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Accepted Manuscript

Low intensity isometric handgrip exercise has no transient effect on blood pressure in
patients with coronary artery disease

Karla Goessler, PhD, Roselien Buys, PhD, Véronique A. Cornelissen, PhD

PII: S1933-1711(16)30275-3
DOI: 10.1016/j.jash.2016.04.006
Reference: JASH 904

To appear in: Journal of the American Society of Hypertension

Received Date: 25 February 2016


Revised Date: 30 March 2016
Accepted Date: 12 April 2016

Please cite this article as: Goessler K, Buys R, Cornelissen VA, Low intensity isometric handgrip
exercise has no transient effect on blood pressure in patients with coronary artery disease, Journal of
the American Society of Hypertension (2016), doi: 10.1016/j.jash.2016.04.006.

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Low intensity isometric handgrip exercise has no transient effect on

blood pressure in patients with coronary artery disease.

Running title: Isometric handgrip exercise in CAD

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Karla Goessler, PhD; Roselien Buys, PhD; Véronique A Cornelissen, PhD

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Research Group for Cardiovascular Rehabilitation, Department of Rehabilitation Sciences, KU

Leuven, Leuven, Belgium.

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Address for Correspondence
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Dr VA Cornelissen

Department of Rehabilitation Sciences


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O&N4 – Herestraat 49

3000 Leuven
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Belgium
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Phone: 003216329152

E-mail: Veronique.cornelissen@faber.kuleuven.be
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Conflicts of interest : none


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ABSTRACT

Hypertension is highly prevalent among patients with coronary artery disease (CAD). Exercise-

based cardiac rehabilitation reduces blood pressure (BP). However, less is known about the

transient effect of a single bout of exercise on BP. Isometric handgrip exercise has been

proposed as a new non-pharmacological tool to lower BP. We aimed to investigate the acute

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effect of isometric handgrip exercise on BP in CAD patients. Twenty one male CAD patients

were included. All patients completed two experimental sessions in random order: one control

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and one low intensity isometric handgrip session. BP was measured by means of a 24h

ambulatory BP monitor pre-intervention, for one hour in the office and subsequently for 24hrs.

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Our results suggest that isometric handgrip exercise performed at low intensity is safe in

patients with coronary artery disease but does not induce a transient reduction in BP.

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Key words: acute, isometric handgrip, resistance exercise, coronary artery disease, postexercise
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INTRODUCTION.

Hypertension is an independent risk factor for cardiovascular disease and mortality(Chobanian,

2007) and is present in approximately 69% of patients with a first myocardial infarction and in

74% of patients with chronic heart failure.(Lloyd-Jones; et al., 2009) Despite improvements in

blood pressure (BP) management, 43.3 million persons with cardiovascular diseases still have

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uncontrolled hypertension.(Bertoia; et al., 2011) Therefore, BP management remains one of the

core components in the treatment of patients with coronary artery diseases (CAD) and includes

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both pharmacological therapy as well as healthy lifestyles education.(Piepoli; et al., 2014)

Moreover, a meta-analysis on BP targets in CAD concluded that in patients with CAD,

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intensive systolic BP control to < 130 mmHg is associated with modest reductions in stroke and

heart failure.(Bangalore; et al., 2013) It is well established that exercise-based cardiac

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rehabilitation is associated with reduced all-cause and cardiac mortality.(Jolliffe; et al., 2001;
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Taylor; et al., 2004) Furthermore, it has been shown to result in greater systolic BP (SBP)

reductions compared to control in the majority of patients,(Jolliffe; et al., 2001; Taylor; et al.,
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2004) although many patients do not receive the benefits to BP from this mainly aerobic-based
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exercise interventions.(Conraads; et al., 2015; Jolliffe; et al., 2001; Rice; et al., 2002) Recent
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studies suggest isometric exercise may elicit greater BP reductions (−10.9 SBP, −6.2 DBP

mmHg), compared with dynamic resistance training (−1.8 SBP, −2.5 DBP mmHg), and aerobic
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training (−3.5 SBP, −3.7 DBP mmHg) in healthy normotensive and hypertensive

individuals.(Carlson; et al., 2014; Cornelissen; Smart, 2013; Inder; et al., 2015; Millar; et al.,
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2014) Based on these results, it was suggested that this exercise modality may become a new
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tool in the non-pharmacological treatment of high BP.(Inder; et al., 2015; Millar; et al., 2014)

