TABLE 3.

Effects of exercise on sarcopenia associated with PAD in experimental and clinical studies

Reference	Population	Number studied (symptomatic/controls)	Exercise therapy		Outcomes measured			Main results
			Exercise program	Duration	Muscle strength	Muscle mass/quality	Physical performance
Nagase et al., 2017, PLoS One 63	Mice, PAD	6/4	Treadmill training	2 weeks (twice a week)	‐	Quantitative analysis of mRNA levels	‐	Treadmill training significantly reduced the mRNA expression of skeletal muscle regeneration markers (P < 0.05) compared with the non‐exercised PAD group
Lejay et al., 2017, Front Physiol 61	Mice, CLI	10/10	Treadmill training	3 weeks (5 times per week)	‐	Histological analysis	Functional score	Treadmill training reduced tissue damage (with a score of 1.9 for the exercised group vs. 4.0 for the non‐exercised group at day 30, P < 0.01), enhanced muscle function (with a score of 1.4 for the exercised group vs. 2.8 for the non‐exercised group at day 30, P < 0.01), stimulated mitochondrial biogenesis and anti‐oxidant defences
Hain et al., 2011, Am J Physiol Regul Integr Comp Physiol 62	Rats, PAD	Ns	Electrical stimulation causing repeated muscle contractions and mimicking exercise	5 days	‐	Fibre cross‐sectional area	‐	Repeated cycles of muscle contraction decreased the mean fibre cross‐sectional area by 35% (1834 ± 219.9 μm2 in the exercised group vs. 2834 ± 132.5 μm2 in the non‐exercised group, P < 0.05)
Schieber et al., 2019, J Vasc Surg 80	Human, PAD	47/−	Supervised walking exercise	6 months (3 times per week)	Plantar flexor strength	‐	Walking distance, gait biomechanics	Supervised walking exercise improved muscle strength, walking distance and gait biomechanics
Vun et al., 2016, J Vasc Surg 73	Human, PAD	36/−	Supervised treadmill exercise program	12 weeks (twice a week)	‐	Whole‐body dual‐energy X‐ray absorptiometry	Pain‐free walking distance 6‐min walking distance	Supervised treadmill exercise improved pain‐free walking distance (213 ± 93 m after 12 weeks vs. 165 ± 78 m at baseline, P = 0.001) and 6‐min walk distance (421 ± 68 m after 12 weeks vs. 395 ± 78 m at baseline, P = 0.004)
Gardner et al., 2014, J Am Heart Assoc 67	Human, PAD	60/−	Step‐monitored home walking to mild‐to‐moderate claudication pain	12 weeks (3 times per week)	‐	‐	6‐min walking distance Walking speed	Home walking exercise improved 6‐min walk distance (372 ± 119 m after the 12‐week test vs. 328 ± 108 m at pre‐test, P < 0.001), peak walking time (490 ± 350 s vs. 380 ± 274 s at pre‐test, P < 0.001), and daily ambulatory activity notably with improvement in average cadence (11.8 ± 3.0 strides/min vs. 11.1 ± 2.7 strides/min, P < 0.01)
Januszek et al., 2014, J Cardiol 75	Human, PAD	67/−	Supervised treadmill training	12 weeks (3 times per week)	‐	‐	Maximal walking time	Treadmill training improved maximal walking time (+90%, P < 0.001) and flow‐mediated dilatation (+43%, P < 0.001) in PAD patients in comparison to baseline
Pilz et al., 2014, Wien Klin Wochenschr 82	Human, PAD	42/−	Supervised exercise training on strength (couch pedal ergometer work on lower legs) and endurance (walk sessions)	6 months (twice a week)	Pushing power Pulling power Tip‐toe standing power	‐	Pain‐free walking distance Walking‐speed	Combined exercise program improved walking distance (568.9 ± 461.5 m after 6 months vs. 446.3 ± 276.6 m at baseline, P < 0.05), walking speed (4.39 ± 1.08 km/h vs. 4.17 ± 0.85 km/h at baseline, P < 0.05), pushing power (662.4 ± 530.4 J vs. 348.6 ± 270.3 J, P < 0.01), pulling power (96.4 ± 51.5 J vs. 58.7 ± 37.7 J, P < 0.0001), and tiptoe standing power (83.5 ± 48.6 repetitions vs. 49 ± 21.5 repetitions, P < 0.0001)
