superiority treadmill walkingexercise versus strength ...€¦ · graded treadmill testing was...

1866

Superiority of Treadmill Walking ExerciseVersus Strength Training for Patients With

Peripheral Arterial DiseaseImplications for the Mechanism of the Training Response

William R. Hiatt, MD; Eugene E. Wolfel, MD;Robert H. Meier, MD; Judith G. Regensteiner, PhD

Background In patients with intermittent claudication, asupervised walking exercise program increases peak exerciseperformance and community-based functional status. Patientswith peripheral arterial disease also have muscle weakness inthe affected extremity that may contribute to the walkingimpairment. However, the potential benefits of training mo-dalities other than walking exercise, such as strength training,have not been critically evaluated in this patient population.The present study tested the hypothesis that a strength train-ing program would be as effective as treadmill walking exerciseand that combinations of strengthening and walking exercisewould be more effective than either alone in improving exer-cise performance.Methods and Results Twenty-nine patients with disabling

claudication were randomized to 12 weeks of supervisedwalking exercise on a treadmill (3 h/wk at a work intensitysufficient to produce claudication), strength training (3 h/wk ofresistive training of five muscle groups of each leg), or a

nonexercising control group. Graded treadmill testing wasperformed to maximally tolerated claudication pain to definechanges in peak exercise performance. After 12 weeks, pa-tients in the treadmill training program had a 74+58% in-crease in peak walking time as well as improvements in peakoxygen consumption (Vo2) and the onset of claudicationpain. Patients in the strength-trained group had a 36±48%

Peatients with peripheral arterial disease (PAD)develop atherosclerotic occlusions of the lower-extremity arterial circulation. Clinically, pa-

tients with this disease experience muscle aching orcramping during walking exercise secondary to ischemiain the calf, thigh, or buttocks.1,2 This exercise-inducedischemic pain (intermittent claudication) limits peakexercise performance and oxygen consumption duringgraded treadmill exercise testing.3,4 The reduced exer-cise performance is associated with a restricted range ofability to perform ambulatory activities at home, in theworkplace, and during leisure time.

Received February 8, 1994; revision accepted May 10, 1994.From the Department of Medicine, Section of Vascular Medi-

cine; the Division of Cardiology; and the Department of PhysicalMedicine and Rehabilitation, University of Colorado HealthSciences Center, Denver.Correspondence to William R. Hiatt, MD, Section of Vascular

Medicine, University of Colorado Health Sciences Center, 4200 ENinth Ave, Box B-180, Denver, CO 80262.

(01994 American Heart Association, Inc.

increase in peak walking time but no change in peak Vo2 orclaudication onset time. Control subjects had no changes inany of these measures over the 12-week period. After the first12 weeks, patients in the initial walking exercise group contin-ued for 12 more weeks of supervised treadmill training. Thisresulted in an additional 49±53% increase in peak walkingtime (total of 128±99% increase over the 24 weeks). After theinitial 12 weeks, patients in the strength-trained group began12 weeks of supervised treadmill training, and patients in thecontrol group participated in a 12-week combined program ofstrengthening and treadmill walking exercise. The combinedstrength and treadmill training program and treadmill trainingafter 12 weeks of strength training resulted in increases in peakexercise performance similar to those observed with 12 weeksof treadmill training alone.

Conclusions A supervised treadmill walking exercise pro-gram is an effective means to improve exercise performance inpatients with intermittent claudication, with continued im-provement over 24 weeks of training. In contrast, 12 weeks ofstrength training was less effective than 12 weeks of supervisedtreadmill walking exercise. Finally, strength training, whethersequential or concomitant, did not augment the response to awalking exercise program. (Circulation. 1994;90:1866-1874.)Key Words * claudication * exercise * oxygen a

clinical trials

Walking exercise has been recommended as a non-surgical treatment for claudication.5 Most training stud-ies have been conducted in a supervised setting andused treadmill exercise as the primary training modal-ity. In a supervised program, the patient typically walkson a treadmill at an exercise intensity sufficient to bringon claudication pain. The walking exercise is inter-rupted by rest periods to relieve the claudication pain,and then walking exercise is resumed for a total rest andexercise time of 1 hour.6 Supervised treadmill walkingexercise is very effective in improving treadmill exerciseperformance and community-based walking ability.6-9

In addition to treadmill walking exercise, other activ-ities have been incorporated into the training sessions ofsome programs. These activities have included isotonicexercise of specific muscle groups, bicycle exercise,gymnastic exercise, and stair climbing, often under thesupervision of a physical therapist.10,1 However, therelative benefits of other training activities comparedwith walking exercise have not been studied. The obser-vation that patients with PAD have muscle weakness12provides a rationale for strength training muscle groups

by guest on May 1, 2017

http://circ.ahajournals.org/D

ownloaded from

http://circ.ahajournals.org/

Hiatt et al Exercise Training for Peripheral Arterial Disease 1867

of the lower extremity to improve walking ability. Thepresent study tested the hypothesis that a strengthtraining program would be as effective as and thatcombinations of strengthening and walking exerciseswould be more effective than a walking exercise pro-gram in improving peak exercise performance. Twenty-nine patients with PAD were initially randomized to 12weeks of treadmill walking exercise, a strength trainingprogram, or a nonexercising control group followed byan additional 12 weeks of a combination of theseprograms. The results demonstrate that treadmill walk-ing exercise remains the most effective exercise trainingprogram for patients with intermittent claudication.

