BAGIAN ILMU BEDAH JOURNAL READING

FAKULTAS KEDOKTERAN OKTOBER 2019

UNIVERSITAS PATTIMURA

Safety and efficacy of exercise training in patients with abdominal aortic aneurysm: A meta-analysis of
randomized controlled trials
“Keamanan dan Kelebihan Olahraga pada Pasien dengan Aneurisma Aorta Abdominal: Sebuah meta-
analisis dari Randomized Controlled Trials”
Michitaka Kato, PhD, Akira Kubo, MD, PhD, Fumi Nihei Hijau, MS, dan Hisato Takagi, MD, PhD,Shizuoka dan Tokyo, Jepang

OLEH:
NAZLIAH AWWALIAH RUSTAM SYARBIN
2018-84-077

PEMBIMBIN

dr. Ninoy Mailoa, Sp.B

DIBAWAKAN DALAM RANGKA TUGAS KEPANITERAAN KLINIK PADA BAGIAN ILMU

BEDAH
RSUD dr. M. HAULUSSY
FAKULTAS KEDOKTERAN UNIVERSITAS PATTIMURA
AMBON
2019

Safety and efficacy of exercise training in patients with

abdominal aortic aneurysm: A meta-analysis of randomized
controlled trials
 Michitaka Kato, PhD,a Akira Kubo, MD, PhD,a Fumi Nihei Green, MS,b and Hisato Takagi, MD, PhD,c
Shizuoka and Tokyo, Japan

ABSTRACT
Objective: Low exercise capacity preoperatively leads to increased postoperative complications, perioperative mortality, length of
stay, and inpatient costs among patients going through elective abdominal aortic aneurysm (AAA) surgery. Therefore, exercise
training may be extremely important for reducing perioperative adverse events in AAA patients. This paper aimed to perform a
meta-analysis of randomized controlled trials to evaluate the safety of exercise training and its effects on exercise capacity in AAA
patients.

Methods: We searched for randomized controlled trials published up to December 2017 that compared exercise training vs usual
care without exercise training in AAA patients. The primary outcome was safety, specifically the occurrence of cardiovascular
adverse events during the study. Secondary outcomes were changes in AAA diameter, inflammation

markers, and exercise capacity based on peak oxygen consumption (peak V_O2) and anaerobic threshold (AT).

Results: We identified 341 trials, and after an assessment of relevance, 7 trials with a combined total of 489 participants were
analyzed. There were a total of two cardiovascular adverse events during the exercise test and training, and the cardiovascular
event rate and its 95% confidence interval (CI) were 0.8% and 0.2% to 3.1%. Exercise training did not tend to increase AAA diameter,
and it also tended to decrease high-sensitivity C-reactive protein level in patients with AAA. All studies that evaluated the changes in
AAA diameter or high-sensitivity C-reactive protein level involved patients with AAA

diameter <55 mm at baseline; there was no study involving participants with AAA diameter > 55 mm at baseline. Exercise

training significantly increased peak V_ O2 (pooled mean difference, 1.67 mL/kg/min; 95% CI, 0.69-2.65; P < .001) and AT (pooled mean
difference, 1.98 mL/kg/min; 95% CI, 0.77-3.19; P < .001) in AAA patients. The result of meta-regression suggested that the effects of
exercise training on peak V_O2 and AT were not modulated by the exercise duration.

Conclusions: Our analyses suggested that exercise training among AAA patients is generally safe, although future research
should be carried out to further clarify the safety among patients with large AAAs. Exercise training improved

peak V_O2 and AT in AAA patients. More data are required to identify the optimal exercise duration for improving exercise

capacity in patients with AAA. (J Vasc Surg 2018;-:1-11.)

Keywords: Abdominal aortic aneurysm; Exercise training; Safety; Exercise capacity

Abdominal aortic aneurysm (AAA) is a degenerative
condition of the abdominal aorta and is frequently lethal
if it ruptures.1 The incidence of AAA is high in Japan in
comparison with other countries because of the high
prevalence of hypertension, a large proportion of elderly
in the population, and the high availability of computed
tomography, which facilitates the diagnosis of aortic
From the Department of Shizuoka Physical Therapy, Faculty of Health Science, Tokoha
University, Shizuokaa; the Anti-aging Center, Ginza Hospital, Tokyob; and the
Department of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka. c
Author conflict of interest: none.
Correspondence: Michitaka Kato, PhD, Department of Shizuoka Physical Therapy, Faculty
of Health Science, Tokoha University, 1-30 Mizuochi-cho, Aoi-ku, Shizuoka-city,
Shizuoka 420-0831, Japan (e-mail: katomanzooo@sz. tokoha-u.ac.jp).
The editors and reviewers of this article have no relevant financial relationships to disclose
per the JVS policy that requires reviewers to decline review of any manuscript for
which they may have a conflict of interest.
0741-5214
Copyright © 2018 by the Society for Vascular Surgery. Published by Elsevier Inc.
https://doi.org/10.1016/j.jvs.2018.07.069
diseases.2 More than 13,000 open or endovascular AAA
repairs are performed in Japan each year. 3
AAA typically develops in elderly persons with arterio-
sclerosis. AAA is found in 5% to 7.5% of men and 1.5%
to 3% of women older than 65 years. 1 In elderly AAA
patients, exercise capacity is often poor as a conse-
quence of comorbid diseases, sedentary lifestyle, and
age.4 Exercise capacity is known to be associated with
AAA repair outcomes; low exercise capacity preopera-
tively leads to increased postoperative complications,
perioperative mortality, length of stay, and inpatient
costs.5-7 Therefore, to reduce perioperative adverse
events, exercise training may be extremely important for
AAA patients. However, exercise training in AAA patients
has received little attention in the literature. Some small
randomized controlled trials (RCTs) have reported that
exercise training is safe and leads to increased exercise
capacity in AAA patients, but no systematic review or
meta-analysis has been carried out to date. Given the
limited evidence, physicians and other health care
providers may hesitate to recommend
1
2 Kato et al
exercise training to AAA patients. Therefore, it is neces-
sary to determine the safety of exercise training and its
effects on exercise capacity among AAA patients.
This paper aimed to perform a meta-analysis of RCTs on
the safety of exercise training and its effects on exercise
capacity in AAA patients.
METHODS
Search strategy. Medline, Embase, Cochrane Central
Register of Controlled Trials, Cochrane Database of Sys-
tematic Reviews, Cumulative Index to Nursing and Allied
Health Literature, Web of Science, PEDro, and abstracts
from major cardiology conferences up to December
2017 were queried to identify published and unpub-
lished trials. The following search string was used in
PubMed: (“abdominal” AND (“aorta” OR “aortic”) AND
(“aneurysm” OR “aneurysms”) AND (“exercise” OR “interval
training” OR “resistance training” OR “weight training” OR
“physical fitness” OR “rehabilitation”) AND (“randomized”
OR “randomly” OR “randomization” OR “randomized
controlled trial”). The search was limited to human
studies in English. We used reference lists from retrieved
manuscripts and PubMed’s related article search feature
to ensure that the search was comprehensive. When
data were insufficient, investigators of each trial were
contacted as needed.
There was no ethical approval because this study did
not include confidential personal data and did not involve
patient intervention.
Inclusion and exclusion criteria. The inclusion criteria for
our analysis were as follows: AAA managed nonoper-
atively or AAA scheduled for an elective operation; AAA
with aortic diameter ≥30 mm8; RCT; exercise interven-
tion group received exercise training; control group
received usual care without exercise training; and
outcome includes safety and exercise capacity. The
exclusion criteria were as follows: >85 years old; morbid
obesity (body mass index ≥39 kg/m2); deterioration in
cardiac function (left ventricular ejection fraction <20% or
New York Heart Association class III or IV); and inability to
perform the exercise. Three reviewers (M.K., H.T., and
A.K.) each reviewed all eligible trials and determined
whether they fulfilled the selection criteria. Disagree-
ments were resolved by discussion.
The manuscript was prepared in accordance with the
standards set forth by the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses statement.9
Study variables and outcome. The following data were
extracted from each report: study design, number of
patients assigned to each group, baseline characteristics
of the participants, and details of the exercise interven-
tion (mode, intensity, time, frequency, and duration).
Journal of Vascular Surgery
---2018
The primary outcome was the occurrence of cardiovas-
cular adverse events during the study. Cardiovascular
adverse events included myocardial infarction, unstable
angina, serious adverse arrhythmia, aortic rupture, and
other AAA-related events. The secondary outcomes
were change in AAA diameter, inflammation markers,
and exercise capacity. The change in AAA diameter was
assessed using transabdominal ultrasound and was
determined by the maximal anterior-posterior diameter
obtained in the sagittal imaging plane. For inflammation
markers, we analyzed the level of high-sensitivity C-
reactive protein (hs-CRP) because hs-CRP is known as
a parameter of aortic aneurysm progression and rate of
expansion.10 For exercise capacity, peak oxygen capac-
ity (peak V_O2) was measured using a treadmill or an
ergometer with a respiratory gas analyzer, and anaerobic
threshold (AT) was determined using the V-slope
method. Data were extracted in duplicate by two inves-
tigators (A.K. and M.K.) and verified independently by a
third (H.T.). Some data were calculated by the authors
using the Cochrane Handbook for Systematic Reviews of
Interventions methods.11
Assessment of risk of bias and quality in the studies
included. The risk of bias for each study was assessed by
two investigators (M.K. and A.K.) using the risk of bias tool
in the Cochrane Handbook for Systematic Reviews of
Interventions.12 Furthermore, we assessed quality of the
studies included using the Tool for the assessment of
Study quality and reporting in Exercise (TESTEX), which
consists of 15 different items and has been shown to be a
reliable tool for performing a comprehensive review of
exercise training trials.13 Disagreements were resolved by
discussion.
Statistical analysis. Dichotomous variables were
analyzed using risk ratio with 95% confidence interval
(CI). Continuous outcome measures were expressed as
a change in the mean standard deviation (SD) from
baseline to follow-up and were pooled as the mean dif-
ference (MD) with 95% CI. When the values of SD for each
group were not available, they were reconstructed from
the P value of the difference in the means between
groups using the RevMan calculator (The Cochrane
Collaboration, London, United Kingdom). Statistical
heterogeneity was evaluated according to Higgins I2
statistic. I2 values of 0% to 24.9%, 25% to 49.9%, 50% to
74.9%, and 75% to 100% were considered no, low,
moderate, and high statistical heterogeneity, respec-
tively.14 To consider for statistical heterogeneity, we used
random-effects model based on DerSimonian and Laird’s
methods.15 Random-effects metaregression was
performed to determine whether the effects of exercise
training on peak V_O2 and AT were modulated by the
exercise duration.
Journal of Vascular Surgery
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Records identified through database searching
(n = 769)
(n = 341)
(n = 39)
(n = 7)
Fig 1. Flow chart of the systematic literature research for the meta-analysis.
It is well known that when the diameter of the aneu-
rysm exceeds 55 mm, the risk of rupture is markedly
increased.2 The enlargement rate of an aneurysm is also
influenced by aneurysm diameter. 16 Therefore, we
categorized patients into large (AAA diameter
>55 mm) or small (AAA diameter <55 mm) AAA and per-
formed subgroup analyses regarding cardiovascular
adverse events, AAA diameter, and hs-CRP level.P value
of <.05 was considered statistically significant.
Analyses were carried out using Review Manager (version
5.3; The Cochrane Collaboration) and ProMeta version 3.0
(available from https://idostatistics.com/prometa3/).
RESULTS
Eligible studies. Of the total of 769 references that were
initially screened, there were 341 unique studies. After
review of the titles and abstract, 302 were rejected. We
conducted a full-text review of these 39 studies for potential
inclusion (Fig 1). Ultimately, seven studies with a combined
total of 489 patients were included in the analyses. 4,17-22 No
additional studies were found when we manually searched
the references of the selected articles, relevant reviews, and
meta-analyses. All the studies included were designed to
compare exercise training with continuation of the patient’s
lifestyle or usual care without exercise training (the control)
in AAA patients.
Study and patient characteristics. The baseline charac-
teristics of the patients of the included studies are
presented in Table I. The sample sizes ranged from 25
Kato et al 3
Full-text articles
(n = 32)
to 140, and the mean age, body mass index, and AAA
diameter ranged from 70 to 75 years, 26.6 to 28.1 kg/m2,
and 30 to 62 mm, respectively. The proportion of men
ranged from 80% to 100%. At baseline, mean peak V_O 2
and AT ranged from 16.1 to 20.2 mL/kg/min and 10.5 to
14.6 mL/kg/min, respectively. Two studies included
patients with large (>55 mm) AAA who were scheduled
for surgery, and patients of these studies underwent
surgery after the exercise intervention. The remaining
studies included patients with small (<55 mm) AAA who
were not scheduled for surgery.
Exercise intervention in included studies. Table I also
presents the details of exercise interventions of the
included studies. The training types were endurance and
resistance training in four studies, endurance training
alone in two studies, and high-intensity interval training
alone in one study. The training intensities were moder-
ate (6%-80% of heart rate reserve, 12-14 on the Borg 6-20
scale) in six studies and moderate to high (5-7 on the
Borg 0-10 scale) in one study. Training time, frequency,
and duration of exercise training ranged from 40 to
60 min/session, 2 or 3 times/wk, and 4 to 48 weeks,
respectively.
Risk of bias and quality in the studies included. The risk
of bias is summarized in Table II. There was a lack of
blinding of participants and personnel (performance bias)
because personnel had to teach and supervise patients
during exercise training. The mean 6 SD of the
4 Kato et al Journal of Vascular Surgery
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Table I. Karakteristik yang termasuk dalam penelitian

