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REVIEW ARTICLE
Evidence for the Role of Isometric Exercise Training in Reducing
Blood Pressure: Potential Mechanisms and Future Directions
Philip J. Millar
•
Cheri L. McGowan
•
Ve
´
ronique A. Cornelissen
•
Claudio G. Araujo
•
Ian L. Swaine
Ó Springer International Publishing Switzerland 2013
Abstract Hypertension, or the chronic elevation in rest-
ing arterial blood pressure (BP), is a significant risk factor
for cardiovascular disease and estimated to affect *1 bil-
lion adults worldwide. The goals of treatment are to lower
BP through lifestyle modifications (smoking cessation,
weight loss, exercise training, healthy eating and reduced
sodium intake), and if not solely effective, the addition of
antihypertensive medications. In particular, increased
physical exercise and decreased sedentarism are important
strategies in the prevention and management of hyperten-
sion. Current guidelines recommend both aerobic and
dynamic resistance exercise training modalities to reduce
BP. Mounting prospective evidence suggests that isometric
exercise training in normotensive and hypertensive (med-
icated and non-medicated) cohorts of young and old par-
ticipants may produce similar, if not greater, reductions in
BP, with meta-analyses reporting mean reductions of
between 10 and 13 mmHg systolic, and 6 and 8 mmHg
diastolic. Isometric exercise training protocols typically
consist of four sets of 2-min handgrip or leg contractions
sustained at 20–50 % of maximal voluntary contraction,
with each set separated by a rest period of 1–4 min.
Training is usually completed three to five times per week
for 4–10 weeks. Although the mechanisms responsible for
these adaptations remain to be fully clarified, improve-
ments in conduit and resistance vessel endothelium-
dependent dilation, oxidative stress, and autonomic regu-
lation of heart rate and BP have been reported. The clinical
significance of isometric exercise training, as a time-effi-
cient and effective training modality to reduce BP, war-
rants further study. This evidence-based review aims to
summarize the current state of knowledge regarding the
effects of isometric exercise training on resting BP.
1 Introduction
Hypertension or the chronic elevation of resting arterial
blood pressure (BP) is estimated to affect 1 billion people
worldwide (approximately one in seven) and remains one
of the most significant modifiable risk factors for cardio-
vascular disease (CVD; e.g. coronary artery disease, stroke,
heart failure) [1, 2]. Hypertension is directly responsible
for as many as 7 million global deaths annually [3, 4],
representing a significant societal and economic burden [4,
5]. The traditional objective of clinical practice has been to
achieve a resting BP target of B140/90 mmHg [1, 6, 7].
However, as higher than normal resting BP ((Pre-hyper-
tension; 120–140/80–90 mmHg) also increases the risk of
CVD [8–10] guidelines are proposing lower optimal BP
targets to maximize reductions in morbidity and mortality,
P. J. Millar
Division of Cardiology, University Health Network and Mount
Sinai Hospital, Toronto, ON, Canada
C. L. McGowan
Department of Kinesiology, University of Windsor, Windsor,
ON, Canada
V. A. Cornelissen
Department of Rehabilitation Sciences, Faculty of Movement
and Rehabilitation Sciences, KU Leuven, Leuven, Belgium
C. G. Araujo
Exercise and Sport Sciences Graduate Program, Gama Filho
University, Rio de Janeiro, Brazil
I. L. Swaine (&)
Department of Sport Science, Tourism and Leisure, Canterbury
Christ Church University, North Holmes Road,
Canterbury CT1 1QU, Kent, UK
e-mail: ian.swaine@canterbury.ac.uk
Sports Med
DOI 10.1007/s40279-013-0118-x
particularly in patients with other co-morbidities such as
renal disease and diabetes [1, 6, 7].
Current national and international treatment guidelines
for primary and secondary prevention of hypertension
universally recommend non-pharmacological lifestyle
changes (smoking cessation, weight loss, exercise training,
healthy eating and reduced sodium intake) as the first-line
of therapy [1, 7]. These lifestyle changes are to be con-
tinued even in the case of a need to start antihypertensive
pharmacologic treatment [1, 7]. Substantial evidence sup-
ports the benefits of these lifestyle modifications on
reducing resting BP [11], with reduced sedentarism and
increased regular physical exercise being particularly
effective [1, 12]. As a result, it is recommended that
individuals participate in aerobic exercise training of at
least moderate intensity for C30 min on most (preferably
all) days of the week, to reduce the risk of developing
hypertension or to manage high BP [1, 7, 13]. Dynamic
resistance training (i.e. weightlifting) has also been advo-
cated, but because of a smaller body of evidence, especially
in hypertensive populations, is considered to be a second-
ary adjunct exercise modality [1, 13–15].
These collective recommendations are reinforced by
meta-analytic evidence demonstrating small, but signifi-
cant, mean reductions in resting BP following aerobic
exercise training (D 2–4/1–3 mmHg; class I, level of evi-
dence A) [16–21], and dynamic resistance training (D 3–5/
3–4 mmHg; class IIA, level of evidence B) [20–25]. The
largest reductions in BP are observed following aerobic
exercise training in participants with hypertension [D 6–7/
5 mmHg (means)] [17, 19, 20]. To date, relatively little
attention has been paid to the effects of isometric exercise
training on resting BP.
