Received: 22 April 2022 | Accepted: 5 July 2022

DOI: 10.1111/cpf.12779

ORIGINAL ARTICLE

Acute hemodynamic responses from low‐load resistance

exercise with blood flow restriction in young and older
individuals: A systematic review and meta‐analysis of
cross‐over trials

William R. Pedon1 | Francisco V. Lima2 | Gerson Cipriano Jr.3 |

Weder A. da Silva | Marcos V. S. Fernandes | Natalia S. Gomes1 |
1 1

Adriana M. G. Chiappa4 | Rafael Pena de Sousa1 | Maria Eduarda Pereira da Silva1 |

1
Gaspar R. Chiappa

1
Postgraduate Program in Human Movement
and Rehabilitation of Evangelical University of
Goias, Goiânia, Brazil
2
Cancer Institute of São Paulo State,
São Paulo, Brazil
3
Postgraduate Program in Health Sciences and
Technologies and Rehabilitation Sciences,
University of Brasilia, Brasília, Brazil
4
Intensive Care Unit, Hospital de Clínicas de
Porto Alegre, Porto Alegre, Brazil
Correspondence
Gaspar R. Chiappa, Avenida Universitária S/N,
Bairro Universitário, Anápolis 75083‐515,
Goiás, Brazil.
Email: gaspar.chiappa@gmail.com
Funding information
Conselho Nacional de Desenvolvimento
Científico e Tecnológico,
Grant/Award Number: 422416/2018‐5
Abstract
Objective: To summarize the existing evidence on the acute response of low‐load
(LL) resistance exercise (RE) with blood flow restriction (BFR) on hemodynamic
parameters.
Data Sources: MEDLINE (via PubMed), EMBASE (via Scopus), SPORTDiscus,
Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic
Reviews, Web of Science and MedRxiv databases were searched from inception to
February 2022.
Review Methods: Cross‐over trials investigating the acute effect of LLRE + BFR
versus passive (no exercise) and active control methods (LLRE or HLRE) on heart rate
(HR), systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure responses.
Results: The quality of the studies was assessed using the PEDro scale, risk of bias
using the RoB 2.0 tool for cross‐over trials and certainty of the evidence using the
GRADE method. A total of 15 randomized cross‐over studies with 466 participants
were eligible for analyses. Our data showed that LLRE + BFR increases all
hemodynamic parameters compared to passive control, but not compared to
conventional resistance exercise. Subgroup analysis did not demonstrate any
differences between LLRE + BFR and low‐ (LL) or high‐load (HL) resistance exercise
protocols. Studies including younger volunteers presented higher chronotropic
responses (HR) than those with older volunteers.
Conclusions: Despite causing notable hemodynamic responses compared to no
exercise, the short‐term LL resistance exercise with BFR modulates all hemodynamic
parameters HR, SBP, DBP and MBP, similarly to a conventional resistance exercise
protocol, whether at low or high‐intensity. The chronotropic response is slightly

© 2022 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Clin Physiol Funct Imaging. 2022;1–17. wileyonlinelibrary.com/journal/cpf | 1

