calculated using the integrated software (SCOR Px
7.1, AtCor Medical, Sydney, Australia). Participants remained in the supine position for
BP measurements that were obtained prior to PWV measurements. Prior to electrode
placement, any excess hair was removed with a razor and the area cleaned with alcohol
wipes. Surface pre-gelled Ag-AgCl electrodes (Ambu, Ballerup, Denmark) were placed on the
participant's chest: 1 cm below the suprasternal notch on the sternum, 1 cm above the
xiphoid process on the sternum, and 3 cm above the left iliac crest. Distal and proximal
measurements were then measured and recorded for each participant. The measurements of PWV
and carotid-to-radial pulse transit time standard deviation (PTT SD) were used for
subsequent analysis.  The common carotid artery was imaged non-invasively using commercial B-mode ultrasound
(Sonoite Micromaxx) equipped with a 6–13 MHz linear array transducer. Ultrasound was
applied to find local arterial stiffness (β), where β = Ln(SBP/DBP)/(∆D/Dd) and is defined
by the arterial diameter over the cardiac cycle relative to change in blood pressure26). Blood pressure of the common carotid
artery was recorded using applanation tonometry as described above. Blood pressure at the
brachial artery, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse
pressure (PP) were sampled from four 6-second video recordings. For each participant, the
probe was placed on the common carotid artery opposite to that of the stroke-affected side
at a perpendicular (90°) angle to the vessel, 1 to 2 cm below bifurcation. Ultrasound
global and probe-dependent settings were all standardized. Participants held their breath
during each of the four 6-second video recordings with the common carotid artery diameters
extending across the entire imaging plane. The four 6-second diameter measurements of
systolic diameter (Dsys), diastolic diameter (Ddia), and the difference between systolic
diameter and diastolic diameter (Dist) were collected and averaged. Additionally,
distensibility coefficient (DC) and compliance coefficient (CC) measurements were obtained
via ultrasound; where DC is the relative rise of arterial cross-sectional area for a given
increase in pressure, and CC is the absolute rise in cross-sectional area for a given
increase in arterial pressure, and assumes that the length of the vessel is unaltered by
the pulse wave.  A repeated measures Analysis of Variance (ANOVA) was performed to determine differences
in dependent variables versus time (time [pre-WBV, post-WBV, pre-control, post-control] x
intervention). Data gathered was analyzed using SPSS software (version 21, SPSS Inc.,
Chicago, IL, USA). The level of statistical significance was set at p < 0.05 and all
values are expressed as mean±standard deviation (SD).

BODY.RESULTS:
All six participants completed the required 12 sessions of WBV and four weeks of control,
on average it took 4.5±0.5 weeks (mean±SD) to complete 12 WBV sessions. Following a
one-month follow-up, no participant suffered any further strokes, symptoms of stroke, or any
other complications associated with WBV training.  There was no significant interaction effect of intervention and time, and no main effect of
intervention or time for any of the PWA measurements (Table 2Table 2.PWV, PWA, blood pressure, and carotid artery diameter values for pre and post WBV