Patients’ characteristics
Total No. AAA diameter, Peak V_O2,
Author (Ex/Uc) Age, years Male, % BMI, kg/m2 mm mL/kg/min AT, mL/kg/min
Kothmann, 2009 25 (17/8) 70 (61-79) 80 N/A 40 (30-51) N/A 10.5 6 2.0
Myers, 2010 57 (26/31) 71 6 8 93 27.5 6 3.9 30-50 20.2 6 7.2 N/A
Tew, 2012 25 (11/14) 73 6 7 84 28.1 6 3.2 40 6 7 18.5 6 5.1 12.5 6 3.0
Myers, 2014 140 (72/68) 72 6 7 92 28.1 6 3.7 34 6 5 19.7 6 6.1 14.6 6 4.7
Barakat, 2016 124 (62/62) 73 6 7 90 27.0 6 3.9 62 68 17.5 6 4.5 12.5 6 3.9
Lima, 2018 65 (33/32) 72 6 7 100 28.0 6 3.3 37 6 5 19.2 6 5.2 14.4 6 4.2
Tew, 2017 53 (27/26) 75 6 6 94 26.6 6 3.8 59 6 4 16.1 6 3.4 11.0 6 2.4
AAA, Abdominal aortic aneurysm; AT, anaerobic threshold; BMI, body mass :index; ET, endurance training; Ex, exercise training; HIT, high-intensity
interval training; HR, heart rate; N/A, not applicable; RT, resistance training; V O2, oxygen consumption; Uc, usual care.
Data are shown as mean 6 standard deviation or as mean (range) for continuous variables.

Table II. Risiko bias dan kualitas ddan laporan penelitian

The Cochrane Collaboration Tool
Random Blinding of Blinding of
sequence Allocation participants outcome Incomplete Selective
Studies generation concealment and personnel assessment outcome data reporting
Kothmann, 2009 Low Unclear High Low Low Low
Myers, 2010 High High High Low Low Unclear
Tew, 2012 Low Low High Low High Unclear
Myers, 2014 High High High Low Low Unclear
Barakat, 2016 Low Low High Unclear High Low
Lima, 2018 High High High Low Low High
Tew, 2017 Low Low High Low Unclear Low
Low risk of bias, % 57 43 0 86 57 43
High risk of bias, % 43 43 100 0 29 14
Unclear, % 0 14 0 14 14 43
Low, Low risk; High, high risk.

total TESTEX score, study quality score, and reporting

training. The cardiovascular event rate during the exer-
score of the studies included were 9.0 6 0.8, 3.7 6 0.8,
cise test and training and its 95% CI were 0.8% and 0.2%
and 5.3 6 1.1, respectively (Table II).
to 3.1%.
Primary outcomes. All seven studies evaluated cardio-
Secondary outcome. Two trials included measurement
vascular adverse events, but only during the exercise test
of AAA diameter before and after the exercise training.18,19
and training, not during the entire study duration. We
However, the meta-analysis for AAA diameter was not
could not compare the rate of cardiovascular events
performed because there were only two studies and one
during the exercise test and training between the exer-
of the two studies had a very high weight. Tew et al18
cise and the control groups because the control group,
reported that the MD of AAA diameter in exercise training
who did not receive the exercise test and training, is
compared with usual care was —0.2 mm (95% CI, —5.42
essentially defined to have zero events. A total of
to 5.02) per 12 weeks, indicating that the exercise did not
2 cardiovascular adverse events were reported during
increase AAA diameter compared with the control (AAA
the exercise test and training in 248 patients of the
growth rates per year for exercise and control groups:
intervention group: cardiac arrest and short-lived angina.
2.0 mm and 2.8 mm, respectively). In addition, Myers et al19
There were no AAA ruptures during exercise
showed that the MD of AAA diameter in exercise training
Journal of Vascular Surgery Kato et al 5

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Table I. Continued.
Exercise intervention
Time, Frequency, Duration,
Mode min/session times/wk weeks Intensity
ET 40 2 7 Moderate (range of 12-14 on the Borg 6-20 scale)
ET þ RT 55 3 48 Moderate (target HR: 60%-80% of HR reserve, range of 12-14 on the Borg 6-20 scale)
ET 45 3 12 Moderate (range of 12-14 on the Borg 6-20 scale)
ET þ RT 55 3 48 Moderate (target HR: 60%-80% of HR reserve, range of 12-14 on the Borg 6-20 scale)
ET þ RT 60 3 6 Moderate
ET þ RT 55 3 12 Moderate (target HR: 60%-80% of HR reserve, range of 12-14 on the Borg 6-20 scale)
HIT 47 3 4 Moderate to high (high-intensity cycling interspersed with 2-minute rest)

Table II. Continued.