MethodsStudy Population

Subjects were evaluated for the study who had intermittentclaudication, defined as pain in the calf, thigh, or buttocks thatlimited walking ability and that was relieved by rest within 10minutes.13 All patients reported that claudication was thelimiting symptom during community-based activities as well as

with treadmill exercise in the laboratory. The severity ofclaudication was stable over a 3-month period before enroll-ment (change, <1 block in walking distance by history). Theclaudication pain was also considered disabling, defined as

severe enough to interfere with the ability of the patient toperform social, recreational, or vocational activities. PAD was

confirmed by an ankle/arm systolic blood pressure ratio of<0.94 at rest that decreased to <0.73 after exercise.14 Thestudy was approved by the University of Colorado School ofMedicine Human Subjects Committee, and informed consentwas obtained from all enrolled subjects.

Forty-four male patients with PAD were screened for thestudy, but 15 were excluded before randomization. Reasonsfor exclusion included leg pain at rest, ischemic ulceration, or

gangrene. Patients were also excluded who were unable towalk on the treadmill at a speed of at least 2 mph or whoseexercise capacity was limited by symptoms of angina, conges-tive heart failure, chronic obstructive pulmonary disease, or

arthritis. Diabetics were excluded because the degree ofglycemic control may affect the response to a conditioningprogram.15 Patients who had undergone vascular surgery or

angioplasty within the previous year were also excluded fromthe study. Patients taking chronic medications were continuedon their drugs, but the dosage was not changed during thestudy. Twenty-nine patients were subsequently enrolled andrandomized into the study.

DesignAll patients underwent an initial series of evaluation proce-

dures and then were randomized to one of two treatmentgroups or a control group (Table 1). Control subjects were

instructed to maintain their usual level of activity and not toexercise on a regular basis, and treated subjects were enrolledin a 12-week program of either supervised treadmill walkingexercise or strength training. Two subjects in the control grouprefused to return for the 12-week evaluation; therefore, al-though they were included in the initial characterization of thepatient groups, they were excluded from further analysis. Afterthe first 12 weeks of the study, the relative benefits of the twotraining programs were compared with the responses in thecontrol group (see below).

In the second phase of the study, patients in the treadmillgroup were continued for an additional 12 weeks of supervisedwalking exercise to determine whether a total of 24 weeks oftraining produced better results than 12 weeks alone. Onesubject refused to continue in the second phase, leaving ninesubjects completing the full 24 weeks. Subjects randomizedinitially to strength training were crossed over to treadmill

TABLE 1. Study Design

Study Week

0 12 12 24TM (10) ------- (10) -> TM (9) --------- (9)S (9) --------- (9) -> TM (6) ---------- (6)C (10) --------- (8) -> TM+S (6) ------- (6)

Twenty-nine patients with peripheral arterial disease wererandomized to either a treadmill training program (TM), strengthtraining (S), or a nontreatment control group (C). After the initial12 weeks, subjects in the treadmill training program continuedwith an additional 12 weeks of treadmill training. For the final 12weeks, subjects in the strength training program crossed over totreadmill training, and subjects in the control group crossed overto the combined strength and treadmill training program(TM+S). Numbers in parentheses refer to the number of sub-jects at each time point.

training in the second 12 weeks to determine whether an initialperiod of muscle strengthening would accentuate the trainingeffects of supervised walking exercise. Three of these subjectsrefused to participate in the treadmill exercise program,leaving 6 subjects completing the full 24-week program. Fi-nally, if strength training and walking exercise improve exer-cise performance by different mechanisms, combining thesemodalities in a 12-week program might be more effective thaneither method alone. Therefore, 6 of 8 subjects initiallyrandomized to the control group (2 declined to participate)entered a combined program of strengthening and treadmillwalking exercises in the second 12 weeks.

After randomization, 2 control subjects did not return for the12-week evaluation, and 6 additional subjects did not completethe full 24 weeks of therapy (as described above). Thesesubjects had ankle/arm ratios and peak treadmill walking timessimilar to those of the remaining subjects in the study.

Treadmill Testing ProtocolsSubjects were tested on both a graded and constant-load

treadmill protocol (conducted on separate days) on entry andafter 12 and 24 weeks. Subjects had a familiarization gradedtreadmill test during the initial visit, with a second test on asubsequent day used for data analysis. The graded treadmillprotocol has been described.6,16 Subjects walked on the tread-mill at an initial workload of 2 mph, 0% grade for 3 minutes.Subsequent stages increased 3.5% in grade every 3 minutes(with no change in speed) to maximal claudication pain.During exercise, heart rate (by 12-lead ECG) and brachialblood pressure were monitored every minute. Change in theseverity of the claudication pain during the test was recordedon a scale of 1 to 5, with 1 indicating no pain; 2, onset ofclaudication; 3, mild; 4, moderate; and 5, severe pain. Allsubjects (at all evaluations) reached a maximal level of clau-dication pain that limited exercise during the graded treadmilltest.During all treadmill tests, an Ametek metabolic system

(Ametek/Thermox Instruments) was used to measure rates ofoxygen consumption (Vo2) and carbon dioxide production(Vco2). The instrument was calibrated with known concentra-tions of 02 and CO2 before each test. Peak oxygen consump-tion was determined from the average of the final minute ofdata from the graded treadmill protocol. The respiratoryexchange ratio (RER) was calculated as Vco2/Vo2.

