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Exercise and Six-Minute Walk Test in Lower Extremity Occlusive Peripheral Arterial Disease

Tales de Carvalho About the author

Peripheral Arterial Disease; Intermittent Claudication; Anaerobic Threshold; Exercise; Walk Test; Physical Activities of Daily Living

The article “Exercise Intensity During 6-min Test in Patients with Peripheral Artery Disease”11. Farah BQ, Ritti-Dias RM, Montgomery P, Cucato GG, Gardner A. Exercise Intensity during 6-Minute Walk Test in Patients with Peripheral Artery Disease. Arq Bras Cardiol. 2020; 114(3):486-492 provides original, practically useful information to be considered in the diagnosis, prognosis and mainly in the functional assessment that allows a better prescription of physical exercise in the medical treatment of the disease. The study was conducted with the aim of determining whether overground walking would allows the detection of the first ventilatory threshold, also known as anaerobic threshold (AT), in symptomatic patients with lower extremity occlusive peripheral arterial disease (LE-OPAD). AT is a marker of exercise intensity, useful for the determination of the optimal zone for physical training focused on improvement in cardiorespiratory fitness.22. Neder JA, Nery LE. Teste de Exercício Cardiopulmonar. J Pneumol. 2002; 28(Supl 3): 166-206.

LE-OPAD is an important public health problem. According to global epidemiology report, the disease affected 202 million individuals in 2010, and 237 million in 2015, with a 22% increase during this period.33. Song P, Rudan D, Zhu Y, Fowkes FJI, Rahimi K, Fowkes FGR, et al. Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis. Lancet Glob Health. 2019;7(8): e1020–e1030. The association of OPAD with major cardiovascular events (MACE) has been well documented; in the severe stage of the disease, with presence of critical ischemia, there is a high risk of cardiovascular events, lower limb amputation and death,44. Beckman JA, Duncan MS, Damrauer SM, Wells QS, Barnett JV, Wasserman DH, et al. Microvascular disease, peripheral artery disease, and amputation. Circulation. 2019;140(6):449–58. with association with elevated levels of cardiac troponin and N terminal pro-brain natriuretic peptide (NT-proBNP).55. Matsushita K, Kwak L, Yang C, Pang Y, Ballew SH, Sang Y, et al. High-sensitivity cardiac troponin and natriuretic peptide with risk of lower extremity peripheral artery disease: the Atherosclerosis Risk in Communities (ARIC) Study. Eur Heart J. 2018;39(25):2412–9.

LE-OPAD is highly suspected in the presence of pain in lower limbs when walking, without apparent orthopedic problem, and an ankle brachial index (ABI) lower than 0.90 at rest. Walking tests should be performed to help in the diagnosis, particularly when the ABI is greater than 0.91, and in the functional classification and exercise prescription.66. Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, Cohnert T, et al; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763–816.Field walking tests allow the identification of intermittent claudication, with determination of the distance walked to symptom onset (initial claudication) and to maximum functional limitation (absolute claudication). In treadmill tests, the measurement of the ABI has been proposed, both at rest and after exercise. The presence of the disease is strongly suspected when ABI is reduced by at least 20% and 30mmHg after exercise compared with rest.77. Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135(12):e686-e725. However, resting ABI, which has been widely used in clinical practice, can produce false negative results, which is of particular importance in patients with poorly compressible arteries. In the study by Tóth-Vajna et al.,88. Tóth-Vajna Z, Tóth-Vajna G, Gombos Z, Szilágyi B, Járai Z, Berczeli M, Sótonyi P. Screening of peripheral arterial disease in primary health care. Vascular Health Risk Manag. 2019 Aug 20;15:355-63. almost one fourth of the individuals with a diagnosis had poorly compressible arteries or was considered symptomatic with a negative ABI. Therefore, in case of suspicion of LE-OPAD, a deeper investigation is recommended despite normal ABI values.

In symptomatic patients, exercise can affect morbidity and mortality, with improvement of symptoms and quality of life and increase of maximum walking distance, and thus must be part of the optimized treatment.66. Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, Cohnert T, et al; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763–816.,77. Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135(12):e686-e725. Therefore, all patients with intermittent claudication should receive optimized medical treatment, i.e., a combination of lifestyle changes with pharmacological therapy, considering the body of evidence showing a reduction in cardiovascular events and improvement of the outcomes related to the lower limbs.99. Arya S, Khakharia A, Binney ZO, DeMartino RR, Brewster LP, Goodney PP, et al. Association of Statin Dose With Amputation and Survival in Patients With Peripheral Artery Disease. Circulation. 2018;137(14):1435-46.