Isometric resistance exercise involves sustained contraction against an immovable load or

resistance with no or minimal change in length of the involved muscle group. However, one of

the main concerns with resistance training in cardiac patients has been the potentially

uncontrolled elevation of BP, which could increase the risk of adverse cardiovascular

events.(Vanhees; et al., 2012) Therefore, guidelines have recommended that with regard to the
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BP response in CAD patients, only dynamic resistance training (in contrast to isometric strength

training) should be applied.(Vanhees; et al., 2012)

However, BP increases during exercise primarily depend on controllable factors including the

magnitude of the isometric component, the load intensity, the amount of muscle mass involved

and the load duration.(Vanhees; et al., 2012) Current isometric handgrip protocols are

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performed at low intensity (30% MVC) and use only the small muscle groups of the lower arm.

Hence, it could be anticipated that the pressure effect of this exercise protocol is most likely not

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that harmful as expected. Therefore, if we could prove its safety and efficacy this type of

exercise could become an interesting adjunct in the combat against uncontrolled BP in patients

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with CAD as it’s cheap and can be performed at any time and any place, including bedside.

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In addition, post exercise hypotension (PEH) defined as sustained BP reductions below control
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levels following acute exercise is now considered an important tool in BP management as it

offers hypertensive patients the health-related benefit of having their BP transiently lowered
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during the day.(Pescatello; et al., 2015) However, to the best of our knowledge only Fagard and
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Vanhees(Fagard; Vanhees, 2000) investigated PEH in patients with CAD. They showed no
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difference in ambulatory BP after a cardiac rehabilitation exercise session compared to the non-

exercise day in seven stable CAD patients. To date, it is not known whether a single bout of
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isometric handgrip exercise has an effect on BP in the hours following the exercise session in

patients with CAD.


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Therefore, the main aim of this study was to investigate the acute BP response to isometric

handgrip exercise immediately after the exercise and during the consequent activities of daily

life in patients with CAD.

METHODS

Experimental Approach to the Problem


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This study was performed according to a randomized controlled cross-over trial whereby each

participant completed both an isometric handgrip intervention and a control session. The

randomization order was determined by an online computer program

(http://www.randomization.com).

All measurements were performed between 8 AM – 12 AM in a quiet and temperature

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controlled room by the same unblinded investigator (KG). To control for diurnal variation and

timing of medication intake, measurements were performed on the same time of day for each

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individual patient. An interval of at least 3 days (range: 4-15) was kept between the two

experimental sessions.

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Each session started with a 15 minutes supine rest period (pre-intervention). After this, resting

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BP and HR were assessed twice by means of an automated device (Watch BP O3; Microlife,
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Widnau, Switzerland). The average of these two measurements was used to define pre-

intervention BP. Subsequently during the isometric handgrip session patients performed a
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bilateral isometric handgrip protocol consisting of four sets of two minute sustained
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contractions at 30% of maximal volitional contraction (MVC) and separated by 1 minute rest
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periods using a programmed digital hand dynamometer (Zona Plus, ZonaHealth, Boise, ID,

USA). Before the start of the session, a MVC was performed with each hand so that the
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handgrip device could calculate the 30% MVC threshold. During the session, the participants

received visual and auditory feedback to ensure compliance with the IHG protocol. During the
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control session, participants sat in a comfortable chair for 15 minutes, which equaled the
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duration of one isometric exercise session. After both interventions, the participants were

repositioned in the supine position for one hour (post-intervention). An ambulatory BP monitor

(ABP) device (Microlife® Watch® 03), measured BP and HR immediately post-intervention

and every 15 minutes during this one hour post exercise or control rest period.

