Yihua Liao

Treadmill exercise and resistance training in patients with peripheral arterial disease with and without intermittent claudication: A randomized controlled trial

CONTEXT Neither supervised treadmill exercise nor strength training for patients with peripheral arterial disease (PAD) without intermittent claudication have been established as beneficial. OBJECTIVE To determine whether supervised treadmill exercise or lower extremity resistance training improve functional performance of patients with PAD with or without claudication. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled clinical trial performed at an urban academic medical center between April 1, 2004, and August 8, 2008, involving 156 patients with PAD who were randomly assigned to supervised treadmill exercise, to lower extremity resistance training, or to a control group. MAIN OUTCOME MEASURES Six-minute walk performance and the short physical performance battery. Secondary outcomes were brachial artery flow-mediated dilation, treadmill walking performance, the Walking Impairment Questionnaire, and the 36-Item Short Form Health Survey physical functioning (SF-36 PF) score. RESULTS For the 6-minute walk, those in the supervised treadmill exercise group increased their distance walked by 35.9 m (95% confidence interval [CI], 15.3-56.5 m; P < .001) compared with the control group, whereas those in the resistance training group increased their distance walked by 12.4 m (95% CI, -8.42 to 33.3 m; P = .24) compared with the control group. Neither exercise group improved its short physical performance battery scores. For brachial artery flow-mediated dilation, those in the treadmill group had a mean improvement of 1.53% (95% CI, 0.35%-2.70%; P = .02) compared with the control group. The treadmill group had greater increases in maximal treadmill walking time (3.44 minutes; 95% CI, 2.05-4.84 minutes; P < .001); walking impairment distance score (10.7; 95% CI, 1.56-19.9; P = .02); and SF-36 PF score (7.5; 95% CI, 0.00-15.0; P = .02) than the control group. The resistance training group had greater increases in maximal treadmill walking time (1.90 minutes; 95% CI, 0.49-3.31 minutes; P = .009); walking impairment scores for distance (6.92; 95% CI, 1.07-12.8; P = .02) and stair climbing (10.4; 95% CI, 0.00-20.8; P = .03); and SF-36 PF score (7.5; 95% CI, 0.0-15.0; P = .04) than the control group. CONCLUSIONS Supervised treadmill training improved 6-minute walk performance, treadmill walking performance, brachial artery flow-mediated dilation, and quality of life but did not improve the short physical performance battery scores of PAD participants with and without intermittent claudication. Lower extremity resistance training improved functional performance measured by treadmill walking, quality of life, and stair climbing ability. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00106327.

Associations of borderline and low normal ankle-brachial index values with functional decline at 5-year follow-up: the WALCS (Walking and Leg Circulation Study).

OBJECTIVES We studied associations of borderline and low normal ankle-brachial index (ABI) values with functional decline over a 5-year follow-up. BACKGROUND The associations of borderline and low normal ABI with functional decline are unknown. METHODS The 666 participants included 412 with peripheral arterial disease (PAD). Participants were categorized as follows: severe PAD (ABI <0.50), moderate PAD (ABI 0.50 to 0.69), mild PAD (ABI 0.70 to 0.89), borderline ABI (0.90 to 0.99), low normal ABI (1.00 to 1.09), and normal ABI (ABI 1.10 to 1.30). Outcomes were assessed annually for 5 years. Mobility loss was defined as loss of the ability to walk one-quarter mile or walk up and down 1 flight of stairs without assistance among participants without baseline mobility impairment. Becoming unable to walk for 6 min continuously was defined as stopping during the 6-min walk at follow-up among those who walked for 6 min continuously at baseline. Results were adjusted for age, sex, race, comorbidities, and other confounders. RESULTS Hazard ratios (HRs) for mobility loss according to ABI category were as follows: severe PAD, HR: 4.16 (95% confidence interval [CI]: 1.58 to 10.92); moderate PAD, HR: 3.82 (95% CI: 1.66 to 8.81); mild PAD, HR: 3.22 (95% CI: 1.43 to 7.21); borderline ABI, HR: 3.07 (95% CI: 1.21 to 7.84); and low normal ABI, HR: 2.61 (95% CI: 1.08 to 6.32; p trend = 0.0018). Similar associations were observed for becoming unable to walk for 6 min continuously (p trend < 0.0001). CONCLUSIONS At 5-year follow-up, persons with borderline ABI values have a higher incidence of mobility loss and becoming unable to walk for 6 min continuously compared with persons who have a normal baseline ABI. A low normal ABI is associated with an increased incidence of mobility loss compared with persons who have a normal ABI.

