NIH Public Access

Author Manuscript
J Vasc Surg. Author manuscript; available in PMC 2011 March 1.
Published in final edited form as: J Vasc Surg. 2010 March ; 51(3): 628633. doi:10.1016/j.jvs.2009.09.053.

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

WALKING ECONOMY BEFORE AND AFTER THE ONSET OF CLAUDICATION PAIN IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASE
Andrew W. Gardnera, Raphael M. Ritti-Diasd, Julie A. Stonerb, Polly S. Montgomerya, Kristy J. Scotta, and Steve M. Blevinsc a CMRI Diabetes and Metabolic Research Program, Harold Hamm Oklahoma Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK
b

Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
c

General Internal Medicine Section, University of Oklahoma Health Sciences Center, Oklahoma City, OK
d

School of Physical Education, Pernambuco University, Pernambuco, Brazil

Abstract
PurposesTo determine the walking economy before and after the onset of claudication pain in patients with peripheral arterial disease (PAD), and to identify predictors of the change in walking economy following the onset of claudication pain. MethodsA total of thirty-nine patients with PAD were studied, in which 29 experienced claudication (Pain group) during a constant load walking economy treadmill test (speed = 2.0 mph, grade = 0%) and 10 were pain-free during this test (Pain-Free group). Patients were characterized on walking economy (i.e., oxygen uptake during ambulation), as well as on demographic characteristics, cardiovascular risk factors, baseline exercise performance measures, and the ischemic window calculated from the decrease in ankle systolic blood pressure following exercise. ResultsDuring the constant load treadmill test, the Pain group experienced onset of claudication pain at 323 195 seconds (mean standard deviation) and continued to walk until maximal pain was attained at 759 332 seconds. Walking economy during pain-free ambulation (9.54 1.42 ml.kg1.min1) changed (p < 0.001) after the onset of pain (10.18 1.56 ml.kg1.min1). The change in walking economy after the onset of pain was associated with ischemic window (p < 0.001), hypertension (p < 0.001), diabetes (p = 0.002), and height (p = 0.003). In contrast, the Pain-Free group walked pain-free for the entire 20-minute test duration without a change in walking economy (p = 0.36) from the second minute of exercise (9.20 1.62 ml.kg1.min1) to the nineteenth minute of exercise (9.07 1.54 ml.kg1.min1).

Address correspondence to: Andrew W. Gardner, Ph.D., Hobbs-Recknagel Professor, General Clinical Research Center, University of Oklahoma Health Sciences Center, 1122 N.E. 13th Street, Suite 150, Oklahoma City, OK 73117. Telephone (405) 271-4272 ext. 42743, FAX: 405-271-4273, andrew-gardner@ouhsc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Gardner et al.

Page 2

ConclusionPainful ambulation at a constant speed is associated with impaired walking economy, as measured by an increase in oxygen uptake in patients limited by intermittent claudication, and the change in walking economy is explained, in part, by severity of PAD, diabetes, and hypertension.

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

INTRODUCTION
Intermittent claudication is a symptom of peripheral arterial disease (PAD), and is associated with elevated rates of mortality(14) and morbidity.(5) Intermittent claudication afflicts 5% of the US population older than 55 years of age,(6) and occurs during ambulation when the peripheral circulation is inadequate to meet the metabolic requirement of the active leg musculature. Thus, intermittent claudication impairs ambulation,(7;8) daily physical activity, (9) and health-related quality of life.(10) Walking economy, defined as the oxygen uptake during ambulation, is a key aspect in sustaining ambulatory activities.(11) Patients with intermittent claudication have poor walking economy, as their oxygen uptake of pain-free ambulation is higher than age-matched controls. (11) This may be a consequence of an altered gait pattern observed even before the development of claudication pain,(1214) but this is not a consistent finding. (1517) When the impaired walking economy (i.e., high oxygen uptake) of patients with intermittent claudication is considered along with their low peak oxygen uptake,(1820) pain-free ambulation at any given pace is performed at a higher relative metabolic cost than compared to controls.(11) The onset of claudication may impair walking economy even further, thereby increasing the relative metabolic cost of painful ambulation and reducing exercise tolerance of patients with intermittent claudication. However, surprisingly no information is available comparing the walking economy while ambulating pain-free and with leg pain. Therefore, the purposes of our study were to determine the walking economy before and after the onset of claudication pain in patients with PAD, and to identify predictors of the change in walking economy following the onset of claudication pain. The hypotheses were that walking economy worsens (i.e., oxygen uptake is increased) after the onset of claudication pain, and that the severity of PAD is predictive of the change in walking economy.

