Research

JAMA Cardiology | Brief Report

Effect of Exercise Training on Ambulatory Blood Pressure

Among Patients With Resistant Hypertension
A Randomized Clinical Trial
Susana Lopes, MSc; José Mesquita-Bastos, MD, PhD; Catarina Garcia, MSc; Susana Bertoquini, PhD;
Verónica Ribau, MSc; Manuel Teixeira, MSc; Ilda P. Ribeiro, PhD; Joana B. Melo, PhD; José Oliveira, PhD;
Daniela Figueiredo, PhD; Guilherme V. Guimarães, PhD; Linda S. Pescatello, PhD; Jorge Polonia, MD, PhD;
Alberto J. Alves, PhD; Fernando Ribeiro, PhD

Supplemental content
IMPORTANCE Limited evidence suggests exercise reduces blood pressure (BP) in individuals
with resistant hypertension, a clinical population with low responsiveness to drug therapy.

OBJECTIVE To determine whether an aerobic exercise training intervention reduces

ambulatory BP among patients with resistant hypertension.

DESIGN, SETTINGS, AND PARTICIPANTS The Exercise Training in the Treatment of Resistant
Hypertension (EnRicH) trial is a prospective, 2-center, single-blinded randomized clinical trial
performed at 2 hospital centers in Portugal from March 2017 to December 2019. A total of 60
patients with a diagnosis of resistant hypertension aged 40 to 75 years were prospectively
enrolled and observed at the hospitals’ hypertension outpatient clinic.

INTERVENTIONS Patients were randomly assigned in a 1:1 ratio to a 12-week moderate-

intensity aerobic exercise training program (exercise group) or a usual care control group. The
exercise group performed three 40-minute supervised sessions per week in addition to usual
care.

MAIN OUTCOMES AND MEASURES The powered primary efficacy measure was 24-hour
ambulatory systolic BP change from baseline. Secondary outcomes included daytime and
nighttime ambulatory BP, office BP, and cardiorespiratory fitness.

RESULTS A total of 53 patients completed the study, including 26 in the exercise group and 27
in the control group. Of these, 24 (45%) were women, and the mean (SD) age was 60.1 (8.7)
years. Compared with the control group, among those in the exercise group, 24-hour
ambulatory systolic BP was reduced by 7.1 mm Hg (95% CI, −12.8 to −1.4; P = .02).
Additionally, 24-hour ambulatory diastolic BP (−5.1 mm Hg; 95% CI, −7.9 to −2.3; P = .001),
daytime systolic BP (−8.4 mm Hg; 95% CI, −14.3 to −2.5; P = .006), and daytime diastolic BP
(−5.7 mm Hg; 95% CI, −9.0 to −2.4; P = .001) were reduced in the exercise group compared
with the control group. Office systolic BP (−10.0 mm Hg; 95% CI, −17.6 to −2.5; P = .01) and
cardiorespiratory fitness (5.05 mL/kg per minute of oxygen consumption; 95% CI, 3.5 to 6.6;
P < .001) also improved in the exercise group compared with the control group.

CONCLUSIONS AND RELEVANCE A 12-week aerobic exercise program reduced 24-hour and
daytime ambulatory BP as well as office systolic BP in patients with resistant hypertension.
These findings provide clinicians with evidence to embrace moderate-intensity aerobic
exercise as a standard coadjutant therapy targeting this patient population.

TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03090529

Author Affiliations: Author

affiliations are listed at the end of this
article.
Corresponding Author: Fernando
Ribeiro, PhD, Institute of Biomedicine
(iBiMED), School of Health Sciences,
University of Aveiro, Bldg 30, Agras
do Crasto, Campus Universitário de
JAMA Cardiol. 2021;6(11):1317-1323. doi:10.1001/jamacardio.2021.2735 Santiago, 3810-193 Aveiro, Portugal
Published online August 4, 2021. (fernando.ribeiro@ua.pt).