Subjects were also tested on a constant-load treadmillprotocol to determine whether changes in steady-state Vo2and other metabolic responses occurred as a result of thetraining programs. The workload for the constant-load proto-col was individually set as the treadmill grade at whichclaudication pain first began on the graded protocol. Thegrade of the constant-load test ranged from 0% to 7%, with an



ownloaded from


1868 Circulation Vol 90, No 4 October 1994

average of 2% in all subjects. Throughout the remainder of thestudy, this workload was held constant for subsequent evalu-ations. Subjects were instructed to walk to maximal claudica-tion pain on the constant-load protocol. However, the test wasstopped after 40 to 50 minutes if the subject had not reachedmaximal claudication pain that limited exercise.

Hemodynamic MeasurementsAt rest and after graded treadmill exercise, ankle/arm

systolic blood pressure ratios were measured as previouslydescribed.614 A continuous-wave Doppler ultrasonic instru-ment (Parks Electronics) was used to detect the arterial pulsein both the dorsalis pedis and posterior tibial arteries in eachleg and in each arm. If the two arm pressures were within 10mm Hg, they were averaged to yield the arm pressure used foranalysis, or if the difference was >10 mm Hg, then the highestpressure was used (under the assumption that the higherpressure was more representative of the "true" central arterialpressure). The pressure in each ankle vessel was measured induplicate, then averaged, and ankle/arm ratios were calculatedfor the right and left dorsalis pedis and posterior tibial arteries.The higher pressure of the two arteries at the ankle was usedfor analysis at rest and after exercise. The more diseased legwas designated as the leg with the lower ankle/arm ratio atrest. Finally, 1 minute after exercise, pressures were deter-mined in the arm with the higher pressure at rest (ie, left orright) and in each ankle in the artery with the higher pressureat rest. Postexercise ankle/arm ratios were calculated fromthese pressures.

Strength TestingStrength testing was performed in all subjects on a Cybex

Dynamometer (Lumex Inc). Testing of the gastrocnemiusmuscle was performed in the supine position with the leg fullyextended. Joints not being tested were stabilized to preventrecruitment of other muscle groups. Each subject flexed andextended the foot with maximal effort on a pedal at a regulatedspeed of 60°/s for a total of five repetitions. This sequence wasperformed a second time, and the single maximal value foreach muscle group (expressed in foot-pounds of peak torque)was used for analysis.17 No subject experienced claudicationpain during strength testing.

Blood Collection and Assay MethodsA 20-gauge intravenous catheter with a three-way stopcock

to facilitate blood drawing was placed in a forearm vein, andpatency was maintained with heparinized saline. Blood forlactate analysis was obtained at rest and every minute duringgraded treadmill exercise. During the constant-load treadmilltest, blood was obtained at rest, at minutes 3 and 6, and at theend of exercise. For each determination, 25 ,L of blood wasimmediately deproteinized in 3% perchloric acid and storedon ice for lactate analysis.18

Training ProgramsSubjects randomized to the treadmill walking exercise pro-

gram were trained as previously described.6 Briefly, patientsreported to the Cardiovascular Rehabilitation Center threetimes per week for 1-hour training sessions. After a 5-minutewarm-up period, patients walked on a motor-driven treadmillat a rate and grade designed to produce moderate claudicationpain after 3 to 5 minutes of exercise. Once the subjectexperienced moderate claudication pain, he would step off themoving treadmill and rest until pain subsided, then repeat thisintermittent walking activity for a total of 50 minutes. At theend of each session, there was a 5-minute cooldown period.The intensity of the treadmill training program was increasedon a weekly basis as tolerated by increasing both walking speedand grade. Subjects were also encouraged to continue thewalking program on their own an additional 2 days per week.

Supervised strength training was conducted three times perweek by a physical therapist (one therapist for two patients).Each 1-hour session began with 5 minutes of warm-up andended with 5 minutes of cooldown activities. During theremaining 50 minutes, subjects performed resistive, isotonictraining of five specific muscle groups in each leg (see below).The training program consisted of applying a resistance toeach muscle group with a cuff weight secured to the appropri-ate part of the leg. On entry, the weight that caused fatigue inthe muscle group after six contractions (maximum-intensityrepetitions, or 6 rep-max) was established. Every 2 weeks, the6 rep-max was reassessed, and the weights were changedaccordingly. Exercise training consisted of the subject's per-forming six contractions of the five muscle groups on a givenleg, followed by a rest period, and then repeating this circuitfor a total of three sets per session. Training in the other legwas performed in an identical manner.The gastrocnemius-soleus muscles were trained with one-leg

heel-raises, initially against the subject's body weight and thenby additional weight applied in the form of a weight beltaround the waist. The anterior tibial muscles were trained bydorsiflexion against a resistance applied to the forefoot. Thequadriceps femoris muscles were trained with the subject inthe seated position, applying full extension against a weightattached to the ankle. The hamstrings were trained with thesubject in the prone position performing leg curls with a weightat the ankle. Conditioning of the gluteus maximus and gluteusmedius muscles occurred with the patient in the prone orlateral position on an exercise table, contracting the muscleagainst an appropriate amount of weight applied to the ankle.

Patients in the combined strength and treadmill walkingexercise program participated in three 90-minute sessions perweek. Treadmill training was conducted for 60 minutes asdescribed above, followed by 30 minutes of strength training ofthe gastrocnemius-soleus, the anterior tibial, and the gluteusmaximus muscles of each leg. Subjects were also encouraged tocontinue the walking program at home twice a week.

Data AnalysisThe sample size for this study was estimated from our

previous experience with the treadmill training program.6Differences between groups on entry were determined with abetween-subjects ANOVA for continuous variables and the X2statistic for categorical variables. Changes within groups acrossthe three time points (entry, 12 weeks, and 24 weeks) wereassessed with the nonparametric Quade test,19 since the datawere not normally distributed. Percent change in treadmillwalking time with each treatment was determined individuallyfor each patient, and then the results were averaged. Compar-isons of the percent change from entry to 12 weeks betweentreadmill and strength training were made with an unpaired ttest. Values are reported as mean±SD and are consideredsignificant when P<.05 with a two-tailed test.