Over the last 20 years, a number of randomized, con-
trolled and uncontrolled, proof-of-concept studies have
investigated a role for isometric hand and leg exercise
training to reduce BP in individuals with and without
hypertension. In comparison to aerobic and dynamic
resistance exercise training, meta-analytic evidence sug-
gests that isometric exercise training may produce larger
mean reductions in resting BP (D 10–14/6–8 mmHg),
although overall sample sizes remain small [20, 25–27]. In
the most recent scientific statement on alternative (non-
pharmacological) approaches to lowering BP by the
American Heart Association, isometric exercise training is
given a class IIB level of evidence C recommendation,
demonstrating the emergence of this modality as a potential
treatment strategy for individuals with hypertension and
the need for additional investigations [21].
In this review, we aim to summarize (i) the available
literature on the effects of isometric exercise training on
resting BP; (ii) the current evidence for specific isometric
training protocols; (iii) issues of safety; (iv) potential
mechanisms that may be responsible for these training
adaptations; and (v) general recommendations for future
studies.
1.1 Literature Search
Studies for this review were identified in PubMed using an
advanced search with the combined keywords: ‘training’,
‘exercise’, ‘isometric’ and ‘blood pressure’. All identified
articles were reviewed and excluded if they (i) were not
related to the specific topic; (ii) did not involve humans; or
(iii) did not perform [3 weeks of isometric exercise
training.
2 Isometric Exercise and Blood Pressure (BP)
Reductions Following Training
2.1 Isometric Exercise Training
An isometric or static contraction is defined as a sustained
muscle contraction (i.e. increase in tension) with no change
in length of the involved muscle group [28]. Although pure
static contractions are observed only with in vitro models,
for the purposes of this review an isometric contraction will
be considered a sustained contraction with minimal change
in muscle length.
The most widely studied isometric training protocols
consist of four sets of 2-min handgrip or leg contractions at
30–50 % maximal voluntary contraction (MVC) or an
equivalent electromyographic value, with each set sepa-
rated by a timed rest period that ranges from 1 to 4 min,
performed three to five times per week for 4–10 weeks [29,
31–35, 37, 38, 43, 44]. Similar protocols with shorter (45 s)
[29, 36] or longer (3 min) [30] contraction lengths and
reduced intensities (B20 % MVC) [39–42] have also been
studied (Tables 1, 2). In general, a systematic evaluation of
isometric exercise protocols has not been completed and
continued use of individual protocols appears to persist
based largely on past success in eliciting training adapta-
tions [30]. It should be appreciated from this brief
description that isometric exercise training involves a
markedly smaller time commitment (11–20 min/session),
compared with traditional aerobic exercise training rec-
ommendations of C30 min/day [13].
2.2 Effects of Isometric Exercise Training on Resting
BP
We identified 16 prospective trials investigating the effects
of isometric exercise training on resting BP [29–44]. These
studies involved both normotensive (Table 1) and pre-
hypertensive and hypertensive (medicated and
P. J. Millar et al.
Table 1 Prospective studies examining the effects of isometric exercise training on resting blood pressure in normotensive subjects
Reference (year) Study design Participants
(n)
Age (years; range
or mean ± SD)
Initial BP
status
Exercise mode and intensity Intervention
(frequency; duration)
Major findings
Wiley et al. (1992)
[29]
Cohort Ex: 10 29–52 Normotensive Alternating unilateral IHG
a
4 9 45 s, 1-min rest periods, 50 % MVC
59/week; 5 weeks ; in SBP 10 mmHg
; in DBP 9 mmHg
Ray and Carrasco
(2000) [30]
Cohort
controlled
Ex: 9
Sham: 7
Con: 8
19–35 Normotensive Unilateral IHG
4 9 3 min, 5-min rest periods, 30 % MVC
49/week; 5 weeks ; in DBP 5 mmHg
; in MAP 4 mmHg
$ in MSNA
Howden et al. (2002)
[31]
Cohort
controlled
Ex: 8
Con: 8
21 ± 1 Normotensive Bilateral arm flexion
4 9 2 min, 3-min rest periods, 30 % MVC
39/week; 5 weeks ; in SBP 12 mmHg
Ex: 10
Con: 8
Normotensive Bilateral leg extension
4 9 2 min, 3-min rest periods, 20 % MVC
39/week; 5 weeks ; in SBP 10 mmHg
McGowan et al.