(Reprinted) 1317
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 Research Brief Report Effect of Exercise Training on Ambulatory Blood Pressure Among Patients With Resistant Hypertension

R
esistant hypertension persists as a clinical challenge,
as it is a puzzling problem without a clear solution.1 Key Points
The available treatment options to lower blood pres-
Question Is aerobic exercise training an effective
sure (BP) in these patients, namely antihypertensive medica- antihypertensive treatment in patients with resistant
tions and kidney denervation, have had limited success,2-4 hypertension?
while permanent implant-based therapies await appropriate
Findings In this randomized clinical trial including 53 patients, a
assessment.5 Despite the renewed clinical interest in kidney
12-week exercise training intervention promoted a clinically
denervation,6-8 the invasive nature and health care costs meaningful reduction in 24-hour and daytime ambulatory systolic
of this procedure along with the increasing prevalence of and diastolic blood pressure.
hypertension clearly demonstrate the need for other effec-
Meaning The findings show that aerobic exercise added to
tive treatment options, namely lifestyle strategies for the man-
optimized medical therapy reduces blood pressure in patients with
agement of treatment-resistant hypertension. low responsiveness to drug treatment and has the potential to be
Although exercise is recommended globally as a first-line incorporated in the standard care of these patients.
approach for the treatment of hypertension,9,10 specific rec-
ommendations for those with treatment-resistant hyperten-
sion are lacking. Two trials11,12 provide preliminary evidence Figure 1. Flow Diagram Depicting the Study Design
of the beneficial BP effects of exercise in individuals with treat-
ment-resistant hypertension. However, uncertainty persists 365 Assessed for eligibility
regarding the efficacy of exercise training for those with
resistant hypertension because of limitations of these 305 Excluded
271 Not meeting inclusion criteria
studies; they did not disclose the timing of the ambulatory BP
73 Secondary hypertension
assessments and important information regarding the 33 Evidence of target organ
damage
exercise training program, so the exercise dose cannot be
27 Heart failure
replicated.11 Furthermore, the exercise programs were very 19 Acute cardiovascular
event (≤1 y)
distinct in terms of exercise modality (treadmill exercise11
7 Peripheral artery disease
vs heated water–based exercise12) and intensity-monitoring strat- 27 Kidney failure
egies (target lactate concentrations11 vs perceived exertion12). The 16 Chronic obstructive
pulmonary disease
need for specialized personnel and infrastructures to conduct 37 Limitations to physical
activity
laboratory exercise assessments and deliver heated water–
3 Regular exercise training
based exercise is challenging and further complicates replica- 29 Change of antihypertensive
medication ≤3 mo
tion in a clinical setting. The Exercise Training in the Treatment
22 Declined to participate
of Resistant Hypertension (EnRicH) randomized clinical trial 12 Other reasons
was designed to overcome these methodological shortcom-
ings by testing with a rigorous design if exercise training com- 60 Randomized
pared with usual care indeed reduces ambulatory BP among
patients with resistant hypertension.
30 Allocated to 12 wk of aerobic 30 Allocated to 12 wk of
exercise training usual care

4 Lost to follow-up 3 Lost to follow-up

Methods 2 Family issues (severe health 1 Started a new medication
problems in close relatives) (not associated with
Study Design and Settings 2 Lack time to attend exercise hypertension) and asked to
The EnRicH trial is a prospective, 2-center, single-blinded ran- sessions be removed from the study
2 Refused to participate in
domized clinical trial with a parallel 2-arm group performed in follow-up assessment
Portugal from March 2017 to December 2019. Patients were ran-
domly assigned to a 12-week aerobic exercise training program 26 Analyzed 27 Analyzed
plus usual care (exercise group) or to usual care (control group).
The primary and secondary outcomes were assessed at base-
line and after the 12-week intervention, which was conducted tals’ hypertension outpatient clinics.1 On initial screening,
48 hours after the last exercise session. All patients provided writ- automated 24-hour ambulatory BP monitoring was per-
ten informed consent. The study was approved by the Ethics formed, adherence to medications was documented by the
Committee of the Centro Hospitalar do Baixo Vouga and regis- 8-item Morisky Medication Adherence Scale, and the diag-
tered on ClinicalTrials.gov. The trial protocol can be found in nosis of resistant hypertension was confirmed. Patients
Supplement 1. This study followed the Consolidated Standards were required to have a mean systolic BP of 130 mm Hg or
of Reporting Trials (CONSORT) reporting guideline. greater on 24-hour ambulatory BP monitoring and/or 135
mm Hg or greater during daytime hours while taking maxi-
Participants mally tolerated doses of at least 3 antihypertensive agents,
We prospectively enrolled patients with a diagnosis of resis- including a diuretic, or to have a controlled BP while taking
tant hypertension aged 40 to 75 years observed at the hospi- 4 or more antihypertensive agents.1 Exclusion criteria are

