Artigo_Exercise Training for Patients With Peripheral Arterial Occlusive Disease 2023

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M E D I C I N E
Review Article
Exercise Training for Patients With 
 Peripheral Arterial Occlusive Disease
Efficacy and Adherence
Maja Ingwersen, Ina Kunstmann, Carolin Oswald, Norman Best, 
Burkhard Weisser, Ulf Teichgräber
A bout one-third of all persons with peripheral arterial 
occlusive disease (PAOD) suffer from intermittent 
claudication (1). Their quality of life is affected by 
calf pain (1). In addition, they are at high cardiovascular 
risk (amputation-free survival after five years ranges be-
tween 52% and 91%, depending on age and comorbid-
ities) (2). Progression of the disease is to be expected in 
about one-quarter of patients (1).
Summary
Background: One-third of all persons with peripheral arterial occlusive disease (PAOD) suffer from intermittent claudication. 
 Exercise training under appropriate supervision is recommended in the pertinent guidelines, but physicians order it too rarely, 
and so-called vascular exercise groups are not available everywhere. This situation needs improvement in view of the impor -
tance of walking ability and cardiorespiratory fitness for patients’ quality of life and long-term disease outcome. 
Methods: We review the scientific evidence on exercise training and on ways to lower barriers to the ordering of exercise train-
ing and to patient participation, on the basis of pertinent articles retrieved by a search of PubMed and in specialized sports 
science journals.
Results: 10 meta-analyses, 12 randomized controlled trials (RCTs), and 7 cohort studies were considered for this review. Large-
scale cohort studies have shown that exercise is associated with a lower risk of death (relative risk 0.65–0.78 after 12 months of 
exercise training, compared to an inactive lifestyle). Exercise training also improves the maximal walking distance by a mean of 
136 m (training at home) or 180–310 m (supervised training). An additional improvement by a mean of 282 m can be expected 
from a combination of exercise training and endovascular revascularization. Further behavior-modifying interventions, such as 
goal-setting, planning, and feedback, increase both the maximum walking distance and the weekly duration of exercise. 
Conclusion: Exercise improves walking ability and lowers mortality. To attract patients with intermittent claudication to exercise 
training, a broad assortment of analog, digital and telemetric tools and a dense network of vascular exercise groups should be 
made available, along with regular contact between physicians and patients. 
Cite this as: 
Ingwersen M, Kunstmann I, Oswald C, Best N, Weisser B, Teichgräber U: Exercise training for patients with peripheral arterial 
occlusive disease—efficacy and adherence. Dtsch Arztebl Int 2023; 120: 879–85. DOI: 10.3238/arztebl.m2023.0231
Institute of Diagnostic 
and Interventional 
Radiology, Jena 
 University Hospital, 
Jena, Germany: Dr. 
med. vet. Maja Ing-
wersen, Dr. med. Ina 
Kunstmann, Carolin 
Oswald, Prof. Dr. 
med. Ulf Teichgräber
Institute of Physical 
and Rehabilitation 
Medicine, Sophien 
and Hufeland Hospi-
tal Weimar, Academic 
Teaching Hospital, 
University of Jena, 
Jena, Germany: PD 
Dr. med. Norman 
Best
Institute of Sports 
Science, Department 
of Sports Medicine, 
Kiel University, Kiel, 
Germany: Prof. Dr. 
med. Burkhard 
Weisser
Exercise can improve the symptoms, the quality 
of life and the prognosis of PAOD patients (3–19). 
A significant inverse dose-response relationship is 
found between exercise and all-cause mortality (7, 
10, 11, 20). Despite the fact that, due to the signifi-
cant evidence in support of this association, exer-
cise training under appropriate supervision is 
clearly recommended in the pertinent guidelines as 
part of con servative treatment ( level of evidence: 
1; grade of recommendation: A) (21–26), this rec-
ommendation is rarely followed in practice (27). 
Patients are often not informed about the risks and 
possibilities of influencing the disease and are not 
given much support in making the necessary be -
havioral changes. Until today, so-called vascular 
exercise groups are not available everywhere in 
Germany (28–31).