(2007) [35]
Cohort Ex: 11 28 ± 14 Normotensive Unilateral IHG
4 9 2 min, 4-min rest periods, 30 % MVC
39/week; 8 weeks ; in SBP 5 mmHg
$ BMAD or BABF
Millar et al. (2008)
[37]
RCT Ex: 25
Con: 24
66 ± 6 Normotensive Alternating unilateral IHG
a
4 9 2 min, 1-min rest periods, 30–40 %
MVC
39/week; 8 weeks ; in SBP 10 mmHg
; in DBP 3 mmHg
Wiles et al. (2010)
[39]
RCT Ex: 11
Con: 11
18–34 Normotensive Bilateral leg extension
4 9 2 min, 2-min rest periods, 75 % HR
peak
(*10 % MVC)
39/week; 8 weeks ; in SBP 4 mmHg
; in DBP 3 mmHg
; in MAP 3 mmHg
Ex: 11 Normotensive Bilateral leg extension
4 9 2 min, 2-min rest periods, 95 % HR
peak
(*20 % MVC)
39/week; 8 weeks ; in SBP 5 mmHg
; in DBP 3 mmHg
; in MAP 3 mmHg
Devereux et al. (2010)
[40]
Crossover n = 13 21 ± 2 Normotensive Bilateral leg extension
4 9 2 min, 2-min rest periods, 95 % HR
peak
(*20 % MVC)
39/week; 4 weeks ; in SBP 5 mmHg
; in DBP 3 mmHg
; in MAP 3 mmHg
Badrov et al. (2013)
[44]
RCT Ex: 12
Con: 9
19–45 Normotensive Alternating unilateral IHG
a
4 9 2 min, 1-min rest periods, 30 % MVC
39/week; 8 weeks ; in SBP 6 mmHg
: in RV endothelial function
by 42 %
Ex: 11 Normotensive Alternating unilateral IHG
a
4 9 2 min, 1-min rest periods, 30 % MVC
59/week; 8 weeks ; in SBP 6 mmHg
: in RV endothelial function
by 57 %
All blood pressure values are reported as means
BABF brachial artery blood flow, BMAD brachial mean artery diameter, BP blood pressure, Con control, DBP diastolic blood pressure, Ex exercise, HR
peak
peak heart rate, IHG isometric handgrip, MAP
mean arterial pressure, MSNA muscle sympathetic nerve activity, MVC maximal voluntary contraction, n number of subjects, RCT randomized controlled trial, RV resistance vessel, SBP systolic blood
pressure, SD standard deviation, ; indicates reduction, : indicates increase, $ indicates no change
a
Changing hands with each contraction
Isometric Exercise Training on Blood Pressure
Table 2 Prospective studies examining the effects of isometric exercise training on resting blood pressure in pre-hypertensive and hypertensive subjects
Reference (year) Study
design
Participants
(n)
Age (years; range
or mean ± SD)
Initial BP status Exercise mode and intensity Intervention
(frequency; duration)
Major findings
Wiley et al. (1992) [29] RCT Ex: 8
Con: 10
20–35 Pre-hypertensive Unilateral IHG
4 9 2 min, 3-min rest periods, 30 %
MVC
39/week; 8 weeks ; in SBP 13 mmHg
; in DBP 15 mmHg
Taylor et al. (2003) [32] RCT Ex: 9
Con: 8
69 ± 6 Medicated
hypertensive
Alternating unilateral IHG
a
4 9 2 min, 1-min rest periods, 30 %
MVC
39/week; 10 weeks ; in SBP 19 mmHg
; in MAP 11 mmHg
McGowan et al. (2006)
[33]
Cohort Ex: 17 67 ± 6 Medicated
hypertensive
Unilateral IHG
4 9 2 min, 4-min rest periods, 30 %
MVC
39/week; 8 weeks : in BA FMD by 61 %
$ in MAP
McGowan et al. (2007)
[34]
Cohort Ex: 7 62 ± 11 Medicated
hypertensive
Alternating unilateral IHG
a
4 9 2 min, 1-min rest periods, 30 %
MVC
39/week; 8 weeks ; in SBP 15 mmHg
Ex: 9 66 ± 19 Medicated
hypertensive
Unilateral IHG
4 9 2 min, 4-min rest periods, 30 %
MVC
39/week; 8 weeks ; in SBP 9 mmHg
Peters et al. (2006) [36] Cohort Ex: 10 52 ± 5 Hypertensive Alternating unilateral IHG
a
4 9 45 s, 1-min rest periods, 50 % MVC
39/week; 6 weeks ; in SBP 13 mmHg
; in DBP 2 mmHg
Millar et al. (2013) [38] Cohort
controlled
Ex: 13
Con: 10
66 ± 6 Medicated
hypertensive
Unilateral IHG
4 9 2 min, 4-min rest periods, 30 %
MVC
39/week; 8 weeks ; in SBP 5 mmHg
; in MAP 3 mmHg
Stiller-Moldovan et al.
(2012) [42]
RCT Ex: 11
Con: 9
60 ± 9 Medicated
hypertensive
Alternating unilateral IHG
a
4 9 2 min, 1-min rest periods, 30 %
MVC
39/week; 8 weeks $ in resting or 24-h
ambulatory BP
Baross et al. (2012) [41] RCT Ex: 10
Con: 10
55 ± 5 Pre-hypertensive and
hypertensive
Bilateral leg extension
4 9 2 min, 2-min rest periods, 85 %
HR
peak
(*14 % MVC)
39/week; 8 weeks ; in SBP 11 mmHg
; in MAP 5 mmHg
; HR
Ex: 10 Pre-hypertensive and
hypertensive
Bilateral leg extension
4 9 2 min, 2-min rest periods, 70 %
HR
peak
(*8 % MVC)
39/week; 8 weeks $ in resting BP
Badrov et al. (2013)
[43]
RCT Ex: 12
Con:12
51–74 Medicated
hypertensive
Alternating unilateral IHG
a
4 9 2 min, 1-min rest periods, 30 %
MVC
39/week; 10 weeks ; in SBP 8 mmHg
; in DBP 5 mmHg
; in MAP 6 mmHg
; in PP 4 mmHg
All blood pressure values are reported as means
BA FMD brachial artery flow mediated dilation, BP blood pressure, Con control, DBP diastolic blood pressure, Ex exercise, HR heart rate, HR
peak
peak heart rate, IHG isometric handgrip, MAP mean
arterial pressure, MVC maximal voluntary contraction, n number of subjects, PP pulse pressure, RCT randomized controlled trial, SBP systolic blood pressure, SD standard deviation, ; indicates reduction, :
indicates increase, $ indicates no change
a
Changing hands with each contraction
P. J. Millar et al.
unmedicated) populations (Table 2), and employed either
isometric handgrip or leg exercise training protocols. The
results of these small-scale (\50 participants) studies are
not uniform, with mean reductions in systolic and diastolic
BP ranging between 0 and 19, and 0 and 15 mmHg,
respectively. Unfortunately, only *50 % of these trials
employed randomized controlled trial (RCT) [29, 32, 37,
39, 41–44] or crossover [40] designs, increasing the risk of
a type I error. In those studies employing a control group,
only one employed an active sham-training control [30].