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 Effect of Exercise Training on Ambulatory Blood Pressure Among Patients With Resistant Hypertension Brief Report Research

Table. Baseline Demographic and Clinical Characteristics

Mean (SD)
Characteristic Exercise group (n = 26) Control group (n = 27) P value
Age, y 59.3 (8.2) 60.8 (9.2) .53
Male, No. (%) 14 (54) 15 (56) .90
Weight, kg 81.5 (14.7) 83.0 (15.6) .70
Body mass indexa 29.8 (4.9) 30.4 (5.0) .64
Fat mass, % 34.3 (8.0) 35.0 (9.6) .80
Medical history, No. (%)
Currently smoking 5 (19) 3 (11) .41
Diabetes 3 (12) 6 (22) .30
Hyperlipidemia 20 (77) 21 (78) .94
Family history of hypertension 17 (65) 15 (56) .47
Obesity 11 (42) 14 (52) .49
Overweight 12 (46) 10 (37) .50
Stroke 3 (12) 1 (4) .28
Transient ischemic attack 1 (4) 2 (7) .58
Myocardial infarction 3 (12) 4 (15) .73
Medication, No. (%)
Antihypertensive drugs, mean (SD), No. 4.6 (0.9) 4.7 (0.6) .66
Controlled BP on ≥4 drugs 14 (54) 14 (52) .88
Diuretics 26 (100) 27 (100) NA
ACE inhibitors/angiotensin receptor antagonists 26 (100) 26 (96) .32
Calcium channel blockers 26 (100) 26 (96) .32
β-Blockers 16 (62) 16 (59) .87
Centrally acting sympatholytic agent 8 (31) 13 (48) .20
Direct-acting vasodilators 26 (100) 27 (100) NA
Aldosterone antagonist 10 (39) 11 (41) .87
Antiplatelet drug 4 (15) 7 (26) .34
Hypoglycemic drug 3 (12) 6 (22) .30
Lipid-lowering drugs 20 (77) 21 (78) .94
Lipid, metabolic, and urinary parameters
Fasting glucose, mg/dL 114.0 (41.7) 105.5 (17.5) .34
Total cholesterol, mg/dL 174.8 (36.5) 183.7 (52.2) .49
HDL cholesterol, mg/dL 48.9 (12.9) 49.8 (15.3) .84
LDL cholesterol, mg/dL 102.4 (30.1) 108.9 (39.9) .53
Triglycerides, mg/dL 117.4 (49.4) 126.2 (79.9) .64
Hemoglobin A1c, % 5.8 (1.1) 5.8 (0.5) .88
Urinary sodium excretion, mmol/24 h 168.2 (69.5) 166.2 (48.7) .91
Urinary potassium excretion, mmol/24 h 80.4 (25.8) 71.8 (24.6) .24
Microalbuminuria, median (IQR), mg/24 h 14.6 (6.9-19.2) 14.5 (10.5-115.2) .53
BP, mm Hg
24-h
Systolic BP 127.4 (12.2) 126.1 (17.2) .75
Diastolic BP 75.6 (7.8) 73.3 (10.2) .37
Mean BP 92.9 (8.0) 90.8 (11.6) .46
Daytime
Systolic BP 133.0 (12.3) 131.9 (18.0) .81
Diastolic BP 79.4 (8.1) 77.3 (10.5) .42
Mean BP 97.2 (8.0) 95.4 (12.0) .52
Nighttime
Systolic BP 115.0 (15.0) 115.4 (16.5) .93
Diastolic BP 67.3 (9.4) 66.2 (9.6) .69

(continued)