The Tool for the assEssment of Study qualiTy and reporting in Exercise (TESTEX)

Total score (/15) Study quality score (/5) Study reporting score (/10)
8 5 3
9 3 6
10 4 6
9 3 6
9 4 5
8 3 5
10 4 6

compared with usual care was —0.3 mm (95% CI, —2.08 to

1.48) per 48 weeks (AAA growth rates per year for exercise
and control groups: 1.5 mm and 1.8 mm, respectively).
Both of these studies involved patients with AAA
diameter <55 mm at baseline; there was no study
involving patients with AAA diameter $55 mm at baseline
(Table III).
Two trials included measurement of hs-CRP level.17,18
The meta-analysis for hs-CRP level was not performed
because there were only two studies and one of the two
studies had a very high weight. Myers et al17 reported that
the MD of hs-CRP level in exercise training compared
with usual care was —0.3 mg/dL (95% CI, 0.54 to
— indicating
0.06), — decrease in the exercise group. Tew et
al18 showed that the MD of hs-CRP level in exercise
training compared with usual care
was —0.8 mg/dL (95% CI, —1.81 to 0.21). Both of these
studies involved patients with AAA diameter <55 mm
at baseline; there was no study involving patients with
AAA diameter $55 mm at baseline (Table III).
Six trials assessed peak V_O2 with a total of 231 patients in
the intervention group and 233 patients in the control
group.17-22 Exercise training significantly increased peak V_
O2 compared with the usual care among AAA patients
(pooled MD, 1.67 mL/kg/min; 95% CI, 0.69-2.65; P < .001;
Fig 2; Table IV). There was low heterogeneity across
studies for peak V_ O2 (I2 ¼28%). The metaregression coef-
ficient (slope of the metaregression line) was not statisti-
cally significant (1.378; P ¼ .158; Fig 3).
Six trials assessed AT with a total of 187 patients in the
intervention group and 174 patients in the control
group.4,18-22 Exercise training significantly increased AT
in AAA patients, with pooled MD of 1.98 mL/kg/min
(95% CI, 0.77-3.19; P < .001; Fig 4; Table IV). However, there
was a high degree of statistical heterogeneity across
studies for AT (I2 ¼ 81%). Subanalysis was performed
6 Kato et al Journal of Vascular Surgery
---2018

Table III. Cardiovascular adverse events and changes in abdominal aortic aneurysm (AAA) diameter and high-sensitivity C-reactive
protein (hs-CRP) level
AAA diameter, mm
Cardiovascular adverse
events Baseline Follow-up Absolute change
Author Ex Uc Ex Uc Ex Uc Ex Uc
Kothmann, 2009 1 (cardiac arrest) N/A N/A N/A N/A N/A N/A N/A
Myers, 2010 0 N/A N/A N/A N/A N/A N/A N/A
Tew, 2012 0 N/A 40.9 6 7.0 39.3 6 6.4 41.4 6 7.0 40.0 6 5.7 0.5 6 7.0 0.7 6 6.1
Myers, 2014 0 N/A 34.7 6 5.1 33.7 6 5.1 36.2 6 5.6 35.5 6 5.6 1.5 6 5.4 1.8 6 5.4
Barakat, 2016 0 N/A N/A N/A N/A N/A N/A N/A
Lima, 2018 0 N/A N/A N/A N/A N/A N/A N/A
Tew, 2017 1 (angina) N/A N/A N/A N/A N/A N/A N/A
Ex, Exercise training; N/A, not applicable; Uc, usual care.
Data are shown as mean 6 standard deviation.

using only five studies with exercise training >4 weeks
because increase in exercise capacity is greatly affected by
exercise duration and most previous studies define short-
term exercise training as #4 weeks. In the results, exercise
training of >4 weeks significantly increased AT among AAA
patients and the degree of statistical hetero- geneity
became low (MD, 2.40 mL/kg/min; 95% CI, 1.55-3.24; P <
.001, I2 ¼ 32%; Fig 5). The metaregression analysis was
performed with all six studies and the coef- ficient was not
statistically significant (1.058; P ¼ .152; Fig 6).
DISCUSSION
Main findings. This meta-analysis, which included 489
patients, aimed to evaluate the safety of exercise training
and its effects on exercise capacity in AAA patients.
Although included studies did not report the rate of
cardiovascular adverse events during the study, all seven
studies reported the rate of cardiovascular adverse
events during the exercise test and training. Our results
suggested that there were only a few cardiovascular
adverse events with the exercise test and training (event
rate, 0.8%) in AAA patients. Exercise training also tended
not to increase AAA diameter and to decrease hs-CRP
level in patients with AAA diameter <55 mm. Further-
more, exercise training significantly improved peak V_O2
and AT in AAA patients. To our knowledge, this is the first
meta-analysis to assess the safety and potential benefits
of exercise training in AAA patients.
Safety. This study showed that the cardiovascular event
rate and its 95% CI were 0.8% and 0.2% to 3.1% in patients
of the exercise training group. There were no AAA rup-
tures. Similar to our findings, the incidence of cardiovascu-
lar adverse events with exercise training among AAA
patients was very low in some observational studies. One
study evaluated the safety of treadmill exercise stress
testing in 262 patients who had AAA diameter $40 mm,
and the rate of aneurysm rupture was 0.4%.23 Another
observational study evaluated the incidence of cardio-
vascular adverse events during exercise training among 27
AAA patients and reported only one cardiovascular
adverse event (event rate, 3.7%). 24 Furthermore, two
studies with a total of 40 AAA patients reported no car-
diovascular events with the exercise program.25,26
Consistent with our results, these four studies, which
were not included in our meta-analysis, reported only a
few cardiovascular adverse events with the exercise test
and training. Therefore, it seems that it is generally safe for
AAA patients to participate in exercise training programs.
There is a possibility that exercise training expands AAA
diameter because it increases blood pressure and heart
rate temporarily during exercise, resulting in increased
aortic wall tension.18 In addition, a study showed that
hs-CRP is released from aneurysmal arteries with degen-
erating elastic lamina during AAA formation.27 Therefore,
we also analyzed changes in AAA diameter and hs-CRP
level as a parameter of safety. As a result, the AAA diam-
eter tended not to increase in the exercise group
compared with the usual care group when the baseline
AAA diameter was <55 mm. A previous long-term study
also observed 140 patients with small AAAs and reported
no significant differences in the need for surgical AAA
repairs between exercise and no-exercise groups.28
Moreover, Tew et al22 evaluated changes in AAA
diameter before and after exercise training in AAA
patients with a diameter of 55 to 70 mm. The results
showed that the mean 6 SD for AAA diameter was 60
6 0.4 mm and 59 6 0.4 mm at baseline and 5 weeks after
exercise training, respectively. This study also
demonstrated that hs-CRP level tended to decrease in
the exercise group compared with the usual care group
when the baseline AAA diameter is <55 mm. This finding
is consistent with previous studies that suggested lower
Journal of Vascular Surgery Kato et al 7

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Table III. Continued.

hs-CRP level, mg/dL
Baseline Follow-up Absolute change
Ex Uc Ex Uc Ex Uc
N/A N/A N/A N/A N/A N/A
0.43 6 0.34 0.39 6 0.23 0.32 6 0.05 0.58 6 0.67 —0.1 6 0.3 0.2 6 0.6
1.4 6 1.1 2.3 6 1.5 0.9 6 0.9 2.6 6 1.6 —0.5 6 1.0 0.3 6 1.6
N/A N/A N/A N/A N/A N/A
N/A N/A N/A N/A N/A N/A
N/A N/A N/A N/A N/A N/A
N/A N/A N/A N/A N/A N/A

Fig 2. Forest plot comparing exercise training and usual care in terms of peak oxygen consumption (V_ O2; mL/kg/ min)
changes in abdominal aortic aneurysm (AAA) patients. CI, Confidence interval; IV, inverse variance; SE, standard error. If the
mean difference (MD) is positive, it means that peak V_ O2 increased more in the exercise training group from baseline to
follow-up compared to the control group.

inflammation with exercise training among AAA patients.

Windsor et al29 reported that tumor necrosis factor a, one
of the inflammation markers, significantly decreased after
a bout of exercise training in patients with AAA. In addi-
tion, regular exercise training is also associated with lower
systemic markers of inflammation relevant to AAA.30 How-
ever, there was no study involving participants with AAA
diameter $55 mm regarding changes in AAA diameter and
inflammation markers. More data are required to further
evaluate the safety of exercise training in patients with
large AAA.
Exercise capacity. Exercise capacity measurements such
as peak V_O2 and AT are independent predictors of short-
and long-term survival after elective AAA repair.6,31
Therefore, the cardiopulmonary exercise test
could become an increasingly important tool in deter-
mining the risk, and preoperative exercise training may
be extremely important for reducing postoperative
adverse events for AAA patients.32 This study showed
that exercise training significantly improved peak
also showed that a 6-week supervised exercise program
improved peak V_ O2 and AT with an MD of 1.8 and 2.2 mL/
kg/min, respectively, in 20 patients awaiting AAA repair. 25
In addition, a systematic review of five RCTs reported that
preoperative exercise training among AAA patients had
beneficial effects on various physical fitness variables. 7
These published studies are consistent with the results
of our quantitative analyses showing that exercise
training improved exercise capacity in AAA patients.
In this study, there was a high degree of statistical het-
erogeneity across studies (I2 ¼ 81%) for the analysis of AT,
and thus we conducted a subanalysis with exercise
training of #4 weeks and >4 weeks. Whereas the five
studies with exercise training of >4 weeks significantly
increased AT, one study by Tew et al reported that exer-
cise training of #4 weeks did not significantly increase peak
V_ O2 and AT among AAA patients (MD, 0.50 mL/kg/ min
[95% CI, —0.68 to 1.68; P ¼ .40]; MD, 0.30 mL/kg/
min [95% CI, —0.29 to 0.89; P ¼ .32], respectively). Previ-
ous studies reported that endurance training of five
V_O2 times per week for 4 weeks could improve exercise ca-

and AT compared with the usual care with a pooled MD of 1.67 and 1.98 mL/kg/min, respectively. A previous study
pacity such as peak V_O2 and AT in patients with cardio-
vascular disease and healthy patients. 33,34 A possible
8 Kato et al Journal of Vascular Surgery
---2018