Furthermore, in all trials the exercisers and investigators
have not been blinded, preventing the exclusion of both a
placebo effect and investigator bias on outcomes. Finally,
although most studies have determined BP as the average
of multiple measurements taken using an automated
oscillatory device after a rest period (as opposed to manual
auscultatory methods [29, 32, 36]) [30, 31, 33–35, 37–44],
the length of time between measurement and the last
exercise session does not appear to be standardized, with
the majority describing that measurements were taken
between 2 and 7 days following training [29, 31, 33, 35,
37–40, 42–44].
No prospective studies directly compared the effects of
isometric exercise training on BP against dynamic aerobic
or resistance exercise training adaptations or antihyper-
tensive medications. However, a number of studies report
reductions in resting BP within participants already
engaged in regular dynamic aerobic and resistance training
[32, 34, 35, 37, 39, 40]. These observations may suggest an
independent mechanism of action and the potential for
additional incremental benefits of combining exercise
modalities. The prospective observations of reduced resting
BP have been confirmed in four meta-analyses of either
RCT data [21, 25, 26] or RCT and cohort-controlled data
[27]. However, each of these analyses included
B5 studies
and \125 total participants (exercisers plus controls)
(Table 3), and did not comment on issues of exercise
safety, isometric exercise protocols, or potential mecha-
nisms responsible for the reductions in resting BP. Overall,
these results highlight the need for future investigations to
corroborate reductions in BP in a large-scale RCT with an
intention-to-treat analysis against established hypertensive
treatments.
Similar to aerobic exercise training, the largest isometric
training reductions in resting BP have been demonstrated
in hypertensive patients [29, 32, 36]. A strong correlation
has been reported between the magnitude of change fol-
lowing isometric exercise training and baseline BP, such
that the reductions are greatest in those with higher pre-
training BP [41, 44, 45]. Even so, significant reductions in
BP have been found in young normotensive females, using
an RCT design, suggesting a robust stimulus for adaptation
[44]. An important limitation given the small individual
study sample sizes and widespread use of non-randomized
designs, is the potential that the observed findings represent
a ‘regression to the mean’. While this possibility should not
be discounted, the risk appears mitigated by the increasing
RCT evidence and the observation that the majority of
studies report run-in or familiarization procedures [29, 30,
34–44] and multiple measurements of BP at each time
point [29–32, 34–44].
An important consideration not detailed when reporting
simple mean group reductions, a practice common in the
literature to date, is the overall inter-individual response
rates. Thus, while the available evidence appears to dem-
onstrate a high consistency in producing post-training
reductions in mean group resting BP, it should be noted
that a high inter-individual variability does exist, whereby
Table 3 Meta-analytic data on
the effects of isometric exercise
training on resting blood
pressure
All blood pressure values
reported as means
Con control, DBP diastolic
blood pressure, Ex exercise,
n number of subjects, SBP
systolic blood pressure,
; indicates reduction
a
Range dependent on random-
or fixed-effect model
Reference (year) Included studies Participants (n) Major findings
Kelley and Kelley (2010) [26] Wiley et al. [29] Ex: 42 ; in SBP of 13 mmHg
Taylor et al. [32] Con: 39 ; in DBP of 6–8 mmHg
a
Millar et al. [37]
Owen et al. (2010) [27] Wiley et al. [29] Ex: 64 ; in SBP of 10 mmHg
Howden et al. [31] Con: 58 ; in DBP of 7 mmHg
Taylor et al. [32]
Millar et al. [37]
Wiles et al. [39]
Cornelissen et al. (2011) [25] Wiley et al. [29] Ex: 42 ; in SBP of 13 mmHg
Taylor et al. [32] Con: 39 ; in DBP of 6–8 mmHg
a
Millar et al. [37]
Cornelissen and Smart (2013) [20] Wiley et al. [29] Ex: 64 ; in SBP of 11 mmHg
Taylor et al. [32] Con: 50 ; in DBP of 6 mmHg
Millar et al. [37]
Wiles et al. [39]
Isometric Exercise Training on Blood Pressure
some participants respond to isometric exercise training,
while others do not [33, 42, 45]. In general, a reduction in
resting systolic or diastolic BP of C2 mmHg has been
considered to be clinically relevant [1, 13]. Published and
unpublished response rates based on this criterion are
estimated to be between 50 and 83 % in medicated (i.e.
antihypertensive drug treated) hypertensive patients [33,
34, 42, 43, 45] and between 60 and 96 % in unmedicated
normotensive and hypertensive patients [35–37]; however,
the majority of studies have failed to publish this statistic.
We identified two published neutral studies, both
involving individuals medicated for hypertension [33, 42].
Specifically, one of these studies may have been limited by
its cohort design without the use of a control group [33],
while the other was an RCT that failed to detect statisti-
cally significant reductions in resting BP yet reported
clinically meaningful reductions in mean ambulatory 24-h
systolic BP and night-time systolic BP [*3–4 mmHg
(means)] [42]. The reason for the lower response rate in
individuals receiving pharmacotherapy to treat their
hypertension is unknown, but may involve overlap between
the mechanisms mediating the isometric training response
and specific classes of antihypertensive drug therapies.
