IMPORTANCE: Clinical practice guidelines support home-based exercise for patients with peripheral artery disease (PAD), but no randomized trials have tested whether an exercise intervention without ...periodic medical center visits improves walking performance. OBJECTIVE: To determine whether a home-based exercise intervention consisting of a wearable activity monitor and telephone coaching improves walking ability over 9 months in patients with PAD. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 3 US medical centers. Patients with PAD were randomized between June 18, 2015, and April 4, 2017, to home-based exercise vs usual care for 9 months. Final follow-up was on December 5, 2017. INTERVENTIONS: The exercise intervention group (n = 99) received 4 weekly medical center visits during the first month followed by 8 months of a wearable activity monitor and telephone coaching. The usual care group (n = 101) received no onsite sessions, active exercise, or coaching intervention. MAIN OUTCOMES AND MEASURES: The primary outcome was change in 6-minute walk distance at 9-month follow-up (minimal clinically important difference MCID, 20 m). Secondary outcomes included 9-month change in subcomponents of the Walking Impairment Questionnaire (WIQ) (0-100 score; 100, best), SF-36 physical functioning score, Patient-Reported Outcomes Measurement Information System (PROMIS) mobility questionnaire (higher = better; MCID, 2 points), PROMIS satisfaction with social roles questionnaire, PROMIS pain interference questionnaire (lower = better; MCID range, 3.5-4.5 points), and objectively measured physical activity. RESULTS: Among 200 randomized participants (mean SD age, 70.2 10.4 years; 105 52.5% women), 182 (91%) completed 9-month follow-up. The mean change from baseline to 9-month follow-up in the 6-minute walk distance was 5.5 m in the intervention group vs 14.4 m in the usual care group (difference, −8.9 m; 95% CI, −26.0 to 8.2 m; P = .31). The exercise intervention worsened the PROMIS pain interference score, mean change from baseline to 9 months was 0.7 in the intervention group vs −2.8 in the usual care group (difference, 3.5; 95% CI, 1.3 to 5.8; P = .002). There were no significant between-group differences in the WIQ score, the SF-36 physical functioning score, or the PROMIS mobility or satisfaction with social roles scores. CONCLUSIONS AND RELEVANCE: Among patients with PAD, a home-based exercise intervention consisting of a wearable activity monitor and telephone coaching, compared with usual care, did not improve walking performance at 9-month follow-up. These results do not support home-based exercise interventions of wearable devices and telephone counseling without periodic onsite visits to improve walking performance in patients with PAD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02462824
Supervised exercise therapy (SET) improves walking ability in people with peripheral artery disease (PAD). However, the effects of SET on cardiovascular health in PAD remain unclear. Using data from ...a randomized clinical trial, this post hoc analyses investigated the effects of a 6-month SET intervention, compared with a control group, on changes in blood pressure (BP) and heart rate (HR) during a graded treadmill exercise test in people with PAD.
We randomized 210 participants with PAD to either SET (3× weekly) or control (1× weekly health lectures) for 6 months. A graded treadmill exercise test, 6-minute walk test, and Walking Impairment Questionnaire were completed at baseline and the 6-month follow-up. BP and HR were measured at the end of each 2-minute stage of the graded treadmill exercise test. Mixed effects regression models compared the overall mean 6-month change in systolic BP, diastolic BP, pulse pressure (PP), and HR during the first 5 stages of the graded treadmill exercise test between groups.
Of the 210 randomized participants with PAD, 176 (67 ± 9 years; 72 41% female, 115 65% Black) completed the graded treadmill exercise test at baseline and the 6-month follow-up. Compared with the control group at the 6-month follow-up, SET significantly decreased overall mean systolic BP (–12 mm Hg; P < .001), PP (–9 mm Hg; P < .001), and HR (–7 b/min; P < .01) during a graded treadmill exercise test but not diastolic BP. Among participants randomized to SET, a greater decrease in systolic BP, PP, and HR during a graded treadmill exercise test was significantly associated with a greater improvement in 6-minute walk distance (systolic BP, r = –0.19 P = .03 and PP, r = –0.23 P < .01; and HR, r = –0.21 P < .01) and with maximal treadmill walking distance (systolic BP, r = –0.21 P < .01 and PP, r = –0.17 P = .03) at the 6-month follow-up. A greater decrease in the HR during a graded treadmill exercise test was significantly associated with a better WIQ distance score (r = –0.27; P = .03) at the 6-month follow-up.
In people with PAD, compared with a control group, SET improved cardiovascular health, measured by changes in BP and HR during exercise. The degree of improvement in cardiovascular health correlated with the degree of improvement in walking performance in people with PAD. NCT: 01408901.