This article has been certified by the North Rhine Academy for Continuing 
 Medical Education. Participation in the CME certification program is possible 
only over the internet: cme.aerzteblatt.de. The deadline for submission is 26 
December 2024.
cme plus
Deutsches Ärzteblatt International | Dtsch Arztebl Int 2023; 120: 879–85 879
M E D I C I N E
The aim of this review is to provide an overview of 
the available research evidence on exercise training 
for patients with PAOD to shed light on the problem 
of treatment adherence and to propose motivation 
concepts.
Methods
We searched the PubMed database, using the following 
search terms: “peripheral artery disease“, “claudi-
cation”, “intermittent claudication”, “supervised exer-
cise”, ”home-based exercise”, “exercise therapy”, 
“physical activity”, “walking training”, and “exercise 
program”. In addition, we considered references from 
the field of sports science as well as online documents 
of the German Federal Ministry of Health (BMG, 
 Bundesgesundheitsministerium), the German Federal 
Joint Committee (G-BA, Gemeinsamer Bundesaus -
schuss), the German Society for Angiology – Society 
for Vascular Medicine e.V. (DGA), the German Vascu-
lar League e.V. (Deutsche Gefäßliga e. V.), and the 
UK’s National Institute for Health and Care Excellence 
(NICE).
Management and secondary prevention of intermittent 
claudication
Exercise training is just as much an integral part of 
guideline-adherent therapy of PAOD as is the control of 
blood pressure and blood glucose levels and the use of 
statins and antiplatelet agents. It is also essential that 
smokers quit their nicotine habits (21, 22, 31). In addi-
tion, it is possible to address overweight and systemic 
inflammatory processes through diet. Fruit, vegetables, 
nuts, pulses, whole grains, and fish are considered 
healthy foods (32).
Ideally, exercise training is supervised by certified 
persons (German Society for the Prevention and Re-
habilitation of Cardiovascular Diseases [DGPR, 
Deutsche Gesellschaft für Prävention und Rehabili-
tation von Herz-Kreislauferkrankungen e. V.]) (33, 
34). Apart from a heart group leader’s license, those 
who take on the supervision of vascular exercise 
groups should also be qualified as vascular exercise 
coaches (“Gefäßsporttrainer“, DGPR). Home training 
is an alternative or complementary option (35–39). In 
severely impaired patients, endovascular revascular-
ization should be considered as a supportive measure 
(40).
Efficacy of exercise training
There is a substantial body of evidence to support a re-
duction in risk through exercise (eTable 1) (4, 8–14). In 
addition, lack of exercise has been found to be an inde-
pendent risk factor for mortality and morbidity (15, 16). 
Exercise training plays a significant role in increasing 
cardiorespiratory fitness (CRF), a factor which is 
strongly associated with both the risk of cardiovascular 
events, such as arrhythmia and thrombosis, and mortal-
ity.
CRF is in fact a stronger predictor of mortality than 
diabetes (e1–e3). It describes the maximum perform-
ance, i.e. the aerobic capacity of the body (maximum 
oxygen uptake VO2-max in mL/kg/min). The resting 
oxygen uptake capacity corresponds to a metabolic 
equivalent of task (MET). A healthy middle-aged 
adult has a CRF of 8 to 12 MET. CRF declines with 
age and is lower in women. A meta-analysis of 33 
 cohort studies showed that an increase in CRF by 
1 MET was associated with a decrease in mortality by 
13% (pooled relative risk [RR] 0.87; follow-up: 1–26 
years) (e4).
Furthermore, it is well supported by evidence that 
exercise training improves walking ability and quality 
of life in patients with PAOD (eTable 2) (17–19, 33, 
34, 37–39, e5–e8). The exact mechanism is not yet 
fully understood. Improvements in endothelial func-
tion and increases in capillarydensity in muscle tissue 
have been described. Exercise training improves 
 mitochondrial function in muscle cells, while inflam-
matory mediators decrease. Consequently, muscular 
microcirculation and metabolism are improved. In ad-
dition, there is an increase in cardiac stroke volume, 
oxygen transport and metabolism as well as insulin 
sensitivity (23, e9). After about four weeks of 
 exercise training, an improvement in walking ability 
can be expected (e10).
With regard to walking ability, combining exercise 
training and revascularization has been shown to be 
more effective overall than either measure alone (19, 
e5, e7, e8). In addition, patients who engaged in exer-
cise training after a peripheral revascularization 
 procedure required repeat revascularization less 
 frequently (3, e11) (eTable 2).