Table IV. Changes in peak oxygen consumption (V_O2) and anaerobic threshold (AT)
Peak V_O2, mL/kg/min
Baseline Follow-up Absolute change
Author Ex Uc Ex Uc Ex Uc
Kothmann, 2009 N/A N/A N/A N/A N/A N/A
Myers, 2010 18.5 6 5.9 21.6 6 7.8 20 6 5.5 20.2 6 7.9 1.5 6 5.7 —1.4 6 7.9
Tew, 2012 19.3 6 4.5 17.9 6 5.4 21.1 6 6.7 18.0 6 5.7 1.8 6 5.9 0.1 6 5.6
Myers, 2014 19.6 6 6.0 20.2 6 6.5 20.9 6 5.9 19.6 6 6.1 1.3 6 6.0 —0.6 6 6.3
Barakat, 2016 18.4 6 4.4 19.6 6 4.4 20 6 3.3 18.4 6 3.6 1.6 6 4.0 —1.2 6 4.1
Lima, 2018 18.8 6 4.8 19.7 6 5.5 19.9 6 4.5 19.6 6 6.0 1.1 6 4.7 —0.1 6 5.8
Tew, 2017 N/A N/A 16.8 16.3 MD of absolute change, 0.5
(95% CI, —0.68 to 1.68)
CI, Confidence interval; Ex, exercise training; MD, mean difference; N/A, not applicable; Uc, usual care.
Data are shown as mean 6 standard deviation.

explanation for the discrepancy might be that there was

a difference in exercise frequency. All studies included in
our meta-analysis prescribed exercise training for two or
three times a week. Therefore, when the frequency of ex-
ercise training is lower at two or three times a week, ex-
ercise duration of >4 weeks may be necessary to
sufficiently improve exercise capacity in AAA patients.
We performed metaregression to determine whether
the effects of exercise training on peak V_O2 and AT

were modulated by the exercise duration. However, the

metaregression coefficients were not statistically signifi-
cant, which suggested that the effects of exercise
training on peak V_O2 and AT were not modulated by
the exercise duration. More studies and investigation are
required to identify the optimal exercise duration for
improving exercise capacity in patients with AAA.
Furthermore, previous studies showed that peak V_O2
$15 mL/kg/min and AT $10 mL/kg/min preoperatively are
associated with decreased risk of early death after AAA
repair.6,35 Some of the patients included in our
meta-analysis had V_O2 and AT values above these thresh-
olds, whereas others did not. Targeting patients with
peak V_O2 <15 mL/kg/min and AT <10 mL/kg/min may
be the priority for exercise training in patients awaiting
AAA repair.
Limitations. This meta-analysis has several limitations.
First, the numbers of included studies and patients were
relatively small with only 7 RCTs and 489 patients, which
may not be sufficient for a valuable meta-analysis.
Furthermore, some of the outcomes were reported in
only a few of these seven studies. Second, although our
primary goal was to compare the occurrence of cardio-
vascular adverse events between the exercise and con-
trol groups, this was not possible because of insufficient
data in the included studies. Instead, we were able to
report the occurrence of cardiovascular adverse events
during the exercise test and training only in the
Fig 3. Metaregression analysis of the exercise duration (weeks) on
the mean difference (MD) for the peak oxygen consumption (V_O2).
intervention group. Third, as several studies had missing
SDs for the changes from baseline to follow-up, we
needed to reconstruct these data from the P value for
differences in means between groups. Fourth, the size of
AAA that becomes high risk for rupture is reported to be
different between men and women.36 However, the pa-
tients were not divided by sex because it was difficult to
analyze men and women separately in this meta-
analysis. Fifth, we stated that exercise duration of
>4 weeks may be necessary when the frequency of ex-
ercise training is two or three times a week to improve
exercise capacity in the discussion. However, it is un-
known whether exercise training >4 weeks is safe in
patients with AAA $55 mm. Therefore, exercise training
to patients with large AAA may need additional super-
vision or regular examination, such as transabdominal
ultrasound by a physician, to detect AAA expansion.
Finally, the study focused on the safety of exercise
Journal of Vascular Surgery Kato et al 9

Volume -, Number -

Table IV. Continued.

AT, mL/kg/min
Baseline Follow-up Absolute change
Ex Uc Ex Uc Ex Uc
10.6 6 2.0 10.4 6 2.0 12.1 6 2.2 10.8 6 1.6 1.5 6 2.1 0.4 6 1.8
N/A N/A N/A N/A N/A N/A
12.8 6 2.4 12.2 6 3.3 15.3 6 3.9 12.2 6 3.1 2.5 6 3.4 0.0 6 3.2
13.7 6 4.7 16 6 5 15 6 3.5 13.7 6 4.3 1.3 6 4.2 —2.3 6 4.7
12 6 3 12.3 6 2.7 13.9 6 3.3 12.1 6 3.0 1.9 6 3.2 —0.2 6 2.9
13.3 6 3.3 15.6 6 4.7 15.0 6 3.4 14.3 6 3.8 1.7 6 3.4 —1.3 6 4.3
N/A N/A 11.7 11.4 MD of absolute change, 0.3
(95% CI, —0.29 to 0.89)

Fig 4. Forest plot comparing exercise training and usual care in terms of anaerobic threshold (AT; mL/kg/min) changes in
abdominal aortic aneurysm (AAA) patients. CI, Confidence interval; IV, inverse variance; SE, standard error. If the mean
difference (MD) is positive, it means that AT increased more in the exercise training group from baseline to follow-up
compared to the control group.

Fig 5. Subanalysis forest plot comparing exercise training and usual care in terms of anaerobic threshold (AT; mL/kg/min)
changes in abdominal aortic aneurysm (AAA) patients. CI, Confidence interval; IV, inverse variance; SE, standard error. If the
mean difference (MD) is positive, it means that AT increased more in the exercise training group from baseline to follow-
up compared to the control group.

training and its effect on exercise capacity but did not

decrease postoperative organ-specific morbidity score.22
evaluate the rate of postoperative complications or
Therefore, further studies will be needed to compare the
duration of hospital stays. Two of the studies included in
effects on postoperative complications or duration of
our meta-analysis evaluated these outcomes but had
hospital stay in this population of patients.
contradictory results. Barakat et al 20 reported that pre-
operative exercise training reduced the incidence of
CONCLUSIONS
postoperative cardiac, pulmonary, and renal complica-
Our analyses suggested that exercise training among
tions and duration of hospital stay compared with the
AAA patients is generally safe, although future research
no-exercise group. On the other hand, another study
should be carried out to further clarify the safety among
suggested that preoperative exercise training did not
patients with large AAAs. Exercise training improved
10 Kato et al
Fig 6. Metaregression analysis of the exercise duration (weeks) on
the mean difference (MD) for the anaerobic threshold (AT).
peak V_ O2 and AT in AAA patients. More data are required
to identify the optimal exercise duration for improving
exercise capacity in patients with AAA.
AUTHOR CONTRIBUTIONS
Conception and design: MK, HT
Analysis and interpretation: MK, AK, FG, HT
Data collection: MK, AK, HT
Writing the article: MK, FG
Critical revision of the article: MK, AK, FG, HT
Final approval of the article: MK, AK, FG, HT
Statistical analysis: MK, HT
Obtained funding: Not applicable
Overall responsibility: MK
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Submitted Mar 31, 2018; accepted Jul 26, 2018.