2 |
higher in younger healthy individuals despite the similarity regarding pressure
parameters.
KEYWORDS
blood pressure, exercise, heart rate, hemodynamic, upper extremity (arm)
1 | INTRODUCTION
Partial or complete blood flow restriction (BFR) is used as a training
method in association with exercise (Scott et al., 2015). Exercise with
BFR was first described by Dr. Yoshiaki Sato (2005), denominated
Kaatsu exercise, and now, a few decades later, it is performed
worldwide using automatic or pneumatic occlusion systems
(Loenneke, Wilson, Balapur et al., 2012; Wernbom et al., 2008).
This technique has been utilized in more proximal regions, in
both lower or upper limbs (Pignanelli et al., 2021). Physiologically, the
compression limits the venous flow, reducing venous blood flow and
accumulating blood volume in the capillaries of the obstructed limbs.
This reduction drastically reduces oxygen circulation, causing hypoxia
of the vascular beds (Manini & Clark, 2009), generating greater stress
in the active muscles and stimulating greater muscle adaptation.
Current studies usually focus on muscle performance outcomes,
such as strength gain and hypertrophy, and there is a lack of studies
reporting hemodynamic responses or possible harmful effects.
Exercise with BFR can generate abnormal heart rate (HR) and blood
pressure responses through direct action of the metaboreflex
(ischaemia‐induced sympathoexcitatory pressor reflex originating in
skeletal muscle) (Kacin et al., 2015). During muscle contractions,
there is an increase in intramuscular pressure below the cuff (Kacin
et al., 2015), causing further blood flow reduction in systolic blood
pressure (SBP) and an increase in HR (Domingos & Polito, 2018).
Although results have also shown that blood accumulation can
be influenced by the applied pressure, studies report substantial
variability in protocols, using different exercise intensities and types
(modalities) and various occlusion pressures (Kacin et al., 2015; Vieira
et al., 2013).
Information on possible harmful effects of using the BFR exercise
technique (e.g., numbness, pain, etc.) and safety seems to be poorly
reported in the literature. This information may be particularly
important for individuals with a medical history of prior risk,
particularly individuals with blood clotting disorders, ischaemia‐
reperfusion injury, venous distention or any muscle disorder or
damage, such as rhabdomyolysis (Cristina‐Oliveira et al., 2020). For
example, a previous study from our group (Vieira et al., 2013),
observed an intense hemodynamic response and skeletal muscle
metaboreflex following BFR application during a warm‐up phase in
both young and older volunteers; however, some volunteers reported
pain discomfort during the intervention.
Thus, the purpose of the current study was to analyze whether
low‐load (LL) resistance exercise (LLRE) with BFR alters hemo-
dynamic variables (HR, SBP, diastolic blood pressure [DBP] and mean
PEDON ET AL.
blood pressure [MBP]) significantly compared to both passive (no
exercise) and active control groups (conventional resistance exercise
[CRE]). The secondary purposes were to (1) compare LLRE + BRF with
CRE applied with low (LL) and high‐load (HL) intensities and (2)
compare LLRE + BFR hemodynamic response between young and
older volunteers.
2 | METHODS
The present study follows the standard recommendations of the
Cochrane Handbook for Systematic Reviews of Interventions, and
the Preferred Reporting Items for Systematic Reviews and Meta‐
analysis (PRISMA) guidelines (Moher et al., 2015). This meta‐analysis
was registered in the database of Prospectively Registered System-
atic Reviews (PROSPERO) (registration number: CRD42021234757).
2.1 | Search strategy
Two reviewers (W. P. R. and G. R. C.) independently conducted an
electronic search in seven databases—MEDLINE (via PubMed),
EMBASE (via Scopus), SPORTDiscus, Cochrane Central Register of
Controlled Trials, Cochrane Database of Systematic Reviews, Web of
Science and MedRxiv, from inception to February 2022; disagree-
ments were resolved by consensus or involving a third researcher
(M. F.). The research strategy adopted was as follows: ‘healthy
volunteers’ OR ‘Health’ OR ‘Healthy aging’ OR ‘Aged’ AND ‘Ex-
ercise’ OR ‘Resistance Training’ OR ‘Endurance Training’ OR ‘High‐
Intensity Interval Training’ OR AND ‘Blood Flow Restriction’ OR
‘Occlusion Training’ OR ‘Vascular Occlusion’ OR ‘Kaatsu’ OR ‘Ischae-
mic Training’ OR ‘Exercise Test’ OR ‘Blood pressure’ OR ‘Heart rate’,
adapted according to the assessed database. The reference lists of
studies included in previous systematic reviews and meta‐analyses
were also reviewed for any additional inclusions.
2.2 | Study selection
Studies involving the effects of exercise with BFR on hemodynamic
responses were included in this systematic review. Inclusion criteria
were: (1) type of studies: cross‐over trials; (2) type of participants:
healthy adults and older people (without previous disease); (3) type of
intervention: resistance exercise (low and high intensities) with
vascular occlusion; (4) type of comparison: resistance exercise
PEDON ET AL.
without BFR or no exercise; and (5) outcomes: HR (bpm),
SBP (mmHg), DBP (mmHg) and MBP (mmHg). Exclusion criteria
were: (1) individuals over 75 years of age; (2) subjects with
cardiovascular or respiratory diseases; (3) nonrandomized, observa-
tional and cohort studies; (4) conference abstracts without a full‐
published article; (5) studies with inconsistencies or that did not
provide enough data to calculate the effect size.
The term adult was used for those individuals over the age of 20
years, middle‐aged for individuals between 38 and 58 years of
age and older adults for individuals over 60 years of age (Kalache &
Gatti, 2003).
2.3 | Search and data extraction
EndNote 20 (Clarivate Analytics) and the Rayyan 13 Platform
(Ouzzani et al., 2016) were used to remove any duplicates and select
eligible studies from the database results and other sources. Two
independent reviewers (W. R. P. and G. R. C.) with experience
conducting systematic reviews selected eligible studies (Ouzzani
et al., 2016). Any disagreements between reviewers were resolved by
consensus or by a third reviewer (W. A. S.).
A standardized form was used to extract relevant data by three
reviewers (W. R. P., G. R. C. and W. A. S). The main characteristics of
the selected studies were summarized in a table, including the
following information: (1) characteristics of the studies: source, year
of publication, sample size; (2) sample characteristics: young or older
adults, number of samples included in each group, as well as
percentage of women in the investigated groups and average age; (3)