Asymptomatic Peripheral Arterial Disease Is Associated With More Adverse Lower Extremity Characteristics Than Intermittent Claudication

Background— This study assessed functional performance, calf muscle characteristics, peripheral nerve function, and quality of life in asymptomatic persons with peripheral arterial disease (PAD). Methods and Results— PAD participants (n=465) had an ankle brachial index <0.90. Non-PAD participants (n=292) had an ankle brachial index of 0.90 to 1.30. PAD participants were categorized into leg symptom groups including intermittent claudication (n=215) and always asymptomatic (participants who never experienced exertional leg pain, even during the 6-minute walk; n=72). Calf muscle was measured with computed tomography. Analyses were adjusted for age, sex, race, ankle brachial index, comorbidities, and other confounders. Compared with participants with intermittent claudication, always asymptomatic PAD participants had smaller calf muscle area (4935 versus 5592 mm2; P<0.001), higher calf muscle percent fat (16.10% versus 9.45%; P<0.001), poorer 6-minute walk performance (966 versus 1129 ft; P=0.0002), slower usual-paced walking speed (P=0.0019), slower fast-paced walking speed (P<0.001), and a poorer Short-Form 36 Physical Functioning score (P=0.016). Compared with an age-matched, sedentary, non-PAD cohort, always asymptomatic PAD participants had smaller calf muscle area (5061 versus 5895 mm2; P=0.009), poorer 6-minute walk performance (1126 versus 1452 ft; P<0.001), and poorer Walking Impairment Questionnaire speed scores (40.87 versus 57.78; P=0.001). Conclusions— Persons with PAD who never experience exertional leg symptoms have poorer functional performance, poorer quality of life, and more adverse calf muscle characteristics compared with persons with intermittent claudication and a sedentary, asymptomatic, age-matched group of non-PAD persons.

Home-Based Walking Exercise Intervention in Peripheral Artery Disease: A Randomized Clinical Trial

IMPORTANCE Clinical practice guidelines state there is insufficient evidence to support advising patients with peripheral artery disease (PAD) to participate in a home-based walking exercise program. OBJECTIVE To determine whether a home-based walking exercise program that uses a group-mediated cognitive behavioral intervention, incorporating both group support and self-regulatory skills, can improve functional performance compared with a health education control group in patients with PAD with and without intermittent claudication. DESIGN, SETTING, AND PATIENTS Randomized controlled clinical trial of 194 patients with PAD, including 72.2% without classic symptoms of intermittent claudication, performed in Chicago, Illinois between July 22, 2008, and December 14, 2012. INTERVENTIONS Participants were randomized to 1 of 2 parallel groups: a home-based group-mediated cognitive behavioral walking intervention or an attention control condition. MAIN OUTCOMES AND MEASURES The primary outcome was 6-month change in 6-minute walk performance. Secondary outcomes included 6-month change in treadmill walking, physical activity, the Walking Impairment Questionnaire (WIQ), and Physical and Mental Health Composite Scores from the 12-item Short-Form Health Survey. RESULTS Participants randomized to the intervention group significantly increased their 6-minute walk distance ([reported in meters] 357.4 to 399.8 vs 353.3 to 342.2 for those in the control group; mean difference, 53.5 [95% CI, 33.2 to 73.8]; P < .001), maximal treadmill walking time (intervention, 7.91 to 9.44 minutes vs control, 7.56 to 8.09; mean difference, 1.01 minutes [95% CI, 0.07 to 1.95]; P = .04), accelerometer-measured physical activity over 7 days (intervention, 778.0 to 866.1 vs control, 671.6 to 645.0; mean difference, 114.7 activity units [95% CI, 12.82 to 216.5]; P = .03), WIQ distance score (intervention, 35.3 to 47.4 vs control, 33.3 to 34.4; mean difference, 11.1 [95% CI, 3.9 to 18.1]; P = .003), and WIQ speed score (intervention, 36.1 to 47.7 vs control, 35.3-36.6; mean difference, 10.4 [95% CI, 3.4 to 17.4]; P = .004). CONCLUSION AND RELEVANCE A home-based walking exercise program significantly improved walking endurance, physical activity, and patient-perceived walking endurance and speed in PAD participants with and without classic claudication symptoms. These findings have implications for the large number of patients with PAD who are unable or unwilling to participate in supervised exercise programs. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00693940.