Keamanan dan Kelebihan Olahraga pada Pasien dengan Aneurisma Aorta
Abdominal: Sebuah meta-analisis dari Randomized Controlled Trials
Michitaka Kato, PhD, Akira Kubo, MD, PhD, Fumi Nihei Hijau, MS, dan Hisato Takagi, MD,
PhD,Shizuoka dan Tokyo, Jepang

ABSTRAK
Tujuan: Kapasitas olahraga yang rendah sebelum operasi menyebabkan peningkatan komplikasi
pasca operasi, mortalitas perioperatif, lama tinggal, dan biaya rawat inap pasien elektif aneurisma
aorta abdominal (AAA). Oleh karena itu, olahraga mungkin sangat penting untuk mengurangi efek
samping perioperatif pada pasien AAA. Jurnal ini bertujuan untuk melakukan metaanalisis dari uji
coba terkontrol secara acak (Rondomized Controlled Trials (RCT)) untuk mengevaluasi keamanan
dari olahraga dan dampak kapasitas olahraga pada pasien AAA.
Metode: Kami mencari uji coba terkontrol secara acak yang diterbitkan sampai dengan Desember
2017 yang membandingkan olahraga dengan perawatan biasa tanpa olahraga pada pasien AAA.
Hasil utamaya adalah aman, khususnya efek samping kardiovaskular yang merugikan. Hasil
sekundernya adalah perubahan diameter AAA, penanda peradangan, dan kapasitas olahraga
berdasarkan di puncak komsumsi oksigen (peak VO2) dan ambang anaerobik (AT; Anaerobe
Threshold).
Hasil: Kami teridentifikasi 341 uji coba, dan setelah penilaian, 7 percobaan dengan total gabungan
dari 489 peserta dianalisis. Ada total dua efek samping kardiovaskular selama uji olahraga dan
pelatihan, dan tingkat kejadian kardiovaskular dan yang 95% Confidence Interval (CI) adalah
0,8% dan 0,2% menjadi 3,1%. Olahraga tidak cenderung meningkatkan diameter AAA, dan juga
cenderung menurunkan protein C-reaktif pada pasien AAA. Semua penelitian yang mengevaluasi
perubahan diameter AAA atau protein C-reaktif yang melibatkan pasien AAA dengan diameter
<55 mm; tidak ada penelitian yang melibatkan peserta dengan diameter AAA ≥ 55 mm. Olahraga
secara signifikan meningkat peak VO2 (pooled mean difference, 1,67 mL / kg / menit; 95% CI,
0,69-2,65; P <0,001) dan AT (pooled mean difference, 1,98 mL / kg / min; 95% CI, 0,77-3,19; P
<0,001) pada pasien AAA. Hasil meta-regresi menyarankan bahwa efek olahraga terhadap peak
VO2 dan AT tidak dipengaruhi oleh durasi latihan.
Kesimpulan: Analisis kami menunjukkan bahwa olahraga pada pasien AAA umumnya aman,
meskipun penelitian masa depan harus dilakukan untuk lebih memperjelas keamanan pada pasien
dengan AAA yang besar. Olahraga telah terbukti pada pasien AAA dengan peak VO2 dan AT.
Lebih banyak data yang diperlukan untuk mengidentifikasi durasi olahragayang optimal untuk
meningkatkan kapasitas latihan pada pasien dengan AAA.
Kata kunci: Aneurisma Aorta Abdominalis; olahraga; Keamanan; kapasitas latihan

Aneurisma aorta abdominal (AAA) adalah suatu kondisi degeneratif dari aorta abdominal
dan sering mematikan jika pecah. Insiden AAA tinggi di Jepang dibandingkan dengan negara-
negara lain, karena prevalensi hipertensi yang tinggi, sebagian besar populasi adalah lanjut usia,
dan adanya CT-scan yang memfasilitasi diagnosis penyakit aorta. Lebih dari 13.000 perbaikan
AAA terbuka atau endovaskular dilakukan di Jepang setiap tahun.
AAA biasanya berkembang pada orang tua dengan arteriosklerosis. AAA ditemukan di
5%-7,5% pada pria dan 1,5%-3% dari wanita yang lebih tua dari 65 tahun. Kejadian AAA pada
pasien lanjut usia dikarenakan jarang berolahraga, perubahan gaya hidup, dan usia sehingga
menimbulkan penyakit komorbiditas lansia. Kapasitas olahraga mempengaruhi hasil perbaikan
AAA. Kapasitas olahraga yang rendah saat pre-operatif menyebabkan peningkatan komplikasi
pasca-operasi, mortalitas perioperatif, lama tinggal, dan biaya rawat inap. Oleh karena itu, untuk
mengurangi efek samping perioperatif, olahraga mungkin sangat penting bagi pasien AAA.
Namun, belum banyak penelitian terkait olahraga pada pasien AAA. Beberapa RCT telah
melaporkan bahwa olahraga aman dan menyebabkan peningkatan kapasitas olahraga pada pasien
AAA, namun belum ada tinjauan sistematis atau meta-analisis yang telah dilakukan sampai saat
ini. Mengingat bukti-bukti yang masih terbatas, dokter dan penyedia layanan kesehatan lain
mungkin ragu-ragu untuk merekomendasikan olahraga untuk pasien AAA. Oleh karena itu, perlu
untuk menentukan keamanan dan dampak kapasitas olahraga pada pasien AAA. Makalah ini
bertujuan untuk melakukan meta-analisis dari RCT tentang keamanan olahraga dan dampaknya
pada pasien AAA.

METODE
Strategi pencarian
Pencarian dilakukan pada Medline, Embase, Cochrane Central Register of Controlled
Trials, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health
Literature, Web of Science, PEDro, dan abstrak konferensi besar kardiologi Desember 2017
yang dipublikasian dan tidak dipublikasikan. Pencarian terbatas pada penelitian terhadap manusia
yaitu PubMed: (“abdominal” AND (“aorta” OR “aortic”) AND (“aneurysm” OR “aneurysms”)
AND (“exercise” OR “interval training” OR “resistance training” OR “weight training” OR
“physical fitness” OR “rehabilitation”) AND (“randomized” OR “randomly” OR
“randomization” OR “randomized controlled trial”). Peneliti menggunakan daftar referensi dari
naskah yang diambil dan fitur pencarian artikel terkait PubMed untuk memastikan bahwa
pencarian itu komprehensif. Ketika data tidak mencukupi, penelitinya langsung dihubungi. Tidak
ada persetujuan etis karena penelitian ini tidak memasukkan data pribadi rahasia dan tidak
melibatkan intervensi pasien.

Kriteria inklusi dan ekslusi

Kriteria inklusinya adalah menagemen AAA yang non-operatif atau AAA dengan operasi
elektif;diameter aorta AAA ≥ 30 mm;RCT adalah kelompok yang melakukan olahraga; kelompok
kontrol adalah kelompok yang hanya mendapatkan perawatan tanpa melakukan olahraga; dan yang
dinilai adalah keamanan dan kapasitas olahraganya. Kriteria ekslusi adalah usia >85 tahun,
obesitas (indeks massa tubuh ≥ 39 kg/m2), gangguan fungsi kardiak (fraksi ejeksi ventrikel kiri
<20% atau NYHA kelas III/IV), dan tidak mampu untuk melakukan olahraga.

Gambar 1. Alur penelitian literatur sistematis untuk meta-analisis.

Hasil dan variabel penelitian
Data diambil dari setiap laporan: desain penelitian, jumlah pasien ditugaskan untuk
masing-masing kelompok, karakteristik dasar dari peserta, dan rincian dari intervensi
olahraga (mode, intensitas, waktu, frekuensi, dan durasi). Efek merugikan yang dapat
terjadi berupa gangguan kardiovaskular selama penelitian. Efeknya termasuk infark
miokard, angina tidak stabil, aritmia yang serius, pecahnya aorta, dan lainnya. Hasil
sekunder adalah perubahan diameter AAA, peradangan, dan kapasitas olahraga.
Perubahan diameter AAA dinilai menggunakan ultrasound transabdominal dan
ditentukan oleh diameter anterior-posterior maksimal diperoleh pada bidang pencitraan
sagital. Untuk penanda peradangan, kami menganalisis tingkat sensitivitas tinggi protein
C-reaktif (hs-CRP) karena hs-CRP dikenal sebagai parameter perkembangan dan tingkat
ekspansi aneurisma aorta.10 Untuk kapasitas olahraga, kapasitas puncak oksigen dengan
tredmill atau ergometer analisis gas pernapasan, dan AT diukur menggunakan metode V-
slope. Beberapa data diambil dari duplikasi oleh dua peneliti (A.K dan M.K) dan
diverifikasi oleh peneliti ketiga (H.T). Beberapa data dihitung oleh penulis menggunakan
Cochrane Handbook for Systematic Reviews of Interventions Methods.
Penilaian risiko bias dan kualitas penelitian
Risiko bias untuk setiap studi dinilai oleh dua peneliti (MK dan AK) menggunakan
risiko alat bias dalam Cochrane Handbook for Systematic Reviews of Interventions
Methods.12 Secara kualitas, kami menilai penelitian menggunakan TESTEX (The Tool for
The Assessment of Study Quality and Reporting in Exercise), yang terdiri dari 15 data
yang berbeda dan telah terbukti menjadi alat yang handal untuk melakukan kajian
komprehensif dari uji coba olahraga .13 Ketidaksepakatan diselesaikan dengan diskusi.
Analisis statistik

Variabel dikotomis yang dianalisis menggunakan rasio risiko dengan CI 95%.