characteristics about the intervention used: duration of the tech-
nique, frequency, type and regimen of training exercises; and (4)
outcomes assessed: such as HR, SBP, DBP and PAM. Disagreements
in data collection were resolved by consensus.
2.4 | Classification of the outcome
The objective of the study was to assess the responses of HR in bpm,
SBP in mmHg, DBP in mmHg or MBP in mmHg caused by vascular
occlusion and resistance exercise.
2.5 | Quality of studies and risk of bias assessment
The quality of the studies was assessed using the Physiotherapy
Evidence Database (PEDro) scale (Maher et al., 2003; Sterne et al.,
2019). The PEDro scale (Maher et al., 2003) includes 11 assessment
items (e.g., analysis, comparisons between groups, point esti-
mates and variability). The maximum score that can be obtained is
10 points (with the eligibility criteria item not contributing to the total
score), where scores from 9 to 10 points are considered as excellent
quality, from 6 to 8 points, good, from 4 to 5 points, regular and
below 4 points low quality (Elkins et al., 2013).
| 3
The risk of bias of the studies was performed using the
2nd version of the Cochrane risk of bias tool for cross‐over studies.
The following aspects of methodological quality were evaluated in
the crossover studies (J. Higgins et al., 2021; Sterne et al., 2019): (1)
Domain 1a: Risk of bias resulting from the randomization process; (2)
Domain S: Risk of bias derived from period and carry‐over effects; (3)
Domain 2: Risk of bias due to deviations from intended interventions
(attribution of effect to intervention); (4) Domain 3: Risk of bias due
to lack of outcome data; (5) Domain 4: Risk of bias in outcome
measurement; (6) Domain 5: Risk of bias in the selection of the
reported result.
We considered the study as low risk of bias if the study was
rated as low risk in all domains, some concerns if there was at least
one domain rated as some concerns, and high risk of bias if there was
at least one domain rated as high risk or multiple domains rated as
some concerns that may affect the validity of the results. Study
quality and risk of bias were assessed in duplicate, and consensus was
verified by a third reviewer (G. R. C).
2.6 | Certainty of evidence
The included studies were assessed according to the Grade of
Recommendations, Assessment, Development and Evaluations
(GRADE) (G. H. Guyatt, Oxman, Akl et al., 2011; G. H. Guyatt,
Oxman, Montori et al., 2011) method to examine the quality of
evidence according to the Cochrane Handbook (Cumpston et al.,
2019). The GRADE method assesses five domains: (1) risk of bias
(Guyatt, Oxman, Vist et al., 2011), (2) imprecision of measures (G. H.
Guyatt, Oxman, Kunz et al., 2011), (3) inconsistency of the results
(G. H. Guyatt, Kunz, Woodcock, Brozek et al., 2011), (4) indirectness
of interventions (G. H. Guyatt, Oxman, Kunz, Woodcock et al.,
2011) and (5) publication bias (G. H. Guyatt, Oxman, Vist et al., 2011).
An overall designation of ‘high’, ‘moderate’, ‘low’ or ‘very low’ is
assigned to each article based on the strength of the five domain
ratings.
2.7 | Statistical analysis
All analyses were performed using Review Manager version 5.4.
Differences between means and confidence intervals (95% CI) were
used for continuous order variables. The standard deviation (SD) was
calculated for each study, based on the change scoring method. The
heterogeneity between studies was explored qualitatively, according
to the Cochrane Handbook for Systematic Reviews of Interventions
(Cumpston et al., 2019), comparing the characteristics of the
studies and quantitatively, using the χ2 heterogeneity test and I2
statistics (J. Higgins, 2021). Where appropriate, study results were
combined for each outcome to determine the overall estimate of
treatment effect. When data on the SD of change in baseline results
were lacking, estimates were based on the standard errors, 95%
CI and p values to calculate the SD. For data presented in figure
4 |
format, the webPlotDigitizer was used as directed (Rohatgi, 2021). The
effect model for meta‐analysis was chosen based on qualitative and
quantitative analyses and publication bias analysis. Sensitivity
analyses were performed by dividing the studies according to age
(subgroup: younger: <65 years old and older: >65 years old) to assess
the robustness of the summary estimates and to detect whether any
study accounted for a large proportion of heterogeneity among
LLRE + BFR pooled estimates.
3 | RESULTS
3.1 | Studies
The database search found 39 385 articles, which were reviewed
based on the title and abstract, after discarding duplicates (n = 3790).
Fifteen studies (Bazgir et al., 2016; Crisafulli et al., 2018; Curty et al.,
2017; D. Kim et al., 2016; Downs et al., 2014; Kacin & Strazar, 2011;
Loenneke, Wilson, Balapur et al., 2012; Maior et al., 2015; Neto et al.,
2015; Poton, 2014; Sardeli et al., 2017; Staunton et al., 2015; Takano
et al., 2005; Vieira et al., 2013; Vilaça‐Alves et al., 2016) met the final
inclusion criteria and were selected for this systematic review and
meta‐analysis (Figure 1, Supporting Information: Table S1), including
a total sample of 466 participants. Excluded studies with reasons are
available in Supporting Information: Table S2 (Abe et al., 2010; Araujo
et al., 2014; Brandner et al., 2015; Conceicao et al., 2019; de Oliveira
FIGURE 1 Study flow diagram
PEDON ET AL.
et al., 2016; Fahs et al., 2011; J. Kim et al., 2017; Kumagai et al.,
2012; Loenneke et al., 2010; Okuno et al., 2014; Pinto et al., 2018;
Pinto & Polito, 2016; Rossow et al., 2012; Rossow et al., 2011; Sprick
& Rickards, 2017; Taylor et al., 2016).
3.2 | GRADE scale results
All 15 of the included studies were randomized trials, separated
according to age. Thirteen studies were related to healthy adult
individuals, divided according to each outcome evaluated (HR = 13;
SBP = 15; DBP = 15; MBP = 12 studies). The quality of the evidence
across these studies was very low (Supporting Information: Table S3).
Five studies included healthy older adults (>65 years old). The quality
of the evidence across these studies was low (Supporting Information:
Table S4).
3.3 | Summarizing data
Supporting Information: Tables S1, 1 and 2 present descriptive
information for the 15 studies included in the review. The age of the
included participants in the systematic review ranged between 21
and 69 years of age. Different clinical conditions were analyzed in the
included studies: middle‐aged and older adults in five studies (D. Kim
et al., 2016; Junior et al., 2019; Sardeli et al., 2017; Staunton et al.,
TABLE 1 Included studies comparing LLRE + BFR versus passive control group
PEDON