Physical training has been shown to be safe, and the walking tests with claudication symptom induction considered the best option.66. Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, Cohnert T, et al; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763–816.,77. Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135(12):e686-e725. However, when walking tests cannot be performed, other exercises such as cycling, resistance exercise and exercises using an upper extremity ergometer have been shown effective.55. Matsushita K, Kwak L, Yang C, Pang Y, Ballew SH, Sang Y, et al. High-sensitivity cardiac troponin and natriuretic peptide with risk of lower extremity peripheral artery disease: the Atherosclerosis Risk in Communities (ARIC) Study. Eur Heart J. 2018;39(25):2412–9.,66. Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, Cohnert T, et al; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763–816. It is worth mentioning that patients with critical ischemia cannot perform physical exercises, but should be considered eligible as soon as the interventionist approach is successfully completed.1010. Klaphake S, Buettner S, Ultee KH, van Rijn MJ, Hoeks SE, Verhagen HJ. Combination of endovascular revascularization and supervised exercise therapy for intermittent claudication: a systematic review and meta-analysis. J Cardiovasc Surg (Torino). 2018;59(2):150-7.,1111. Saratzis A, Paraskevopoulos I, Patel S, Donati T, Biasi L, Diamantopoulos A, et al. Supervised Exercise Therapy and Revascularization for Intermittent Claudication: Network Meta-Analysis of Randomized Controlled Trials. JACC Cardiovasc Interv. 2019;12(12):1125-36.

Many clinical trials have consistently shown that supervised treadmill training improves the gait of patients with LE-OPAD. In a meta-analysis, Fakhry et al.1212. Fakhry F, van de Luijtgaarden KM, Bax L, den Hoed PT, Hunink MG, Rouwet EV, Spronk S. Supervised walking therapy in patients with intermittent claudication. J Vasc Surg. 2012;56(4):1132-42. evaluated 1,054 patients from 25 studies and concluded this type of exercise training was effective in increasing maximum walking distance (mean increase of 180 meters) and pain-free walking distance (mean increase of 11 meters).1212. Fakhry F, van de Luijtgaarden KM, Bax L, den Hoed PT, Hunink MG, Rouwet EV, Spronk S. Supervised walking therapy in patients with intermittent claudication. J Vasc Surg. 2012;56(4):1132-42.

Three randomized clinical trials that evaluated 493 patients with LE-OPAD, showed that home-based exercise programs that included behavior change techniques, improved walking capacity, and higher performance gain on the six-minute walk test compared with supervised treadmill training.1313. McDermott MM, Polonsky T. Home-based exercise: a therapeutic option for peripheral artery disease. Circulation. 2016; 134(16):1127–9.,1414. McDermott MM, Guralnik JM, Criqui MH, Liu K, Kibbe MR, Ferrucci L. Six-minute walk is a better outcome measure than treadmill walking tests in therapeutic trials of patients with peripheral artery disease. Circulation. 2014; 130(1):61–8.In other words, while supervised treadmill walking programs are superior in the improvement of treadmill walking performance, the home-based programs are superior in improving overground walking, which is more related to daily life activities.1414. McDermott MM, Guralnik JM, Criqui MH, Liu K, Kibbe MR, Ferrucci L. Six-minute walk is a better outcome measure than treadmill walking tests in therapeutic trials of patients with peripheral artery disease. Circulation. 2014; 130(1):61–8.

Although home-based overground walking programs have been recently shown effective in improving the performance in daily life activities, apart from being more convenient and cheaper compared with supervised treadmill exercise,1414. McDermott MM, Guralnik JM, Criqui MH, Liu K, Kibbe MR, Ferrucci L. Six-minute walk is a better outcome measure than treadmill walking tests in therapeutic trials of patients with peripheral artery disease. Circulation. 2014; 130(1):61–8.small older studies showed little or no benefit. Therefore, the American College of Cardiology/American Heart Association 2006 Practice Guidelines state that there was no evidence to support the recommendation for the patient “to go home to walk”. However, since 2011, successful clinical trials with home-based exercise interventions that included much more than recommendations like “go home to walk”, such as the instructions for patients to stablish exercise goals and monitor their exercises, thereby promoting a change of focus. Even adding behavior change techniques, home-based exercises require fewer resources and less cost compared with supervised treadmill exercise, and thus are more accessible and probably more acceptable by many patients, which may ultimately lead to higher treatment compliance.1313. McDermott MM, Polonsky T. Home-based exercise: a therapeutic option for peripheral artery disease. Circulation. 2016; 134(16):1127–9.

In functional assessment of patients with LE-OPAD, six-minute walk test has gained popularity as a validated measure and better related to physical activity levels compared with the treadmill test, with no association with the learning effect of repeated tests.1313. McDermott MM, Polonsky T. Home-based exercise: a therapeutic option for peripheral artery disease. Circulation. 2016; 134(16):1127–9. In patients with LE-OPAD, compared with treadmill tests, changes in the performance on six-minute walk test have been more associated with outcomes as mortality and loss of mobility.1414. McDermott MM, Guralnik JM, Criqui MH, Liu K, Kibbe MR, Ferrucci L. Six-minute walk is a better outcome measure than treadmill walking tests in therapeutic trials of patients with peripheral artery disease. Circulation. 2014; 130(1):61–8.