Ukuran hasil terus menerus dinyatakan sebagai perubahan dalam rata-rata (mean)±
standar deviasi (SD) dari hasil baseline sampai follow up dan dikumpulkan sebagai
mean difference (MD) dengan CI 95%. Ketika nilai-nilai SD untuk setiap kelompok
yang tidak tersedia, mereka direkonstruksi dari nilai P dari perbedaan cara antara
kelompok menggunakan RevMan kalkulator (The Cochrane Collaboration, London,
Inggris Raya). Heterogenitas dievaluasi menurut statistik Higgins I2. nilai-nilai I2 0%
sampai 24,9%, 25% menjadi 49,9%, 50% untuk 74,9%, dan 75% sampai 100%
dianggap tidak ada, rendah, sedang, dan tinggi. Heterogenesitas statistik menggunaan
DerSimonian dan metode Lairds. Uji acak metaregresi dinilai dengan efek pelatihan
olahraga VO2 dan AT dinilai dari durasi olahraga. Diketahui diameter aneurisma
meningkat sebesar 55 mm, risiko ruptur meningkat. Pembesaran aneurisma dipengaruhi oleh
diameter aneurisma. Sehingga kita menggelompokan menjadi (diameter yang besar AAA ≥55
mm) atau kecil (< 55 mm) dan dibentuk menjadi subkelompok kardiovaskular, diameter AAA,
dan kadar hs-CRP. Nilai P <0,05 yang menunjukkan hasil yang signifikan. Analisis
menggunakan Review Manager (version 5.3; The Cochrane Collaboration) and ProMeta
version 3.0 (available from https://idostatistics.com/prometa3/).
HASIL
Penelitian yang memenuhi syarat
Dari total 769 referensi yang awalnya disaring, ada 341 studi yang unik. Setelah
meninjau judul dan abstrak, 302 ditolak. Kami melakukan review penuh-teks ini 39 studi
potensi inklusi (Gambar 1). Pada akhirnya, tujuh studi dengan total gabungan dari 489 pasien
dimasukkan dalam analisis. Tidak ada studi tambahan yang ditemukan ketika kita secara
manual mencari referensi dari artikel yang dipilih, ulasan relevan, dan meta-analisis. Semua
studi termasuk dirancang untuk membandingkan latihan olahraga dengan kelanjutan dari gaya
hidup pasien atau perawatan biasa tanpa pelatihan olahraga (kontrol) pada pasien AAA.
Karakteristik penelitian dan pasien
Dalam hal ini disajikan dalam tabel I. Ukuran sampel berkisar antara 25-140, dan
usia rata-rata, indeks massa tubuh, dan diameter AAA masing-masing berkisar 70-75 tahun, 26,6-
28,1 kg / m2, dan 30-62 mm. Proporsi laki-laki berkisar antara 80% sampai 100%. Pada awal,
puncak VO2 dan AT berkisar 16,1-20,2 mL / kg / menit dan, masing-masing 10,5-14,6 mL / kg /
menit. Dua penelitian termasuk pasien dengan diameter AAA yang besar (> 55 mm) telah
dijadwalkan untuk operasi, dan pasien dari studi ini menjalani operasi setelah intervensi latihan.
Studi yang tersisa termasuk pasien dengan kecil (<55 mm) AAA yang tidak dijadwalkan untuk
operasi.
Intervensi olahraga yang termasuk dalam penelitian-penelitian ini
Tabel 1 juga menyajikan rincian intervensi pelaksanaan studi termasuk. Jenis pelatihan
terkait daya tahan dan resistensi ada pada empat penelitian, daya tahan pelatihan saja dalam dua
studi, dan interval olahraga dengan intensitas tinggi sendirian dalam satu penelitian. Intensitas
pelatihan yang moderat (6% -80% dari cadangan denyut jantung, 12-14 pada skala Borg 6-20) di
enam studi dan moderat ke tinggi (5-7 pada skala Borg 0-10) dalam satu penelitian. Waktu
pelatihan, frekuensi, dan durasi latihan masing-masing olahraga berkisar antara 40 sampai 60
menit / sesi, 2 atau 3 kali / minggu, dan 4-48 minggu.
Risiko bias dan kualitias dalam penelitian ini
Risiko bias diringkas dalam tabel II. Ada kurangnya menyilaukan peserta dan personil
(kinerja bias) karena personil harus mengajar dan mengawasi pasien selama latihan
olahraga. Mean SD dari skor total TESTEX, skor kualitas studi, dan skor pelaporan studi
masing-masing termasuk yang 9,0 ± 0,8, 3,7 ± 0,8, dan 5,3 ± 1,1 (tabel II).

Table I. Karakteristik yang termasuk dalam penelitian

Patients’ characteristics
Total No. AAA diameter, Peak V_O2,
Author (Ex/Uc) Age, years Male, % BMI, kg/m2 mm mL/kg/min AT, mL/kg/min
Kothmann, 2009 25 (17/8) 70 (61-79) 80 N/A 40 (30-51) N/A 10.5 6 2.0
Myers, 2010 57 (26/31) 71 6 8 93 27.5 6 3.9 30-50 20.2 6 7.2 N/A
Tew, 2012 25 (11/14) 73 6 7 84 28.1 6 3.2 40 6 7 18.5 6 5.1 12.5 6 3.0
Myers, 2014 140 (72/68) 72 6 7 92 28.1 6 3.7 34 6 5 19.7 6 6.1 14.6 6 4.7
Barakat, 2016 124 (62/62) 73 6 7 90 27.0 6 3.9 62 68 17.5 6 4.5 12.5 6 3.9
Lima, 2018 65 (33/32) 72 6 7 100 28.0 6 3.3 37 6 5 19.2 6 5.2 14.4 6 4.2
Tew, 2017 53 (27/26) 75 6 6 94 26.6 6 3.8 59 6 4 16.1 6 3.4 11.0 6 2.4
AAA, Abdominal aortic aneurysm; AT, anaerobic threshold; BMI, body mass :index; ET, endurance training; Ex, exercise training; HIT, high-intensity interval training;
HR, heart rate; N/A, not applicable; RT, resistance training; VO2, oxygen consumption; Uc, usual care.
Data are shown as mean 6 standard deviation or as mean (range) for continuous variables.

Tabel II. Risiko bias dan kualitas ddan laporan penelitian

The Cochrane Collaboration Tool
Random Blinding of Blinding of
sequence Allocation participants outcome Incomplete Selective
Studies generation concealment and personnel assessment outcome data reporting
Kothmann, 2009 Low Unclear High Low Low Low
Myers, 2010 High High High Low Low Unclear
Tew, 2012 Low Low High Low High Unclear
Myers, 2014 High High High Low Low Unclear
Barakat, 2016 Low Low High Unclear High Low
Lima, 2018 High High High Low Low High
Tew, 2017 Low Low High Low Unclear Low
Low risk of bias, % 57 43 0 86 57 43
High risk of bias, % 43 43 100 0 29 14
Unclear, % 0 14 0 14 14 43
Low, Low risk; High, high risk.
Hasil utama

Ketujuh penelitian dievaluasi efek samping kardiovaskular, tetapi hanya selama uji
latihan dan pelatihan, tidak selama seluruh durasi penelitian. Kita tidak bisa
membandingkan tingkat kejadian kardiovaskular selama uji latihan dan pelatihan antara
kelompok yang berolaharga dan yang kontrol karena kelompok kontrol yang tidak
menerima tes latihan dan pelatihan, pada dasarnya tidak ada. Ditemukan 2 efek samping
kardiovaskular yang dilaporkan selama uji latihan dan pelatihan dalam 248 pasien dari
kelompok intervensi: serangan jantung dan angina singkat. Tidak ada pecah AAA selama
pelatihan olahraga. Tingkat kejadian kardiovaskular selama uji olahraga dan pelatihan
dan itu dengan CI 95% adalah 0,8% dan 0,2% menjadi 3,1%.

Hasil sekunder

Dua percobaan termasuk pengukuran diameter AAA sebelum dan sesudah latihan
olahraga. Namun, meta-analisis untuk diameter AAA tidak dilakukan karena hanya ada
dua penelitian dan salah satu dari dua penelitian memiliki bobot yang sangat tinggi. Tew
et al melaporkan bahwa MD diameter AAA dalam pelatihan olahraga dibandingkan
dengan perawatan biasa adalah -0,2 mm (95% CI, -5,42 untuk 5,02) per 12 minggu,
menunjukkan bahwa olahraga tidak meningkatkan diameter AAA dibandingkan dengan
kontrol (AAA tingkat pertumbuhan per tahun untuk latihan dan kelompok kontrol
masing-masing 2.0 mm dan 2,8 mm,). Selain itu, Myers et al menunjukkan bahwa MD
diameter AAA dalam pelatihan olahraga dibandingkan dengan perawatan biasa adalah
0,3 mm (95% CI, -2,08 1,48) per 48 minggu (tingkat pertumbuhan AAA per tahun untuk
latihan dan kelompok kontrol masing-masing 1,5 mm dan 1,8 mm). Kedua penelitian ini
melibatkan pasien dengan diameter AAA <55 mm pada awal; tidak ada penelitian yang
melibatkan pasien dengan AAA diameter ≥55 mm pada awal (tabel III). Dua percobaan
termasuk pengukuran tingkat hs-CRP. Meta-analisis untuk tingkat hs-CRP tidak
dilakukan karena hanya ada dua penelitian dan salah satu dari dua penelitian memiliki
bobot yang sangat tinggi. Myers et al melaporkan bahwa MD tingkat hs-CRP dalam
pelatihan olahraga dibandingkan dengan perawatan biasa adalah -0,3 mg / dL (95% CI,
0,54-0,06 mg/dL), menunjukkan penurunan pada kelompok latihan. Tew et al
menunjukkan bahwa MD tingkat hs-CRP dalam pelatihan latihan dibandingkan dengan
perawatan biasa adalah -0,8 mg/dL (95% CI, -1,81 0,21). Kedua penelitian ini melibatkan
pasien dengan diameter AAA <55 mm pada awal; tidak ada penelitian yang melibatkan
pasien dengan AAA diameter ≥ 55 mm pada awal (tabel III). Enam percobaan dinilai
puncak VO2 dengan total 231 pasien pada kelompok intervensi dan 233 pasien pada
kelompok kontrol. Olahraga secara signifikan meningkat puncak VO2 dibandingkan
dengan perawatan biasa diantara pasien AAA (pooled MD, 1,67 mL / kg / min; 95% CI,
0,69-2,65; P <0,001; Gambar 2; tabel IV). Ada heterogenitas rendah di penelitian untuk
puncak VO2 (I2 28%). Koefisien metaregrasi (kemiringan garis metaregresi) tidak secara
statistik signifikan (1,378; P ¼ 0,158;Gambar 3). Enam percobaan dinilai AT dengan total
187 pasien pada kelompok intervensi dan 174 pasien pada kelompok kontrol. Olahraga
secara signifikan meningkat AT pada pasien AAA, dengan MD 1,98 mL / kg / min (95%
CI, 0,77-3,19; P <0,001; Gambar 4; tabel IV). Namun, ada tingkat heterogenitas yang
tinggi statistik di penelitian untuk AT (I2 ¼ 81%). Subanalisis dilakukan hanya
menggunakan lima penelitian dengan latihan > 4 minggu latihan dan penelitian dengan
latihan olahraga jangka pendek selama ≤ 4 minggu karena peningkatan kapasitas latihan
sangat dipengaruhi oleh durasi. Hasilnya, pelatihan olahraga > 4 minggu secara signifikan
meningkat AT antara pasien AAA dan tingkat statistik heterogenisitas menjadi rendah
(MD, 2,40 mL / kg / min; 95% CI, 1,55-3,24; P <0,001, I2 ¼ 32%;Gambar 5). Analisis
metaregresi dilakukan pada keenam penelitian dan koefisien secara statistik tidak
signifikan (1,058; P ¼ ;Gambar 6).