Description of protocol
Intervention Cuff
ET AL.

Studies (year) Design type Exercise location Cuff device Cuff size (cm) Occlusion pressure Protocol exercise

Crisafulli CO BFR Resistance Arm A manual sphygmomanometer NI In the first week, the occlusion Hemodynamic responses were
et al. (2018) exercise (WelchTM AllymTM DS44) was set at 75% of resting assessed at rest, during handgrip
SBP (always obtained after exercises, and during PEM
3 min of resting) and (metaboreflex activation), before
increased 25% every week (T0) and after 4 weeks (T1) of low‐
until reaching 150% of intensity BFR training. All
resting SBP in week four assessments took place within 1−3
days before T0 and after T1

Kacin & NIa BFR Resistance One‐leg Contour shape 13 × 30 cm Resting pressure 230 mmHg Performed knee‐extension exercise
Strazar (2011) exercise for 4 weeks (four sessions/week)
at 15% maximal voluntary muscle
contraction. One leg was trained
with free blood flow (C‐leg) and
the other leg (I‐leg) ischaemia.

Loenneke, Wilson, CO BFR Resistance Upper Knee wraps (Red‐Line, Harbinger)b 76 mm wide NI Two sets of bilateral leg extensions
Balapur exercise thigh of with 30% 1RM (8−10 repetitions)
et al. (2012) both to muscular failure under normal
legs conditions (CON) and the other
trial completing the same protocol
with BFR.

Sardeli et al. (2017) CO
BFR Resistance Inguinal Vascular Doppler probe (DV‐600, 175 mm wide 60 mmHg High load resistance exercise (HL),
exercise fold Martec) to determine blood and with four sets until voluntary
pressure cuff (AOP, arterial 920 mm failure at 80% 1RM; low load
occlusion pressure) long resistance exercise (LL), with
four sets until voluntary failure at
30% 1RM; low load resistance
exercise with BFR (LL‐BFR), with
1 × 30 + 3 × 15 repetitions at 30%
1RM and 50% BFR maintained
throughout the exercise session;
control (without BFR).

Stauton CO BFR Resistance Both thighs Automatic tourniquet Cuffs (86 cm long, 60% AOP LEG PRESS trial, the first set
et al. (2015) exercise system (ATS 3000, 10.5 cm wide; comprised 30 repetitions followed
Zimmer Inc.) bladder by three sets of 15 repetitions with
width 8 cm) the load equivalent to 20% 1‐RM.

(Continues)
|
5
6 | PEDON ET AL.

The cuff was inflated until the sound of blood flow could not be heard by the Doppler equipment. This point was considered as the blood flow value to be used in the BFR session. The BFR value was based on
2015; Vieira et al., 2013), and young healthy subjects in 14 studies

combined with BFR (LI + BFR) and

resistance exercise (HI), (b) a low‐
(Crisafulli et al., 2018; Fahs et al., 2012; Kacin & Strazar, 2011;

exercise (LI), (c) a low‐intensity

intensity 20% 1RM resistance
intensity (30% of 1 repetition

20% 1RM resistance exercise

Individuals performed single‐arm
biceps curl exercise at low Loenneke, Wilson, Balapur et al., 2012; Neto et al., 2015; Staunton

(a) A high‐intensity 80% 1RM

et al., 2015; Vieira et al., 2013). Additionally, different strength
maximum) for 3 min. exercise protocols were examined in the studies selected: LLRE +

(d) control (CON).

BFR versus LLRE, and LLRE + BFR versus HLRE.