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 Research Brief Report Effect of Exercise Training on Ambulatory Blood Pressure Among Patients With Resistant Hypertension
Table. Baseline Demographic and Clinical Characteristics (continued)
Characteristic
Mean BP
Office
Systolic BP
Diastolic BP
Mean BP
Cardiorespiratory fitness, mL/kg per min of oxygen consumption
Abbreviations: ACE, angiotensin-converting enzyme; BP, blood pressure;
HDL, high-density lipoprotein; IQR, interquartile range; LDL, low-density
lipoprotein; NA, not applicable.
SI conversion factors: To convert glucose to millimoles per liter, multiply by
provided in the eMethods in Supplement 2. Medication
adherence and the antihypertensive medication regimen
remained unchanged throughout the study.
Randomization and Allocation
Computer-based stratified randomization was generated (1:
1), with the strata defined by age (age 40 to 55 years, 56 to 65
years, and 66 to 75 years) and sex. Allocation was concealed
in opaque envelopes until the beginning of the exercise or
control intervention.
Outcomes
The primary efficacy end point was change in 24-hour
ambulatory systolic BP from baseline to 3 months. Second-
ary outcomes included mean changes in all other BP vari-
ables, heart rate, body composition, cardiorespiratory fitness
(maximum oxygen uptake; VO2 max), and adverse events
(eg, hypertensive crisis, being hospitalized, or death by any
cause), including adverse effects during or after the exercise
sessions (eg, severe hypotension). A detailed description of
the assessment procedures is provided in the eMethods in
Supplement 2.
Study Treatment
Patients in the exercise group underwent a 12-week aerobic
exercise training program composed of 3 supervised training
sessions per week. Each session included a 10-minute warm-
up, 40 minutes of aerobic exercise consisting of cycling and/or
walking at 50% to 70% of VO2 max (11 to 14 on the Borg scale),
and a 10-minute cooldown. Patients started with 20 minutes
of exercise at 50% of VO2 max, and progression occurred
weekly, alternating between a 5-minute increase in session
duration and a 5% of VO2 max increase in intensity, until
achieving 40 minutes at 70% of VO2 max, if tolerated. The
control group received usual care, including advice on appro-
priate lifestyle behavior and optimal or best-tolerated drug
treatment provided by their physicians.
Statistical Analysis
The EnRicH trial was powered for the primary outcome mea-
sure of 24-hour ambulatory systolic BP. Exploratory data analy-
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Mean (SD)
Exercise group (n = 26) Control group (n = 27) P value
83.1 (10.3) 82.7 (11.1) .89
140.7 (16.6) 141.1 (15.3) .94
84.3 (8.8) 84.4 (10.0) .96
103.0 (10.1) 103.2 (10.9) .95
34.8 (5.6) 32.4 (6.8) .20
0.0555; cholesterol to millimoles per liter, multiply by 0.0259; and triglycerides
to millimoles per liter, multiply by 0.0113.
a
Calculated as weight in kilograms divided by height in meters squared.
sis and Shapiro-Wilk tests were performed to determine the
normality of the data distribution. Continuous variables are ex-
pressed as means with SDs or medians with interquartile
ranges; mean differences are expressed with their 2-sided 95%
CIs. Between-group differences at baseline and in the change
from baseline to the end of the study were tested with un-
paired t tests. Analysis of covariance was also used to adjust
for baseline BP measurements. Paired t tests were performed
for within-group comparisons from baseline to the end of the
study. For categorical variables, counts and percentages are
presented. Between-group comparisons at baseline in cat-
egorical variables were tested with the χ2 test. The level of sig-
nificance was set as a 2-sided P value less than .05. All analy-
ses were conducted with SPSS version 24.0 (SPSS Inc). The
eMethods in Supplement 2 includes further statistical analy-
sis details, including the sample size calculation.
Results
Participants
From the 94 patients who met the enrollment criteria, 60
patients agreed to participate. Seven terminated the study pre-
maturely; thus, 53 patients completed the follow-up assess-
ments and were included in the analysis (Figure 1). Of these,
24 (45%) were women, and the mean (SD) age was 60.1 (8.7)
years. Patients’ characteristics are shown in the Table.
BP Effects of Exercise Training
The change in 24-hour ambulatory systolic BP was signifi-
cantly different between groups by −7.1 mm Hg (95% CI, −12.8
to −1.4; P = .02), with a mean (SD) change of −6.2 (12.2) mm Hg
in the exercise arm vs 0.9 (8.1) mm Hg in the control arm
(Figure 2; eTable 1 in Supplement 2). Similarly, 24-hour ambu-
latory diastolic BP was significantly reduced in the exercise arm
compared with the control arm (−5.1 mm Hg; 95% CI, −7.9 to
−2.3; P = .001) (Figure 2; eTable 1 in Supplement 2).
Daytime ambulatory systolic BP (−8.4 mm Hg; 95% CI,
−14.3 to −2.5; P = .006) and diastolic BP (−5.7 mm Hg; 95% CI,
−9.0 to −2.4; P = .001) as well as office systolic BP (−10.0 mm
Hg; 95% CI, −17.6 to −2.5; P = .01) were also significantly re-
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 Effect of Exercise Training on Ambulatory Blood Pressure Among Patients With Resistant Hypertension Brief Report Research