		52/−		12 months (twice a week)				Combined exercise program further improved walking distance (647.8 ± 496.3 m after 12 months vs. 500.2 ± 427.9 m at baseline, P < 0.001), walking speed (4.53 ± 0.80 km/h vs. 4.03 ± 0.90 km/h at baseline, P < 0.0001), pushing power (637.8 ± 407.1 J vs. 337.2 ± 232.9 J, P < 0.001), pulling power (97.5 ± 59.8 J vs. 55.6 ± 38.8 J, P < 0.0001), and tiptoe standing power (84.9 ± 69.3 repetitions vs. 39.8 ± 15.3 repetitions, P < 0.0001)
Parmenter et al., 2013, J Am Geriatr Soc 81	Human, PAD	7/−	High‐intensity progressive resistance training (weight lifting)	6 months (3 times per week)	‐	‐	6‐min walking distance	Progressive resistance training increased 6‐min walking distance (381.8 ± 151.6 m after 24 weeks of training vs. 321.9 ± 109.1 m at baseline, P = 0.02)
Mosti et al., 2011, Scand J Med Sci Sports 71	Human, PAD	10/−	Leg press maximal strength training and plantar flexion endurance training	8 weeks (3 times per week)	Leg press maximal force Rate of force development	‐	Plantar flexion endurance	Exercise training improved muscle strength, notably with increased rates of force development (3675 ± 1315 N/s post‐test vs. 1943 ± 1027 N/s pre‐test, P < 0.01) and leg press maximal strength (152 ± 33 kg vs. 110 ± 24 kg, P < 0.01); but also walking distance (1203 ± 451 m vs. 1099 ± 463 m, P < 0.01)
Cousin et al., 2011, Ann Phys Rehabil Med 69	Human, PAD	31/−	Walking sessions, selective muscle strengthening, general physical exercise	4 weeks (5 days per week)	Ankle plantar and dorsal flexors strength Concentric contractions at the angular velocity of 30°/s, 120°/s and 180°/s for muscle fatigue	‐	Walking distance on a treadmill <400 m	Rehabilitation program improved walking distance (977.4 ± 854.2 m upon completing the program vs. 282.4 ± 239.8 m at baseline, P < 0.0001)
Saetre et al., Angiology, 2011 66	Human, PAD	29/−	Supervised exercise training	8 weeks (twice a week)	‐	Quantitative analysis of plasma inflammatory levels	Pain‐free walking distance, maximal walking distance	Exercise training reduced the plasma levels of E‐selectin (45.5 before training to 40.4 ng/ml after training, P = 0.013) and ICAM‐1 (342.0 to 298 ng/ml) in PAD patients. Both walking distance increased after exercise training (P < 0.01)
Wang et al., 2010, Scand J Med Sci Sports 70	Human, PAD	10/−	Maximal strength training (dynamic leg press)	8 weeks (3 times per week)	Leg press force Rate of force development	‐	Walking economy test	Maximal strength training improved rates of force development (2901 ± 1848 N/s after the 8‐week training program vs. 1368 ± 893 N/s in the control period, P < 0.05), maximal strength (148 ± 33 kg vs. 114 ± 25 kg) and walking time to exhaustion (1095 ± 426 s vs. 1009 ± 448 s, P < 0.05)
McDermott et al., 2009, JAMA 78	Human, PAD	156/−	Supervised treadmill walking training vs.resistance training	24 weeks (3 times per week)	‐	‐	6‐min walk performance, short physical performance battery, treadmill walking performance, walking impairment questionnaire, overall physical functioning score	Supervised treadmill walking training improved 6‐min walk performance (by 35.9 m, P < 0.001), maximal treadmill walking time (by 3.44 min, P < 0.001) and overall quality of life (P = 0.02) compared to untrained controls. Resistance training increased maximal treadmill walking time (by 1.90 min, P = 0.009), stair climbing (P = 0.03) and overall quality of life (P = 0.04)