METHODS
SUBJECTS RecruitmentPatients were evaluated in the General Clinical Research Center at the University of Oklahoma Health Sciences Center (HSC). Patients were recruited by referrals from the HSC vascular clinic, as well as by newspaper advertisements for possible enrollment into an exercise study. The procedures used in this study were approved by the Institutional Review Board at the University of Oklahoma HSC. Written informed consent was obtained from each subject prior to investigation. ScreeningPatients with intermittent claudication secondary to vascular insufficiency were included in this study if they met the following criteria: (a) a history of intermittent claudication, (b) ambulation during a graded treadmill test limited by intermittent claudication,(7) (c) an ankle-brachial index (ABI) 0.90 at rest,(6) or an ABI 0.73 after exercise,(21) and (d) for those experiencing pain during the constant load, walking economy treadmill test (Pain group), at least one minute of oxygen uptake data was necessary during both pain-free and painful ambulation to compare the two conditions. Patients were excluded from this study for the following conditions: (a) absence of PAD (ABI > 0.90 at rest and ABI > 0.73 after exercise), (b) inability to obtain an ABI measure due to non-compressible vessels, (c) asymptomatic PAD determined from the medical history and verified during the graded treadmill test, (d) use of medications indicated for the treatment of intermittent claudication (cilostazol and
J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

Gardner et al.

Page 3

pentoxifylline) initiated within three months prior to investigation, (e) exercise tolerance limited by factors other than leg pain (e.g., severe coronary artery disease, dyspnea, poorly controlled blood pressure), and (f) active cancer, renal disease, or liver disease. A total of 80 patients were evaluated for this study, and 39 patients were deemed eligible. MEASUREMENTS All of the measurements described below were part of an overall baseline evaluation. Medical History, Physical Examination, and AnthropometryDemographic information, height, weight, body mass index (BMI), waist and hip circumferences,(22) cardiovascular risk factors, co-morbid conditions, claudication history, blood samples, and a list of current medications were obtained from a medical history and physical examination at the beginning of the study. Walking Impairment Questionnaire (WIQ)Self-reported ambulatory ability was assessed using a validated questionnaire for PAD patients that assesses ability to walk at various speeds and distances, and to climb stairs.(23) Graded Treadmill Test Claudication Times and Peak Oxygen Uptake: Patients performed a progressive, graded treadmill protocol to determine study eligibility, as well as to obtain outcome measures related to peak exercise performance.(7) The claudication onset time (COT), defined as the walking time at which the patient first experienced pain, and the peak walking time (PWT), defined as the walking time at which ambulation could not continue due to maximal pain, were both recorded to quantify the severity of claudication. Peak oxygen uptake was measured by oxygen uptake obtained during the peak exercise work load with a Medical Graphics VO2000 metabolic system (Medical Graphics Inc, St. Paul, MN). Using these procedures, the test-retest intraclass reliability coefficient is R = 0.89 for COT,(7) R = 0.93 for PWT,(7) and R = 0.88 for peak oxygen uptake.(24) ABI and Ischemic Window: As previously described, ABI measures were obtained from the more severely diseased lower extremity before and 1, 3, 5, and 7 minutes after the treadmill test.(7;25) The reduction in ankle systolic blood pressure after treadmill exercise from the resting baseline value was quantified by calculating the area under the curve, referred to as the ischemic window.(26) Because the ischemic window is a function of both PAD severity and the amount of exercise performed, the ischemic window was normalized per meter walked. 6-Minute Walk TestPatients performed an over ground, 6-minute walk test supervised by trained exercise technicians.(27) The pain-free and total distance walked during the test were recorded. The test-retest intraclass reliability coefficient is R = 0.75 for distance to onset of claudication pain, and R = 0.94 for total 6-minute walking distance. (27) Ambulatory Activity MonitoringDaily ambulatory activity was assessed using a step activity monitor (Step Watch 3, Cyma Inc., Mountlake Terrace, WA) as previously described. (28) Ambulatory activity was measured during seven consecutive days in which patients were instructed to wear the monitor during waking hours and to remove it before retiring to bed. The step activity monitor was attached to the right ankle above the lateral malleolus using elastic Velcro straps, and continuously recorded the number of steps taken on a minute-tominute basis. The accuracy of the step activity monitor exceeds 99% 1% in patients with intermittent claudication.(28)