After one hour, patients left the laboratory wearing the ABP on the left arm until waking the

next morning. The ABP was programmed to measure BP every 20 minutes. Participants were
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instructed to stop any muscular activity and keep their arms still during BP measurements and

were asked to perform their normal daily routine. They were further asked to perform one

isometric handgrip exercise session one hour before going to bed to investigate the potential of

isometric handgrip exercise to affect nighttime BP. To see if there were differences in physical

activity patterns between both test days participants also wore a SenseWear® Mini armband

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(Body Media Inc.,Pittsburgh, PA, USA) on the upper posterior aspect of the right arm

throughout all day. The SenseWear armband is a wireless, noninvasive monitor that includes

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five sensors: a triaxial accelerometer, two galvanic sensors, a skin temperature sensor and a heat

flux sensor to allow a valid assessment of physical activity.(Scheers; Philippaerts; Lefevre,

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2012) Data from the ABP were downloaded to laboratory computers using the Microlife

software (Watch BP O3; Microlife, Widnau, Switzerland). Participants should have at least one

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reading per hour to be included in the final analysis. The 24-h ABP monitoring data were
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analyzed as average 24-h, daytime and nighttime periods.(Castro; et al., 2015) Daytime and

night-time BP and HR were defined according to the actual out-of-bed and in-bed periods.
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Subjects
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Thirty male CAD patients were recruited from a community based phase III cardiac

rehabilitation program (HARPA vzw, Leuven, Belgium) to participate in a randomized


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controlled cross-over study. Eligibility criteria were 1) patients with only a history of CAD

(previous acute myocardial infarction, percutaneous coronary intervention or coronary artery


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bypass grafting); 2) non-smokers; 3) aged 40 years or older; 4) stable with regard to symptoms
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5) on stable pharmacological therapy for at least 6 months and 6) having a resting BP 120

mmHg ≤ SBP of < 160 mmHg or 80 ≤ DBP < 100 mmHg or both. During the first visit the

participants received information about the risks and potential benefits of the study and were

asked to fill in a standardized health questionnaire. Subsequently, they signed a written

informed consent prior to randomization. Twenty one (median age 70; range 55-80 yrs) out of

30 volunteers fulfilled the inclusion criteria and were randomized into the study. All

participants completed both experimental protocols. However, as the number of successful BP


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readings (<70%) was too low for at least one of the sessions in 7 participants (4 patients took off

the device for more than two hours, 3 patients had insufficient readings), ambulatory BP data

during daily life could only be reported for 14 patients. Patients’ characteristics and medication

are summarized in table 1. All patients were physically active and were attending community

based cardiac rehabilitation classes at least once a week. Measurements were planned in

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function of the weekly routine of the patients in order to avoid patients exercising on the

day prior to the measurements. To this end, patients were also tested on the same day and

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at the same time and were asked not to do any strenuous physical activities on the day

prior to the test days. Patients were asked not to exercise the day prior to the measurements.

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All patients were treated with at least one anti-hypertensive drug.

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The study was approved by the Ethical Committee of the KU Leuven and complied with the
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World Medical Association Declaration of Helsinki on ethics in medical research. Thirty male

CAD patients initially volunteered for this study with


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Statistical analysis
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Data analysis was performed using Statistical Package for the Social Science (SPSS,

17.0, Chicago, USA). The data are reported as mean and standard deviation (SD). The Shapiro-
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Wilk test was utilized to check the normality. Dependent Student’s T-tests were performed to

compare control versus handgrip session pre-intervention values of BP and HR, daytime and
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night-time BP and HR. As data on physical activity were not normally distributed, Wilcoxon
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Signed Rank tests were used to compare physical activity data across the different modes. For

the office BP analysis, repeated measures analysis of variance (RMANOVA) were performed

with time (pre-exercise, post 1 minute, post 30 min, post 60 min) and intervention (isometric vs

control) as repeated factors. Post hoc comparisons were made using Bonferonni corrections and

least significant difference (LSD) tests. Statistical significance was established as P<0.05 (two-

tailed).
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RESULTS

As shown in table 2, pre-intervention resting BP and HR showed no statistical significant

differences between both experimental sessions (p>0.05 for all) for the 21 patients. Pre-

intervention systolic and diastolic BP averaged 135±11/78±7 mmHg on the control day and

