Exercise Therapy For Intermittent Claudication

Wang Yan 王焱 Ph D.

Xiamen Heart Center

Zhongshan Hospital Xiamen University

• Peripheral arterial disease(PAD)

Intermittent Claudication: A typical symptom of PAD, defined as walking induced pain in one or both legs that dose not go away with continued walking and is relieved only by rest.

Peripheral arterial disease

Superior mesenteric artery & celiac artery (Intestines)

Common iliac artery (Legs)

Ischemia:decreased oxygen-rich blood to an area, which can cause pain and dysfunction

Narrowed artery

Carotid artery (Brain)

Aorta (to body)

Decreased quality of life

Limit activities of daily livingLimit recreational activitiesPossible amputation(s) with progression of underlying PAD

Decreasedlife expectancy

PAD shortens life expectancy by 10 years

Increased mortality rate

3 fold increased risk of death from all causes and 6 fold increase in risk of cardiovascular related death in patients with large vessel PAD compared with age and gender-matched patients with same risk factors but without PAD

Am J Cardiol. 2001;87 (suppl):3D-13D

Treatments For Claudication

N Engl J Med, Vol. 347, No. 24,1941

Be considered first

Introduction of TASC

Number 1, Part 2:S93

VASCULAR

Management of Peripheral Arterial Disease (PAD)TransAtlantic Inter-Society Consensus (TASC)

TASC

SURGERY

J O U R N A L O FSUPPLEMENT TO

VOLUME 31 NUMBER 1 PART 2 JANUARY 2000

Mosby

Section A: IntroductionSection B: Intermittent Claudication

Section C: Acute Limb IschemiaSection D: Critical Limb Ischemia

Developed by theTASC Working Group

In order to ensure an appropriate management algorithms and to achieve the optimal outcome for PAD patients, a group of experts in managing these patients had formulated the TransAtlantic Inter-Society Consensus (TASC). The TASC Working Group consisted of 14 MD societies across United States & Europe who had formulated the TASC Guidelines in the management of PAD based in current evidence-based medicine.

J Vasc Surg. 2000;31(1 Part 2):S1-S296

• 107 Recommendations• 47 Critical Issues

• Functional Benefits of Exercise Therapy

• Potential Mechanisms of Improvement

• Exercise Prescription

Functional Benefits of Exercise Therapy

• Meta-analysis*: Improved pain-free walking

distance by an average of 179%, maximal walking distance of 122%

• Cochrane Collaboration#: Improved maximal walking time

by 150% (74~230%)

* JAMA 1995;274:975-80

# Cochrane Database Syst Rev 2000 2 CD00990

Effects of Exercise Training on Claudication

Gardner AW, Poehlman ET. JAMA. 1995;274:975-980.

Exercise Training

Control

200

0

20

40

60

80

100

120

140

160

180

Onset of Claudication Pain

Maximal Claudication Pain

Change in T

readm

ill W

alk

ing

Dis

tance

(%

)

Meta-analysis of 21 Studies

*

*

* P < 0.05

Functional Benefits of Exercise Therapy

• Meta-analysis*: Improved pain-free walking

distance by an average of 179%, maximal walking distance of 122%

• Cochrane Collaboration#: Improved maximal walking time

by 150% (74~230%)

* JAMA 1995;274:975-80

# Cochrane Database Syst Rev 2000 2 CD00990

Potential Mechanisms of Improvement

• Formation of Collateral Vessels and angiogenesis • Changes in Endothelial Function• The Hemorheologic Hypothesis• Increases in Muscle Metabolism and Oxygen Extration• Inflammation and Muscle Injury• Effects to Risk Factors of Atherosclerosis

Formation of Collateral Vessels and angiogenesis

In healthy subjects, exercise therapy up-regulated the expression of vascular endothelial growth factor (VEGF) messenger RNA (mRNA) in calf muscle, with the size of the increase related in a dose-dependent fashion to the degree of metabolic stress. Am J Pisol 1999,276 H679

Formation of Collateral Vessels and angiogenesis (2)

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Changes in Endothelial Function

• Endothelial vasodilator function was impaired in patients with claudication

• Short term exercise stimulates endothelium-dependent vasolidatation by enhancing the release of nitric oxide and prostacyclin

Changes in Endothelial Function

Exercise improved endothelial-dependent dilation, and

calf blood flow in older PAD patients with intermittent claudication.

Am J Crdio 2001 87 324-9

The Hemorheologic Hypothesis

• Enhance collateral-dependent blood flow to the hind-muscles

but in humans are moderately* or limited#

• Redistribution of blood flow: from inactive to active muscles

• improved blood and plasma-viscosity, filtered the ability of autologous red cells and red-cell

aggregation

* Circulation 1990;81:602-9.#J Am Geriatr Soc 2001;49:755-62

2 months of exercise therapy improved Plasma viscosity, blood cell filterability, and maximal walking distance significantly(Exercise vs.contrl, P<0.05)

Circulation 1987:76:1110-4.