ResultsSubjectsOn entry, the 29 subjects were well matched by age

and weight (Table 2). A similar number of patients ineach group had a history of coronary artery disease(previous myocardial infarction or coronary bypass sur-gery), cerebrovascular disease (previous stroke, tran-sient ischemic attack, or carotid surgery), and chronicobstructive pulmonary disease, but none of these con-ditions were limiting during graded treadmill exercise.Seven patients had a history (>1 year before enroll-ment) of peripheral vascular bypass surgery or angio-plasty. All patients had a history of smoking, and themajority were current smokers, with a similar number ofpack-years of smoking between groups. Finally, the



ownloaded from



TABLE 2. Patient Characteristics

Initial Randomization

Treadmill Strength Control(N=10) (N=9) (N=10)

Demographics

Age,y 67±7 67±6 67±5

Weight, kg 69.9±11.6 70.4±8.3 81.6±17.3

Vascular disease status

Duration of claudication, y 4±2 2±1* 4±3

Rest ankle/arm index 0.55±0.15 0.52±0.27 0.61±0.15

Postexercise ankle/armindex 0.21±0.11 0.23±0.25 0.29±0.10

Risk factors and comorbidconditions

Vascular surgery/angioplasty 3 0 4

Coronary artery disease 2 3 4

Cerebrovascular disease 3 3 0

Hypertension 7 4 3

Hyperlipidemia 2 4 1

Current smoker 6 5 8

Pack years 51±34 48±21 42±25

Chronic obstructivepulmonary disease 0 2 2

Medications

Pentoxifylline 3 3 3

Aspirin 5 3 5

P-Adrenergic blocker 1 1 2

Calcium channel blocker 2 1 0

Other antihypertensive 6 3 2

*P<.05 for strength group compared with treadmill or control groups.

prevalence of hypertension, hyperlipidemia, and the useof cardiovascular medications was similar betweengroups.

Patients randomized to the strength training programreported fewer years of claudication than did patients inthe other two groups (Table 2). However, the ankle/armsystolic blood pressure index at rest in the more dis-eased leg was similar between groups on entry andremained unchanged in all subjects over the 24 weeks offollow-up (data not shown). After exercise, the ankle/arm index was significantly decreased compared withresting values, and the postexercise values were alsounaffected by the training programs during the fol-low-up period. Therefore, there was no evidence ofarterial disease progression during the 6-month studyperiod.

Peak Exercise Response to TrainingPatients in the treadmill training program had a

74+58% increase in peak walking time after 12 weeks oftraining (Table 3; Figure). These subjects also had anincrease in the time to onset of claudication pain andpeak Vo2. Peak heart rate, RER, and blood lactateconcentration were unaffected by the 12 weeks oftreadmill training. Patients in the strength training

program had a 36±48% increase in peak walking time.The change in peak walking time in the treadmill grouptended to be greater than in the strength group (P=.07).However, strength-trained subjects had no changes inclaudication onset time, peak Vo2, or the other mea-sures of peak performance. Control subjects had nochange in any measure of peak treadmill performanceafter 12 weeks.

After 12 additional weeks of treadmill training (24weeks total) in the group originally randomized totreadmill training, there was an additional 49±53%increase in peak walking time and an increase inclaudication onset time compared with values at 12weeks (Table 3; Figure). Thus, the 24 weeks of treadmilltraining increased peak walking time a total of128±99%. After 24 weeks of training, peak Vo2 wasincreased compared with baseline values, peak RERwas increased over entry and 12-week values, and bloodlactate concentration was increased over entry values.Thus, 24 weeks of treadmill training produced greaterincreases in peak exercise performance compared withonly 12 weeks of training.The addition of 12 weeks of treadmill training in

patients who completed the strength program or incontrol subjects who participated in treadmill training in



ownloaded from



TABLE 3. Changes in Graded Treadmill Performance and Metabolism With Training

Entry Week 12 Week 24

Peak walking time, min

TM

S

CClaudication onset, min

TM

S

CPeak V02, mL- kg-' min-

TM

S

CPeak heart rate, beats/minTM

S

CPeak respiratory exchangeratio

TM

S

C

Peak lactate concentration,mmol/L

TM

S

C

9.6±5.7

6.5+2.9

7.4±3.3

3.3±2.0

2.6±0.9

3.8±2.3

15.0+2.4

1 4.7±2.9

14.3+2.3

122±18

112+18

108±13

TM1 4.7+7.3*

8.5±5.2*

7.3±2.7

6.7+4.3* TM

2.9±1.1

3.1+ 1.3

TM

TM+S

1 6.9+4.8* TM

TM14.4+4.2

13.9±3.5

111 ±23

1 16+20

112+13

17.2±7.3*t

TM 11.8+6.0*t

TM+S 13.2±6.6*t

1 0.2+7.2*t

3.1±+1.7

5.1 +3.9

1 7.8+4.7*

15.3+4.5

TM+S 14.7+2.8

TM

TM

TM+S

117±21

114±12

110±16

0.97+0.09 0.97+0.09 TM 1.01 +0.09*t0.95+0.1 1 0.96+0.10 TM 0.99+0.13

0.91 ±0.04 0.91 +0.06 TM+S 0.95+0.06

2.2± 1.2

1 .6±0.7

1.4±0.3

2.4+ 1.8

2.1 + 1.3

1.4+0.5

TM

TM

TM+S

3.1 +1.2*

3.0+-1 .9*t

1.7+0.9

Abbreviations as in Table 1.*P<.05 compared with entry value; tP<.05 week 24 compared with week 12.

combination with strength training resulted in signifi-cant increases in peak treadmill walking time for eachgroup compared with the values after the first 12 weeks(Table 3; Figure). The change in peak walking time inthese two groups was similar to the change in peakwalking time after the first 12 weeks of training in thetreadmill group. However, in contrast to 12 weeks oftreadmill training alone, patients crossing over from thestrength or control groups had no improvements inclaudication onset time or peak Vo2 with treadmilltraining.