Figure 2. Changes in Ambulatory and Office Blood Pressure (BP)

Baseline 12-wk

A 24-h Change in ambulatory systolic BP B 24-h Change in ambulatory diastolic BP

Difference, –7.1 mm Hg; 95% CI, –12.8 to –1.4; P = .02 Difference, –5.1 mm Hg; 95% CI, –7.9 to –2.3; P = .001

Change from baseline, Change from baseline, Change from baseline, Change from baseline,
180 –6.2 ± 12.2 mm Hg 0.9 ± 8.1 mm Hg 120 –4.4 ± 6.1 mm Hg 0.7 ± 3.9 mm Hg

24-h Ambulatory diastolic BP, mm Hg

P =.02 P =.57
24-h Ambulatory systolic BP, mm Hg

P =.001 P =.39
160
100
140
120 80
100
60
80
60 40
40
20
20
0 0
Exercise group Control group Exercise group Control group

C Change in daytime ambulatory systolic BP D Change in daytime ambulatory diastolic BP

Difference, –8.4 mm Hg; 95% CI, –14.3 to –2.5; P = .006 Difference, –5.7 mm Hg; 95% CI, –9.0 to –2.4; P = .001

Change from baseline, Change from baseline, Change from baseline, Change from baseline,
180 –7.3 ± 12.7 mm Hg 1.1 ± 8.2 mm Hg 120 –5.0 ± 6.9 mm Hg 0.7 ± 4.8 mm Hg
Daytime ambulatory diastolic BP, mm Hg
Daytime ambulatory systolic BP, mm Hg

P =.007 P =.51 P =.001 P =.44

160
100
140
120 80
100
60
80
60 40
40
20
20
0 0
Exercise group Control group Exercise group Control group

E Change in office systolic BP F Change in office diastolic BP

Difference, –10.0 mm Hg; 95% CI, –17.6 to –2.5; P = .01 Difference, –4.5 mm Hg; 95% CI, –10.1 to –1.2; P = .12
Change from baseline to the end of
Change from baseline, Change from baseline, Change from baseline, Change from baseline, treatment in 24-hour and daytime
–10.9 ± 15.2 mm Hg –0.9 ± 12.0 mm Hg –5.9 ± 11.1 mm Hg –1.4 ± 9.3 mm Hg ambulatory BP as well as office
180 P =.001 P =.70 120 P =.01 P =.45
systolic and diastolic BP in the
160 exercise and control groups.
100
Office diastolic BP, mm Hg

140 Significant changes from baseline to

Office systolic BP, mm Hg

the end of the intervention in

120 80
24-hour, daytime, and office systolic
100 and diastolic BP were observed in the
60
80 exercise group compared with the
60 40
control group. There was a significant
between-group difference in favor of
40 the exercise group for 24-hour and
20
20 daytime ambulatory systolic and
0 0 diastolic BP and for office systolic BP.
Exercise group Control group Exercise group Control group Error bars indicate standard
deviations.

duced in the exercise arm compared with the control arm Cardiorespiratory Fitness and Other
(Figure 2; eTable 1 in Supplement 2). Mean BP changes are Clinical Effects of Exercise Training
provided in eFigure 1 in Supplement 2. There were no differ- Individuals in the exercise arm improved cardiorespiratory fit-
ences in nighttime ambulatory BP and office diastolic BP ness by 14% (mean [SD] change of 4.7 [3.1] mL/kg per minute
between groups (eFigure 2 and eTable 1 in Supplement 2). of oxygen consumption; P < .001), while it remained un-
Individual BP changes from baseline to the end of the exer- changed in those in the control arm (eTable 2 in Supple-
cise and control interventions are provided in eFigure 3 in ment 2), resulting in a between-group difference of 5.05 mL/kg
Supplement 2. per minute of oxygen consumption (95% CI, 3.5 to 6.6;

