Training and exercise treatment of PAD patients

escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-20/training-and-exercise-treatment-of-pad-patients

Vol. 20, N° 8 - 28 Jul 2021

Dr. Luca Moderato

Prof. Massimo F. Piepoli , FESC, FHFA

Lower extremity artery disease (LEAD) is an occlusive atherosclerotic disease that affects
peripheral arteries, reducing the blood flow to the lower limbs. In the early stages, LEAD
is usually asymptomatic but, with its progression, intermittent claudication (IC) appears,
with a progressive decrease in walking performance. Both aerobic (such as walking) and

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strength training can be effective for improving quality of life, walking distance and
cardiovascular outcome; healthcare professionals must recommend and refer to
structured, supervised exercise programmes, which must be made available both in
community health services and at hospitals. New technology, telemedicine, coaching, and
strategies for facilitating exercise in a home-based setting could be game changing if well
structured (Figure 1).

Peripheral Artery Disease

Figure 1. Physical exercise in LEAD

Background
Lower extremity artery disease (LEAD) is an occlusive atherosclerotic disease that affects
peripheral arteries, reducing the blood flow to the lower limbs. The prevalence of LEAD is
high: globally, 202 million people are affected, including 40 million in Europe. Its
prevalence is slightly higher in men than in women, particularly in the younger age
groups, and it is more common in non-Hispanic blacks (7.8%) than in whites (4.4%) [1].

LEAD usually develops after the age of 50 years, with an exponential increase after the
age of 65 years [1].

LEAD shares the major cardiovascular risk factors, with some differences in their relative
importance. Tobacco use and diabetes mellitus are major contributors to LEAD [2].

In the early stages, LEAD is usually asymptomatic but, with its progression, intermittent
claudication (IC) appears, with a progressive decrease in walking performance as LEAD
severity increases [3]. IC affects the patient’s functional level as well as quality of life
(QOL).

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Reduced physical activity due to leg pain can lead the patients into a vicious circle of a
sedentary lifestyle, which again increases the progression of the disease.

A structured or supervised physical activity programme can break this circle and
dramatically improve QOL, functional capacity and cardiovascular outcome.

Effects of exercise

As ESC recent guidelines state, exercise therapy (ExT) is highly recommended and
effective for improving symptoms, walking distance and QOL [4].

ExT can work through multiple paths, e.g., by increasing blood flow, improving endothelial
function, providing long-term reduction in inflammation and oxidative stress, inducing
angiogenesis or modifying muscle morphology and metabolism [5].

Despite the fact that the mechanisms are still debated, it is unanimously recognised that
ExT can dramatically change the QOL of patients with IC.

However, ExT is still underused. A recent meta-analysis highlighted that ExT improves
cardiorespiratory fitness, pain-free and total flat-ground walking distances, as well as
graded treadmill performance in LEAD patients [6].

A Cochrane review found that ExT increased maximal walking time by almost five
minutes compared with usual care [7]. Notably, supervised ExT seems superior to
surgical treatment in improving treadmill walking performance, even for those with
aortoiliac peripheral artery disease [8].

Therefore, the promotion of ExT in patients with LEAD/IC is the most important non-
pharmacological strategy not only to treat and prevent the disease, but also for
cardiovascular mortality and morbidity [9].

Functional assessment
Functional assessments allow an objective evaluation of the functional limitation in order
to assess the stability of the clinical status, and to evaluate changes in performance after
revascularisation, pharmacological treatment or rehabilitation intervention.

Constant load or ramp protocols are the most used protocols on the treadmill. Constant-
load tests involve walking patients at a constant speed and slope (2.3 km/hr at 7.5%, 3.0
or 3.2 km/hr at 10%) until symptoms appear.

Ramp protocols involve a fixed walking speed (e.g., 3.2 or 3.5 km/hr) with increases in
slope at predetermined time intervals (3.5% every 3 minutes or 2% every 2 minutes) until
pain threshold is reached.

The key parameters obtained through these tests, useful for assessing walking
performance, are absolute claudication distance (ACD), total walking distance (TWD),
and maximal walking distance (MWD). These acronyms are used to indicate the total

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distance that the subject with LEAD is able to walk before the ischaemic pain becomes so
severe that he/she must stop walking.

