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Physical Performance in Peripheral Arterial Disease: A Slower Rate of Decline in Patients Who Walk More

Mary McGrae McDermott, MD; Kiang Liu, PhD; Luigi Ferrucci, MD, PhD; Michael H. Criqui, MD, MPH; Philip Greenland, MD; Jack M. Guralnik, MD, PhD; Lu Tian, ScD; Joseph R. Schneider, MD, PhD; William H. Pearce, MD; Jin Tan, MS; and Gary J. Martin, MD
[+] Article and Author Information

From Northwestern University Feinberg School of Medicine, Chicago, Illinois; Evanston Northwestern Hospital, Evanston, Illinois; National Institute on Aging, Baltimore, Maryland; and University of California at San Diego, La Jolla, California.


Potential Financial Conflicts of Interest: None disclosed.

Grant Support: By the National Heart, Lung, and Blood Institute (grant numbers R01-HL58099 and R01-HL64739) and by the National Center for Research Resources, National Institutes of Health (grant number RR-00048).

Requests for Single Reprints: Mary M. McDermott, MD, 675 North St. Clair, Suite 18-200, Chicago, IL 60611; e-mail, mdm608@northwestern.edu.

Current Author Addresses: Drs. McDermott and Martin: 675 North St. Clair, Suite 18-200, Chicago, IL 60611.

Drs. Liu, Greenland, and Tian and Mr. Tan: 680 N. Lake Shore Drive, Suite 1102, Chicago, IL 60611.

Dr. Ferrucci: National Institute on Aging, Clinical Research Branch, Harbor Hospital, 3001 South Hanover Street, Fifth Floor, Baltimore, MD 21225.

Dr. Criqui: University of California at San Diego, Family & Preventive Medicine, 9500 Gilman Drive, La Jolla, CA 92093.

Dr. Guralnik: National Institute on Aging, Gateway Building, Room 3-C309, 7201 Wisconsin Avenue, Bethesda, MD 20892.

Dr. Schneider: Evanston Northwestern Hospital, Department of Surgery, 2650 Ridge Avenue, Burch 100, Evanston, IL 60201.

Dr. Pearce: 201 East Huron, Suite 10-105, Chicago, IL 60611.

Author Contributions: Conception and design: M.M. McDermott, K. Liu, L. Ferrucci, P. Greenland, J.M. Guralnik, J.R. Schneider, G.J. Martin.

Analysis and interpretation of the data: M.M. McDermott, K. Liu, L. Ferrucci, M.H. Criqui, P. Greenland, J.M. Guralnik, L. Tian, J. Tan, G.J. Martin.

Drafting of the article: M.M. McDermott, M.H. Criqui.

Critical revision of the article for important intellectual content: M.M. McDermott, L. Ferrucci, M.H. Criqui, P. Greenland, J.M. Guralnik, J.R. Schneider, G.J. Martin.

Final approval of the article: M.M. McDermott, K. Liu, M.H. Criqui, P. Greenland, J.M. Guralnik, L. Tian, J.R. Schneider, W.H. Pearce, J. Tan, G.J. Martin.

Provision of study materials or patients: J.R. Schneider, W.H. Pearce, G.J. Martin.

Statistical expertise: K. Liu, L. Tian.

Obtaining of funding: M.M. McDermott, K. Liu, M.H. Criqui, G.J. Martin.

Administrative, technical, or logistic support: W.H. Pearce, J. Tan.

Collection and assembly of data: M.M. McDermott, W.H. Pearce.


Ann Intern Med. 2006;144(1):10-20. doi:10.7326/0003-4819-144-1-200601030-00005
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Methods for this longitudinal observational study of men and women with and without PAD have been described elsewhere (4). The protocol was approved by the institutional review boards of Northwestern University and Catholic Health Partners Hospital. Participants gave informed consent.

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Figures

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Figure 1.
Description of potential study participants.
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Figure 2.
Associations between frequency of self-directed walking exercise and functional decline in patients with peripheral arterial disease of the lower extremities.PP

Adjusted for age, sex, ethnicity, ankle–brachial index, body mass index, previous year's performance, leg symptoms, cigarette use, depressive symptoms, education level, comorbid conditions, and patterns of missing data. Exercise frequency was entered as a time-dependent variable. for trend = 0.037, 0.005, 0.013, and 0.053 for 6-minute walk distance, normal-pace 4-meter walking velocity, fast-pace 4-meter walking velocity, and summary performance score, respectively. *  < 0.05 for comparison with no-exercise group.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Associations between frequency of self-directed walking exercise and functional decline in asymptomatic patients with peripheral arterial disease.P

Adjusted for age, sex, ethnicity, ankle–brachial index, body mass index, previous year's performance, cigarette use, depressive symptoms, education level, comorbid conditions, and patterns of missing data.  = 0.107, 0.065, 0.311, and 0.115 for 6-minute walk distance, normal-pace 4-meter walking velocity, fast-pace 4-meter walking velocity, and summary performance score, respectively.