Tabel I. L Lanjutan
Exercise intervention
Time, Frequency, Duration,
Mode min/session times/wk weeks Intensity
ET 40 2 7 Moderate (range of 12-14 on the Borg 6-20 scale)
ET þ RT 55 3 48 Moderate (target HR: 60%-80% of HR reserve, range of 12-14 on the Borg 6-20 scale)
ET 45 3 12 Moderate (range of 12-14 on the Borg 6-20 scale)
ET þ RT 55 3 48 Moderate (target HR: 60%-80% of HR reserve, range of 12-14 on the Borg 6-20 scale)
ET þ RT 60 3 6 Moderate
ET þ RT 55 3 12 Moderate (target HR: 60%-80% of HR reserve, range of 12-14 on the Borg 6-20 scale)
HIT 47 3 4 Moderate to high (high-intensity cycling interspersed with 2-minute rest)
Tabel II. Lanjutan.
The Tool for the assEssment of Study qualiTy and reporting in Exercise (TESTEX)

Total score (/15) Study quality score (/5) Study reporting score (/10)
8 5 3
9 3 6
10 4 6
9 3 6
9 4 5
8 3 5
10 4 6

Table III. Efek merugikan kardiovaskular dan perubahan diameter AAA dan hs-CRP level
AAA diameter, mm
Cardiovascular adverse events
Baseline Follow-up Absolute change
Author Ex Uc
Ex Uc Ex Uc Ex Uc
Kothmann, 2009 1 (cardiac arrest) N/A N/A N/A N/A N/A N/A N/A
Myers, 2010 0 N/A N/A N/A N/A N/A N/A N/A
Tew, 2012 0 N/A 40.9 6 7.0 39.3 6 6.4 41.4 6 7.0 40.0 6 5.7 0.5 6 7.0 0.7 6 6.1
Myers, 2014 0 N/A 34.7 6 5.1 33.7 6 5.1 36.2 6 5.6 35.5 6 5.6 1.5 6 5.4 1.8 6 5.4
Barakat, 2016 0 N/A N/A N/A N/A N/A N/A N/A
Lima, 2018 0 N/A N/A N/A N/A N/A N/A N/A
Tew, 2017 1 (angina) N/A N/A N/A N/A N/A N/A N/A
Ex, Exercise training; N/A, not applicable; Uc, usual care. Data
are shown as mean 6 standard deviation.

DISKUSI

Temuan utama

Metaanalisis, termasuk 489 pasien, yang bertujuan untuk mengevaluasi keamanan dari
latihan olahraga dan dampak kapasitas olahraga pada pasien AAA. Meskipun penelitian
termasuk tidak melaporkan tingkat efek samping kardiovaskular selama penelitian, tujuh
penelitian melaporkan tingkat efek samping kardiovaskular selama uji latihan dan
pelatihan. Hasil kami menunjukkan bahwa hanya ada beberapa efek samping
kardiovaskular dengan tes latihan dan pelatihan (tingkat kejadian 0,8%) pada pasien
AAA. Pelatihan olahraga juga cenderung untuk tidak meningkatkan diameter AAA dan
untuk mengurangi tingkat hs-CRP pada pasien dengan diameter AAA <55 mm. Lebih
lanjut, pelatihan olahraga secara signifikan meningkatkan puncak VO2 dan AT pada
pasien AAA. Untuk pengetahuan kita, ini adalah pertama meta-analisis untuk menilai
keamanan dan potensi manfaat dari latihan olahraga pada pasien AAA.

Keamanan

Penelitian ini menunjukkan bahwa tingkat kejadian kardiovaskular dan yang 95% CI
adalah 0,8% dan 0,2% menjadi 3,1% pada pasien dari kelompok latihan olahraga. Tidak
menyebabkan struktur AAA ruptur. Mirip dengan temuan kami, kejadian efek samping
kardiovaskular dengan latihan olahraga antara pasien AAA sangat rendah dalam beberapa
penelitian observasional. Satu penelitian mengevaluasi keamanan stres latihan treadmill
pengujian di 262 pasien yang memiliki diameter AAA ≥40 mm, dan tingkat pecahnya
aneurisma adalah 0,4%. Penelitian observasional lain mengevaluasi kejadian efek
samping kardiovaskular selama pelatihan olahraga di antara 27 pasien AAA dan
dilaporkan hanya satu kejadian kardiovaskular yang merugikan (tingkat kejadian, 3,7%).
Selanjutnya, dua penelitian dengan total 40 pasien AAA melaporkan tidak ada gangguan
kardiovaskular dengan selama pelatihan olahraga. Konsisten dengan hasil kami, empat
penelitian ini, yang tidak termasuk dalam meta-analisis kami, dilaporkan hanya efek
samping kardiovaskular beberapa dengan tes latihan dan pelatihan. Oleh karena itu,
tampaknya itu umumnya aman bagi pasien AAA untuk berpartisipasi dalam program
latihan olahraga. Ada kemungkinan bahwa olahraga pelatihan memperluas diameter
AAA karena meningkatkan tekanan darah dan denyut jantung sementara selama latihan,
mengakibatkan peningkatan ketegangan dinding aorta. Selain itu, sebuah penelitian
menunjukkan bahwa hs-CRP dilepaskan dari arteri aneurisma akibat proses degeneratif
lamina elastis selama pembentukan AAA. Oleh karena itu, kami juga dianalisis perubahan
diameter AAA dan tingkat hs-CRP sebagai parameter keselamatan. Akibatnya, diameter
AAA cenderung tidak meningkat pada kelompok latihan dibandingkan dengan kelompok
perawatan biasa ketika diameter dasar AAA adalah <55 mm. Sebuah penelitian jangka
panjang sebelumnya juga mengamati 140 pasien dengan diameter AAA yang kecil dan
melaporkan tidak ada perbedaan yang signifikan dalam kebutuhan untuk perbaikan bedah
AAA antara kelompok olahraga dan yang kontrol. Selain itu, Tew et al menyatakan
perubahan diameter AAA dievaluasi sebelum dan sesudah pelatihan latihan pada pasien
AAA dengan diameter 55-70 mm. Hasil penelitian menunjukkan bahwa rata-rata SD
(Standar Deviasi) untuk diameter AAA masing-masing adalah 60±0,4 mm dan 59±0,4
mm pada awal dan 5 minggu setelah latihan olahraga. Penelitian ini juga menunjukkan
bahwa tingkat hs-CRP cenderung menurun pada kelompok latihan dibandingkan dengan
kelompok perawatan biasa ketika diameter dasar AAA adalah <55 mm. Merintis ini
konsisten dengan penelitian sebelumnya yang menunjukkan lebih rendah peradangan
dengan latihan olahraga di antara pasien AAA. Windsor et al melaporkan bahwa tumor
necrosis factor (TNF), salah satu di penanda Peradangan, secara signifikan menurun
setelah serangan latihan olahraga pada pasien dengan AAA. Dalam hasil penjumlahan,
pelatihan olahraga teratur juga dihubungkan dengan penanda sistemik lebih rendah dari
peradangan yang relevan dengan AAA. Meskipun, tidak ada penelitian yang melibatkan
peserta dengan diameter AAA ≥ 55 mm mengenai perubahan diameter AAA dan penanda
peradangan. Data lebih diwajibkan untuk lebih mengevaluasi keamanan dari latihan
olahraga pada pasien dengan AAA besar.