Absolute claudication time (ACT), maximal walking time (MWT), and peak walking time
(PWT), on the other hand, refer to the maximum walking time the patient is able to
manage before the ischaemic pain forces him/her to stop.

Pain-free walking distance (PFWD), and intermittent claudication distance/initial

claudication distance (ICD) represent the walking distance covered without ischaemic
pain.

The severity of the symptoms experienced by the patient during the test can also be
evaluated through a pain scale ranging from 0 to 4 (0 = no pain, 1 = onset of claudication,
2 = mild pain, 3 = moderate pain, 4 = severe pain).

One of the most known and diffuse protocols is the 6-minute walk test or six-minute
walking test. This easy-to-perform test consists of patients walking the maximum possible
distance in 6 minutes. Once claudication appears, the patient informs the physician by
continuing to walk until the claudication becomes unbearable. Once walking is interrupted
due to pain, the patient can resume the test as soon as possible. After the 6 minutes have
elapsed, the total distance walked is calculated and the distance at the onset of
symptoms (PFWD) is noted. In absolute terms, a walking distance of less than 300 m is
considered an unfavourable prognostic value in terms of short-term cardiovascular
morbidity and mortality.

Type of exercise

Before exercise prescription, cardiovascular and injury risk should be assessed by the
exercise physiologist or health professional prescribing exercise guided by a cardiologic
framework (e.g., an electrocardiogram [ECG], cardiac imaging, and/or stress testing).
Routine stress testing in asymptomatic patients is not required, as a low rate of
complications (1 in 10,340 patients) has been described previously [10].

The cardiologist in conjunction with the physiotherapist or kinesiologist should have four
main objectives for prescribing supervised exercise (SET):-

- Select the most appropriate exercise modalities (resistance training, strength training,
combination training, etc.).

- Select the appropriate intensity of exercise.

- Educate the patient on what to expect from the exercise programme by providing a
progression of training (with planned increases in intensity and duration over time).

- Have the subject understand the exercise routine and what to expect from it. Patients
should be informed that it typically takes 4 to 6 weeks to realise improvements in walking
performance.

Endurance training

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Endurance training is set around endurance and is based on the ability to tolerate
physical exertion for a certain period of time. Also called aerobic training, it includes
activities that increase heart rate and respiratory rate. Examples include walking,
swimming and cycling.

For those patients who can walk, interval walking at the maximum tolerable speed is the
most frequently recommended exercise modality for this population. Three sessions per
week, of at least 40 minutes of walking in each session, consistently lead to
improvements in walking ability [6].

There should be warm-up and cool-down periods of 5-10 minutes each. The initial
workload of the treadmill is set to a speed and grade that elicit claudication symptoms
within 3-5 minutes; patients should walk at this pace until claudication of moderate
severity occurs, then rest standing or sitting for a brief period to permit symptoms to
subside. The exercise–rest–exercise pattern should be repeated throughout the exercise
session. As the patient’s walking ability improves, the exercise workload should be
increased by modifying the treadmill grade or speed (or both) to ensure that the stimulus
for claudication pain always occurs during the workout. As walking ability improves, and a
higher heart rate is reached, there is the possibility that cardiac signs and symptoms may
appear. These symptoms should be appropriately diagnosed and treated [4].

For those patients who find it difficult to complete walking because of early or intolerable
claudication pain, or other comorbidities, other forms of aerobic exercise such as lower
extremity aerobic circuit training (which is a type of overload training performed in a circuit
of multiple sets of exercises using medium to high repetitions, low intensities, with no
breaks, or very short breaks between exercises, generally involving the calf, quadriceps,
and hamstrings), and Nordic Pole walking (walking while using poles), have been shown
to be effective in improving walking ability [11].

Strength training

Increasing strength and muscle mass, increasing connective tissue strength, and
decreasing the risk of injury are the main benefits of this type of physical activity.

A minimum of two, ideally three, sessions per week, performed on non-consecutive days,
is recommended.

Resistance training is usually prescribed in addition to walking or other forms of aerobic

exercise, although it should be noted that the effects of this combined approach have not
been systematically examined in PAD.