Grahic Jump Location
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Figure 4.
Associations between weekly duration of self-directed walking exercise and functional decline in patients with peripheral arterial disease.P

 = 0.008, 0.007, 0.012, and 0.040 for 6-minute walk distance, normal-pace 4-meter walking velocity, fast-pace 4-meter walking velocity, and summary performance score, respectively.

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Tables

References

Letters

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Solvitur Ambulando - all is solved by walking
Posted on January 11, 2006
Steven T. Johnson
University of Alberta, Canada
Conflict of Interest: None Declared

To the Editor:

We read with great interest the most recent article by McDermott and colleagues (1) that serves to strengthen the growing body of evidence for the health benefits of regular walking.

Not only have the authors shown that walking for physical activity on at least 3 days/week is feasible among a cohort known to have reduced quality of life (2) due to peripheral arterial disease (PAD), but they have also shown that self-directed outside of the supervised clinic, is possible. The cost implications of this finding have enormous potential requiring further economic analysis.

The attenuation of functional decline among those who indicated a walking frequency of > 3 days/week is an important finding; however, when combined with the average walking speed of ~3.9 km/hr (average of the functional measures of ambulation in table 1), we feel these data become even more meaningful. Those who walked less frequently also walked more slowly, making it difficult to separate the effects of frequency from intensity. Although walking speeds of < 4.0km/hr are often defined as less than moderately intense physical activity (< 3 METS) (3), the long term benefit of higher functional capacity by walking more than 3 times/week at the slightly slower than moderate speeds is clinically relevant. Maintaining functional capacity would contribute to sustaining or improving cardiorespiratory fitness, which is a powerful and well established predictor of cardiovascular disease (CVD) morbidity and mortality.(4)

Defining and translating an understandable and efficacious walking goal is imperative for clinicians and their patients. Although these authors highlight the importance of walking frequency, the contribution of walking speed to reducing the decline in functional capacity is also likely important. We have shown that among a group of people with Type 2 diabetes, who are considered high risk for PAD, "normal" walking speed approximates 3.3km/hr.(5) When these subjects increase their walking speed up to ~ 5.1 km/hr, 3 times/week fro 30 minutes, we observed significant improvements in resting heart rate, suggesting improved cardiorespiratory fitness (unpublished data). Thus, we would suggest a walking goal prescription in symptom-limited groups, such as those with PAD, that includes frequency, speed (intensity) and time components. We would suggest a walking prescription speed of ~ 5.0 km/hr which equates to a patient"“friendly, pedometer-based pace of ~ 120 steps/min or 3600 steps/30 mins on at least 3 days/week.

References:

1. McDermott MM, Liu K, Ferrucci L, Criqui MH, Greenland P, Guralnik JM, Tian L, Schneider JR, Pearce WH, Tan J, Martin GJ. Physical performance in peripheral arterial disease: a slower rate of decline in patients who walk more. Ann Intern Med. 2006;144(1):10-20.

2. Kugler CF, Rudofsky G. Do age and comorbidity affect quality of life or PTA-induced quality-of-life improvements in patients with symptomatic pad? J Endovasc Ther. 2005 Jun;12(3):387-93.

3. Ainsworth BE, Haskell WL, Whitt MC, Irwin, ML, Swartz AM, Strath SJ, OBrien WL, Bassett DR Jr, Schmitz KH, Emplaincourt PO, Jacobs DR Jr, Leon AS. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc. 2000; 32 (Suppl.9):S498-S504.

4. Stevens J, Cai J, Evenson KR, et al. Fitness and fatness as predictors of mortality from all casues and from cardiovascular fitness in men and women in the lipid research clinics study. Am J Epidemiol. 2002;156:832-841.

5. Johnson ST, McCargar LJ, Tudor-Locke C, Bell RC. Measuring habitual walking speed of people with type 2 diabetes: Are they meeting recommendations? Diabetes Care 2005; 28(6):1503-1504.