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

Gardner et al.

Page 4

Walking Economy Treadmill TestThis test was the experimental protocol used to obtain the two primary outcome measures consisting of walking economy (oxygen uptake expressed as ml.kg1.min1) and the change in walking economy ( in oxygen uptake expressed as ml.kg1.min1) following the onset of claudication pain. Additionally, this test was used to group patients into a Pain group and a Pain-Free group as described in the results section. Patients performed the walking economy treadmill test in which the work rate was at a constant speed of 2 mph and a grade of 0% until maximal claudication pain was attained, or for a maximum of 20 minutes.(29) Oxygen uptake was measured throughout the test with a Medical Graphics VO2000 metabolic system. During the test, patients indicated when they experienced the onset of claudication pain, and if the pain increased to a maximal level forcing them to discontinue exercise. Oxygen uptake was recorded each minute during the test. Data obtained during the first and last minute of exercise were not used for analyses because of the possibility that data was not recorded for a full 60 seconds during these time points, and because the oxygen uptake does not approach a steady-state value during the first minute. Additionally, oxygen uptake obtained during the minute in which the onset of claudication occurred in the Pain group was not used for analyses because it was not possible to precisely separate the data before and after the onset of pain within the minute. Walking economy was calculated as the average oxygen uptake from the entire test. The change in walking economy was calculated as the difference in average oxygen uptake during pain-free and painful ambulation in the Pain group, and between the second minute and 19th minute of exercise in the Pain-Free group. STATISTICAL ANALYSES A paired t-test was used to compare the mean change in walking economy following the onset of claudication pain in the patients in the Pain group, and between the second and nineteenth minute time points in the patients in the Pain-Free group. The Pearson correlation coefficient was estimated to summarize the correlation between continuous clinical characteristics or baseline exercise performance with walking economy measures. Mean walking economy measures were compared between the two groups of patients using a two sample t-test. Linear regression was used to identify clinical and baseline exercise performance measures that were independently correlated with walking economy measures. The measures that were correlated with the walking economy measures univariately at a 0.10 alpha level were entered into a multiple linear regression model. These measures were deleted from the multiple regression model until all terms were significant at the 0.05 alpha level. The clinical and baseline exercise performance measures that were considered in the modeling were age, sex, height, weight, BMI, ABI, ischemic window, COT, PWT, peak oxygen uptake, daily ambulatory activity, current smoking, obesity, abdominal obesity, hypertension, and diabetes. A separate regression model was fit for walking economy and the change in walking economy. All analyses were performed using the SAS statistical package (System for Windows, version 9.1, SAS Institute Inc., Cary, NC).

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript RESULTS

Patients were grouped according to whether they experienced claudication during the relatively low demanding walking economy treadmill test. During this test, 29 patients experienced claudication (Pain group) and 10 did not experience claudication (Pain-Free group). The clinical characteristics of the Pain and Pain-Free groups were similar (p > 0.05), except for a non-significant trend (p = 0.059) of a lower ABI in the Pain group (Table I). Baseline measures of exercise performance were worse in the Pain group, as they had lower values for COT (p = 0.009), PWT (p < 0.001), 6-minute walk pain-free distance (p = 0.019) and total distance (p = 0.023), WIQ walking distance score (p = 0.001), WIQ walking speed score (p <

J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

Gardner et al.

Page 5

0.001), WIQ stair climbing score (p < 0.001), and daily ambulatory activity (p = 0.036) (Table II).