Constant-Load Treadmill PerformancePatients in the three groups were also evaluated with a

constant-load treadmill protocol. Twelve weeks of tread-mill training resulted in an increase in total walking timeand claudication onset time on the constant-load treadmillprotocol (Table 4). In contrast to the findings with gradedtreadmill testing, 12 weeks of strength training resulted inno change in total walking time or claudication onset time.Control subjects actually had a decrease in total walkingtime and no change in claudication onset time. After atotal of 24 weeks of treadmill training, subjects in thetreadmill group had a 332±283% improvement in totalwalking time. In the strength and control groups, the

addition of treadmill training in the second 12 weeks of thestudy resulted in an increase in total walking time. Thischange in walking time was of a magnitude similar to thatobserved during the initial 12 weeks of treadmill trainingin the treadmill group.On entry into the study, total walking time on the

constant-load treadmill protocol was claudication-limitedin all but one subject. After 12 weeks, 3 subjects in thetreadmill group and 1 subject in the strength group werenot claudication-limited. The inability to achieve a claudi-cation-limited exercise end point was the result of atraining-induced increase in exercise performance thatwas beyond the dynamic range of the constant-load pro-tocol. After 24 weeks (when all subjects had been exposedto the walking exercise program), 9 of 21 subjects (43%)were not claudication-limited during constant-load tread-mill exercise. These results emphasize the enhanced utilityof the graded treadmill protocol to define maximal walk-ing time in patients with claudication compared with theconstant-load treadmill test.20The constant-load treadmill exercise test was also

used to evaluate changes in heart rate and metabolicresponses to exercise under steady-state conditions be-fore and after the training programs. All subjects hadreached steady state with respect to the parameters of



ownloaded from



20

15+-

E

-J

tY

W

0-0 TM-TMA-A S-TM*- C-TM+S

0

T1

*A.l

Ul-4 0 4 8 12 16

WEEKS

Graph showing changes in peak walking tintreadmill protocol with training. Subjects rar

treadmill group (TM) were treated with a 2,training program. Subjects randomized initiallying (S) crossed over to treadmill training in thethe study. Subjects in the control group (C) ccombined treadmill and strength (TM +S) trainirfinal 12 weeks of the study. *P<.05 compared+P<.05 week 24 compared with week 12.

interest by 4 minutes. On entry, subjectsthe treadmill training program performecexercise (based on the previously desig]signment) at an exercise intensity t80±11% of their individually defined pe

4). After 12 weeks of treadmill training, t]Vo2 (at the same grade and speed as

reduced 15% compared with entry valsince peak Vo2 was also increased in tworkload of the constant-load test rep63±17% of the of peak Vo2 at 12 weekheart rate, RER, and blood lactate concminutes of exercise were also reduced centry values. The additional 12 weektraining did not augment these effects c

exercise measurements.Subjects in the strength and control k

changes in steady-state exercise respo

weeks. However, the addition of treadnthe second 12 weeks reduced the steadypercent of peak Vo2 similar to that se

treated with 12 weeks of treadmill trainiThese observations suggested that the i]

stant-load treadmill walking time with thigrams was related, in part, to a lower metalexercise. This concept was supported by i

the change in steady-state Vo2 as related toof improvement in total walking time. WIwere considered after the initial 12 weeks othe 27 subjects had a .10-minute increasetime on the constant-load protocol. In thesteady-state Vo2 (as a percent of peak Vo:24±5% (P<.01). In contrast, the remainwho had a <10-minute increase in total w£no change in their steady-state Vo2 (decreC

Effects of Training on Muscle StrengtlWith muscle strength testing, limbs w

ated on the basis of the ankle/arm inde,diseased and less-diseased limbs for eachsubjects, gastrocnemius muscle strength

ft-lb in the more-diseased legs, which was less than theT * + value of 31.5±9.7 ft-lb in the less-diseased legs (P<.05

for the difference between legs). After the initial 12+ weeks of strength training, muscle strength increased

4* 4.8±4.7 ft-lb in the more-diseased legs and increased* + 3.9±3.1 ft-lb in the less-diseased legs (both P<.05

l compared with baseline values). However, musclestrength remained unchanged in treadmill-trained andcontrol subjects. After 24 weeks, subjects in the strengthgroup who crossed over to treadmill training loststrength in both legs compared with values at 12 weeks,and subjects in the combined program did not increase

20 24 28 gastrocnemius strength.

ne on a graded Discussionidomized to the This trial demonstrated that 12 weeks of supervised4-week treadmill treadmill training improved peak walking time and peakto strength train- tramfinal 12 weeks of Vo2 as well as claudication onset time on a graded:rossed over to a treadmill protocol. As suggested by previous studies, 24ig program in the weeks of treadmill training was more effective than 12with entry value; weeks in improving peak exercise performance.82' Al-

though strength training enhanced gastrocnemius mus-cle strength, the muscle strengthening program was lessrandomized to effective than treadmill training in improving peak

constant- oad treadmill walking time. Finally, control subjects had nonated load as- changes in exercise performance over a period of 12that averaged weeks, confirming a lack of spontaneous improvementaVo,(Table in functional status in patients not provided specifiche steady-state therapy.