Conflict of Interest:

None declared

Exercise and Peripheral Arterial Disease
Posted on January 27, 2006
Dae Hyun Kim
Jefferson Medical College
Conflict of Interest: None Declared

TO THE EDITOR: Dr. McDermott and colleagues found that self-directed walking exercise at least three times a week was associated with a slower rate of functional decline in patients with peripheral arterial disease, after adjusting for sociodemographic and clinical characteristics, including aspirin, statin, and angiotensin-converting enzyme inhibitor use. (1) They did not, however, adjust for the use of pharmacologic interventions for claudication, such as pentoxifylline and cilostazol, which might have more significant and direct effects on functional performance than the use of aspirin, statin, and angiotensin-converting enzyme inhibitor for concurrent cardiovascular risk factor modification. In a meta-analysis, pentoxifylline, a methylxanthine derivative, was shown to increase total walking distance on a treadmill by almost 44 m (95% confidence interval, 14 ?74 m). (2) Cilostazol, a phosphodiesterase type 3 inhibitor with antiplatelet and vasodilator effects, also significantly improved maximal walking distance, quality of life, and functional status in randomized, placebo-controlled trials. (3, 4) Therefore, it is hard to attribute the slower rate of functional decline observed among those who walk for exercise regularly to the beneficial effect of self-directed exercise, without taking into consideration the use of pentoxifylline or cilostazol in addition to the proportion of patients who were participating in supervised exercise programs, which was already noted by the authors in their discussion. (1)

REFERENCES 1. McDermott MM, Liu K, Ferrucci L, et al. Physical performance in peripheral arterial disease: a slower rate of decline in patients who walk more. Ann Intern Med. 2006;144(1):10-20. 2. Girolami B, Bernardi E, Prins MH, et al. Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis. Arch Intern Med. 1999;159(4):337-45. 3. Beebe HG, Dawson DL, Cutler BS, et al. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med. 1999;159(17):2041-50. 4. Dawson DL, Cutler BS, Meissner MH, Strandness DE, Jr. Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial. Circulation. 1998;98(7):678-86.

Conflict of Interest:

None declared

No Title
Posted on February 27, 2006
Mary M McDermott
Northwestern University's Feinberg School of Medicine
Conflict of Interest: None Declared

We agree with Dr. Kim that cilostazol and pentoxifylline, the only two FDA- approved drugs for treating walking impairment due to peripheral arterial disease (PAD), have modest effects on walking performance in patients with PAD. Therefore, we repeated the analyses reported in our manuscript (1), adding additional statistical adjustment for use of pentoxifylline or cilostazol. Our results shown in the table below are not substantially changed from those reported in our manuscript. Thus, self-directed walking exercise is associated with slower rates of functional decline in persons with PAD, independent of use of pentoxifylline and cilostazol in addition to other confounders.

We appreciate the comments of Mr. Johnson and Dr. Bell. Unfortunately, we did not measure the intensity of walking exercise of participants in our study. Thus, we are not able to comment on associations between intensity of walking exercise and functional decline in our cohort. However, a randomized controlled clinical trial reported by Gardner and colleagues demonstrated similar improvement in walking performance in PAD patients randomized to a low-intensity vs. a high-intensity exercise walking rehabilitation program (2).

Although we did not measure walking speed during exercise, our analyses adjusted for performance during the prior year. Thus, our findings demonstrating less functional decline in the four-meter walk among PAD participants who walked for exercise more frequently was independent of walking speed during the prior year visit. In addition, to determine whether our findings were comparable among PAD patients with different levels of performance, we repeated our analyses after stratifying participants according to baseline performance (1). Our results suggested that PAD participants with poorest baseline performance, such as those with slowest walking speed, achieved similar or greater benefit from the self-directed exercise program compared to other participants with PAD (1).

Mary M. McDermott, MD Kiang Liu PhD Lu Tian ScD

Northwestern University Feinberg School of Medicine Chicago, IL

REFERENCES

1. McDermott MM, Liu K, Ferrucci L, et al. Physical performance in peripheral arterial disease: A slower rate of decline in patients who walk more. Ann Intern Med 2006;144(1):10-20.

2. Gardner AW, Montgomery PS, Flinn WR, Katzel LI. The effect of exercise intensity on the response to exercise rehabilitation in patients with intermittent claudication. J Vasc Surg 2005;47:702-709.