Clinical ResearchPeripheral Vascular DiseaseAssociations of Borderline and Low Normal Ankle-Brachial Index Values With Functional Decline at 5-Year Follow-Up: The WALCS (Walking and Leg Circulation Study)

OBJECTIVES We studied associations of borderline and low normal ankle-brachial index (ABI) values with functional decline over a 5-year follow-up. BACKGROUND The associations of borderline and low normal ABI with functional decline are unknown. METHODS The 666 participants included 412 with peripheral arterial disease (PAD). Participants were categorized as follows: severe PAD (ABI <0.50), moderate PAD (ABI 0.50 to 0.69), mild PAD (ABI 0.70 to 0.89), borderline ABI (0.90 to 0.99), low normal ABI (1.00 to 1.09), and normal ABI (ABI 1.10 to 1.30). Outcomes were assessed annually for 5 years. Mobility loss was defined as loss of the ability to walk one-quarter mile or walk up and down 1 flight of stairs without assistance among participants without baseline mobility impairment. Becoming unable to walk for 6 min continuously was defined as stopping during the 6-min walk at follow-up among those who walked for 6 min continuously at baseline. Results were adjusted for age, sex, race, comorbidities, and other confounders. RESULTS Hazard ratios (HRs) for mobility loss according to ABI category were as follows: severe PAD, HR: 4.16 (95% confidence interval [CI]: 1.58 to 10.92); moderate PAD, HR: 3.82 (95% CI: 1.66 to 8.81); mild PAD, HR: 3.22 (95% CI: 1.43 to 7.21); borderline ABI, HR: 3.07 (95% CI: 1.21 to 7.84); and low normal ABI, HR: 2.61 (95% CI: 1.08 to 6.32; p trend = 0.0018). Similar associations were observed for becoming unable to walk for 6 min continuously (p trend < 0.0001). CONCLUSIONS At 5-year follow-up, persons with borderline ABI values have a higher incidence of mobility loss and becoming unable to walk for 6 min continuously compared with persons who have a normal baseline ABI. A low normal ABI is associated with an increased incidence of mobility loss compared with persons who have a normal ABI.

Associations Between Lower Extremity Ischemia, Upper and Lower Extremity Strength, and Functional Impairment with Peripheral Arterial Disease

OBJECTIVES: To identify associations between lower extremity ischemia and leg strength, leg power, and hand grip in persons with and without lower extremity peripheral arterial disease (PAD). To determine whether poorer strength may mediate poorer lower extremity performance in persons with lower arterial brachial index (ABI) levels.

Decline in Functional Performance Predicts Later Increased Mobility Loss and Mortality in Peripheral Arterial Disease

OBJECTIVES We hypothesized that a greater 2-year decline in office-based functional performance measures would be associated with greater mobility loss and mortality in people with peripheral arterial disease (PAD). BACKGROUND Associations of decline in functional performance with clinically important outcomes in patients with PAD are unknown. METHODS A total of 440 men and women with PAD completed the 6-min walk test and measures of walking velocity at baseline and annually for 2 years. Participants were categorized into tertiles according to their functional decline between baseline and 2-year follow-up and were followed annually after the functional change assessment. Cox proportional hazard models were used to assess relations between the 2-year change in functional performance with later mortality and mobility loss, with adjustments for age, sex, race, ankle brachial index, comorbidities, and other confounders. RESULTS A total of 102 participants (23.2%) died during a median follow-up of 44.5 months after functional change was assessed. Of 319 participants without baseline mobility disability, 60 (18.8%) developed mobility loss after functional change was assessed. Participants in the tertile with the greatest 6-min walk decline had the highest subsequent mobility loss (hazard ratio [HR]: 3.50; 95% confidence interval [CI]: 1.56 to 7.85; p = 0.002), all-cause mortality (HR: 2.16; 95% CI: 1.28 to 3.64; p = 0.004), and cardiovascular disease mortality (HR: 2.45; 95% CI: 1.08 to 5.54; p = 0.031), compared with those with the smallest 6-min walk decline. Greater declines in fastest-paced 4-m walking velocity were associated with higher mobility loss (p trend = 0.018), all-cause mortality (p trend = 0.01), and cardiovascular mortality (p trend = 0.004). CONCLUSIONS Participants with PAD with declining functional performance are at increased risk for later mobility loss and mortality.

