1. Upper vs. Lower Body Aerobic Training in Patients with Claudication Diane Treat-Jacobson, PhD, RN Assistant Professor of Nursing Center for Gerontological Nursing

2. Peripheral Arterial Disease and Claudication Peripheral Arterial Disease (PAD) Peripheral Arterial Disease (PAD) A disorder caused by atherosclerosis that limits blood flow to the limbs Claudication Claudication A symptom of PAD characterized by pain, aching, or fatigue in working skeletal muscles. Claudication arises when there is insufficient blood flow to meet the metabolic demands of working skeletal muscles

3. Exercise Training for Claudication Efficacy of treadmill training to improve walking distance in patients with claudication from is well established Mechanisms by which exercise training improves walking distance have not been fully elucidated

4. What is the mechanism of improvement in walking distance? Local conditioning effect – changes in muscle metabolism stimulated by exercising specific muscles affected by limited blood flow Local conditioning effect – changes in muscle metabolism stimulated by exercising specific muscles affected by limited blood flow Systemic effect – changes in central cardiovascular conditioning and/or vascular function, leading to improved walking ability Systemic effect – changes in central cardiovascular conditioning and/or vascular function, leading to improved walking ability

5. Exercise Training for Claudication There is limited information about the potential of aerobic arm training to improve onset to claudication (OCD) distance and maximal walking distance (MWD) There is limited information about the potential of aerobic arm training to improve onset to claudication (OCD) distance and maximal walking distance (MWD) One study demonstrated equivalent benefit of upper and lower extremity cycle ergometry exercise on walking distance (Walker et. al, 2000) One study demonstrated equivalent benefit of upper and lower extremity cycle ergometry exercise on walking distance (Walker et. al, 2000) No previous studies have compared aerobic arm training to treadmill training in patients with claudication No previous studies have compared aerobic arm training to treadmill training in patients with claudication

6. Potential Mechanisms by Which Exercise Improves Claudication Peripheral arterial disease Reduced oxygen delivery : Ischemia- Reperfusion Poor aerobic capacity Reduced muscle strength & endurance Impaired walking ability Decreased quality of life Deconditioning and worsening: Obesity Hypertension Hyperlipidemia Hyperglycemia Thrombotic risk Effects of exercise training on pathophysiological correlates of claudication Good evidence for improvement Potential improvement Short-term: may worsen Long-term: may improve Systemic inflammation Muscle fiber denervation Muscle fiber atrophy Altered muscle metabolism Endothelial Dysfunction Stewart et al. Medical Progress: Exercise Training for Claudication. NEJM 2002; 347(24):1941-1951

7. Exercise Training for Claudication Study * Specific Aims: –Determine the relative efficacy of supervised treadmill training or arm ergometry alone, or in combination, versus ‘usual care’ in subjects with PAD –Evaluate the extent to which the effects are maintained or improved following completion of supervised program * Funded by a American Heart Association Scientist Development Grant

8. Methods Randomized controlled pretest- posttest design Randomized controlled pretest- posttest design 4 groups 4 groups –Treadmill training –Upper extremity ergometry –Combined training –Control Group

9. Entry Criteria Inclusion Inclusion –Age > 18 years –Resting ABI < 0.90 or 20% drop in post-exercise ABI –Lifestyle limitation due to claudication –Ability to complete study procedures Exclusion Exclusion –Uncontrolled hypertension or diabetes –Recent peripheral or coronary revascularization procedure –Fontaine stage 3 (rest pain) or 4 (tissue loss) –Unstable heart disease –Walking limited by factors than claudication

10. Procedures Screening Visit Screening Visit –Informed consent –Medical History & Physical Exam, including ankle brachial index (ABI) –Quality of life and health status questionnaires –Symptom-limited graded cardiopulmonary treadmill exercise test (x2) –Post-Exercise ABI –Baseline arm ergometry test

11. Exercise Groups Supervised in the exercise laboratory 3 times/week for 12 weeks Supervised in the exercise laboratory 3 times/week for 12 weeks Sessions 70 minutes in length, 5 minutes warm-up, 60 minutes of exercise, 5 minutes cool down Sessions 70 minutes in length, 5 minutes warm-up, 60 minutes of exercise, 5 minutes cool down Recording of daily exercise outside supervised setting Recording of daily exercise outside supervised setting

12. Treadmill Exercise Program Treadmill walking Treadmill walking Speed: 2.0 mph Speed: 2.0 mph Grade increased by 0.5% every 8 minutes until onset of moderate claudication (rating: 4 out of 5) Grade increased by 0.5% every 8 minutes until onset of moderate claudication (rating: 4 out of 5) After 7% grade is reached, increase speed at 0.1 MPH intervals After 7% grade is reached, increase speed at 0.1 MPH intervals Time: 60 minutes including rest periods Time: 60 minutes including rest periods

13. Upper Body Exercise Program Arm Ergometry Arm Ergometry Watts start at one level below maximal test Watts start at one level below maximal test 2 minutes exercise, 2 minutes rest 2 minutes exercise, 2 minutes rest Gradually increase watts, exercise-rest intervals throughout program as tolerated Gradually increase watts, exercise-rest intervals throughout program as tolerated Time: 60 minutes including rest periods Time: 60 minutes including rest periods