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

The walking economy values of the two groups are shown in Table III. In this study, the average time to the onset of pain in the Pain group was 323 seconds, and they continued to walk until maximal pain was attained at an average time of 759 seconds. All patients in the Pain-Free group completed 20 minutes of walking without experiencing claudication. The walking economy value increased in the Pain group after the onset of claudication pain (p < 0.001), whereas no change (p = 0.36) was observed in the Pain-Free group between the second and nineteenth minute of the treadmill test. In the Pain group, walking economy was correlated with baseline peak oxygen uptake (r = 0.51, p =0.004), and with diabetes (p =0.046) (Table IV). Using multiple regression procedures (Table V), baseline peak oxygen uptake (p = 0.005) was the only predictor of walking economy. The change in walking economy following the onset of claudication was correlated with ischemic window (p = 0.027), ABI (p =0.037) and diabetes (p = 0.007). Using multiple regression procedures, the change in walking economy following onset of claudication was predicted by ischemic window (p < 0.001), hypertension (p < 0.001), diabetes (p = 0.002), and height (p = 0.003).

DISCUSSION
The major findings of this investigation are that (1) development of claudication pain while ambulating at a constant speed is associated with impaired walking economy, as measured by an increase in oxygen uptake, and (2) the change in walking economy with claudication pain is primarily related to the ischemic window, diabetes, and hypertension. Walking economy worsened after the onset of claudication pain in patients ambulating at a constant work rate, with patients having more severe PAD, as measured by lower ABI and higher ischemic window, experiencing the greater changes in walking economy. Although this study does not address mechanisms for the changes in walking economy, it has been observed that a gradual increase in oxygen uptake occurs during severe exercise compared to light exercise, thus preventing oxygen uptake from reaching a steady-state plateau during exercise at a constant work load.(30) After the onset of pain, an increase in oxygen uptake may be exaggerated in patients with greater severity of PAD because a given exercise work load becomes relatively more difficult to perform than for those with mild PAD. Another possible reason why patients with more severe PAD have worse walking economy after the onset of pain is that they may have a greater recruitment of fast-twitch motor units, which would increase oxygen uptake during exercise.(31;32) Muscle denervation observed in PAD patients (33) may impair optimal motor unit recruitment during a constant load exercise task, becoming more evident in patients with greater severity of PAD. Cardiovascular risk factors also were associated with the change in walking economy after the onset of pain, as patients with diabetes had a blunted increase in oxygen uptake, whereas patients with hypertension had a greater increase. Diabetes slows whole-body as well as leg skeletal muscle oxygen uptake kinetics during exercise,(34;35) and may compromise perfusion in more distal portions of the leg, which may partially explain the blunted increase in oxygen uptake after onset of pain in patients with diabetes. Conversely, hypertension increases the perfusion of the calf musculature,(36) which may increase oxygen uptake during exercise in patients with intermittent claudication. Walking economy during ambulation represents the metabolic cost of exercise. Less economical walking, measured by higher oxygen uptake at a constant work rate, indicates that exercise is performed at a higher percentage of exercise capacity, thereby reducing the tolerance
J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

Gardner et al.