on entry) was Previous studies have demonstrated that patientsues. However, with PAD have muscle weakness'222 and that gastroc-his group, the nemius muscle strength is positively correlated with)resented only exercise performance on the treadmill.'2 Many rehabil-,s. In addition, itation programs for claudication combine isotonic ex-centration at 6 ercises with walking exercise,8,23 but the relative benefits-ompared with of strength training or combinations of training activi-s of treadmill ties have not been directly compared with a walking)n steady-state exercise program. Therefore, a goal of the present study

was to determine whether strength training beforegroups ftad 12 treadmill training or in combination with treadmillnses ater 12 training would result in greater increases in exercise

,-state V2 and performance than treadmill training alone. The resultsdemonstrate that when treadmill training followed,en in subjects strength training or when strength and treadmill train-

crealone.incon ing were combined there was an increase in peakncreasein con- walking time on the graded treadmill protocol. How-

)olic cost of the ever, the magnitude of improvement in patients receiv-examination of ing simultaneous or serial strength and treadmill train-themagnitude ing was not greater than the response to treadmillhen all subjects training alone. The lack of improvement in peak Vo2 orf training, 10 of claudication onset time in these groups compared within total walking treadmill training alone is further evidence that strengthse subjects, the training was not additive to treadmill training in PAD2) decreased by patients. Thus, in patients with PAD, modifying theing 17 subjects strength of muscles in the lower extremity that arealking time had important for walking is not a major determinant of thease of 2±23%). training response. The strength training program was

resource intensive, requiring special equipment and oneh physical therapist to treat two subjects, whereas eightiere differenti- subjects could be trained by one therapist in the tread-x as the more- mill program. Since the strength training benefits werepatient. In all modest, this form of exercise therapy cannot be recom-

L was 28.3+±8.3 mended as a cost-effective treatment for claudication.

io+



ownloaded from



TABLE 4. Changes in Constant-Load Treadmill Performance and MetabolismWith Training

Entry Week 12 Week 24Total walking time, min

TM

S

C

Claudication onset, minTM

S

C

V02, mL. kg` * min-1TM

S

C

Percent of peak V02TM

S

C

Heart rate, beats/minTM

S

C

Respiratory exchange ratio

TM

S

C

Lactate concentration, mmol/LTM

S

C

13.2+10.9 30.5±17.9* TM 39.2±19.6*t

10.4±7.5

8.9±4.9

3.5+2.0

2.5± 1.3

3.0±0.9

11.9± 1.7

12.9±2.8

11.7±1.8

80+11%

88±+11%

85±8%

104±10

103±20

96±14

12.7±+11.7 TM 24.7+20.3*t7.5+5.4* TM+S 22.3±14.5*t

18.3+22.7* TM 30.7+27.9*

2.8± 1.5

2.5±1.1

10.1 +1.9*

11.7±1.8

11.3+ 1.4

TM 3.4± 1.5*

TM+S 12.4±23.4

TM 9.9±1 .3*

TM 10.3±1.5*

TM+S 11.1±3.4

63±+ 17%* TM

86+27%

83±17%

87±15*

99±16

98±14

TM

TM+S

TM

TM

TM+S

58±17%*

69±13%*

76±23%

86+14*

90±8

93±16

0.89±0.07 0.82+0.04* TM 0.83±0.05*

0.89±0.07 0.86±0.05 TM 0.85±0.04

0.89±0.06 0.87±0.06

1.4±0.4

1.4±0.4

0.9±0.3

1.0±0.5*

1.4±0.9

1.1 ±0.3

TM+S 0.85±+0.03

TM

TM

TM+S

0.9+0.2*

1.1 ±0.5

1.5±0.8

Measurements of Va2, percent peak V02, heart rate, respiratory exchange ratio, and blood lactateconcentration are reported for 6 minutes of exercise. Abbreviations as in Table 1.*P<.05 compared with entry value; tP<.05 week 24 compared with week 12.

Potential Mechanisms of the ExerciseTraining Response

In the present study, constant-load treadmill testingwas used to evaluate the metabolic and heart rateresponses to exercise training under steady-state exer-cise conditions. Previous studies of exercise training inpatients with PAD have shown that at a given submax-imal workload on a graded protocol, exercise trainingdecreased heart rate6,24 and oxygen consumption.6 Thepresent study confirmed these altered responses withtreadmill exercise training under fixed load testingconditions (Table 4). If the onset of claudication is dueto an oxygen demand-delivery mismatch, the lower Vo2at a given workload might contribute to the ability tosustain walking exercise for longer distances beforeclaudication pain limits the activity. Although exercisetraining in normal elderly subjects does not alter theVo2-workload relation,25 conditioning in older cardiacpatients has been shown to decrease Vo2 during con-

stant-load treadmill exercise.26 The lower steady-stateVo2 observed with training in PAD patients may be theresult of a modification in gait or the biomechanics ofwalking that allows for less energy expenditure tosupport a given level of exercise. Therefore, in patientswith cardiovascular disease, a decrease in the oxygencost of walking exercise may allow the activity to besustained for longer periods of time. This concept wassupported by the observation that the patients with thegreatest improvement in constant-load walking timealso had the greatest decrease in steady-state Vo2.However, since there was no further decrease in steady-state Vo2 after 24 weeks versus 12 weeks of treadmilltraining, the continued increase in peak exercise perfor-mance at 24 weeks may involve factors other thanchanges in walking efficiency.