In the paper “Exercise Intensity During 6-min Test in Patients with Peripheral Artery Disease”,11. Farah BQ, Ritti-Dias RM, Montgomery P, Cucato GG, Gardner A. Exercise Intensity during 6-Minute Walk Test in Patients with Peripheral Artery Disease. Arq Bras Cardiol. 2020; 114(3):486-492 AT was reached in 60% of patients, and peak oxygen consumption and ABI during treadmill test were higher in the other 40% patients. The six-minute walk test was more difficult for women and patients with low cardiorespiratory fitness, indicating a higher relative intensity of exercise effort for these patients. This is relevant in practice, since it is recommended that exercise training be performed above the AT aiming at improving cardiovascular function.1515. Temfemo A, Chlif M, Mandengue SH, Lelard T, Choquet D, Ahmaidi S. Is there a beneficial effect difference between age, gender, and different cardiac pathology groups of exercise training at ventilatory threshold in cardiac patients? Cardiol J. 2011;18(6):632-8. Therefore, the study corroborates the use of overground walking as the exercise mode of choice for women and patients with low cardiorespiratory fitness. More intense exercise training should be considered for men and patients with better cardiovascular fitness including cycle and elliptical ergometers, and even treadmills, to reach the AT and consequently improve physical fitness.

Finally, it is worth pointing out that the article “Exercise Intensity During 6-min Test in Patients with Peripheral Artery Disease” provides original and interesting results, but since it is an observational, monocentric study, it has limitations that prevent firm conclusions being drawn. Therefore, the study provides important information that are applicable to clinical practice and should be considered as the subject of future research.

References

  • 1
    Farah BQ, Ritti-Dias RM, Montgomery P, Cucato GG, Gardner A. Exercise Intensity during 6-Minute Walk Test in Patients with Peripheral Artery Disease. Arq Bras Cardiol. 2020; 114(3):486-492
  • 2
    Neder JA, Nery LE. Teste de Exercício Cardiopulmonar. J Pneumol. 2002; 28(Supl 3): 166-206.
  • 3
    Song P, Rudan D, Zhu Y, Fowkes FJI, Rahimi K, Fowkes FGR, et al. Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis. Lancet Glob Health. 2019;7(8): e1020–e1030.
  • 4
    Beckman JA, Duncan MS, Damrauer SM, Wells QS, Barnett JV, Wasserman DH, et al. Microvascular disease, peripheral artery disease, and amputation. Circulation. 2019;140(6):449–58.
  • 5
    Matsushita K, Kwak L, Yang C, Pang Y, Ballew SH, Sang Y, et al. High-sensitivity cardiac troponin and natriuretic peptide with risk of lower extremity peripheral artery disease: the Atherosclerosis Risk in Communities (ARIC) Study. Eur Heart J. 2018;39(25):2412–9.
  • 6
    Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, Cohnert T, et al; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763–816.
  • 7
    Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135(12):e686-e725.
  • 8
    Tóth-Vajna Z, Tóth-Vajna G, Gombos Z, Szilágyi B, Járai Z, Berczeli M, Sótonyi P. Screening of peripheral arterial disease in primary health care. Vascular Health Risk Manag. 2019 Aug 20;15:355-63.
  • 9
    Arya S, Khakharia A, Binney ZO, DeMartino RR, Brewster LP, Goodney PP, et al. Association of Statin Dose With Amputation and Survival in Patients With Peripheral Artery Disease. Circulation. 2018;137(14):1435-46.
  • 10
    Klaphake S, Buettner S, Ultee KH, van Rijn MJ, Hoeks SE, Verhagen HJ. Combination of endovascular revascularization and supervised exercise therapy for intermittent claudication: a systematic review and meta-analysis. J Cardiovasc Surg (Torino). 2018;59(2):150-7.
  • 11
    Saratzis A, Paraskevopoulos I, Patel S, Donati T, Biasi L, Diamantopoulos A, et al. Supervised Exercise Therapy and Revascularization for Intermittent Claudication: Network Meta-Analysis of Randomized Controlled Trials. JACC Cardiovasc Interv. 2019;12(12):1125-36.
  • 12
    Fakhry F, van de Luijtgaarden KM, Bax L, den Hoed PT, Hunink MG, Rouwet EV, Spronk S. Supervised walking therapy in patients with intermittent claudication. J Vasc Surg. 2012;56(4):1132-42.
  • 13
    McDermott MM, Polonsky T. Home-based exercise: a therapeutic option for peripheral artery disease. Circulation. 2016; 134(16):1127–9.
  • 14
    McDermott MM, Guralnik JM, Criqui MH, Liu K, Kibbe MR, Ferrucci L. Six-minute walk is a better outcome measure than treadmill walking tests in therapeutic trials of patients with peripheral artery disease. Circulation. 2014; 130(1):61–8.
  • 15
    Temfemo A, Chlif M, Mandengue SH, Lelard T, Choquet D, Ahmaidi S. Is there a beneficial effect difference between age, gender, and different cardiac pathology groups of exercise training at ventilatory threshold in cardiac patients? Cardiol J. 2011;18(6):632-8.

  • Short Editorial related to the article: Exercise Intensity during 6-Minute Walk Test in Patients with Peripheral Artery Disease

Publication Dates

  • Publication in this collection
    06 Apr 2020
  • Date of issue
    May-Jun 2020
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