Increases in Muscle Metabolism and Oxygen Extration

• Exercise

the oxidative capacity of calf skeletal muscle ↑

Up-regulation of muscle enzyme activity

Patients with Patients with claudication claudication have an imbalance have an imbalance between between oxygen supply and oxygen supply and demanddemand

lactate ↑

intermediates of oxidative metabolism ↑

(short-chain acylcarnitines)

Mitochondria ↑

ATP ↑

l.J A pplP hysiol, 1996;8 1:780-78

Inflammation and Muscle Injury

• Ischemia increases free-radical formation, neutrophil action, and systemic vascular endothelial damage

• Exercise can lessen ischemia at any achieved workload and decrease markers of systemic inflammation:

serum amyloid A protein

C-reactive protein

the urinary ratio of albumin to creatinine…

Effects to Risk Factors of Atherosclerosis

• Additional benefits that go beyond improvements in functional capacity and claudication

• Exercise may also improve systemic cardiovascular health: reduce blood pressure improve lipid profile (↑HDL , ↓TG ) better glycemic control (in diabetic patients) reduce central obesity improve weight lose ……

Conclusion of Mechanisms

Exercise therapy

↑Nitric oxide synthase

↑Prostacyclin

↓Free radicals

↑ VEGF

↑ Muscle oxidative capacity

↑ Muscle enzyme activity

↑ Blood viscosity and filterability

↓ Red-cell aggregation

Improved endothelial

function

Reduced inflammation

Possible vascular angiogenesis

Improved muscle metabolism

Improved hemorheology

Key Elements of an Effective PAD Therapeutic Claudication Exercise Program

Primary clinician role:• Establish the PAD diagnosis using the ABI measurement

or other objective vascular laboratory evaluations

• Determine that claudication is the major symptom limiting exercise

• Discuss risk/benefit of claudication therapeutic alternatives, including pharmacological, percutaneous, and surgical interventions

• Initiate systemic atherosclerosis risk modification

• Perform treadmill stress testing

• Provide formal referral to a claudication exercise rehabilitation program

Also see Table 18 of Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192.

Exercise Prescription

Supervised Exercise Rehabilitation

A program of supervised exercise training is recommended as an initial treatment modality for patients with intermittent claudication.

Supervised exercise training should be performed for a minimum of 30 to 45 minutes, in sessions performed at least three times per week for a minimum of 12 weeks.

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- ACC/AHA 2005 Guidelines for the management of Patients with Peripheral Arterial Disease

The PAD Exercise Training Prescription

• Warm-up: Approximately 5 minutes• Repeated exercise periods: End at

moderate claudication level• Rest Periods: Until claudication abates

This exercise interventional program has not been shown to be efficacious in a “home” setting. It requires a specific

procedure and environment, much like invasive interventional procedures.

Exercise Rest Exercise Exercise Cool

Down

Rest

Warm-up

Key Elements of an Effective PAD Therapeutic Claudication Exercise Program

Exercise Guidelines for Claudication:• Warm-up and cool-down period: 5 to 10 minutes each• Types of exercise:

– Treadmill and track walking are the most effective exercise for claudication

– Resistance training has conferred benefit to individuals with other forms of cardiovascular disease, and its use, as tolerated, for general fitness is complementary to but not a substitute for walking

• Intensity:– The initial workload of the treadmill is set to a speed and grade that elicit

claudication symptoms within 3 to 5 minutes

– Patients walk at this workload until they achieve claudication of moderate severity, which is then followed by a brief period of standing or sitting rest to permit symptoms to resolve

Also see Table 18 of Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192.

Exercise Guidelines for Claudication:• Duration:

– The exercise-rest-exercise pattern should be repeated throughout the exercise session

– The initial duration will usually include 35 minutes of intermittent walking and should be increased by 5 minutes each session until 50 minutes of intermittent walking can be accomplished

• Frequency– Treadmill or track walking 3 to 5 times per week

Key Elements of an Effective PAD Therapeutic Claudication Exercise Program

Also see Table 18 of Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192.

Role of Direct Supervision:• As patients improve their walking ability, the exercise workload should be

increased by modifying the treadmill grade or speed (or both) to ensure that there is always the stimulus of claudication pain during the workout

• As patients increase their walking ability, there is the possibility that cardiac signs and symptoms may appear (e.g., dysrhythmia, angina, or ST-segment depression). These events should prompt physician re-evaluation

• These general guidelines should be individualized and based on the results of treadmill stress testing and the clinical status of the patient. A full discussion of the exercise precautions for persons with concomitant diseases can be found elsewhere for diabetes *

*(Ruderman N, Devlin JT, Schneider S, Kriska A. Handbook of Exercise in Diabetes. Alexandria, Va: American Diabetes Association; 2002), (ACSM's Guidelines for Exercise Testing and Prescription. In: Franklin BA, ed. Baltimore, Md: Lippincott Williams & Wilkins; 2000), (Guidelines for Cardiac Rehabilitation and Secondary Prevention/American Association of Cardiovascular and Pulmonary Rehabilitation. Champaign, Ill: Human Kinetics; 1999).

Key Elements of an Effective PAD Therapeutic Claudication Exercise Program

Also see Table 18 of Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192.

PAD Guideline-Based Care:Claudication Treatment via Home Exercise

The usefulness of unsupervised exerciseprograms is not well established as aneffective initial treatment modality forpatients with intermittent claudication.

Hirsch AT, et al. J Am Col Cardiol. 2006;47:1239-1312.

The lack of proven efficacy for home-based, unsupervised exercise may be due to:

• A lack of compliance with the minimum “exercise dose”;• A lack of progression of the workload in the absence of

professional supervision;• A lack of confidence by the patient that it is safe to advance

into moderate claudication discomfort severity.

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Exercise combined with other treatments

• Exercise therapy may augment the effects of other treatments for claudication.

• The combination of revascularization procedures (bypass surgery and angioplasty)and exercise was more effective than either intervention alone.

• Patients may also benefit from the use of pharmacologic therapies

Conclusions• Exercise therapy is an effective

treatment for claudication.

• Increses in functional capacity and lessening of claudication symptoms may be explained by several mechanisms.

• A supervised hospital- or clinic-based prescription, which ensures that patients are receiving a standardized exercise stimulus in a safe enviroment, is effective.

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