Further evidence that treadmill training modified thesystemic responses to a constant exercise workload wasthe 17-beat per minute reduction in heart rate, the



ownloaded from



reduction in RER (greater reliance on fatty acid oxida-tion), and the decrease in blood lactate concentration.Similar training responses in heart rate, RER, andblood lactate concentration have been observed withexercise conditioning both in normal subjects and inpatients with coronary artery disease.25,26 Thesechanges may be interpreted as a training-induced reduc-tion in the relative intensity of a fixed workload due toan increase in either maximal Vo2 or the lactate thresh-old. In other populations, when an exercise workload isperformed at a lower percentage of maximal Vo2, thereis an associated decrease in lactate production, en-hanced fatty acid oxidation, and improved exerciseendurance.27,28 The steady-state heart rate, RER, andblood lactate concentration responses to constant-loadexercise were unchanged in the strength and controlgroups after 12 weeks. Thus, the heart rate and meta-bolic adaptations to exercise training in the treadmillgroup were not simply due to increased familiarity withthe testing procedures but rather were analogous to thephysiological responses to classic aerobic training.29

Evaluation of the Treadmill Testing ProtocolsConstant-load exercise testing has been commonly

used to assess the effects of therapy for claudication.The traditional treadmill protocol for persons with PADhas generally been conducted at a slow speed of 1.5 to 2mph, with the grade typically fixed at a level of 8% to12%.30,31 However, a single workload may not be appro-priate for a heterogeneous population of patients withdifferent walking abilities. Therefore, the workload se-lected for patients in the present study was individual-ized as the specific grade on the graded protocol thatwas associated with the onset of claudication. On entryto the study, this individualized but constant workloadwas sufficient to bring all but one patient to a claudica-tion-limited end point. Despite the initial optimizationof the workload, after training, many of the patientsexperienced large improvements in performance andnever reached a maximal level of claudication painduring the constant-load test. Therefore, in many pa-tients the degree of improvement in total walking timeafter training was underestimated with the constant-load test. This finding has also been observed in patientswith coronary artery disease when training-inducedchanges in endurance exercise performance were as-sessed with constant-load protocols.26 In contrast to thelimitations of the constant-load protocol, the gradedtreadmill test demonstrated a large dynamic range thatallowed all patients to be evaluated at a quantifiablemaximal claudication end point.

ConclusionsPatients with PAD have a chronic disease that pro-

duces a moderate to severe degree of walking impair-ment without spontaneous recovery. Treadmill exercisetraining results in clinically important improvements inpeak exercise performance and claudication pain sever-ity, allowing patients to perform a greater range ofactivities.32 The treadmill training program is also asso-ciated with a decreased metabolic cost of walkingexercise that allows patients to increase their walkingdistance. In contrast, strength training the muscles ofthe lower extremity has limited utility as a treatment forclaudication. A supervised treadmill training program

24 weeks in duration should be considered an importanttreatment option for patients disabled by PAD.

AcknowledgmentsThis study was supported by grant H133G90114 from the

National Institute on Disability and Rehabilitation Research.Dr Hiatt is the recipient of a National Institutes of HealthAcademic Award in Vascular Disease. The authors wish tothank Jeff Falkel, PhD, and Pauline Cerasoli, EdD, and their-staff of physical therapists for conducting the strength trainingactivities. Eric Brass, MD, PhD, provided helpful commentson the manuscript. Mike Himes provided assistance with dataanalysis.

References1. Zatina MA, Berkowitz HD, Gross GM, Maris JM, Chance B. 31P

nuclear magnetic resonance spectroscopy: noninvasive biochemicalanalysis of the ischemic extremity. J Vasc Surg. 1986;3:411-420.

2. Holm S, Bylund-Fellenius AC. Continuous monitoring of oxygentension in human gastrocnemius muscle during exercise. ClinPhysiol. 1981;1:541-552.

3. Hiatt WR, Nawaz D, Brass EP. Carnitine metabolism duringexercise in patients with peripheral vascular disease. JAppl Physiol.1987;62:2383-2387.

4. Hiatt WR, Wolfel EE, Regensteiner JG, Brass EP. Skeletal musclecarnitine metabolism in patients with unilateral peripheral arterialdisease. JAppl Physiol. 1992;73:346-353.

5. Radack K, Wyderski RJ. Conservative management of inter-mittent claudication. Ann Intern Med. 1990;113:135-146.

6. Hiatt WR, Regensteiner JG, Hargarten ME, Wolfel EE, Brass EP.Benefit of exercise conditioning for patients with peripheralarterial disease. Circulation. 1990;81:602-609.

7. Larsen OA, Lassen NA. Effect of daily muscular exercise inpatients with intermittent claudication. Lancet. 1966;2:1093-1096.

8. Mannarino E, Pasqualini L, Menna M, Maragoni G, Orlandi U.Effects of physical training on peripheral vascular disease: a con-trolled study. Angiology. 1989;40:5 -10.

9. Regensteiner JG, Steiner JF, Panzer RJ, Hiatt WR. Evaluation ofwalking impairment by questionnaire in patients with peripheralarterial disease. J Vasc Med Biol. 1990;2:142-152.

10. Ericsson B, Haeger K, Lindell SE. Effect of physical training onintermittent claudication. Angiology. 1970;21:188-192.