Patients should undertake 3 sets of 8-12 repetitions with rest intervals of 1-2 minutes of
progressive whole-body resistance training incorporating 6-8 exercises including the
primary muscle groups involved in walking (i.e., gastrocnemius, tibialis anterior,
quadriceps, hamstrings, and glutes). If time is limited, the focus should be on
strengthening the lower extremity muscles, as improvements in leg muscle function are
often accompanied by improvements in walking ability in LEAD [12].

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Exercise prescriptions for LEAD may consider arm cranking as well as lower limb
exercise, possibly at short vigorous intensity intervals, but only to a threshold of mild pain
[6].

Supervised, unsupervised and tele-exercise

Exercise programmes may be self-directed, supervised, and institution- or home-based.

Supervised exercise has been shown to reduce overall cardiovascular mortality by 52%
and morbidity by 30% [9] and increase maximal walking distance more than unsupervised
exercise in LEAD patients [7].

However, since not all patients can be involved in participation in supervised exercise
programmes, alternative options should be offered. Home-based exercise did not show
significant improvement in symptoms and walking ability, although data are still scarce: a
2015 review highlighted that home-based supervised exercise may improve maximal and
PFWD compared to just giving advice about exercise, but it was less effective than
hospital-based supervised exercise [14].

The recent LITE trial [15], a multicentre study with 305 LEAD patients, showed that high-
intensity home-based exercise with telephone coaching meaningfully improved 6-minute
walking distance; on the other hand, light-intensity home-based exercise and control did
not improve walking performance.

These results underline how modern technology, such as tele-coaching or telemonitoring

associated with wearable monitors and accelerators, could be an option for patients with
LEAD to improve their quality of life and walking distance.

Conclusion
In LEAD, walking turns out to be the most diffuse and effective form of aerobic training,
with an interval mode of exercise and setting its timing mainly on the subjective pain
threshold based on the Borg scale. The studies analysed show that a period of exercise
set around this type of training contributes effectively to an improvement in exercise
performance and functional status of the subject suffering from LEAD.

In particular, there is an increase in timing and total distance during walking and a
lengthening of the walking parameters and time travelled below the threshold of
ischaemic pain.

Strength training involving multiple muscle groups, characterised by activity intervals and
rest periods calculated from the Borg scale, maximum repetitions, or the onset of
perceived ischaemic pain, may yield results similar to or less than endurance-based
training at the level of subjects' walking performance.

Although many studies support exercise as a conservative treatment for LEAD, the idea
of a surgical approach as the only way to improve symptoms, exercise performance, and
quality of life for LEAD subjects remains deep-rooted.

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If the goal is to offer best medical therapy to these patients, healthcare professionals must
recommend and refer to structured, supervised exercise programmes, which must be
made available both in community health services and in hospitals. In addition, new
technology, telemedicine, coaching, and strategies for facilitating exercise in a home-
based setting could be game changing if well structured.