Adjusted Associations between Frequency of Self-Directed Walking Exercise and Functional Decline over Three-Year Follow-up in Persons with Lower Extremity Peripheral Arterial Disease (n=417)*

Walking Exercise Frequency

Outcome Measure No Walking Walking 1-2 times per week Walking > 3 times per week P trend Six-minute walk distance (Feet) -79.19 -73.42 -44.40 0.048 Four meter walking velocity (usual pace) (meters/second) -0.048 -0.030 -0.016 0.019 Four meter walking velocity (fast pace) (meters/second) -0.070 -0.052 -0.025 0.012 Summary performance score -0.498 -0.451 -0.228 0.130

*Analyses adjusted for age, sex, race, prior year functioning, comorbidities, leg symptoms, educational level, ankle brachial index, body mass index, pack- years of smoking, depression score, cilostazol use, pentoxifylline use, and patterns of missing data.

Conflict of Interest:

None declared

In Response
Posted on March 27, 2006
Mary M McDermott
No Affiliation
Conflict of Interest: None Declared

To the Editor,

We agree with Dr. Kim that cilostazol and pentoxifylline, the only two FDA-approved drugs for treating walking impairment due to peripheral arterial disease (PAD), have modest effects on walking performance in patients with PAD. Therefore, we repeated the analyses reported in our manuscript (1), adding additional statistical adjustment for use of pentoxifylline or cilostazol. Our results shown in the table that is published in the accompanying letter in Annals are not substantially changed from those reported in our manuscript. Thus, self-directed walking exercise is associated with slower rates of functional decline in persons with PAD, independent of use of pentoxifylline and cilostazol in addition to other confounders.

We appreciate the comments of Mr. Johnson and Dr. Bell. Unfortunately, we did not measure the intensity of walking exercise of participants in our study. Thus, we are not able to comment on associations between intensity of walking exercise and functional decline in our cohort. However, a randomized controlled clinical trial reported by Gardner and colleagues demonstrated similar improvement in walking performance in PAD patients randomized to a low-intensity vs. a high-intensity exercise walking rehabilitation program (2).

Although we did not measure walking speed during exercise, our analyses adjusted for performance during the prior year. Thus, our findings demonstrating less functional decline in the four-meter walk among PAD participants who walked for exercise more frequently was independent of walking speed during the prior year visit. In addition, to determine whether our findings were comparable among PAD patients with different levels of performance, we repeated our analyses after stratifying participants according to baseline performance (1). Our results suggested that PAD participants with poorest baseline performance, such as those with slowest walking speed, achieved similar or greater benefit from the self-directed exercise program compared to other participants with PAD (1).

Mary M. McDermott, MD
mdm608@northwestern.edu
Kiang Liu PhD
Lu Tian ScD
Northwestern University Feinberg School of Medicine
Chicago, IL

REFERENCES

1. McDermott MM, Liu K, Ferrucci L, et al. Physical performance in peripheral arterial disease: A slower rate of decline in patients who walk more. Ann Intern Med 2006;144(1):10-20.

2. Gardner AW, Montgomery PS, Flinn WR, Katzel LI. The effect of exercise intensity on the response to exercise rehabilitation in patients with intermittent claudication. J Vasc Surg 2005;47:702-709.

Adjusted Associations between Frequency of Self-Directed Walking Exercise and Functional Decline over Three-Year Follow-up in Persons with Lower Extremity Peripheral Arterial Disease (n=417)*

Outcome MeasureWalking Exercise Frequency
No WalkingWalking 1-2 times per weekWalking 3 times per weekP Trend
Six-minute walk distance (Feet)-79.19-73.4244.400.048
Four meter walking velocity (usual pace) (meters/second) -0.048-0.030-0.0160.019
Four meter walking velocity (fast pace) (meters/second) -0.070-0.052-0.0250.012
Summary performance score -0.498-0.451-0.2280.130

*Analyses adjusted for age, sex, race, prior year functioning, comorbidities, leg symptoms, educational level, ankle brachial index, body mass index, pack-years of smoking, depression score, cilostazol use, pentoxifylline use, and patterns of missing data.

Conflict of Interest: None declared

Conflict of Interest:

None declared

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Summary for Patients

Can a Self-Directed Walking Program Help To Limit the Rate of Decline in Physical Ability among People with Blocked Arteries in the Legs?

The summary below is from the full report titled “Physical Performance in Peripheral Arterial Disease: A Slower Rate of Decline in Patients Who Walk More.” It is in the 3 January 2006 issue of Annals of Internal Medicine (volume 144, pages 10-20). The authors are M.M. McDermott, K. Liu, L. Ferrucci, M.H. Criqui, P. Greenland, J.M. Guralnik, L. Tian, J.R. Schneider, W.H. Pearce, J. Tan, and G.J. Martin.

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