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 Research Brief Report Effect of Exercise Training on Ambulatory Blood Pressure Among Patients With Resistant Hypertension

P < .001). There was also a significant between-group differ-
ence in the change in heart rate (24-hour and daytime) in fa-
vor of the exercise arm (eTable 2 in Supplement 2). There were
no between-group differences in body composition (eTable 2
in Supplement 2) or biochemical or urinary parameters
(eTable 3 in Supplement 2).
Safety and Compliance
Patients in the exercise arm attended a mean (SD) of 98.8%
(3.2%) of the 36 total exercise sessions (median adherence rate,
100%; minimum, 89%). There were no major adverse events
or complications registered during the study. Two patients
reported dizziness after 2 of the exercise sessions, and 2
patients reported musculoskeletal complaints (knee and hip
soreness) in the first weeks of the exercise intervention.
nervation clinical trials. For instance, the SPYRAL HTN-ON
MED trial7 reported a decrease of 7.4 mm Hg for systolic BP and
4.2 mm Hg for diastolic BP at 6 months after kidney denerva-
tion compared with sham control.
From a public health perspective, the results of the En-
RicH trial are quite promising. There is mounting evidence the
reduction of systolic BP is linearly associated with a lower risk
of cardiovascular morbidity and mortality in adults with
hypertension.13 For instance, a reduction in systolic BP of 10
mm Hg or diastolic BP of 4 mm Hg is associated with approxi-
mately 30% lower risk of stroke and approximately 20% lower
risk of myocardial infarction.14 Altogether, the results of the
EnRicH trial reaffirm the safety and efficacy of exercise train-
ing reported in previous trials among those with hypertension15
and improve our understanding in the context of treatment-
resistant hypertension.

Discussion
The EnRicH trial showed 12 weeks of moderate-intensity aero-
bic exercise training decreased the powered primary efficacy
end point of 24-hour systolic BP in patients with resistant hy-
pertension by 7.1 mm Hg compared with usual care. Daytime
BP (systolic, −8.4 mm Hg; diastolic, −5.7 mm Hg), 24-hour dia-
stolic BP (−5.1 mm Hg), and office systolic BP (−10.0 mm Hg)
were also significantly reduced after exercise training com-
pared with usual care. The magnitude of these differences in
BP are clinically meaningful and associated with lower risk
of cardiovascular morbidity and mortality in adults with
hypertension.13
From a clinical perspective, these results are encourag-
ing because the exercise prescription tested in the EnRicH trial
is easily reproducible and has the potential to be applied on a
larger scale in a setting more representative of clinical prac-
tice for which integrating drug treatment and exercise train-
ing are recommended. Our results confirm that aerobic exer-
cise training, which is already recommended as first-line
treatment for hypertension, should be extended to those with
resistance to pharmacological treatment. The exercise inter-
vention resulted in a reduction in 24-hour ambulatory BP com-
parable with the reduction observed in successful kidney de-
Limitations
Limitations of the EnRicH trial should be acknowledged. On
average, our sample consisted of patients with baseline bio-
chemical parameters near or at the recommended levels,
which limits the generalizability of our findings to patients
with a more adverse cardiometabolic profile. Also, the
EnRicH trial was not powered to detect potential effects in
subgroups of interest (eg, men compared with women). Addi-
tionally, results of the EnRicH trial are specific to aerobic
exercise and may not be generalizable to other types of exer-
cise (eg, resistance exercise).
Conclusions
In conclusion, the EnRicH trial showed a significant reduc-
tion in systolic and diastolic BP in patients with resistant hy-
pertension after a 12-week moderate-intensity aerobic exer-
cise program, both under ambulatory conditions and in the
office. In this study, when added to optimized medical therapy,
aerobic exercise reduced BP to clinically meaningful levels in
a patient population with a low responsiveness to drug treat-
ment and has the potential to be incorporated into the stan-
dard care of these patients.