References

1. Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM,

Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. Comparison of
global estimates of prevalence and risk factors for peripheral artery disease in 2000
and 2010: a systematic review and analysis. Lancet. 2013;382:1329-40.
2. Criqui MH, Aboyans V. Epidemiology of Peripheral Artery Disease. Circ Res.
2015;116:1509-26.
3. Silva R de CG, Wolosker N, Yugar-Toledo JC, Consolim-Colombo FM. Vascular
Reactivity Is Impaired and Associated With Walking Ability in Patients With
Intermittent Claudication. Angiology. 2015;66:680-6.
4. Aboyans V, Ricco JB, Bartelink MEL, Björck M, Brodmann M, Cohnert T, Collet JP,
Czerny M, De Carlo M, Debus S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai
L, Naylor AR, Roffi M, Röther J, Sprynger M, Tendera M, Tepe G, Venermo M,
Vlachopoulos C, Desormais I, ESC Scientific Document Group. 2017 ESC
Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in
collaboration with the European Society for Vascular Surgery (ESVS). Eur Heart J.
2018;39:763-816.
5. Rodrigues E, Silva I. Supervised exercise therapy in intermittent claudication: a
systematic review of clinical impact and limitations. Int Angiol. 2020;39:60-75.
6. Parmenter BJ, Dieberg G, Smart NA. Exercise Training for Management of
Peripheral Arterial Disease: A Systematic Review and Meta-Analysis. Sports Med.
2015;45:231-44.
7. Lane R, Ellis B, Watson L, Leng GC. Exercise for intermittent claudication.
Cochrane Database Syst Rev. 2014;(7):CD000990.
8. Murphy TP, Cutlip DE, Regensteiner JG, Mohler ER, Cohen DJ, Reynolds MR,
Massaro JM, Lewis BA, Cerezo J, Oldenburg NC, Thum CC, Goldberg S, Jaff MR,
Steffes MW, Comerota AJ, Ehrman J, Treat-Jacobson D, Walsh ME, Collins T,
Badenhop DT, Bronas U, Hirsch AT; CLEVER Study Investigators. Supervised
Exercise Versus Primary Stenting for Claudication Resulting From Aortoiliac
Peripheral Artery Disease: Six-Month Outcomes From the Claudication: Exercise
Versus Endoluminal Revascularization (CLEVER) Study. Circulation. 2012;125:130-
9.
9. Sakamoto S, Yokoyama N, Tamori Y, Akutsu K, Hashimoto H, Takeshita S. Patients
With Peripheral Artery Disease Who Complete 12-Week Supervised Exercise
Training Program Show Reduced Cardiovascular Mortality and Morbidity. Circ J.
2009;73:167-73.

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 10. Gommans LN, Fokkenrood HJ, van Dalen HC, Scheltinga MR, Teijink JA, Peters
RJ. Safety of supervised exercise therapy in patients with intermittent claudication. J
Vasc Surg. 2015;61:512-8.
11. Langbein WE, Collins EG, Orebaugh C, Maloney C, Williams KJ, Littooy FN,
Edwards LC. Increasing exercise tolerance of persons limited by claudication pain
using polestriding. J Vasc Surg. 2002;35:887-93.
12. Wang E, Hoff J, Loe H, Kaehler N, Helgerud J. Plantar flexion: an effective training
for peripheral arterial disease. Eur J Appl Physiol. 2008;104:749-56.
13. Bäck M, Jivegård L, Johansson A, Nordanstig J, Svanberg T, Adania UW, Sjögren
P. Home-based supervised exercise versus hospital-based supervised exercise or
unsupervised walk advice as treatment for intermittent claudication: a systematic
review. J Rehabil Med. 2015;47:801-8.
14. McDermott MM, Spring B, Tian L, Treat-Jacobson D, Ferrucci L, Lloyd-Jones D,
Zhao L, Polonsky T, Kibbe MR, Bazzano L, Guralnik JM, Forman DE, Rego A,
Zhang D, Domanchuk K, Leeuwenburgh C, Sufit R, Smith B, Manini T, Criqui MH,
Rejeski WJ. Effect of Low-Intensity vs High-Intensity Home-Based Walking Exercise
on Walk Distance in Patients With Peripheral Artery Disease: The LITE Randomized
Clinical Trial. JAMA. 2021;325:1266-76.

Notes to editor

Authors:

Luca Moderato1, MD, PhD; Professor Massimo F. Piepoli2, FESC, FHFA

Cardiology Department, Piacenza Guglielmo da Saliceto Hospital, Piacenza, Italy

1. EJPC Deputy Editor; Young Acute Cardiovascular Care Community Ambassador;

EHJ-CR Junior Reviewer
2. Councillor, European Society of Cardiology; HFA Board Member; European Journal
of Preventive Cardiology - Editor-in-Chief

Address for correspondence:

Dr. Luca Moderato

Cardiology Department, Piacenza Guglielmo da Saliceto Hospital, Via Taverna Giuseppe,
49, 29121 Piacenza PC, Italy

E-mail: Moderatoluca@gmail.com

Author disclosures:

Dr. Moderato has no conflicts of interest to declare.

Professor Piepoli received speaker honorarium, consultancy from Astra Zeneca, CHF
Solution, Novartis, and Servier.

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The content of this article reflects the personal opinion of the author/s and is not
necessarily the official position of the European Society of Cardiology.

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