Wang et al., 2006, Clin J Sport Med 72	Human, PAD	17/−	Supervised treadmill walking training	12 weeks (3 times per week)	Calf‐muscle strength and endurance	‐	Walking capacity	Supervised treadmill‐walking program improved peak torque at 30 degrees/s (175 ± 40 N/m post‐training vs. 159 ± 32 N/m at pre‐training, P < 0.01), mean peak force (358 ± 87 N vs. 314 ± 68 N, P < 0.001), and mean power (80 ± 26 W vs. 66 ± 19 W, P < 0.001). This training program also increased pain‐free walking time (382 ± 261 s vs. 137 ± 70 s, P < 0.001) and maximal walking time (696 ± 191 s vs. 314 ± 138 s, P < 0.001)
Signorelli et al., 2003, Vasc Med 65	Human, PAD	20/20	Treadmill test	1 session	‐	Quantitative analysis of plasma inflammatory levels	‐	One treadmill exercise session increased plasma levels of ICAM‐1 (317 ± 4 at rest to 421 ± 10 ng/ml after exercise), VCAM‐1 (485 ± 14 to 576 ± 16), TNF‐α (14 ± 3 to 27 ± 5) and IL6 (12 ± 1 to 16 ± 2) in PAD patients
McGuigan et al., 2001, J Gerontol A Biol Sci Med Sci 68	Human, PAD	11/−	Progressive resistance training	6 months (3 times per week)	Leg press strength Calf press strength	Biopsies from gastrocnemius muscles	‐	Progressive resistance training improved the 10‐repetition maximum loading leg (by 155%) and calf (by 126%) press strength in the trained subjects, at 24 weeks Training also increased type I (3442 ± 981 μm2 after training vs. 2695 ± 867 μm2 at pre‐training, P < 0.05) and type II muscle fibre area (4273 ± 1113 μm2 vs. 3421 ± 1148 μm2, P < 0.05)
Brevetti et al., 2001, Clin Hemorheol Microcirc 64	Human, PAD	21/18	Maximally tolerated treadmill exercise	1 session	‐	Quantitative analysis of plasma inflammatory levels	‐	One treadmill exercise session increased plasma levels of ICAM‐1 (285 ± 15 at rest to 317 ± 16 ng/ml after exercise, P < 0.01) and VCAM‐1 (671 ± 45 to 751 ± 47 ng/ml, P < 0.05) in PAD patients, while no modifications were observed in controls
Gardner et al., 2000, J Gerontol 79	Human, PAD	63/−	Supervised walking exercise	6 months (3 times per week)	‐	‐	Walking economy	Exercise training improved walking economy by 10% (P < 0.05) compared with the untrained group
Hiatt et al., 1996, J Appl Physiol 74	Human, PAD	26/−	Treadmill walking exercise	12 weeks (3 times per week)	‐	Biopsies from gastrocnemius muscles	Peak exercise performance	Treadmill training was associated with improved exercise performance despite increased denervated fibres (7.6 ± 5.4 before exercise to 15.6 ± 7.5% after exercise, P < 0.05)
Regensteiner et al., 1996, J Vasc Surg 77	Human, PAD	29/−	Supervised treadmill walking training	12 weeks (3 h per week) or 24 weeks (3 h per week)	‐	‐	Functional status (questionnaires on walking ability, habitual physical activity level, and physical/social functioning, well‐being, overall health); monitored activity levels	Exercise training improved functional status and monitored activity level (P < 0.05) after 12 weeks and to a greater extend after 24 weeks
Hiatt et al., 1994, Circulation 76	Human, PAD	29/−	Supervised treadmill walking training vs.strength training (resistive training of five muscle groups of each leg)	12 weeks (3 h per week) or 24 weeks (3 h per week)	‐	‐	Peak exercise performance	Patients in the 12 weeks treadmill training program had higher increase in peak walking time and higher improvement in peak oxygen consumption and onset of claudication pain compared with patients in the strength training program; with further improvements over 24 weeks of training

CLI, critical limb ischemia; Ns, not specified; PAD, peripheral artery disease.