ARTICLE INFORMATION
Accepted for Publication: June 4, 2021.
Published Online: August 4, 2021.
doi:10.1001/jamacardio.2021.2735
Author Affiliations: Institute of Biomedicine
(iBiMED), School of Health Sciences, University of
Aveiro, Aveiro, Portugal (Lopes, Mesquita-Bastos,
Teixeira, F. Ribeiro); Cardiology Department,
Hospital Infante D. Pedro, Centro Hospitalar do
Baixo Vouga, Aveiro, Portugal (Mesquita-Bastos,
Ribau); Research Center in Sports Sciences, Health
and Human Development (CIDESD), University
Institute of Maia, Maia, Portugal (Garcia, Alves);
Centre for Health Technology and Services
Research (CINTESIS), Faculty of Medicine,
University of Porto, Porto, Portugal (Bertoquini,
Polonia); Hypertension and Cardiovascular Risk
Unit, Unidade Local de Saúde Matosinhos,
Matosinhos, Portugal (Bertoquini, Polonia);
University of Coimbra, Cytogenetics and Genomics
Laboratory, Institute of Cellular and Molecular
Biology, Coimbra, Portugal (I. P. Ribeiro, Melo);
Coimbra Institute for Clinical and Biomedical
Research (iCBR) and Center of Investigation on
Environment Genetics and Oncobiology (CIMAGO),
Faculty of Medicine and Clinical Academic Center of
Coimbra (CACC), Coimbra, Portugal (I. P. Ribeiro,
Melo); Research Centre in Physical Activity, Health
and Leisure (CIAFEL), Faculty of Sport, University of
Porto, Porto, Portugal (Oliveira); Center for Health
Technology and Services Research (CINTESIS.UA),
School of Health Sciences, University of Aveiro,
Aveiro, Portugal (Figueiredo); Heart Institute,
School of Medicine, University of São Paulo,
São Paulo, Brazil (Guimarães); Department of
Kinesiology, University of Connecticut, Storrs
(Pescatello); OncoMove, Associação de
Investigação de Cuidados de Suporte em Oncologia
(AICSO), Vila Nova de Gaia, Portugal (Alves).
Author Contributions: Ms Lopes and Dr Fernando
Ribeiro had full access to all of the data in the study
and take responsibility for the integrity of the data
and the accuracy of the data analysis.
Study concept and design: Lopes, Mesquita-Bastos,
Oliveira, Figueiredo, Guimarães, Polonia, Alves, F.
Ribeiro.
Acquisition, analysis, or interpretation of data:
All authors.
Drafting of the manuscript: Lopes, Mesquita-Bastos,
Garcia, Oliveira, Alves, F. Ribeiro.
Critical revision of the manuscript for important
intellectual content: Lopes, Mesquita-Bastos, Berto-
quini, Ribau, Teixeira, I. Ribeiro, Melo, Oliveira,
Figueiredo, Guimarães, Pescatello, Polonia, Alves, F.
Ribeiro.

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 Effect of Exercise Training on Ambulatory Blood Pressure Among Patients With Resistant Hypertension
Statistical analysis: Lopes, Oliveira, Pescatello,
Alves, F. Ribeiro.
Obtained funding: Lopes, Oliveira, Figueiredo,
Alves, F. Ribeiro.
Administrative, technical, or material support:
Lopes, Mesquita-Bastos, Garcia, Bertoquini, Ribau,
Teixeira, I. Ribeiro, Melo, Oliveira, Guimarães.
Study supervision: Mesquita-Bastos, Oliveira,
Figueiredo, Alves, F. Ribeiro.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was funded by the
European Union through the European Regional
Development Fund Operational Competitiveness
Factors Program (COMPETE) and by the
Portuguese government through the Foundation
for Science and Technology (grants P2020-PTDC/
DTP-DES/1725/2014 and
POCI-01-0145-FEDER-016710). Ms Lopes was
awarded with a Portuguese Foundation for Science
and Technology PhD grant (grant
SFRH/BD/129454/2017). The University of Aveiro
Institute of Biomedicine (iBiMED; reference No.
UID/BIM/04501/2020), University of Porto
Research Centre in Physical Activity, Health and
Leisure (CIAFEL; reference No. UID/DTP/00617/
2020), University Institute of Maia Research Center
in Sports Sciences, Health and Human
Development (CIDESD; reference No. UID/DTP/
04045/2020), and Center for Health Technology
and Services Research (CINTESIS; reference No.
UID/IC/4255/2020) are research units supported
by the Portuguese Foundation for Science and
Technology.
Role of the Funder/Sponsor: The funders had no
role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
Data Sharing Statement: See Supplement 3.
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