and controlWBVControlPrePostPrePostPWV (m/s)7.0±2.16.6±1.86.7±1.36.5±0.7Carotid to radial PTT SD (%)6.5±3.26.9±1.96.8±2.65.5±2.8Arterial stiffness (Beta)12.1±2.510.2±2.710.0±3.111.6±2.7DC (10-3 /kPa)19.6±3.2 22.0 ±6.523.1±6.420.0±6.2CC (mm2 /kPa)0.8±0.21.0±0.31.0±0.30.9±0.3AIx@7518.1±5.017.5±5.914.2±6.818.3±5.8cSBP (mmHg)110.8±9.0112.5±12.7111.9±13.3110.3±11.7cDBP (mmHg)76.4±10.077.9±8.677.9±10.076.6±10.1cPP (mmHg)34.3±3.734.6±7.534.0±6.733.8±6.4HR (beats/min)60.3±9.863.3±11.662.0±12.564.3±13.7SBP (mmHg)120.2±10.1123.5±14.5122.8±15.4120.8±14.1DBP (mmHg)75.7±9.777.0±9.777.3±9.476.0±9.8PP (mmHg)44.5±6.446.5±9.845.5±8.744.8±8.2Dsys (mm) *7.6±0.97.8±0.87.7±0.67.8±0.7Ddia (mm) *7.3±0.97.5±0.87.3±0.77.5±0.6Dist (mm)0.3±0.10.4±0.10.4±0.10.3±0.1PWV: pulse wave velocity; Carotid to radial pulse transit time standard deviation
(PTT SD); DC: distensibility coefficient; CC: compliance coefficient; AIx@75:
augmentation index normalized HR 75 bpm; cSBP: central systolic blood pressure; cDBP:
central diastolic blood pressure; cPP: central pulse pressure; HR: heart rate; SBP:
systolic blood pressure; DBP: diastolic blood pressure; PP: pulse pressure (SBP-DBP);
Dsys: systolic diameter; Ddia: diastolic diameter; Dist: difference between Dsys and
Ddia* Significant time effect post intervention for Dsys (p = 0.039) and Ddia (p =
0.040)). However, a decrease in AIx@75 was displayed for WBV and the control
illustrated an increase over time but this time effect was not significant (p = 0.225).
There was a significant time effect post intervention for systolic (p = 0.039) and diastolic
diameter (p = 0.040) (Table 2) but there was no
interaction or intervention effect.  Table 2 illustrates the interaction effect of
PWV over time, demonstrating a decrease over time for both WBV and control but these
measurements were not significant (p = 0.474). Furthermore, there was no significant
difference (p = 0.299) in carotid to radial pulse transit time standard deviation between
WBV and control (Table 2).  Arterial stiffness (Table 2) decreased over
time for WBV. In contrast, arterial stiffness increased over time in the control group, but
the interaction effect was not significant (p = 0.166). For the distensibility coefficient
(DC) (Table 2) there was no significant
interaction effect (p = 0.124) or main effect between the WBV and control groups (p =
0.431). Similarly, there was no significant interaction effect (p = 0.237) or main effect
for compliance coefficient (CC) (Table 2)
between the WBV and control groups (p = 0.496).

BODY.DISCUSSION:
The primary aim of this study was to assess the efficacy of short-term WBV training on
indices of arterial stiffness (carotid arterial stiffness, augmentation index, pulse wave
velocity) in individuals who have experienced chronic stroke. The results of the current WBV
training protocol did not produce any significant positive or negative effects on central
BPs, AIx@75, HR, PWV, carotid arterial stiffness (β), DC, and CC. These results are
supported by recent research, which found no significant changes in blood pressure (SBP and
DBP) following 3 months of WBV in middle-aged and older adults14). However, some studies of acute WBV have shown significant
changes in BP. For example, Figueroa, et al.11) and Rittweger, Beller, Felsenberg27) reported significant increases in SBP after WBV with body-weight
squats, where values returned to baseline 15 min post intervention, with Rittweger et
al.27) showing a significant decrease in
DBP after WBV compared to control (bicycle ergometry). Additionally, an acute WBV study by
Otsuki et al.9) found no significant
changes in blood pressure (SBP, DBP, and PP) after 60 min of WBV or control (no WBV). In
contrast, short-term WBV (6 weeks) showed a significant decrease in SBP 3 min after WBV when
compared to control (no exercise)28).