Page 6

to sustain ambulation.(11) Although patients with intermittent claudication have impaired walking economy than controls for numerous possible reasons, such as inefficient gait,(11) other factors may paradoxically decrease oxygen uptake during ambulation. In our study, diabetes and low peak oxygen uptake were associated with better walking economy (i.e., lower oxygen uptake) than in patients without diabetes and in patients with higher peak oxygen uptake. Rather than considering patients with diabetes and poor cardiopulmonary fitness as having favorable walking economy, the more likely interpretation is that these patients have impaired ability to increase oxygen uptake to meet the metabolic demand of exercise. This interpretation is consistent with previous work showing that diabetics have impaired oxygen uptake kinetics during exercise.(34;35) Collectively, the overall net negative effect of PAD on walking economy (i.e., increased oxygen uptake) is partially masked in patients with diabetes and poor cardiopulmonary fitness. Therefore, walking economy data should be adjusted for diabetes and peak oxygen uptake for more valid comparisons between patients or groups of patients. Walking economy is one of the mechanisms for improving claudication distances following exercise training.(29) Our primary finding of impaired walking economy with the onset of pain has important clinical implications because higher oxygen cost during painful ambulation increases the intensity of exercise,(11) which may reduce exercise tolerance and limit the amount of work that can be performed during exercise training sessions. Consequently, an exercise program that primarily consists of pain-free ambulation may be a preferable alternative to train patients than having them walk to a moderate amount of claudication pain. Indeed, a recent report from our laboratory found that there is no additional benefit of training patients at relatively high exercise intensity (80% of maximum work load) in which a greater amount of painful ambulation is performed than compared to training at relatively low intensity (40% of maximum work load) to improve claudication distances.(37) There are several limitations to this study. The correlation and regression coefficients calculated between walking economy measures and clinical characteristics and baseline exercise performance measures from this cross-sectional design do not allow causality to be established. The present findings are also limited by the relatively small sample sizes, particularly in the Pain-Free group. Additionally, this study is limited to PAD patients who have intermittent claudication, and may not be generalized to patients with less severe or more severe PAD. However, the patients in the current study are typical of patients with intermittent claudication, as there was a good proportion of women and African-Americans, and high prevalence of cardiovascular risk factors for PAD, including smoking, diabetes, hypertension, dyslipidemia, and obesity. Thus, the findings of the present study appear generalizable to patients with intermittent claudication who typically have numerous co-morbid conditions. In conclusion, painful ambulation at a constant speed is associated with impaired walking economy, as measured by an increase in oxygen uptake in patients limited by intermittent claudication, and the change in walking economy is explained, in part, by severity of PAD, diabetes, and hypertension.

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

Acknowledgments
This research was supported by grants from the National Institute on Aging (NIA) (R01-AG-24296; AWG), by a Oklahoma Center for the Advancement of Science and Technology grant (HR04-113S; AWG), and by the University of Oklahoma Health Sciences Center General Clinical Research Center grant (M01-RR-14467), sponsored by the National Center for Research Resources from the National Institutes of Health.

J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

Gardner et al.