3.4 | Quality of the studies and risk of bias

The PEDro score analysis revealed low scores, varying from 3 to 6,

for complete BFR in resting

with only one study being awarded a score of 6 (Bazgir et al., 2016)
80% of the pressure needed

Abbreviations: AOP, arterial occlusion pressure; BFR, blood flow restriction; BP, blood pressure; CO, cross‐over, NI, no informed; 1‐MR, one maximal repetition. and another a score of 5 (D. Kim et al., 2016) (Table 3). When
evaluated by the Cochrane collaboration tool for randomized cross‐
over trials, all studies showed a high risk of bias (Bazgir et al., 2016;
Crisafulli et al., 2018; Curty et al., 2017; Downs et al., 2014; Kacin &
120 mmHg

Strazar, 2011; Loenneke, Wilson, Balapur et al., 2012; Maior et al.,

2015; Neto et al., 2015; Poton, 2014; Sardeli et al., 2017; Staunton
et al., 2015; Takano et al., 2005; Vieira et al., 2013) and when studies
were analyzed according to all individual domains, 100% presented
length 470 mm);

(width 100 mm;

length 540 mm)
Biceps and triceps
(width 60 mm;

extensors and

problems in at least one item. The results of the RoB2 are presented
knee flexors

in Figure 2.
and knee
NI

3.5 | Meta‐analysis
(pneumatic tourniquet

extremities—Riester)

3.5.1 | Exercise resistance with BFR effects on HR

haemostasis in the
A pneumatic cuff was

komprimeter to
A standard BP cuff
placed on the
upper arms

LLRE + BFR significantly increased HR compared to the passive

Other methods of occlusion pressure (knee wraps). Similar to the KAATSU Master Apparatus.

control condition (mean difference [MD] = 7.25, 95% CI:

2.15−12.35 bpm, I2 = 12%), considering all pooled data (6 studies, 7
comparisons, n = 192 subjects) (Figure 3a); however, LLRE + BFR did
not present significant differences from the active control condition
dominant

(LLRE + HLRE) (MD = −4.75, 95% CI: −12.70 to 3.20 bpm, I2 = 83%)
(10 studies, n = 276 subjects, Figure 4a).
Arm

Leg

Subgroup analysis also showed no difference between LLRE +

BFR and HLRE (MD = −9.39, 95% CI: −21.48 to 2.69 bpm, I2 = 83%)
exercise

exercise
Resistance

Resistance

(5 studies, n = 132 subjects) or between LLRE + BFR and LLRE

protocols individually (MD = 0.63, 95% CI: −5.76 to 7.03 bpm,
previous studies of our laboratory (Vieira et al., 2013).

I2 = 46%) (5 studies, n = 144 subjects) (Figure 5a).

Follow‐up study with a duration of 4 weeks.

3.6 | Exercise resistance with BFR effects on blood

pressure
BFR

BFR

Considering all pooled data (5 studies, 7 comparisons, n = 186

(Continued)

Vieira et al. (2013)† CO

CO

subjects), LLRE + BFR significantly increased SBP (MD = 11.67, 95%

CI: 6.17−17.17 mmHg, I2 = 0%) compared to the passive control
Neto et al. (2015)

condition (Figure 3b). Contrarily, there was no difference when

compared to the active control condition (LLRE + HLRE) (MD = 2.17,
TABLE 1

95% CI: −5.62 to 9.96 mmHg, I2 = 77%) (10 studies, n = 264 subjects)
(Figure 4b). Subgroup analysis also showed no difference between
LLRE + BFR and HLRE (MD = −3.67, 95% CI: −13.95 to 6.61 mmHg,
†

b
a
TABLE 2 Included studies comparing low load resistive exercise (LLRE) + BFR versus active control (high load resistive exercise and LLRE)
PEDON

Description of protocol
Intervention
ET AL.

Studies (year) Design type Exercise Cuff location Cuff device Cuff size (cm) Occlusion pressure Exercise protocol

Takano CO Kaatsu Resistance Both leg Special‐designed 33 mm in width and Banding pressure of 1.3 Immediately after Kaatsu, the
et al. (2005) exercise belt, named 880 mm in length times higher than subjects performed bilateral leg
Kaatsu in Japanese resting systolic blood extension exercise with the
pressure, lower extremity positioned at
160−180 mmHg 90° flexion. The intensity of
STLIRE was 20% of 1 RM, which
was measured at least 1 week
before the experiment. The
subjects performed 30
repetitions without rest, and
after a 20 s rest, they performed
three sets again until exhaustion

Vilaça‐Alves CO BFR Resistance BiBFRceps/ Cuff Upper = width 60 mm; 180 mmHg on the upper (a) RE at 70% of 1RM for lower
et al. (2016) exercise Leg (RiesterRi‐san®) length 470 mm; limbs and 220 mmHg limbs (HILL); (b) RE at 70% of
limb = width 1RM for upper limbs (HIUL); (c)
100 mm; length RE at 20% of 1RM with BFR for
540 mm lower limbs (LI + BFRLL); (d) RE
at 20% of 1RM with BFR for
upper limbs (LI + BFRUL).

Curty CO BFR Resistance Leg A vascular Doppler Width 14 cm; 80% of the necessary HI‐ECC protocol corresponded to
et al. (2017) exercise probe (DV‐600, length 52 cm pressure for complete three sets of 10 repetitions with
Martec) was BFR in a resting 130% of maximal
placed over the condition strength (1RM).
radial artery to
determine the
BFR
pressure
(mmHg)

Downs CO BFR Resistance Leg NI Width 10.5 cm 80%−130% AOP HL (80% of 1RM/no cuff), LL (20%
et al. (2014) exercise 1RM/no cuff), BFRDBP (20%
1RM/1.3! supine resting
diastolic blood pressure [DBP]),
BFRSBP (20% 1RM/1.3! supine
resting SBP).