Unfortunately, participant stratification based on medica-
tion class has not been completed, likely as a result of the
small sample of medicated hypertensives and overlapping
drug therapies needed to control BP in many patients [43].
Additional investigation is warranted to determine if the
medicated hypertensive population requires a greater
exposure to the isometric training stimulus (e.g. increased
frequency of training, increased intervention length) to
elicit adaptations. Although not detected in recent funnel
plots [20, 27] or Egger regression [20] analyses, a potential
publication bias against negative studies should not be
overlooked and further strengthens the need for a large-
scale RCT.
2.3 Effects of Isometric Training Protocol Variables
on Resting BP
As mentioned, a systematic evaluation of the variables
involved in the training protocol (intensity, frequency,
duration) has not been undertaken, and current isometric
exercise protocols appear to be based primarily on con-
tinued success [31]. The following sections expand on the
impact of the individual components of the isometric
exercise training protocol on resulting adaptations.
2.3.1 Contraction Intensity
Two RCT studies have directly compared the effects of
isometric bilateral leg extension (four sets of 2-min con-
tractions) at a lower (*10 % MVC) and higher (*20 %
MVC) intensity, demonstrating that the magnitude and rate
(i.e. speed) at which resting BP was reduced is greater in
the higher intensity training group [39, 41]. A possible
threshold for adaptations was also observed as training at
*8 % MVC did not produce reductions in BP [41].
Comparisons between individual studies are difficult due to
the alteration of multiple exercise characteristics.
2.3.2 Training Frequency
In the only published study to directly examine training
frequency, Badrov and colleagues [44] compared the
effects of 39/week and 59/week isometric handgrip
training on resting BP in an RCT design. They observed
that resting systolic BP was reduced equally following
8 weeks of training in both groups of normotensive par-
ticipants, although training 59/week, but not 39/week,
was associated with reductions in systolic BP after
4 weeks. This may suggest that a greater exercise dose may
accelerate adaptations. From comparisons of the available
literature it may also be extrapolated that increased training
frequency does accelerate the time course of training
adaptations [29], but again these interpretations are con-
founded by concomitant differences in contraction inten-
sity and duration.
2.3.3 Training Duration
Current evidence suggests that 4–5 weeks of isometric
exercise training is sufficient to detect significant reduc-
tions in resting BP, if present, with larger reductions
observed after 8–10 weeks [45]. Present studies are limited
to training durations of 4–10 weeks, an important consid-
eration given that a longitudinal BP analysis failed to
detect a plateau in training reductions within this timeframe
[45]. This is particularly relevant considering hypertension
is a chronic disease requiring continuous lifelong treat-
ment. Further research is required to determine the chronic
long-term effects of isometric exercise training on BP.
2.3.4 Muscle Mass
The use of different modes of training, such as unilateral
handgrip and bilateral leg isometric exercise, introduces
the potentially confounding factor of differences in con-
tracting muscle mass. Howden and colleagues [31] com-
pleted a head-to-head cohort-controlled study of bilateral
isometric arm and leg training on BP, with both protocols
similarly reducing mean resting BP (arm, D12/6 mmHg;
leg, D10/4 mmHg). An important limitation of this study,
aside from its non-randomized design, is that the two
protocols were not completed at the same relative intensity
(arm, 30 % MVC; leg, 20 % MVC). In general, isometric
P. J. Millar et al.
bilateral leg training has been conducted at lower relative
intensities than handgrip (or bilateral arm) training proto-
cols, making comparisons difficult. The consistent reduc-
tions in resting BP evident from both of these training
protocols suggests that the effects are largely independent
of the muscle mass involved.
2.3.5 Maintenance of Training Adaptations
No information is available on the long-term maintenance
of isometric training adaptations over periods longer than
10 weeks of time. Investigation of minimal training
requirements to maintain adaptations is important to be
considered a potential hypertension therapy.
Three studies have reported on the effects of detraining
following isometric exercise training. Wiley and colleagues
[29] documented large reductions in resting BP (D
16 mmHg for systolic BP) following 5 weeks of isometric
handgrip training that were reversed significantly after only
2 weeks of detraining and gradually returned to pre-train-
ing values after 5 weeks, a time course equal to the training
period. More recently, reductions in systolic BP [D
5–12 mmHg (means)] were lost after only 7–10 days [31,
40]. The rapid nature of these detraining responses may
suggest that the mechanisms responsible influence cardio-
vascular function rather than structure.
2.4 Safety Considerations of Isometric Exercise
Training
Isometric exercise is described classically as inducing a
pressure load on the heart based on its potential to increase
both systolic and diastolic BP. In comparison, dynamic
aerobic exercise induces a volume load due to concomitant
increases in cardiac output and reductions in total periph-
eral resistance. The large BP responses observed with high-
intensity isometric contractions to fatigue [46–48] raised
concerns that isometric exercise should be avoided in many
clinical populations, including hypertension [28, 49, 50].