CALF MUSCLE CHARACTERISTICS, STRENGTH MEASURES, AND MORTALITY IN PERIPHERAL ARTERIAL DISEASE: A LONGITUDINAL STUDY

OBJECTIVES This study analyzed whether lower calf muscle density and poorer upper and lower extremity strength are associated with higher mortality rates in men and women with peripheral arterial disease (PAD). BACKGROUND Men and women with lower extremity PAD have lower calf muscle density and reduced lower extremity strength compared with individuals without PAD. METHODS At baseline, participants underwent measurement of calf muscle density with computed tomography in addition to knee extension power and isometric knee extension, plantar flexion, and hand grip strength measures. Participants were followed up annually for up to 4 years. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities. RESULTS Among 434 PAD participants, 103 (24%) died during a mean follow-up of 47.6 months. Lower calf muscle density was associated with higher all-cause mortality (lowest density tertile hazard ratio [HR]: 1.80 [95% confidence interval (CI): 1.07 to 3.03], second tertile HR: 0.91 (95% CI: 0.51 to 1.62); highest density tertile HR: 1.00; p trend = 0.020) and higher cardiovascular disease mortality (lowest density tertile HR: 2.39 [95% CI: 0.90 to 6.30], second tertile HR: 0.85 [95% CI: 0.27 to 2.71]; highest density tertile HR: 1.00; p trend = 0.047). Poorer plantar flexion strength (p trend = 0.004), lower baseline leg power (p trend = 0.046), and poorer handgrip (p trend = 0.005) were associated with higher all-cause mortality. CONCLUSIONS These data demonstrate that lower calf muscle density and weaker plantar flexion strength, knee extension power, and hand grip were associated with increased mortality in these participants with PAD, independently of the ankle-brachial index and other confounders.

Social cognitive constructs and the promotion of physical activity in patients with peripheral artery disease.

PURPOSE The purpose of this study was to provide measures and accompanying psychometric support for key constructs from social cognitive theory relevant to the promotion of physical activity in patients with peripheral artery disease (PAD). METHODS Patients (n = 205) were identified from 2 ongoing studies involving PAD, who completed the Geriatric Depression Scale, a 6-minute walk, and the social cognitive measures of interest: pain acceptance, self-efficacy, desire for physical competence, perceived control for walking, and satisfaction with function. Psychometric support for each measure included factor analyses, test-retest reliability, and an evaluation of construct validity by investigating how each measure was related to depression and performance on the 6-minute walk test. RESULTS The measures of interest had good structural integrity, were reliable, and shared expected variance with depressed affect; most had significant linear trends with the 6-minute walk test, suggesting that compromised psychological status is related to poorer mobility. CONCLUSIONS Constructs from social cognitive theory are clearly relevant to the promotion of physical activity in PAD patients. To this end, this study offers measures of relevant constructs that can now be implemented into intervention research.

Women with peripheral arterial disease experience faster functional decline than men with peripheral arterial disease.

OBJECTIVES We hypothesized that women with lower extremity peripheral arterial disease (PAD) would have greater mobility loss and faster functional decline than men with PAD. BACKGROUND Whether rates of mobility loss or functional decline differ between men and women with PAD is currently unknown. METHODS Three hundred eighty men and women with PAD completed the 6-min walk, were assessed for mobility disability, and underwent measures of 4-m walking velocity at baseline and annually for up to 4 years. Computed tomography-assessed calf muscle characteristics were measured biannually. Outcomes included becoming unable to walk for 6 min continuously among participants who walked continuously for 6 min at baseline. Mobility loss was defined as becoming unable to walk for a quarter mile or to walk up and down 1 flight of stairs without assistance among those without baseline mobility disability. Results were adjusted for age, race, body mass index, physical activity, the ankle brachial index, comorbidities, and other confounders. RESULTS At 4 years of follow-up, women were more likely to become unable to walk for 6 min continuously (hazard ratio: 2.30, 95% confidence interval: 1.30 to 4.06, p = 0.004), more likely to develop mobility disability (hazard ratio: 1.79, 95% confidence interval: 1.30 to 3.03, p = 0.030), and had faster declines in walking velocity (p = 0.022) and the distance achieved in the 6-min walk (p = 0.041) compared with men. Sex differences in functional decline were attenuated after additional adjustment for baseline sex differences in calf muscle area. CONCLUSIONS Women with PAD have faster functional decline and greater mobility loss than men with PAD. These sex differences may be attributable to smaller baseline calf muscle area among women with PAD.