Page 7

Reference List
1. Brass EP, Hiatt WR. Review of mortality and cardiovascular event rates in patients enrolled in clinical trials for claudication therapies. Vasc Med 2006;11:14145. [PubMed: 17288119] 2. Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326:38186. [PubMed: 1729621] 3. Dormandy J, Heeck L, Vig S. The natural history of claudication: risk to life and limb. Semin Vasc Surg 1999;12:12337. [PubMed: 10777239] 4. Muluk SC, Muluk VS, Kelley ME, Whittle JC, Tierney JA, Webster MW, et al. Outcome events in patients with claudication: a 15-year study in 2777 patients. J Vasc Surg 2001;33:25157. [PubMed: 11174775] 5. Vogt MT, Wolfson SK, Kuller LH. Lower extremity arterial disease and the aging process: a review. J Clin Epidemiol 1992;45:52942. [PubMed: 1588358] 6. Weitz JI, Byrne J, Clagett GP, Farkouh ME, Porter JM, Sackett DL, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation 1996;94:302649. [PubMed: 8941154] 7. Gardner AW, Skinner JS, Cantwell BW, Smith LK. Progressive vs single-stage treadmill tests for evaluation of claudication. Med Sci Sports Exerc 1991;23:4028. [PubMed: 2056896] 8. Gardner AW, Skinner JS, Vaughan NR, Bryant CX, Smith LK. Comparison of three progressive exercise protocols in peripheral vascular occlusive disease. Angiology 1992;43:66171. [PubMed: 1632569] 9. Sieminski DJ, Gardner AW. The relationship between free-living daily physical activity and the severity of peripheral arterial occlusive disease. Vasc Med 1997;2:28691. [PubMed: 9575600] 10. Feinglass J, McCarthy WJ, Slavensky R, Manheim LM, Martin GJ. Effect of lower extremity blood pressure on physical functioning in patients who have intermittent claudication. The Chicago Claudication Outcomes Research Group. J Vasc Surg 1996;24:50311. [PubMed: 8911399] 11. Womack CJ, Sieminski DJ, Katzel LI, Yataco A, Gardner AW. Oxygen uptake during constantintensity exercise in patients with peripheral arterial occlusive disease. Vasc Med 1997;2:17478. [PubMed: 9546966] 12. Crowther RG, Spinks WL, Leicht AS, Quigley F, Golledge J. Relationship between temporal-spatial gait parameters, gait kinematics, walking performance, exercise capacity, and physical activity level in peripheral arterial disease. J Vasc Surg 2007;45:117278. [PubMed: 17543681] 13. Gardner AW, Forrester L, Smith GV. Altered gait profile in subjects with peripheral arterial disease. Vasc Med 2001;6:3134. [PubMed: 11358158] 14. Scherer SA, Bainbridge JS, Hiatt WR, Regensteiner JG. Gait characteristics of patients with claudication. Arch Phys Med Rehabil 1998;79:52931. [PubMed: 9596393] 15. McCully K, Leiper C, Sanders T, Griffin E. The effects of peripheral vascular disease on gait. J Gerontol A Biol Sci Med Sci 1999;54:B291B294. [PubMed: 10462161] 16. McDermott MM, Ohlmiller SM, Liu K, Guralnik JM, Martin GJ, Pearce WH, et al. Gait alterations associated with walking impairment in people with peripheral arterial disease with and without intermittent claudication. J Am Geriatr Soc 2001;49:74754. [PubMed: 11454113] 17. Scherer SA, Hiatt WR, Regensteiner JG. Lack of relationship between gait parameters and physical function in peripheral arterial disease. J Vasc Surg 2006;44:78288. [PubMed: 17012002] 18. Eldridge JE, Hossack KF. Patterns of oxygen consumption during exercise testing in peripheral vascular disease. Cardiology 1987;74:23640. [PubMed: 3594513] 19. Ryan AS, Katzel LI, Gardner AW. Determinants of peak V(O2) in peripheral arterial occlusive disease patients. J Gerontol A Biol Sci Med Sci 2000;55:B302B306. [PubMed: 10843347] 20. Womack CJ, Hyman BA, Gardner AW. Prediction of peak oxygen consumption in patients with intermittent claudication. Angiology 1998;49:59198. [PubMed: 9717887] 21. Hiatt WR, Marshall JA, Baxter J, Sandoval R, Hildebrandt W, Kahn LR, et al. Diagnostic methods for peripheral arterial disease in the San Luis Valley Diabetes Study. J Clin Epidemiol 1990;43:597 606. [PubMed: 2189949]

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

Gardner et al.

Page 8

22. Lohman, TC.; Roche, AF.; Martorell, R. Anthropometric standardization reference manual. Champaign, IL: Human Kinetics Books; 1988. p. 39-70. 23. Regensteiner JG, Steiner JF, Panzer RL, Hiatt WR. Evaluation of walking impairment by questionnaire in patients with peripheral arterial disease. J Vasc Med Biol 1990;2:14252. 24. Gardner AW. Reliability of transcutaneous oximeter electrode heating power during exercise in patients with intermittent claudication. Angiology 1997;48:22935. [PubMed: 9071198] 25. Gardner AW, Skinner JS, Smith LK. Effects of handrail support on claudication and hemodynamic responses to single-stage and progressive treadmill protocols in peripheral vascular occlusive disease. Am J Cardiol 1991;68:99105. [PubMed: 2058566] 26. Feinberg RL, Gregory RT, Wheeler JR, Snyder SO Jr, Gayle RG, Parent FN III, et al. The ischemic window: a method for the objective quantitation of the training effect in exercise therapy for intermittent claudication. J Vasc Surg 1992;16:24450. [PubMed: 1495149] 27. Montgomery PS, Gardner AW. The clinical utility of a six-minute walk test in peripheral arterial occlusive disease patients. J Am Geriatr Soc 1998;46:70611. [PubMed: 9625185] 28. Gardner AW, Montgomery PS, Scott KJ, Afaq A, Blevins SM. Patterns of ambulatory activity in subjects with and without intermittent claudication. J Vasc Surg 2007;46:120814. [PubMed: 17919876] 29. Womack CJ, Sieminski DJ, Katzel LI, Yataco A, Gardner AW. Improved walking economy in patients with peripheral arterial occlusive disease. Med Sci Sports Exerc 1997;29:128690. [PubMed: 9346157] 30. Poole DC, Schaffartzik W, Knight DR, Derion T, Kennedy B, Guy HJ, et al. Contribution of exercising legs to the slow component of oxygen uptake kinetics in humans. J Appl Physiol 1991;71:124560. [PubMed: 1757346] 31. Shinohara M, Moritani T. Increase in neuromuscular activity and oxygen uptake during heavy exercise. Ann Physiol Anthropol 1992;11:25762. [PubMed: 1642722] 32. Vollestad NK, Wesche J, Sejersted OM. Gradual increase in leg oxygen uptake during repeated submaximal contractions in humans. J Appl Physiol 1990;68:11501156. [PubMed: 2341340] 33. England JD, Regensteiner JG, Ringel SP, Carry MR, Hiatt WR. Muscle denervation in peripheral arterial disease. Neurology 1992;42:99499. [PubMed: 1579257] 34. Bauer TA, Reusch JE, Levi M, Regensteiner JG. Skeletal muscle deoxygenation after the onset of moderate exercise suggests slowed microvascular blood flow kinetics in type 2 diabetes. Diabetes Care 2007;30:28802885. [PubMed: 17675540] 35. Regensteiner JG, Bauer TA, Reusch JE, Brandenburg SL, Sippel JM, Vogelsong AM, et al. Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus. J Appl Physiol 1998;85:310317. [PubMed: 9655791] 36. Acree LS, Comp PC, Whitsett TL, Montgomery PS, Nickel KJ, Fjeldstad AS, et al. The influence of obesity on calf blood flow and vascular reactivity in older adults. Dyn Med 2007;6:4. [PubMed: 17386093] 37. 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;42:7029. [PubMed: 16242558]