11. Ekroth R, Dahllof A, Gundevall B, Holm J, Schersten T. Physicaltraining of patients with intermittent claudication: indications,methods, and results. Surgery. 1978;84:640-643.

12. Regensteiner JG, Wolfel EE, Brass EP, Carry MR, Ringel SP,Hargarten ME, Stamm ER, Hiatt WR. Chronic changes in skeletalmuscle histology and function in peripheral arterial disease.Circulation. 1993;87:413-421.

13. Rose GA, Blackburn H. Cardiovascular Survey Methods. Geneva,Switzerland: WHO Monograph Series No. 56; 1968:172-175.

14. Hiatt WR, Marshall JA, Baxter J, Sandoval R, Hildebrandt W,Kahn LR, Hamman RF. Diagnostic methods for peripheralarterial disease in the San Luis Valley Diabetes Study. J ClinEpidemiol. 1990;43:597-606.

15. Ronnemaa T, Mattila K, Lehtonen A, Kallio V. A controlledrandomized study on the effect of long-term physical exercise onthe metabolic control in type 2 diabetic patients. Acta Med Scand.1986;220:219-224.

16. Hiatt WR, Nawaz D, Regensteiner JG, Hossack KF. The eval-uation of exercise performance in patients with peripheral vasculardisease. J Cardiopulmonary Rehabil. 1988;12:525 -532.

17. Davies GJ. A Compendium of Isokinetics in Clinical Usage. 3rd ed.Onalaska, Wis: S & S Publishers; 1987:1-36.

18. Rosenberg JD, Rush BF. An enzymatic-spectrophotometric deter-mination of pyruvic and lactic acid in blood: methodologic aspects.Clin Chem. 1966;12:299-307.

19. Conover WJ. Practical Nonparametric Statistics. 2nd ed. New York,NY: John Wiley & Sons, Inc; 1980:294-299.

20. Gardner AW, Skinner JS, Cantwell BW, Smith LK. Progressive vssingle-stage treadmill tests for evaluation of claudication. Med SciSports Exerc. 1991;23:402-408.

21. Andriessen MPHM, Barendsen GJ, WoudaAA, de Pater L. Changesof walking distance in patients with intermittent claudication duringsix months intensive physical training. Vasa. 1989;18:63-68.



ownloaded from



22. Gerdle B, Hedberg B, Angquist KA, Fugl-Meyer AR. Isokineticstrength and endurance in peripheral arterial insufficiency withintermittent claudication. Scand J Rehabil Med. 1986;18:9-15.

23. Sorlie D, Myhre K. Effects of physical training in intermittentclaudication. Scand J Clin Lab Invest. 1978;38:217-222.

24. Dahllof A, Holm J, Schersten T, Sivertsson R. Peripheral arterialinsufficiency: effect of physical training on walking tolerance, calfblood flow, and blood flow resistance. Scand J Rehabil Med. 1976;8:19-26.

25. Poulin MJ, Paterson DH, Govindasamy D, Cunningham DA.Endurance training of older men: responses to submaximalexercise. JAppl Physiol. 1992;73:452-457.

26. Ades PA, Waldmann ML, Poehlman ET, Gray P, Horton ED,Horton ES, LeWinter MM. Exercise conditioning in oldercoronary patients: submaximal lactate response and endurancecapacity. Circulation. 1993;88:572-577.

27. Wasserman K. Determinants and detection of anaerobic thresholdand consequences of exercise above it. Circulation. 1987;76(supplVI):VI-29-VI-39.

28. Jones NL, Heigenhauser GJ, Kuksis A, Matsos CG, Sutton JR,Toews CJ. Fat metabolism in heavy exercise. Clin Sci. 1980;59:469-478.

29. Holloszy JO, Coyle EF. Adaptations of skeletal muscle toendurance exercise and their metabolic consequences. J ApplPhysiol. 1984;56:831-838.

30. Skinner JS, Strandness DE. Exercise and intermittent claudication,II: effect of physical training. Circulation. 1967;36:23-29.

31. Laing S, Greenhalgh RM. Treadmill testing in the assessment ofperipheral arterial disease. IntAngiol. 1986;5:249-252.

32. Bruce RA, Kusumi F, Hosmer D. Maximal oxygen intake andnomographic assessment of functional aerobic impairment in car-diovascular disease. Am Heart J. 1973;85:546-562.



ownloaded from


W R Hiatt, E E Wolfel, R H Meier and J G Regensteinerperipheral arterial disease. Implications for the mechanism of the training response.Superiority of treadmill walking exercise versus strength training for patients with

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1994 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation doi: 10.1161/01.CIR.90.4.1866

1994;90:1866-1874Circulation.

http://circ.ahajournals.org/content/90/4/1866World Wide Web at:

The online version of this article, along with updated information and services, is located on the

http://circ.ahajournals.org//subscriptions/

is online at: Circulation Information about subscribing to Subscriptions:

http://www.lww.com/reprints Information about reprints can be found online at: Reprints:

document. Permissions and Rights Question and Answer this process is available in the

click Request Permissions in the middle column of the Web page under Services. Further information aboutOffice. Once the online version of the published article for which permission is being requested is located,

can be obtained via RightsLink, a service of the Copyright Clearance Center, not the EditorialCirculationin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions:



ownloaded from

http://circ.ahajournals.org/content/90/4/1866

http://www.ahajournals.org/site/rights/

http://www.lww.com/reprints

http://circ.ahajournals.org//subscriptions/


superiority treadmill walkingexercise versus strength ...€¦ · graded treadmill testing was...

Documents