14. Combination Exercise Program 20 minutes Arm Ergometry 20 minutes Arm Ergometry 40 minutes Treadmill 40 minutes Treadmill Increase intensity as with other protocols Increase intensity as with other protocols Time: 60 minutes including rest periods Time: 60 minutes including rest periods

15. Control Group Instructed to continue ‘usual care’ Instructed to continue ‘usual care’ Provided specific written walking instructions Provided specific written walking instructions Instructed on completion of daily exercise records Instructed on completion of daily exercise records Weekly follow-up in the laboratory, review of exercise records Weekly follow-up in the laboratory, review of exercise records

16. Post-Training Assessment Re-assessment of all outcome variables within 1 week of completion of training program, or 12 weeks after enrollment for control group Re-assessment of all outcome variables within 1 week of completion of training program, or 12 weeks after enrollment for control group Follow-up 12 weeks following completion of program (approx. 24 weeks) Follow-up 12 weeks following completion of program (approx. 24 weeks)

17. Outcome Measures Walking Distance (pain free, OCD and maximal, MWD) Walking Distance (pain free, OCD and maximal, MWD) Cardiovascular Variables Cardiovascular Variables Quality of Life, Functional Status and Mood Quality of Life, Functional Status and Mood

18. Demographic and Medical Variables VariableMean (sd) Age in Years67.8 (11.61) BMI27.7 (4.32) Pack Years36.6 (20.25) Lowest Resting ABI0.68 (0.13) Variablen (%) Male18 (64.3) Diabetes8 (28.6) Hypertension22 (78.6) Current/Past Smoking25 (89.3) Dyslipidemia26 (92.9) Leg Revascularization9 (32.1) Coronary Heart Disease18 (64.3)

19. Median Onset of Claudication Distance (OCD) and Maximal Walking Distance (MWD) Scores at Baseline and Following 12 Weeks of Exercise Training Training GroupBaseline OCD Median (Range) 12 Week OCD Median (Range) Wilcoxan Z Score (p) Treadmill (n=8)94.3 meters (26.8-482.8) 187.3 meters (78.67-885.1) 2.37 (0.018) Combination (n=10) 147.1 meters (54.0-268.2) 224.4 meters (80.46-481.0) 1.96 (0.05) Arm Ergometry (n=6) 132.3 meters (80.0-268.2) 251.2 meters (134.1-482.8) 2.20 (0.028) Baseline MWD Median (range) 12 Week MWD Median (Range) Wilcoxan Z Score (p) Treadmill (n=9)363.9 meters (320.1-266.8) 764.5 meters (401.0-1402.0) 2.67 (0.008) Combination (n=10) 475.1 meters (114.4-618.7) 796.5 meters (510.0-970.0) 2.80 (0.005) Arm Ergometry (n=6) 385.3 meters (319.2-886.9) 665.0 meters (544.0-1080.0) 2.20 (0.028)

20. Median Change in Onset of Claudication Distance Baseline 12 Weeks 0 100 200 300 Upper Body Ergometer (n=6) Treadmill (n=8). Combination (n=10) Test Meters Treadmill z= 2.37, p<0.018 Upper Body Ergometer z= 2.20, p<0.028 Combination z= 1.96, p=0.05

21. Baseline12 Weeks 0 100 200 300 400 500 600 700 Median Change in Maximal Walking Distance Baseline12 Weeks 0 100 200 300 400 500 600 700 Treadmill (n=9) Upper Body Combination (n=10) Treadmill (n=9) Upper Body Combination (n=10) Treadmill (n=9) Upper Body Ergometer(n=6) Combination (n=10) Test Meters Treadmill z=2.67, p=0.008 Upper Body Ergometer z=2.20, p=0.028 Combination z=2.80, p=0.005 Treadmill z=2.67, p=0.008 Upper Body Ergometer z=2.20, p=0.028 Combination z=2.80, p=0.005

22. Conclusions Preliminary data suggest that arm ergometry and treadmill training offer similar benefits in improving OCD and MWD. Preliminary data suggest that arm ergometry and treadmill training offer similar benefits in improving OCD and MWD. Mechanisms of improvement with both forms of exercise require further study. Mechanisms of improvement with both forms of exercise require further study. For those with severe PAD who cannot perform walking exercise, arm exercise is a promising alternative. For those with severe PAD who cannot perform walking exercise, arm exercise is a promising alternative.

23. Future Research Preliminary data indicate that there is improvement in those performing upper body aerobic exercise training Preliminary data indicate that there is improvement in those performing upper body aerobic exercise training This finding suggests a systemic mechanism of exercise-related improvement This finding suggests a systemic mechanism of exercise-related improvement Assessment of physiological variables associated with endothelial injury, thrombosis/hemostasis, and inflammation in those engaging in ischemic versus non- ischemic exercise is warranted Assessment of physiological variables associated with endothelial injury, thrombosis/hemostasis, and inflammation in those engaging in ischemic versus non- ischemic exercise is warranted

24. A Model of the Impact of Exercise on Patients with Claudication

25. Acknowledgements Clinical Scholar Mentorship Team Clinical Scholar Mentorship Team –Jean Wyman, PhD, RN, FAAN –Nigel Key, MD –Arthur S. Leon, MD –Don Dengel, PhD –Jayne Fulkerson, PhD Research Team Research Team –Ulf Bronas, MS –Arthur S. Leon, MD –Lora Sweezy –Kristie Koch –Kimberly Miller –Kathryn Koch –Judith Regensteiner, Consultant