The practice of exercise training
Classical walking training involves a minimum of three 
weekly sessions, each of 30 to 45 minutes of actual 
walking time. With treadmill training, patients start at a 
comfortable speed with no incline. A short break of 
about one minute is made each time a patient starts to 
experience moderate to severe calf pain. The intensity 
level should be chosen so that patients can walk for 5 to 
10 minutes without stopping. Once they can walk for 
more than 10 minutes without stopping, the intensity 
(speed and incline) can be gradually increased. Ulti-
mately, the success of walking training depends more 
on training intensity than on training duration and fre-
quency. Later in the training program, walking training 
can be supplemented by resistance training. Possible 
 alternatives to classical treadmill training include 
physical activities such as climbing stairs, pedaling in a 
lying position, upper-arm ergometry, cycling training 
or everyday activities. These are particularly useful in 
patients with severe intermittent claudication, previous 
falls and unsteady gait, or if patients are reluctant to 
commit to the training. Training should be ongoing and 
preferably be carried out at moderate to high intensity 
(7, 9–12, 17, 23, 25, e1, e9, e10, e12–e14) (Table 1).
Table 2 lists various examples of the intensity of 
physical activities (e2, e15, e16). A moderate to 
strong intensity corresponds to ≥ 3 MET. The exercise 
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M E D I C I N E
training program should consist of ≥ 500–1000 MET 
minutes per week (9, e10, e12, e13, e16, e17). This 
unit of measurement is based on the intensity (MET) 
and duration (in minutes) of the respective activity. 
Supervised exercise training for a minimum of twelve 
weeks is considered the gold standard. The training 
should then be continued independently as part of 
everyday life. If patients cannot or only for a limited 
time participate in a supervised exercise training 
 program, training at home should be recommended 
as an alternative or in addition. This also leads to 
 improvements in walking ability and CRF, depending 
on training duration and intensity (17, 38, 39) 
 (eTable 2).
Overcoming personal barriers
With regard to the physical activity of PAOD patients, 
the current picture is one of missed opportunities. 
 Presently, primary care physicians and hospital doctors 
discuss exercise training with only one in three patients 
with intermittent claudication (29, 30). A survey study 
on inpatients in German hospitals found that only 11% 
of the PAOD patient in this patient population had ever 
participated in an exercise training program. Only 26% 
felt appropriately informed about the advantage of exer-
cise training by their GP practice and only 25% had 
 access to information about local exercise training pro-
grams. Yet, a majority of these patients (65%) found it 
conceivable that supervised exercise training may im-
prove their walking ability (28, 30). Physicians cited a 
lack of time, inadequate financial compensation and a 
lack of trust in patients‘ willingness to commit to exer-
cise training as reasons for not devoting much time to 
this topic, as well as the lack of vascular exercise groups 
(39). 
According to the transtheoretical model, the stages 
of change are pre-contemplation, contemplation, 
preparation, action, and maintenance (e18, e19). 
Based on this model, a phased approach to counseling 
is advisable. One example of this approach is de-
scribed in the guideline on physical activity advice of 
the National Institute for Health and Care Excellence 
(NICE, Manchester, UK) (see Box) (25).
Identifying risk behavior
Given its prognostic significance, physicians should 
ask patients about their physical activity as a “vital par-
ameter”: whether or not, what kind, for how long, how 
frequently (25, 29). During a routine visit, this should 
take no longer than three to four minutes..
 Recommending action
Once the assessment has been completed, patients are 
informed about the health benefits of physical activity 
(e10, e20). However, appeals and general advice alone 
are usually ineffective (e21, e22).
Exploring willingness
Next, patients are asked whether they are willing to 
change their behavior. Are the patients willing to start 
exercise training? Are there any obstacles? How could 
they start?
TABLE 1 
Recommendations for improving walking ability and cardiovascular fitness 
*1 For an individual prescription of physical activity with high intensity, a clinical examination should be per-
formed, including exercise ECG, especially in the presence of known cardiovascular risk factors, to rule 
out abnormal cardiovascular reactions and to determine the physical fitness. 
*2 Angina pectoris, dyspnea, hemodynamic instability, cardiac arrhythmia, rest pain and ulcers and/or 
 gangrene on the foot require interruption of training and diagnostic workup (23). 
*3 Swimming and water aerobics are viewed rather critically in patients with heart failure due to the 
 increased preload (24, e14). 