134±8/76±6 mmHg on the isometric day. Following the interventions, a significant time-effect

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(p<0.01 for all) was observed for systolic BP, diastolic BP and HR, but the responses were

similar after the no-exercise control and the isometric handgrip session (p-interaction >0.05 for

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all). All patients were able to maintain the target force throughout each of the four sets.

No adverse events were reported.

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Figure 1 shows the ABP and HR after the control and isometric handgrip session. Overall, we

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noted 83 and 84% of valid BP measurements in these patients after isometric and control
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exercise respectively. There was no difference in the time ABP measurements began as the

starting time after each experiment was similar within each single patient. Physical activity
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behavior on both test occasions was comparable as can be depicted from the fact that the median
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number of steps [control: 6630 (1289-14850) vs IHG 6666 (1302-16655)] and the energy
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expended [2012(623-3566 kcal) vs 2272 (534-3689)] was not different on both days (p>0.05 for

both). As can be seen in Figure 1, no significant differences in daytime, nighttime and 24h BP
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and HR could be established between both sessions (P>0.05 for all).


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DISCUSSION
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To the best of our knowledge, this is the first study examining the transient effect of isometric

handgrip exercise on office BP and BP measured during daily life activities in patients with

CAD. The primary finding of the present study was that isometric handgrip exercise performed

at low intensity is safe for stable CAD patients and is not associated with a significant change in

BP following the subsequent hours. However, two single sessions of isometric handgrip

exercise spread throughout the day seem insufficient to significantly lower BP during daily life

in physically fit and stable CAD patients.


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To date, a significant proportion of patients with CAD still do not manage to have their BP

controlled despite the use of different pharmacological drugs.(Catala-Lopez; et al., 2013;

Cohen; Townsend, 2013; Xu; et al., 2013) Sixty seven % of our patients had a SBP ≥ 130

mmHg. Therefore, a continued search for easy applicable and feasible new treatments that could

help in the combat against high and uncontrolled BP remains important. Isometric handgrip

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exercise training could be one of these new adjunct therapies, at least, if proven to be safe and to

be effective. In our study no adverse reactions were observed during and in the hours following

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the execution of the isometric handgrip session. Moreover, one minute after completing the

exercise session, BP and HR were not significantly higher compared to supine pre-intervention

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rest. These results were obtained in physically active middle-aged to older men with stable

CAD without any symptoms of angina or heart failure. Our results however concur with those

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of Araujo et al(Araujo; et al., 2011) who also could not find any clinical adverse reactions to a
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similar isometric handgrip protocol in a mixed population of 41 (36 men) older physically

active normotensive individuals (mean age 64.3 yrs; mean BP 115/69 mmHg), including 28
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cardiac patients. Moreover, they reported that SBP, DBP and HR values, obtained after one
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minute of recovery were approximated pre-intervention values. Similar results were published
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by Mc Gowan et al (McGowan; et al., 2006) and Olher(Olher Rdos; et al., 2013) et al who

showed no effect on BP 4 to 5 minutes after an isometric handgrip protocol in respectively 17


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and 12 medicated, but otherwise healthy, hypertensive patients.