However, the discrepancies between the results of Gil28) and the present study may be attributed to exercise protocols and
the participants' health conditions (overweight and obese women vs. chronic stroke).  In the present study, AIx@75 appeared to decrease post-WBV (0.7±3.1%) and increase
post-control (4.3±4.8%). A non-significant decrease in AIx post-WBV has been reported by
Figueroa, et al11). The authors reported that AIx decreased significantly during 15 and 30
min of recovery following an acute WBV bout involving a static squat compared to a
significant increase in AIx during post-recovery from no-WBV (static squat only). According
to the authors, the decrease in AIx wave magnitude following WBV was unlikely to be
influenced by HR, but rather a result of vasodilation in the peripheral arteries11), which
may explain the decrease in central AIx seen in the present study.  Previously, Otsuki, et al.9) reported that
following acute intermittent WBV (10 × 60 s, interspersed with 60 s rest) performed by
healthy men, brachial-ankle PWV decreased during recovery at 20 and 40 min and returned to
baseline 60 min after compared to no WBV (control), indicating that WBV acutely decreased
arterial stiffness. In a similar study, the vibration protocol was modified slightly to
include a higher frequency (40 Hz) that acquired PWV from carotid-femoral, brachial-ankle,
and femoral-ankle sites11). Femoral-ankle
PWV decreased significantly at 5 min in both the WBV and without WBV (control) groups, where
it continued to remain low during the 30-min recovery post-WBV period and the control
returned to baseline. However, there were no significant changes in carotid-femoral PWV or
brachial-ankle PWV after either trial. It should be noted that brachial-ankle PWV involves
both central and peripheral arterial stiffness, where aortic and leg PWV are the main
independent correlates, explaining 58% and 23% of the total variance in brachial-ankle PWV
respectively29), and as a result any
changes in this measure of arterial stiffness should be interpreted carefully9).  The theory of a local effect may help to explain the current findings. If WBV generates a
local effect on PWV, it would elicit changes in leg PWV rather than aortic or carotid-radial
PWV. This has been demonstrated by changes in femoral-ankle PWV11) and brachial-ankle PWV9), where brachial-ankle PWV was independently correlated with leg
PWV29). The changes seen by Otsuki et
al.9) may represent changes in both
aortic and leg arterial stiffness. However, Otsuki et al.9) did not measure aortic and leg PWV separately, and it cannot be
determined whether leg PWV alone contributed to the improvement. Likewise, Figueroa et
al.11) did not display any significant
changes in brachial-ankle PWV, and it is therefore possible that a local effect could
explain the insignificant findings of the present study.  The findings of the current study revealed no significant change in carotid arterial
stiffness (β), DC, or CC. Although, a significant time effect was evident for both diastolic
diameter (p = 0.040) and systolic diameter (0.039), these significant time effects did not
show any significance for the relative stroke change in diameter (Dist). A previous study
reported that low-intensity resistance exercise in healthy individuals30) acutely increases carotid arterial compliance, systolic
and diastolic diameters, and decreased β stiffness index 30 and 60 min post-exercise.
However, HR and carotid and brachial BPs showed no significant changes. The differences
between the previous and the present study may be attributed to the duration of intervention
and consequently when assessments took place after intervention (acute vs. short-term), mode
of exercise (bench press vs. WBV), and participant characteristics (healthy individuals
compared to chronic stroke).  The aim of this study was to recruit eight participants to undergo a trial based on
previous work that studied six weeks of WBV in overweight/obese women that improved
brachial-ankle PWV by 8%31) and achieved a
power of 0.89 with α = 0.05. However, the research was conducted in an area with a small
stroke community, where only six participants volunteered for the study. Thus, the
non-significant findings of the current study were possibly due to the small sample size.
Furthermore, a longer duration of WBV may have elicited the desired changes. This assumption
is supported by Gil28), who suggested that
it may take longer than 6 weeks to detect changes in PWV.  In conclusion, while there were no significant findings, the present study did identify a
non-significant decrease in carotid arterial stiffness post-WBV compared to pre-WBV, while
control decreased between pre and post. However, no adverse effects were reported,
indicating that WBV is a safe exercise modality for chronic stroke patients.

Question: Compared to control group what was the result of WBV training on (PWV) pulse wave velocity?
Evidence: Table 2 illustrates the interaction effect of
PWV over time, demonstrating a decrease over time for both WBV and control but these
measurements were not significant (p = 0.474). 
Answer: no significant difference