*4 Moderate intensity: 3–6 MET, 55–69% of max. heart rate (individually determined); respiratory rate 
 increased, but talking is still possible, “running without puffing”, Borg scale 11–13 RPE (e14). 
*5 High intensity: 6–9 MET, 70–89% of max. heart rate; fast respiratory rate and talking is difficult, 14–16 
RPE (e14). 
*6 Example: walking fast (5 MET) 30 min on 5 days/week and dancing (6 MET) 60 min on 1 day/week = 750 
MET-min + 360 MET-min = 1110 MET-min
MET, metabolic equivalent; RPE, rate of perceived exertion (on the Borg scale)
Physical activity
Type 
(23, e13, e14)
Intensity
(17, 23, e13, e14)
Frequency 
(13, 17, 25, e13)
Duration 
(7, 10–12, 25, e13)
Amount 
(9, e13)
Pattern 
(7, e14)
Progression 
(e13)
Recommendation for continuous endurance training*1 *2 
● First in intermittent claudication: treadmill training
● Involvement of large muscle groups (legs, arms, trunk)
● Continuous endurance training, e.g. walking, jogging, 
 cycling, swimming*3, rowing, climbing stairs, dancing
 – supplementary dynamic, isometric resistance training 
(strength endurance and muscle building) on ≥ 2 days/
week with moderate*4 to high*5 intensity (especially in 
 persons aged ≥ 65 years), e.g. yoga, weight training, 
 training with resistance bands, training with large equip-
ment (studio)
 – supplementary balance training in persons aged ≥ 65 years, 
e.g. dancing, bowling, Tai-Chi, on ≥ 2 days/week
 – Time without movement /sedentary activities should be 
 interrupted at least once per hour by 3–5 min standing or 
walking (true inactivity1x to 2x/week 
[“weekend warriors“])
● ≥ 150 min/week moderate*4 intensity (initially alsoPAOD)
RCT (35)
(symptomatic PAOD)
3 meta-analyses of 10 RCTs 
(e35)
(adults in a healthcare facil-
ities)
Intervention
Weekly group visits with cogni-
tive behavioral intervention + HT 
vs. weekly lectures on health 
topics (6 months, n = 88/90)
Diverse interventions for 
 behavioral change vs. no or al-
ternative behavioral measures 
(5 months, n = 3350/3713)
ST with use of a mobile appli-
cation vs. medical advice alone 
(3 months, n = 19/20)
Behavioral intervention + HT vs. 
usual care (3 months, n = 
74/74)
Brief counseling vs. no counsel-
ing (1–6 months, activity du-
ration: n = 748, steps: n = 117, 
 MET hours: n = 104)
Elements for behavioral change
● Discussion (45 min) + indoor walking 
distance (45 min). Discussion e.g. 
about the benefits of the training, 
weekly goals, implementation (at least 
5 times/week, up to 50 min/unit), self-
monitoring, pain management
● Weekly individual feedback
● Effective: Planning of activities, in-
structions/tips for implementation, 
stepwise goal setting, feedback, 
 rewarding progress
● Mobile application: weekly targets 
 entered; information on frequency and 
duration of training as well as pain and 
exhaustion. 
● The app reminds users and provides 
feedback on each exercise unit. 
● Comparison to the users
● Motivating and informative personal 
discussions and phone calls on per-
sonal goals und strategies (including 
planning and self-monitoring).
● Enabling independent implementation 
after intervention discussions 
● Brief counseling (5–30 minutes) on 
participation in physical activity 
 programs offered in the healthcare 
 facilities
Primary outcome
Change in 6-min walk distance: 
+ 42 m vs. – 11 m, p0.20]. At 24 months, the effect was no longer 
clinically important (36). A resolution passed by the 
Federal Joint Committee (G-BA) on 24 January 2023 
provides for an assessment of a nationwide implemen-
tation of this care model into routine care.
Vascular Check of the Legs
The “Gefäß-Check der Beine” project is a regional pilot 
project at the Jena University Hospital. It enables 
 community-based physicians to offer patients with sus-
pected PAOD a low-threshold “vascular check of the 
legs”. Based on the walk-in clinic model, the “vascular 
check” is performed in a specialist outpatient clinic at 
short notice without waiting time. The check includes a 
structured sequence of tests, including walking test, 
ankle-brachial index (ABI) and vascular Doppler ultra-
sound. The results should typically be available on the 
same day as the examination, together with treatment 
recommendations. The aim is early detection of PAOD 
so that progression and hospitalization can be 
 prevented. Digitally supported training at home is 
 arranged with patients who are diagnosed with PAOD. 