A transient and sustained reduction in BP could not be established by an isometric handgrip


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session in this population during activities of daily living, not even during the first hour in the
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office after application of the device. Our results are in agreement with Olher et al(Olher Rdos;

et al., 2013) in that a single session of unilateral isometric handgrip exercise, performed at 30 or

50% MVC, induced no significant changes in BP after one hour of recovery in medicated

hypertensive women. In contrast, Millar et al(Millar; MacDonald; McCartney, 2011) who

investigated the acute effect of four different bilateral 12 minute IHG protocols (sham, 4*2 min,

8x1 min and 16*30 s isometric contractions) on BP and neurocardiac reactivity did observe

PEH for SBP, but not DBP, during the first hour of recovery from all three
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interventions.(Millar; et al., 2009) The divergent results for SBP might be explained by the fact

that we and Olher(Olher Rdos; et al., 2013) included participants who were all treated with

antihypertensive drugs whereas Millar(Millar; MacDonald; McCartney, 2011) included a

healthy older but normotensive individuals. Although it is known that responses to exercise are

very heterogeneous and more research is definitively warranted to explain these divergent

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results, previous chronic intervention studies involving isometric handgrip training reported also

lower response rates in individuals receiving pharmacotherapy.(McGowan; et al., 2006; Stiller-

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Moldovan; Kenno; McGowan, 2012) Although others have observed significant BP reductions

after as little as 10 minutes of aerobic exercise at 40% of VO2max(MacDonald, 2002),

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suggesting that PEH is a low threshold phenomenon this was only in non-treated patients.

Moreover, these studies applied aerobic endurance exercises or dynamic resistance exercises

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involving the use of large muscle groups. Therefore, it might be that a 12 minute session of low
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intensity handgrip exercise which involves only the use of the small muscle groups of the lower

arm is insufficient to cause PEH in a medicated population. Further research should determine
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whether larger volumes (i.e. more sets) or the use of larger muscle groups (e.g. legs) can evoke
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PEH in this population.


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Finally, it should be noted that all previous studies to date examined the effect of isometric

handgrip exercise in BP under laboratory conditions for a short time period and data on the
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effect of isometric exercise on BP in normal living conditions is lacking. Our results on ABP

monitoring show no effect of two sessions of isometric handgrip exercise. Fagard and
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Vanhees(Fagard; Vanhees, 2000) focused on the effect of exercise on ABP in cardiac patients.
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Their results were similar to our findings, in that, one session of mainly aerobic endurance

based cardiac rehabilitation of 75 minutes did not affect daytime or nighttime BP.

A few limitations need to be mentioned. First, patients were not blinded to the treatment

they were receiving. However, as patients received both treatments and we focused on the

acute effect we do not anticipate this will have introduced major bias in our results.

Further, we did not measure BP continuously during the execution of the exercise

protocol. However, previous studies have reported that BP increases repetition by


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repetition when lifting loads of 75-90% of RM reaching peak values at the last

repetition.(MacDougall; et al., 1992) On the other hand, recently Gjovaag et al.(Gjovaag;

et al., 2016) showed similar peak BP after each set of 4 RM. Hence, although the BP

measurement immediate after the last BP contraction might have slightly underestimated

the peak BP during exercise we do not expect that BP was dangerously higher than what

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we observed 1 minute post exercise. Future studies should however attempt to measure

BP during isometric handgrip exercise protocols to confirm our results. Finally, a sample

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size calculation indicated that we would need 34 to have a power of 0.8 and effect size 0.5

based on previous data.(Cornelissen; Smart, 2013) Therefore, the study sample might

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have been too small to detect any changes and results need to be interpreted with some

caution.

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In summary, low intensity isometric handgrip exercise is safe to perform in stable medicated
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patients with CAD. However, two sessions performed on one single day seem insufficient to

evoke PEH. Future research should determine whether maybe on the longer term, isometric
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handgrip exercise training can be used as an adjunct tool to control BP in medicated patients
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with CAD. Moreover, on the short-term, it might be interesting to explore whether the use of
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larger volumes or larger muscle groups in isometric exercises performed at low intensity can

induce PEH in medicated populations.