In the context of this review, it is important to remember
that current isometric exercise training studies have been
performed at low-to-moderate intensity. In the only pub-
lished study of acute haemodynamic responses, isometric
handgrip exercise (4 9 2-min, 1-min rests, 30 % MVC)
was reported to modestly increase heart rate [D 3 ± 4 bpm
(mean ± SD)] and BP [D 16 ± 10/7 ± 6 mmHg
(mean ± SD)] in older, primarily coronary artery disease
patients [51]. Further delineation of the acute responses
across a wide range of patient cohorts should be completed
to ensure normative responses. A number of studies have
reported that a single isometric contraction produces
equivalent, or lower, systolic BP and heart rate responses
than dynamic aerobic exercise [52–56], particularly when
the exercise is performed at the same peak tension devel-
opment [57]. As a result, the rate-pressure product (systolic
BP 9 heart rate), an index of myocardial oxygen con-
sumption, can be lower following submaximal isometric
handgrip compared with submaximal treadmill exercise
[58].
Isometric exercise is also associated with an increase in
diastolic BP [28, 59], in contrast to no change with
dynamic aerobic exercise. This may act to increase coro-
nary perfusion pressure [60] and, in combination with a
reduced rate-pressure product, decrease the potential for
exercise-induced myocardial ischaemia [61]. One key facet
of ensuring appropriate BP responses during isometric
exercise protocols is the maintenance of spontaneous
breathing without the use of the Valsalva manoeuvre
(forced expiration against a closed glottis) [62]. Overall,
while low-to-moderate intensity isometric exercise acutely
increases BP, it may be clinically permitted in hypertensive
patients recommended for equivalent intensity dynamic
exercise, with appropriate consideration of standard abso-
lute and relative contraindications to exercise (such as
uncontrolled BP [180/110 mmHg) [14, 63].
Additionally, isometric contractions can be accompa-
nied by secondary symptoms of local paraesthesia and
minor discomfort. This is most often observed near the end
of each set, particularly during protocols with contractions
lasting [2 min, and likely relates to the reduction in
intramuscular blood flow and accumulation of local
metabolites. All symptoms quickly subside upon contrac-
tion release and the restoration of adequate blood flow. In
the collective experience of the authors, who have inde-
pendently completed [25,000 isometric exercise training
sessions, there have been no reports of lasting physical
impairments or significant unfavourable clinical events
during or resulting from isometric exercise training.
3 Potential Mechanisms Responsible for Isometric
Training-Induced Reductions in Resting BP
3.1 General Background
Practically speaking, the mechanism whereby resting BP is
reduced after isometric exercise training must involve one
(or both) factors that determine mean arterial pressure
(MAP): cardiac output and total peripheral resistance. Two
observations may provide insight into potential mecha-
nisms: (i) the lower responder rate in medicated hyper-
tensive patients suggests a potential overlap between
pathways involved in pharmacologically treating high BP;
and (ii) the temporal sequence of training and detraining
adaptations in resting BP suggest at least an initial alter-
ation in cardiovascular function, rather than structure. Of
Isometric Exercise Training on Blood Pressure
course, this latter observation does not preclude the pos-
sibility of a biphasic pattern involving initial adaptations in
function, followed by longer-term structural adaptations, as
observed with aerobic exercise training [64]. The following
sections will discuss the potential mechanisms responsible
for isometric training-induced changes in resting BP.
3.2 Cardiac Adaptations
Studies in young normotensive participants suggest no
significant changes in either stroke volume or cardiac
output following isometric bilateral leg training, despite
concomitant post-training reductions in mean systolic and
diastolic BP (D 4–5/3 mmHg) [39, 40]. Curiously, these
studies also failed to report a change in total peripheral
resistance, suggesting that the re-breathing technique
applied may be insensitive to small changes over time.
Further investigation of cardiac haemodynamics in differ-
ent populations (e.g. older or clinical), with alternative
methodologies (e.g. Doppler ultrasound), and following
larger training-induced reductions in resting BP are
required.
3.3 Autonomic Nervous System Adaptations
3.3.1 Cardiac Autonomic Regulation
The majority of isometric training data have not supported
an adaptation in resting heart rate [29–40, 42–44], a hall-
mark feature of aerobic exercise training associated with
increased vagal modulation [19]. In contrast, Baross and
colleagues [41] recently reported a reduction in resting
mean heart rate (D 5 bpm) in concert with reductions in
resting BP, the first such report, following isometric leg
training in older, unmedicated, pre-hypertensive and
hypertensive men. These results suggest that changes in
resting heart rate may be population specific and influenced
by baseline medication status.
An important consideration is that average resting heart
rate may not accurately represent the beat-to-beat contri-
butions of the autonomic nervous system. The non-inva-
sive assessment of heart rate variability (HRV) provides
insight in to the relative changes in cardiac sympathetic
and vagal modulations [65–67]. The majority of studies
have failed to detect training differences in power spectral
or time-domain measures of HRV [38, 39, 42–44]. In
contrast, both to the weight of the evidence and to pre-
vious research in well-controlled medicated hypertension
[42], Taylor and colleagues [32] reported significant
increases in power spectral high frequency area, a marker
of cardiac vagal modulation [67], concomitant with a
large reduction in mean systolic BP (D 19 mmHg) fol-
lowing 10 weeks of isometric handgrip training in
uncontrolled hypertensive patients. Millar and colleagues
[38] detected increases in non-linear heart rate complexity
(sample entropy), a measure primarily associated with
cardiac vagal modulation [68] and thought to be more
sensitive to subtle modulations than traditional linear
frequency or time-domain HRV measures, in well-con-
trolled medicated hypertensive patients. Taken together,
this work suggests that isometric exercise training may
elicit cardiac neural adaptations in some individuals with
hypertension, and the medication status of the patients
may play a role in determining one’s capacity for change.