Poton CO BFR Resistance Inguinal fold Standard 18 × 90 cm 167.9 ± 16.6 mmHg LI and LI‐BFR, and three sets of
et al. (2014) exercise on the sphygmo- eight repetitions at 80% of 1RM
thigh manometer and a 1 min rest interval
between sets for the HI session.
|

(Continues)
7
 8

TABLE 2 (Continued)
|

Description of protocol
Intervention
Studies (year) Design type Exercise Cuff location Cuff device Cuff size (cm) Occlusion pressure Exercise protocol

Included studies comparing BFR versus other modalities

Bazgir CO BFR Resistance Leg Komprimeter BFR was applied with 90−100 mmHg Low intensity (30% maximal
et al. (2016) exercise Riester® pneumatic cuff voluntary contraction [MVC])
(13 cm width) eccentric RE alone (ECC RE n= 6)
and low intensity (30% MVC)
ECC RE combined with BFR
(ECC RE BFR, n = 10).

Maior CO BFR Resistance Proximal NI Width 140 mm, length The mean restrictive (a) Three sets of BCs at 80% of 1RM
et al. (2015) exercise portion of 200 mm pressure throughout and 120 s rest between sets (HIE
both arms the period of training protocol); and (b) three sets of
was BCs at 40% of 1RM with BFR
109.4 ± 7.33 mmHg. and 60 s rest between sets.

J. Kim CO BFR Resistance Leg KAATSU master; Width: 5 cm, KAATSU 160 mmHg and was 75% maximum voluntary
et al. (2017) exercise Sato Sports master; Sato Sports increased by contraction
Plaza) Plaza) 20 mmHg after the
initial 3 weeks so that
the final arbitrary
training pressure was
180 mmHg
(weeks 4−6)

Sardeli CO BFR Resistance Inguinal fold Vascular Doppler 175 mm wide and 60 mmHg High load resistance exercise (HL),
et al. (2017) exercise probe (DV‐600, 920 mm long with four sets until voluntary
Martec) to failure at 80% 1RM; Low load
determine resistance exercise (LL), with
blood pressure four sets until voluntary failure
cuff (AOP, at 30% 1RM; Low load
arterial resistance exercise with BFR
occlusion (LL‐BFR), with 1× 30 + 3 × 15
pressure) repetitions at 30% 1RM and
50% BFR maintained
throughout the exercise session;
control (without BFR)

Abbreviations: AOP, arterial occlusion pressure; SE:BFR, blood flow restriction; BP, blood pressure; CO, cross‐over, NI, no informed, 1‐MR, one maximal repetition.
PEDON
ET AL.
PEDON ET AL. | 9

TABLE 3 Pedro score of the included studies

PEDro item number Methodological

Study (year) 1 2 3 4 5 6 7 8 9 10 11 Score quality

Crisafulli et al. (2018) Y Y N Y N N N N N Y Y 4 Fair

Kacin & Strazar (2011) Y N N Y N N N Y N Y Y 4 Fair

Loenneke, Wilson, Y Y N Y N N N N N Y Y 4 Fair

Balapur et al. (2012)

Neto et al. (2015) Y Y N Y N N N N N Y Y 4 Fair

Sardeli et al. (2017) Y N N Y N N N N N Y Y 3 Poor

Staunton et al. (2015) Y Y N Y N N N N N Y Y 4 Fair

Vieira et al. (2013) Y Y N Y N N N N N Y Y 4 Fair

Vilaça‐Alves et al. (2016) Y Y N Y N N N N N Y Y 4 Fair

Bazgir et al. (2016) Y Y N Y Y N N Y N Y Y 6 Good

Curty et al. (2017) Y Y N Y N N N N N Y Y 4 Fair

Downs et al. (2014) Y Y N Y N N N N N Y Y 4 Fair

D. Kim et al. (2016) Y Y N Y N N N Y N Y Y 5 Fair

Maior et al. (2015) Y Y N Y N N N N N Y Y 4 Fair

Poton et al. (2014) Y Y N Y N N N N N Y Y 4 Fair

Takano et al. (2005) Y N N Y N N N N N Y Y 3 Poor

Note: Y, yes; N, no. Studies were classified as having excellent (9−10), good (6−8), fair (4−5) or poor (<4) quality. Scale of item score: +, present. The PEDro
scale criteria are (1) eligibility criteria; (2) random allocation; (3) concealed allocation; (4) similarity at baseline on key measures; (5) participant blinding; (6)
instructor blinding; (7) assessor blinding; (8) more than 85% retention rate of at least one outcome; (9) intention‐to‐treat analysis; (10) between‐group
statistical comparison for at least one outcome; and (11) point estimates and measures of variability provided for at least one outcome.