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PRACTICAL APPLICATIONS
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Data gathered in this study show that isometric handgrip exercise, when performed at low
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intensity, is safe for stable patients with coronary artery disease. Although the results of this

study show that two sessions of isometric handgrip exercise, spread throughout the day do not

have an immediate blood pressure lowering effect in this population, given its safety,

randomized controlled trials should now be set-up to investigate the potential chronic effect of

isometric handgrip exercise on BP in growing group of patients.

ACKNOWLEDGEMENTS
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VAC is supported as a postdoctoral research fellow by Research Foundation Flanders (FWO).

KG is supported as a postdoctoral research fellow by a grant from CNPq (Brazil). RB and VAC

are both supported by a research grant from Research Foundation Flanders (FWO). Further the

authors also thank Zona Health for providing the ZonaPlus isometric handgrip devices

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Legend to Figures

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Figure 1: Box plot for 24-hour, daytime, and nighttime systolic blood pressure (top) and

diastolic blood pressure (middle), and heart rate (bottom) after isometric handgrip exercise and

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Control in 14 patients with coronary artery disease.
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Table 1. Participant characteristics of the 21 patients with complete office BP measurements and the

14 patients with complete ABPM measurements

Characteristic Patients (n=21) Patients

(n=14)

Age (years) 68.4±7.0 67.7

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Height (cm) 172±5.9 172.6

Weight (kg) 78.4±9.8 79.2

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BMI (kg/m²) 26.5±3.0 26.5±2.9

Office Systolic BP (mmHg) 136.1±11.1 136.7±13.0

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Office Diastolic BP (mmHg) 78.3±6.8 78.6±7.8

Resting HR (bpm) 55.4±9.9 53.4±9.2

Medication (number)
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ACE-inhibitors 10 (48%) 7 (50%)

Beta-blockers 14 (67%) 10 (71%)


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Calcium channel blockers 4 (19%) 2 (14%)


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Diuretics 1 (4.8%) 1 (7%)


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Antiplatelets 15 (71%) 11 (78%)

Data are reported as mean ± SD or number (%). Abbreviations. BMI, body mass index BP, blood
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pressure; HR, heart rate; ACE, ace converting enzyme.


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Table 2. Office blood pressure and heart rate at rest and during one hour following both sessions in 21 coronary artery disease patients

Pre-intervention Post 1 min Post 30 min Post 60 min P-time P-group P-interaction

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Heart rate (bpm)

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Control 53.5±8.5 55.4±11.4 49.1±7.8 49.9±7.4 F=12.55 F=2.176 F=1.154

Isometric HG 55.0±9.4 55.1±9.6 51.7±8.9 51.2±8.7 <0.001 0.15 0.335

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Systolic BP (mmHg)

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Control 135.4±11.2 134.5±14.6 129.5±10.8* 131.4±10.7 F=0.607 F=0.014 F=0.911

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Isometric HG 133.6±8.4 136.9±14.8 129.7±7.8* 131.5±8.8 <0.01 0.91 0.41

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Diastolic BP (mmHg)

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Control 77.7±7.2 78.1±7.9 74.8±7.0 75.5±7.0 F=4,10 F=0.507 F=1.23

Isometric HG 76.2±6.4 79.5±9.3


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75.1±6.9 77.5±7.1 0.01 0.49 0.30
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Mean BP(mmHg)
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Control 96.9±7.9 96.9±9.4 93.1±7.7 94.1±7.5 F=6.099 F=0.326 F=0.852


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Isometric HG 95.4±6.3 98.6±10.1 93.3±6.5 95.5±7.0 0.001 0.56 0.46

Data are reported as mean ± SD. Post 30 minutes = average of BP 15 minutes and BP 30 minutes; Post 60 minutes = average of BP 45 minutes and BP 60

minutes. * significantly different from pre-intervention value. Abbreviations: BP, blood pressure; HG, handgrip exercise
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• A new non-pharmacological tool (handgrip exercise) is proposed to lower blood pressure
• A single session of isometric handgrip exercise do not induce BP reduction
• Isometric handgrip exercise at low intensity is safe in patients with CAD

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