Studies with adequate statistical power are needed to fully
elucidate the effects of isometric exercise training on
HRV, and should employ assessments of non-linear heart
rate dynamics in addition to the traditional time- and
frequency-domain measures.
3.3.2 Neural Regulation of Vascular Tone
Limited data exists on the impact of isometric exercise
training on peripheral sympathetic nerve activity or the
modulation of vascular tone. Ray and Carrasco [30]
reported that 5 weeks of isometric handgrip training
reduced diastolic BP and MAP in young healthy partici-
pants without altering resting muscle sympathetic nerve
activity (MSNA), assessed by microneurography. In addi-
tion, isometric training did not alter MSNA responses to a
2-min isometric handgrip contraction (30 % MVC) or
subsequent post-exercise muscle ischaemia. These results
suggest that BP reductions in healthy normotensive
patients are not dependent on reductions in central efferent
sympathetic outflow, although it is important to remember
that direct measurements of nerve traffic are not always
correlated with end-organ effects [69], and that in this
small sample, resting MSNA was not elevated (compared
with values typically observed in hypertensive patients).
In contrast, in an RCT of older patients with difficult-to-
control medicated hypertension, Taylor and colleagues [32]
reported that 10 weeks of isometric handgrip training
reduced systolic BP and MAP in concert with significant
reductions in the low-frequency spectra of systolic BP
variability, a marker of baroreflex-mediated peripheral
sympathetic modulation [70, 71]. Thus, in patients with
primary hypertension, a condition characterized by
increased sympathetic outflow [72, 73], isometric training
may reduce BP through attenuations in peripheral sympa-
thetic vasoconstrictor activity. Baross et al. [41], recently
observed increases in femoral artery diameter and vascular
conductance following 8 weeks of bilateral isometric leg
training in healthy normotensive patients, but did not
investigate the mechanism for this alteration. Further work
is required to elucidate the role of isometric exercise
training in altering sympathetic vasomotor tone.
P. J. Millar et al.
3.4 Vascular Adaptations
A number of investigations have examined the effects of
isometric exercise training on conduit artery endothelial
function. McGowan and colleagues [33, 34] reported that
8 weeks of unilateral isometric handgrip training in medi-
cated hypertensive patients increased nitric oxide (NO)-
dependent, but not NO-independent, vasodilation in the
brachial artery of the trained arm only (i.e. no adaptations in
the contralateral untrained arm). These increases in NO-
dependent brachial dilation were not replicated in normo-
tensive participants, despite modest yet significant reduc-
tions in resting BP [35]. This may be interpreted to suggest
that improved systemic NO-dependent vasodilation is not a
required mechanism for the reductions in resting BP fol-
lowing isometric exercise training. However, it is important
to consider the methodology used to assess NO-dependent
vasodilation in these studies, namely brachial artery flow-
mediated dilatation, which measures the response of the NO
vasodilator system to a maximal hyperaemic stimulus. It is
therefore plausible that an increase in the basal capacity of
the NO vasodilator system to produce, release and/or utilize
NO may contribute to the observed training-induced reduc-
tions in resting BP in either population. In support of a vas-
cular mechanism, 4 weeks of isometric handgrip in
normotensive participants increased peak reactive hyperae-
mic blood flow, a marker of functional changes in the
resistance vessel (small arteries and arterioles) vasculature
[35], which are the beds primarily responsible for deter-
mining BP [74]. More recently, 8 weeks of isometric hand-
grip improved reactive hyperaemic blood flow, suggestive of
improved resistance vessel function in a young normotensive
cohort training 39/week or 59/week using a prospective
RCT design [44]. Importantly, while BP was reduced with
59/week training after 4-weeks of training, this was not
accompanied by improvements in the resistance vessel
vasculature, suggesting other mechanisms are also involved.
Thus, whether improved resistance vessel endothelial func-
tion, similar to that observed following aerobic endurance
training [75], principally contributes to the training-induced
reduction in resting BP requires further elucidation.
The evidence that isometric exercise training is a suffi-
cient stimulus to cause adaptations in the local exercising
vasculature is also supported by increases in femoral, but
not brachial artery, diameter, blood flow, and blood
velocity following 8 weeks of isometric bilateral leg
extension training [41]. In this RCT, the changes in resting
femoral diameter strongly correlated with the changes in
resting BP. Unfortunately, it is not possible to distinguish
between structural vessel remodelling or functional chan-
ges in basal vasodilator capacity (likely as a result of the
noted increase in blood velocity) or tonic vasoconstrictor
activity (reduced sympathetic outflow).
Overall, isometric exercise training is associated with
increases in local conduit artery NO-dependent dilatation
in patients with hypertension, but these adaptations are not
observed in normotensive participants. As BP is primarily
regulated at the level of the resistance vessels, evidence
supporting improved resistance vessel function provides
one plausible mechanism responsible for reductions in
resting BP.
3.5 Oxidative Stress
Increased oxidative stress is thought to play a key role in
the pathophysiology of hypertension [76]. Preliminary
evidence suggests that isometric exercise training may
improve oxidative stress, in so far as, in one uncontrolled
trial, 6 weeks of isometric handgrip training improved the
ratio of resting whole blood glutathione to oxidized glu-
tathione and reduced aerobic exercise-induced ROS pro-
duction, in concert with reductions in resting BP in
unmedicated hypertensive patients [36]. Additionally, since
isometric training can increase local conduit artery NO-
dependent vasodilation in individuals with hypertension
[33, 34] and basal NO-dependent resistance vessel function
[35], changes in oxidative stress may be mediated by
increased availability of NO, a potent antioxidant and anti-
inflammatory molecule [76].