I2 = 70%) (5 studies, n = 120 subjects) or between LLRE + BFR and
LLRE protocols individually (MD = 6.66, 95% CI: −1.43
14.75 mmHg, I2 = 53%) (5 studies, n = 144 subjects) (Figure 5b).
Similar to SBP, LLRE‐BFR significantly increased DBP (MD =
2
6.93, 95% CI: 1.24−12.61 mmHg, I = 41%) (5 studies, 7 comparisons,
n = 186 subjects) compared to the passive control condition
(Figure 3c), while there was no difference when compared to the
active control condition (LLRE + HLRE) (MD = 1.41, 95% CI: −6.49 to
9.31 mmHg, I2 = 89%) (11 studies, n = 306 subjects) (Figure 4c). Once
again, subgroup analysis showed no difference between LLRE + BFR
and HLRE (MD = −0.47, 95% CI: −13.43 to 12.50 mmHg, I2 = 93%)
(5 studies, n = 162 subjects) or LLRE + BFR and LLRE protocols
individually (MD = 3.29, 95% CI: −4.98 to 11.56 mmHg, I2 = 73%)
(6 studies, n = 144 subjects) (Figure 5c).
Lastly, LLRE‐BFR significantly increased MBP (MD = 4.80, 95%
CI: −1.29 to 8.30 mmHg, I2 = 4%) (7 studies, 9 comparisons, n = 268
subjects) compared to the passive control condition (Figure 3d),
with no difference to the active control condition (LLRE + HLRE)
(MD = −0.51, 95% CI: −4.28 to 3.26 mmHg, I2 = 13%) (6 studies,
n = 186 subjects) (Figure 4d). Subgroup analysis also showed no
effects between LLRE + BFR and HLRE (MD = −1.16, 95% CI: −11.06
to 8.74 mmHg, I2 = 51%) (3 studies, n = 96 subjects) or between
LLRE + BFR and LLRE protocols individually (MD = ‐0.65, 95% CI:
−4.41 to 3.12 mmHg, I2 = 0%) (3 studies, n = 90 subjects) (Figure 5d).
3.7 | Age‐effects subgroup analysis
to
Data sensitivity was performed through subgroup analysis, as shown
in Figure 5 and Supporting Information: Table S5, separating the
studies according to the age of the subjects.
4 | D IS CU SS IO N
This systematic review and meta‐analysis provides a synthesis of
evidence supporting the use of BFR associated with LLRE training in
young and older healthy individuals. Our data showed that LLRE +
BFR: (1) increases HR, SBP, DBP and MBP compared to the passive
control condition; (2) increases HR, SBP, DBP and MBP similarly to
the CRE protocol, regardless of the resistance exercise training load;
(3) subgroup analysis did not find a difference between the
magnitude of the effect according to the age of the individuals
enroled in the studies.
We detected significant increases in HR and arterial pressure
following exercise with BFR passive control, varying according to the
utilized method. Contrarily, some studies (Fahs et al., 2012; Figueroa
& Vicil, 2011; Neto et al., 2017; Ozaki et al., 2013) did not report
increased hemodynamic responses with BFR exercise compared to
passive control conditions without BFR; however, these studies did
10 | PEDON ET AL.

not control the BFR application duration between the sets of
resistance exercise. In contrast, the studies of Poton and Polito
(Poton, 2014), Takano et al. (2005) and Vieira et al. (2013) controlled
the BFR application and described significant responses.
Neto et al. (2016) suggest that the discrepancies mentioned
above can be explained by the differences found between the
intervention protocols. Kacin & Strazar (2011) used maximum
voluntary contraction (15%) until exhaustion. This method could
have promoted faster muscle fatigue in the BFR protocol.
Therefore, the protocol without BFR may have presented a
greater workload, explaining the increase in hemodynamic
parameters.

FIGURE 2 RoB2 analysis traffic light

PEDON ET AL. | 11

FIGURE 2 Continued
12 | PEDON
Another noteworthy difference not assessed in our review is
related to the chronic effects of the BFR treatment (Poton, 2014;
Takano et al., 2005; Vieira et al., 2013). Neto et al. described
significant reductions after protocols with a duration longer than
6 weeks (Fahs et al., 2012; Neto et al., 2017; Ozaki et al., 2013). On
the other hand, the scientific literature has suggested significant
increases in HR, SBP, DBP and MAP following high‐intensity
protocols compared with low‐intensity protocols with and without
BFR (Poton & Polito, 2015; Poton & Polito, 2016).
Our data demonstrate that despite different resistance exercise
training volumes and vascular occlusion values (see Supporting
Information: Table S5) among the studies using BFR, there were no
significant differences in hemodynamic responses compared to high
intensity or low intensity protocols without BFR. This response
suggests that reducing blood flow may not increase the pressure
ET AL.
F I G U R E 3 Forest plot depicting
LLRE + BFR compared to passive control.
Outcomes: (a) heart rate, (b) systolic blood
pressure, (c) diastolic blood pressure, (d)
mean blood pressure. BFR, blood flow
restriction; CI, confidence interval; LLRE, low
load resistive exercise; SD, standard
deviation.
reflex sensitization, which, in turn, does not increase the autonomic
cardiovascular response, or the effect produced by the resistance
exercise itself.
Loenneke et al. (2013) reported that larger cuff widths (greater
than 13.5 cm) might be more effective in promoting occlusion than
smaller cuffs (Rossow et al., 2012), since smaller cuffs require greater
occlusion pressures to promote arterial occlusion. Our study included
cuff sizes between 6 and 18 cm; 4 studies used cuffs larger than
13.5 cm (Curty et al., 2017; Maior et al., 2015; Poton, 2014; Sardeli
et al., 2017), and 4 smaller than 13.5 cm (Bazgir et al., 2016; Downs
et al., 2014; Takano et al., 2005; Vilaça‐Alves et al., 2016).
Accordingly, the smaller cuffs led to the highest occlusion pressures
observed.
The physiological adjustments observed in the HR, especially
in young volunteers, may be linked to the elevation in the rate
PEDON ET AL. | 13