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

Gardner et al.

Page 9

Table I

Clinical characteristics of the pain group and the pain-free group.

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

Pain Group (n=29)

Pain-Free Group (n=10)

P-value

Mean (SD) Age (years) Weight (kg) Height (cm) Body mass index (kg/m2) 68 (11) 83.5 (16.5) 169.8 (8.8) 29.0 (5.3) 98.6 (12.6) 0.73 (0.20) Percent Sex (% Men) Race (% Caucasian) Current smoking (%) Diabetes (%) Hypertension (%) Dyslipidemia (%) Abdominal obesity (%) (n=20, n = 7) Obesity (%) Bilateral Disease (%)(n=24, n = 9) Medication (%) Statin Aspirin 69% Plavix 21% 52% 59% 59% 31% 28% 86% 79% 60% 41% 63%

Mean (SD) 72 (12) 81.4 (7.5) 173.8 (9.9) 27.2 (3.8) 99.6 (6.4) 0.88 (0.22) Percent 80% 70% 20% 30% 100% 90% 43% 10% 44% 0.32 0.58 0.24 0.32 0.84 0.059 P-value 0.28 0.71 0.69 >0.99 0.56 0.65 0.66 0.12 0.44

Waist girth (cm) (n=20, n=7) Ankle/brachial index

70% 90% 20%

0.46 0.40 1.00

J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

Gardner et al.

Page 10

Table II

Baseline exercise performance measures of the pain group and the pain-free group. Values are means (SD).

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

Pain Group (n=29) Claudication Onset Time (sec) Peak Walking Time (sec) Peak Oxygen Uptake (ml.kg1.min1) Ischemic Window (mmHg.min1.m1) 6-min Walk Pain Free Distance (m) 6-min Walk Distance (m) WIQ Distance Score (%) WIQ Speed Score (%) WIQ Stair Climbing Score (%) Daily Ambulatory Activity (steps/day) 253 (155) 580 (200) 13.8 (3.1) 0.28 (0.36) 178.5 (86.9) 397.0 (75.0) 49 (30) 37 (20) 49 (28) 2654 (1380)

Pain-Free Group (n=10) 568 (277) 991 (248) 17.8 (5.5) 0.23 (0.22) 326.8 (150.2) 460.3 (47.2) 85 (18) 70 (15) 83 (13) 3767 (1294)

P-value 0.009 <0.001 0.086 0.74 0.019 0.023 0.001 <0.001 <0.001 0.036

J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

Table III

Walking economy of the pain group (n = 29) and pain-free group (n = 10). Values are means (SD)
Pain-Free Ambulation Painful Ambulation (Painful Pain-Free) Ambulation 95% CI for Mean Change P-value for

Groups

Gardner et al.