3.6 Summary of Mechanisms
The mechanisms responsible for the reductions in resting
BP following isometric exercise training have not been
fully clarified. It is most likely that multiple adaptations in
the above pathways are collectively responsible for the
post-training reductions in BP and determined by the
individual pathological profiles of each participant. In
general, the current literature investigating the potential
mechanisms responsible for training adaptations is limited
by small sample sizes. Isometric exercise training trials to
date have primarily been powered to detect changes in
resting BP, and inadequately powered to probe the role of
specific regulatory pathways. While the reductions in
resting BP are likely mediated via a reduction in total
peripheral resistance, similar to aerobic exercise training
[19], the specific roles of the sympathetic nervous system,
conduit and resistance vessel structure and function, and
oxidative stress require greater investigation.
4 Clinical Implications
In addition to the discussed interventional studies, Buck
and Donner [77] conducted an epidemiological study of
4,273 men and classified hypertension incidence based on
Isometric Exercise Training on Blood Pressure
occupational isometric activity. They reported that fol-
lowing adjustment for known confounders (age, social
class, obesity, and alcohol consumption), moderate to
heavy occupational isometric exercise was associated with
a lower incidence of hypertension [77]. While this asso-
ciation does not prove causality, it is in agreement with the
prospective data and may suggest a role for isometric
exercise training in both prevention and management of
hypertension.
It is important to remember that for those with or
without hypertension, even small reductions in systolic and
diastolic BP (C2 mmHg) can translate into significant
reductions in the incidence of coronary artery disease,
myocardial infarction, stroke, and mortality [78–80], and
less need for medications and thus less probability of
undesirable side effects. However, while BP remains a
significant contributor to overall cardiovascular health, the
ability of isometric exercise training to modulate other
CVD risk factors, such as insulin sensitivity, cholesterol, or
inflammation remain largely unexplored. We identified
only one study to investigate the effects of isometric
exercise training on additional CVD correlates other than
BP. In this uncontrolled cohort study, isometric handgrip
training did not alter total, high- or low-density cholesterol
[34]. Thus, in comparison to dynamic exercise training
(aerobic and resistance), which consistently demonstrates a
number of important improvements (e.g. body composi-
tion, metabolic, maximal aerobic capacity), the benefits of
isometric training may be confined to BP. Studies designed
to test the clinical efficacy of isometric exercise training
are needed.
5 Future Directions
Isometric exercise training, and in particular isometric
handgrip training, which is easily applicable (i.e. easy to
use and can be performed anytime and anywhere), inex-
pensive and hence accessible to the global population,
could offer a valuable new therapeutic adjunct in the
overall approach for treating hypertension [81]. However,
despite these encouraging findings, a number of important
research questions remain with respect to the (i) value of
the training modality compared with or in addition to
currently recommended aerobic exercise training proto-
cols; (ii) identification of the most effective isometric
exercise program to maximize and maintain BP reductions;
(iii) efficacy of isometric exercise training in lowering
ambulatory 24-h BP, a more clinically relevant measure
[82]; and (iv) mechanisms responsible for the observed BP
reductions. Importantly, each of these issues needs to be
systematically investigated before isometric exercise can
be universally recommended.
6 Conclusion
Hypertension is a global disease with a high residual lifetime
risk (upwards of 90 % in some populations) [10], and rep-
resents a major contributor to the growing pandemic of CVD
and stroke [1]. Approximately 54 % of strokes and 47 % of
heart disease cases are directly attributable to elevated BP
[83]. In the context of this large and growing disease burden,
strategies to improve population health are of utmost
importance. This review has summarized the available liter-
ature on the effects of isometric exercise training on BP [24–
45]. From the current prospective studies and meta-analyses,
isometric exercise training appears to be as or more effective
in lowering BP when compared with dynamic aerobic [16–
20], or resistance exercise training [20, 22–25], even though it
requires substantially less time. The observation that resting
BP can be reduced in participants already undergoing chronic
aerobic and dynamic resistance training [32, 34, 35, 37, 39,
40] suggests a specific adjunct role for isometric exercise
training. However, while these largely preliminary results
appear promising, concerns regarding small samples sizes
and uncontrolled study designs exist. We believe that the
current level of evidence substantiates a large-scale RCT
designed to address these previous limitations and determine
potential clinical significance. Further investigation is also
required to elucidate the mechanisms responsible for these
observations, although much like hypertension pathophysi-
ology, multiple regulatory pathways are likely involved, and
dependent on individual pathological states. The potential
impact of isometric exercise training in combating hyper-
tension warrants future research to delineate important
questions necessary for its adoption as an adjunct exercise
therapy.
Acknowledgments The authors would like to thank Dr. Tony Ba-
ross for assistance in preparing the table. No funding was received to
assist in the preparation, editing or approval of this review. Dr. Millar
has received modest speaking and travel honoraria from ZonaHealth
(2010–2012) [Boise, ID, USA]. Dr. Millar is supported by a Canadian
Institutes of Health Research (CIHR) research fellowship. Dr. Cor-
nelissen is supported as a postdoctoral research fellow by Research
Foundation Flanders (FWO). Dr. Araujo is supported by Brazilian
(CNPq) and State of Rio de Janeiro (FAPERJ) research scholarships.
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