F I G U R E 4 Forest plot depicting LLRE + BFR

compared to active control (HLRE and LLRE).
Outcomes: (a) heart rate, (b) systolic blood
pressure, (c) diastolic blood pressure, (d) mean
blood pressure. BFR, blood flow restriction; CI,
confidence interval; HLRE, high load
resistive exercise; LLRE, low load resistive
exercise; SD, standard deviation.
14 | PEDON ET AL.

F I G U R E 5 Forest plot depicting LLRE + BFR compared to active control (HLRE and LLRE), with subgroup aged analysis. Outcomes: (a) heart
rate; (b) systolic blood pressure, (c) diastolic blood pressure, (d) mean blood pressure. BFR, blood flow restriction; CI, confidence interval; HLRE,
high load resistive exercise; LLRE, low load resistive exercise; SD, standard deviation.

pressure product (RPP) ([RPP = SBP x HR/100]) after exercise
with BFR (Brandner et al., 2015; Neto et al., 2016; Poton,
2014; Vieira et al., 2013). Hemodynamic adjustments are caused
by the increase in muscle tension imposed by the increase in
pressure in the cuff, which can stimulate mechanoreceptor
tendons (Hayes et al., 2005), increasing the chronotropic
response and blood pressure (Fisher et al., 2005). In another
study by our group (Vieira et al., 2013) we showed that activation
of type III muscle fibres and metaboreceptors through a BFR
protocol seems to reduce the low‐frequency component of HR
variability, which may be associated with inhibition of the
parasympathetic and chemoreflex stimulation, increasing the
cardiovascular responses (Coote & Bothams, 2001; Kaufman &
Hayes, 2002).
4.1 | Study limitations
This systematic review with meta‐analysis was based on all the
criteria established by Cochrane to minimize possible bias. However,
it is essential to report some points: (i) through the included methods
of risk of bias assessment (PEDro and RoB2) and quality of evidence
available through GRADE, we verified that, in general, the included
studies and data available for analysis were of low to moderate
PEDON ET AL.
quality of evidence and with a substantial risk of bias; (ii) the sample
size was relatively small, which may be a limiting factor, especially
regarding data extrapolation; (iii) we found wide variation in the
standardization of the study protocols concerning the intensity, load,
repetitions, training volumes and occlusion pressure (Castinheiras‐
Neto & Farinatti, 2010; Domingos & Polito, 2018; Gjovaag et al.,
2016), as well as cuff sizes (see Supporting Informatioin: Tables S4
and S5); (iv) the recovery intervals between exercises were different,
which is also a variable inversely associated with BP increase during
exercise (Castinheiras‐Neto & Farinatti, 2010). In our data, recovery
intervals were generally shorter between BFR exercise sessions
compared to CRE sessions. Finally, the exclusion of studies that used
aerobic exercise with BFR can be considered a limitation of our study.
However, the inclusion of these studies would result in the addition
of other specific analyses as well as subgroup analyses by type of
exercise, which would make the study very extensive. Thus, we
suggest that future studies should be performed, focusing on the
analysis of the effects of aerobic exercise with BFR on these
variables.
5 | C ONC LUS I ON S
Our data demonstrated that despite causing notable hemodynamic
responses compared to no exercise, the short‐term LL resistance
exercise with BFR modulates all hemodynamic parameters HR,
SBP, DBP and MAP, similarly to a CRE protocol, whether low‐ or
high‐intensity.
A C KN O W L E D G E ME N T S
All honour and glory will be given in the name of the Lord my
God. The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
study was supported by the Universal Project of CNPq (Grant No.
422416/2018‐5).
CO NFL I CT OF INTERES T
The authors declare no conflict of interest.
D A TA A V A I L A B I L I T Y S T A T E M E N T
The data sets generated during this study are available from the
corresponding author upon reasonable request.
ORCID
Gaspar R. Chiappa http://orcid.org/0000-0002-0440-8404
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SUPP ORTING INFO RM ATION
Additional supporting information can be found online in the
Supporting Information section at the end of this article.
How to cite this article: Pedon, W.R., Lima, F.V., Cipriano, G.,
da Silva, W.A., Fernandes, M.V.S., Gomes, N.S., et al. (2022)
Acute hemodynamic responses from low‐load resistance
exercise with blood flow restriction in young and older
individuals: a systematic review and meta‐analysis of cross‐
over trials. Clinical Physiology and Functional Imaging, 1–17.
https://doi.org/10.1111/cpf.12779