Tabel III. Lanjutan

hs-CRP level, mg/dL
Baseline Follow-up Absolute change
Ex Uc Ex Uc Ex Uc
N/A N/A N/A N/A N/A N/A
0.43 6 0.34 0.39 6 0.23 0.32 6 0.05 0.58 6 0.67 —0.1 6 0.3 0.2 6 0.6
1.4 6 1.1 2.3 6 1.5 0.9 6 0.9 2.6 6 1.6 —0.5 6 1.0 0.3 6 1.6
N/A N/A N/A N/A N/A N/A
N/A N/A N/A N/A N/A N/A
N/A N/A N/A N/A N/A N/A
N/A N/A N/A N/A N/A N/A
Kapasitas Olahraga

Pengukuran kapasitas latihan seperti sebagai puncak VO2 dan AT adalah prediktor
independen jangka pendek dan jangka panjang kelangsungan hidup setelah perbaikan
AAA elektif. Oleh karena itu, tes latihan kardiopulmonal bisa menjadi alat yang semakin
penting dalam menentukan risiko pra-operasi mungkin sangat penting untuk mengurangi
efek samping pasca-operasi untuk pasien AAA. Penelitian ini juga menunjukkan bahwa
6 minggu program olaharaga diawasi, didapatkan terjadi peningkatan puncak VO2 dan
AT dengan masing-masing MD 1,8 dan 2,2 mL / kg / menit, pada 20 pasien menunggu
perbaikan AAA. Selain itu, tinjauan sistematis lima RCT melaporkan bahwa latihan
olahraga sebelum operasi antara pasien AAA memiliki efek berupa kebugaran fisik.
Penelitian-penelitian yang dipublikasikan konsisten dengan hasil analisis kuantitatif kami
menunjukkan bahwa kapasitas latihan olahraga ditingkatkan pada pasien AAA. Dalam
penelitian ini, ada tingkat heterogenitas statistik yang tinggi dalam penelitian (I2 ¼ 81%)
untuk analisis AT, dan dengan demikian kita melakukan subanalisis dengan pelatihan
olahraga > 4 minggu. Sedangkan lima penelitian dengan latihan olahraga dari > 4 minggu
secara signifikan meningkatkan AT, satu penelitian oleh Tew et al melaporkan bahwa
pelatihan olahraga dari ≥4 minggu tidak secara signifikan meningkatkan puncak VO2
dan AT antara pasien AAA (masing-masing MD 0,50 mL / kg / min [95% CI, -0,68 1,68;
P ¼ 0,40]; MD 0,30 mL / kg /min [95% CI, -0,29 0,89; P ¼ 0,32]). Penelitian sebelumnya
melaporkan bahwa pelatihan olahraga yang optimal sebanyak 5x/minggu selama 4
minggu diperlukan untuk meningkatkan kapasitas latihan pada pasien dengan AAA.
Selain itu, penelitian sebelumnya menunjukkan bahwa puncak VO2 ≥ 15 mL / kg / menit
dan AT ≥ 10 mL / kg / menit sebelum operasi berhubungan dengan penurunan risiko
kematian dini setelah perbaikan AAA. Beberapa pasien termasuk dalam meta-analisis
memiliki nilai-nilai VO2 dan AT di atas threshold, sedangkan yang lain tidak.
Menargetkan pasien puncak VO2 <15 mL / kg / menit dan AT <10 mL / kg / menit
mungkin prioritas untuk pelatihan olahraga pada pasien menunggu perbaikan AAA.
Tabel IV. VO2 dan AT
Peak V_O2, mL/kg/min
Baseline Follow-up Absolute change
Author Ex Uc Ex Uc Ex Uc
Kothmann, 2009 N/A N/A N/A N/A N/A N/A
Myers, 2010 18.5 6 5.9 21.6 6 7.8 20 6 5.5 20.2 6 7.9 1.5 6 5.7 —1.4 6 7.9
Tew, 2012 19.3 6 4.5 17.9 6 5.4 21.1 6 6.7 18.0 6 5.7 1.8 6 5.9 0.1 6 5.6
Myers, 2014 19.6 6 6.0 20.2 6 6.5 20.9 6 5.9 19.6 6 6.1 1.3 6 6.0 —0.6 6 6.3
Barakat, 2016 18.4 6 4.4 19.6 6 4.4 20 6 3.3 18.4 6 3.6 1.6 6 4.0 —1.2 6 4.1
Lima, 2018 18.8 6 4.8 19.7 6 5.5 19.9 6 4.5 19.6 6 6.0 1.1 6 4.7 —0.1 6 5.8
Tew, 2017 N/A N/A 16.8 16.3 MD of absolute change, 0.5
(95% CI, —0.68 to 1.68)
CI, Confidence interval; Ex, exercise training; MD, mean difference; N/A, not applicable; Uc, usual care. Data are
shown as mean 6 standard deviation.

Gambar 3. Analisis metaregresi durasi olahraga (minggu) berdasarkan MD (mean of difference)

berdarakan peak oxygen consumption (VO2)

Batasan penelitian

Metaanalisis memiliki beberapa keterbatasan. Pertama, jumlah penelitian termasuk

pasien relatif sedikit dengan hanya 7 RCT dan 489 pasien, yang mungkin tidak mencukupi
untuk meta-analisis yang berharga. Selain itu, beberapa dari hasil dilaporkan hanya dalam
beberapa tujuh penelitian ini. Kedua, meskipun tujuan utama kami adalah untuk
membandingkan terjadinya efek samping kardiovaskular antara latihan dan kelompok
kontrol, ini tidak mungkin karena insufisiensi data dalam penelitian disertakan.
Sebaliknya, kami mampu melaporkan terjadinya efek samping kardiovaskular selama uji
latihan dan pelatihan hanya dikelompok intervensi. Ketiga, karena beberapa penelitian
telah hilang SD untuk perubahan dari awal untuk menindaklanjuti, kita perlu untuk
merekonstruksi data ini dari nilai P untuk perbedaan berarti antara kelompok. Keempat,
ukuran AAA yang menjadi risiko tinggi untuk pecah dilaporkan berbeda antara pria dan
wanita. Namun, pasien tidak dibagi berdasarkan jenis kelamin karena itu sulit untuk
menganalisis pria dan wanita secara terpisah dalam meta-analisis ini. Kelima, kami
menyatakan bahwa durasi latihan > 4 minggu mungkin diperlukan ketika frekuensi
latihan olahraga adalah dua atau tiga kali seminggu untuk meningkatkan kapasitas latihan
dalam diskusi. Namun, untuk mengetahui apakah latihan olahraga > 4 minggu aman pada
pasien dengan AAA ≥55 mm. Oleh karena itu, pelatihan latihan untuk pasien dengan
AAA besar mungkin perlu pemeriksaan tambahan atau pemeriksaan rutin, seperti USG
transabdominal oleh dokter, untuk mendeteksi ekspansi AAA. Akhirnya, penelitian ini
difokuskan pada keamanan pelatihan olahraga dan efeknya pada kapasitas latihan tapi
tidak mengevaluasi tingkat komplikasi pasca operasi atau durasi tinggal di rumah sakit.
Dua penelitian yang termasuk dalam meta-analisis kami dievaluasi hasil ini, tetapi
memiliki hasil yang bertentangan. Barakat dkk melaporkan bahwa pelatihan olahraga
sebelum operasi mengurangi kejadian jantung pasca operasi, paru, dan komplikasi ginjal
dan durasi tinggal di rumah sakit dibandingkan dengan kelompok tanpa latihan. Di sisi
lain, penelitian lain menunjukkan bahwa latihan olahraga pra operasi tidak menurunkan
skor morbiditas pasca operasi organ-spesifik. Oleh karena itu, penelitian lebih lanjut akan
diperlukan untuk membandingkan efek pada komplikasi pasca operasi atau durasi tinggal
di rumah sakit pada populasi pasien ini.

Tabel IV. Lanjutan

AT, mL/kg/min
Baseline Follow-up Absolute change
Ex Uc Ex Uc Ex Uc
10.6 6 2.0 10.4 6 2.0 12.1 6 2.2 10.8 6 1.6 1.5 6 2.1 0.4 6 1.8
N/A N/A N/A N/A N/A N/A
12.8 6 2.4 12.2 6 3.3 15.3 6 3.9 12.2 6 3.1 2.5 6 3.4 0.0 6 3.2
13.7 6 4.7 16 6 5 15 6 3.5 13.7 6 4.3 1.3 6 4.2 —2.3 6 4.7
12 6 3 12.3 6 2.7 13.9 6 3.3 12.1 6 3.0 1.9 6 3.2 —0.2 6 2.9
13.3 6 3.3 15.6 6 4.7 15.0 6 3.4 14.3 6 3.8 1.7 6 3.4 —1.3 6 4.3
N/A N/A 11.7 11.4 MD of absolute change, 0.3 (95%
CI, —0.29 to 0.89)
Gambar 4. Membandingkan olahraga dan perubahan AT pada AAA

Gambar 5. Subanalisis forest plot yang Membandingkan olahraga dan perubahan AT pada AAA

Gambar 6. Analisis metaregresi durasi olahraga (minggu) berdasarkan MD AT

KESIMPULAN

Analisis kami menunjukkan bahwa latihan olahraga di antara pasien AAA umumnya
aman, meskipun penelitian masa depan harus dilakukan untuk lebih memperjelas
keselamatan di antara pasien dengan besar puncak VO2 dan AT pada pasien AAA. Data
lebih diperlukan untuk mengidentifikasi durasi latihan yang optimal untuk meningkatkan
kapasitas latihan pada pasien dengan AAA.