Follow-up examinations and feedback discussions, 
complementing the consultations with the primary care 
physician, are an integral part of this project.
Conclusion
Despite the strong evidence supporting its efficacy in 
patients with intermittent claudication, exercise train-
ing has not yet been adopted in clinical practice every-
where. Given the great prognostic significance of 
physical activity, a stronger support of PAOD patients 
by their physicians is desirable. This in turn requires 
that more exercise training opportunities are offered.
Conflict of interest statement 
The authors declare that no conflict of interest exists.
Manuscript received on 17 May 2023, revised version accepted on 18 
 October 2023.
Translated from the original German by Ralf Thoene, MD.
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Corresponding author 
Prof. Dr. med. Ulf Teichgräber 
Institut für Diagnostische und Interventionelle Radiologie 
Friedrich-Schiller-Universität Jena 
Universitätsklinikum Jena, 
Am Klinikum 1, 07747 Jena, Germany 
ulf.teichgraeber@med.uni-jena.de
Cite this as: 
Ingwersen M, Kunstmann I, Oswald C, Best N, Weisser B, Teichgräber U: 
Exercise training for patients with peripheral arterial occlusivedisease— 
efficacy and adherence. Dtsch Arztebl Int 2023; 120: 879–85. 
DOI: 10.3238/arztebl.m2023.0231
►Supplementary material
eReferences, eTables: 
www.aerzteblatt-international.de/m2023.0231
Deutsches Ärzteblatt International | Dtsch Arztebl Int 2023; 120: 879–85 885
M E D I C I N E
-- Deutsches Ärzteblatt International | Dtsch Arztebl Int 2023; 120: 879–85 | Supplementary material
Supplementary material to:
Exercise Training for Patients With Peripheral Arterial Occlusive Disease
Efficacy and Adherence
by Maja Ingwersen, Ina Kunstmann, Carolin Oswald, Norman Best, Burkhard Weisser, and Ulf Teichgräber
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M E D I C I N E
Deutsches Ärzteblatt International | Dtsch Arztebl Int 2023; 120: 879–85 | Supplementary material --
eTABLE 1 
Association between physical activity and mortality 
CRF, cardiorespiratory fitness; CV mortality, cardiovascular mortality; FU, follow-up; HR, hazard ratio; CHD, coronary heart disease; MET-h, metabolic equivalent in one hour; ns., 
 non-significant; vs., versus; RR, relative risk 
Study
Samitz, 2011 (12)
Lee, 2012 (16)
Moore, 2012 (11)
Hupin, 2015 (9)
Ekelund, 2016 (8)
Lear, 2017 (14)
Mandsager, 2018 (4)
Dos Santos, 2022 (13)
Lee, 2022 (10)
Jingije, 2022 (15)
Study design
Meta-analysis of 80 cohort 
studies: n = 1 339 143
Analysis of data from large cohort 
studies worldwide (Lancet physi-
cal activity series working group)
Pooled analysis of 6 cohort 
studies: n = 654 827 (median 
 follow-up: 10 years)
Meta-analysis of 9 prospective 
cohort studies: n = 122 417
>60-year-olds
Meta-analysis of 13 prospective 
cohort studies: n = 1 005 791 
Physical activity:
● low: 16 MET-h/week
● high: > 35.5 MET-h/week
Prospective cohort studies: 
n = 168 916
Retrospective cohort studies: 
n = 22 007 (median FU 8.4 
years)
Prospective cohort studies: 
n = 350 978 
(median FU 10.4 years)
Pooled analysis of 2 prospective 
cohort studies: 
n = 116 221 (FU 30 years)
Meta-analysis of 17 prospective 
cohort studies and 2 cross-
 sectional studies: n = 1 451 730
Intervention
Physical activity: 
highest versus lowest inten-
sity 
Physical inactivity
6–224 MET-min/week vs. 
0 MET-min/week
Physical activity vs. inactivity
Time without movement
> 8 h/day
vs.
 3 000 MET-min/
week
vs. 
control: 
p