Pain Group 9.54 (1.42) 10.18 (1.56) 0.64 (0.83) 0.32 to 0.96 <0.001

Walking Economy (ml.kg1.min1)

Pain-Free Group * 9.20 (1.62) 9.07 (1.54) 0.13 (0.44) 0.45 to 0.18 0.36

Walking Economy (ml.kg1.min1)

The value for the pain-free group listed under pain-free ambulation is the oxygen uptake measured during the 2nd minute of walking, and the value listed under painful ambulation is the oxygen uptake

J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

measured during the 19th minute of walking.

NIH-PA Author Manuscript

Page 11

NIH-PA Author Manuscript

NIH-PA Author Manuscript

Gardner et al.

Page 12

Table IV

The association between walking economy and clinical characteristics of patients in the pain group (n = 29).

NIH-PA Author Manuscript NIH-PA Author Manuscript

*

Variables

Walking Economy

(ml.kg1.min1)

Walking Economy: Painful Pain-free Ambulation (ml.kg1.min1)

Continuous Measures (Values are Pearson correlation coefficients) Age Height Weight Body mass index Ankle-brachial index Ischemic Window 6-minute Walk Pain Free Distance 6-minute Walk Distance Peak Oxygen Uptake Daily Ambulatory Activity Categorical Measures (Values are difference in mean VO2) Gender (Male Female) Current smoking (current former/ never) Obesity (obese non-obese) Abdominal obesity (obese non-obese) Hypertension (hypertense nonhypertense) Diabetes (diabetic non-diabetic) Bilateral disease (bilateral unilateral) p0.05, p0.01. 0.36 0.51 0.22 0.04 0.81 1.20* 0.58 0.49 0.33 0.07 0.39 0.76 0.89** 0.048 0.21 0.51** 0.15 0.15 0.090 0.22 0.34 0.06 0.05 0.10 0.15 0.18 0.03 0.05 0.29 0.20 0.03 0.39* 0.41* 0.03

**

NIH-PA Author Manuscript

J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

Table V

Multiple regression models predicting walking economy, and the change in walking economy following the onset of claudication in patients in the pain group (n = 29).
Unstandardized Coefficients Standardized Coefficients

Dependent Variables Peak Oxygen Uptake Ischemic Window (mmHg.min1.m1) 1.25 1.15 0.76 0.036 0.014 to 0.059 0.38 1.21 to 0.32 0.42 0.56 to 1.74 0.48 0.66 to 1.84 0.54 Hypertension Diabetes Height (cm) (ml.kg1.min1) 0.24 0.08 to 0.40 0.51

Independent Variables

Regression Coefficient

95% Confidence Interval

Regression Coefficient

Walking Economy (ml.kg1.min1)*

Walking Economy: Painful Painfree ambulation (ml.kg1.min1)**

Overall model results: F-test statistic = 9.66 with (1, 27) degrees of freedom, p=0.004; R2=0.26

**

Overall model results: F-test statistic = 13.38 with (4, 24) degrees of freedom, p<0.001; R2=0.69

Standardized regression coefficients were calculated by fitting a linear regression model to standardized independent and dependent variables (subtracting the sample mean and dividing by the sample standard deviation) and represent the expected difference, in standard deviations, in the mean dependent variable per 1 standard deviation difference in the independent variable.

J Vasc Surg. Author manuscript; available in PMC 2011 March 1.

The reference group for each unstandardized coefficient for the indicator variables is the group without the condition (normotensive and non-diabetic subjects, respectively).

NIH-PA Author Manuscript

Gardner et al.
95% Confidence Interval 0.17 to 0.86 0.29 to 0.80 0.24 to 0.73 0.66 to 0.17 0.15 to 0.62 P-value 0.004 <0.001 <0.001 0.002 0.003

NIH-PA Author Manuscript

Page 13

NIH-PA Author Manuscript