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Men and women with lower extremity peripheral arterial disease (PAD) have higher levels of inflammatory biomarkers than those without PAD. Observational studies link higher levels of several ...inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, and soluble adhesion molecules, to 1 or more of the following outcomes in people with PAD: more severe PAD, greater lower extremity functional impairment, more adverse calf skeletal muscle characteristics, greater declines in the ankle brachial index, greater declines in lower extremity performance, and higher rates of cardiovascular morbidity and mortality. Higher levels of inflammatory biomarkers are also associated with poorer outcomes after lower extremity revascularization, including graft restenosis and mortality. Increasing levels of CRP are associated with increased mortality and faster functional decline among people with PAD. Statin therapies reduce cardiovascular event rates and may improve walking performance in men and women with PAD, perhaps in part because statins can reduce inflammation. However, no clinical trials have been performed to establish whether therapies that specifically block or lower inflammatory biomarkers improve outcomes in patients with PAD. Family studies show that heritability of PAD ranges from approximately 20% to 45% after adjusting for atherosclerotic risk factors. A genetic marker for PAD has the potential to identify individuals at increased risk for PAD and may also uncover proteins that can help determine mechanisms of development of lower extremity atherosclerosis. However, a genetic marker for PAD has not been identified.
Objectives
To investigate the heterogeneity of clinically meaningful levels of gait speed relative to self‐reported mobility disability (SR‐MD).
Design
Five longitudinal studies with older adults in ...different health states (onset of acute event, presence of chronic condition, sedentary, community living) were used to explore the relationship between gait speed and SR‐MD.
Setting
Lifestyle Interventions and Independence for Elders Pilot (LIFE‐P), LIFE, Trial of Angiotensin‐Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN), Baltimore Hip Fracture Study (BHS2), Invecchiare in Chianti (InCHIANTI).
Participants
Individuals aged 65 and older (N=3,540): sedentary, community dwelling (LIFE‐P/LIFE), with hip fracture (BHS2), random population‐based sample (InCHIANTI), high cardiovascular risk (TRAIN).
Measurements
Usual‐pace gait speed across 3 to 4 m and SR‐MD, defined as inability to walk approximately 1 block or climb 1 flight of stairs.
Results
The mean gait speed of participants without SR‐MD was greater than 1.0 m/s in InCHIANTI and TRAIN, 0.79 m/s in LIFE‐P/LIFE, and 0.46 m/sec in BHS2. Of individuals with SR‐MD, mean gait speed was 0.08 m/s slower in LIFE‐P/LIFE, 0.19 m/s slower in TRAIN, 0.22 m/s slower in BHS2, and 0.36 m/s slower in InCHIANTI. The optimal gait speed cutpoint for minimizing SR‐MD misclassification rates ranged from 0.3 m/s in BHS2 to 1.0 m/s in TRAIN. In longitudinal analyses, development of SR‐MD was dependent on initial gait speed and change in gait speed (p<.001).
Conclusion
The relationship between absolute levels of gait speed and SR‐MD may be context specific, and there may be variations between populations. Across diverse clinical populations, clinical interpretations of how change in usual pace gait speed relates to development of SR‐MD depend on where on the gait speed continuum change occurs.
IMPORTANCE: Benefits of granulocyte-macrophage colony-stimulating factor (GM-CSF) for improving walking ability in people with lower extremity peripheral artery disease (PAD) are unclear. Walking ...exercise may augment the effects of GM-CSF in PAD, since exercise-induced ischemia enhances progenitor cell release and may promote progenitor cell homing to ischemic calf muscle. OBJECTIVES: To determine whether GM-CSF combined with supervised treadmill exercise improves 6-minute walk distance, compared with exercise alone and compared with GM-CSF alone; to determine whether GM-CSF alone improves 6-minute walk more than placebo and whether exercise improves 6-minute walk more than an attention control intervention. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial with 2 × 2 factorial design. Participants were identified from the Chicago metropolitan area and randomized between January 6, 2012, and December 22, 2016, to 1 of 4 groups: supervised exercise + GM-CSF (exercise + GM-CSF) (n = 53), supervised exercise + placebo (exercise alone) (n = 53), attention control + GM-CSF (GM-CSF alone) (n = 53), attention control + placebo (n = 51). The final follow-up visit was on August 15, 2017. INTERVENTIONS: Supervised exercise consisted of treadmill exercise 3 times weekly for 6 months. The attention control consisted of weekly educational lectures by clinicians for 6 months. GM-CSF (250 μg/m2/d) or placebo were administered subcutaneously (double-blinded) 3 times/wk for the first 2 weeks of the intervention. MAIN OUTCOMES AND MEASURES: The primary outcome was change in 6-minute walk distance at 12-week follow-up (minimum clinically important difference, 20 m). P values were adjusted based on the Hochberg step-up method. RESULTS: Of 827 persons evaluated, 210 participants with PAD were randomized (mean age, 67.0 SD, 8.6 years; 141 67% black, 82 39% women). One hundred ninety-five (93%) completed 12-week follow-up. At 12-week follow-up, exercise + GM-CSF did not significantly improve 6-minute walk distance more than exercise alone (mean difference, −6.3 m 95% CI, −30.2 to +17.6; P = .61) or more than GM-CSF alone (mean difference, +28.7 m 95% CI, +5.1 to +52.3; Hochberg-adjusted P = .052). GM-CSF alone did not improve 6-minute walk more than attention control + placebo (mean difference, −1.4 m 95% CI, −25.2 to +22.4; P = .91). Exercise alone improved 6-minute walk compared with attention control + placebo (mean difference, +33.6 m 95% CI, +9.4 to +57.7; Hochberg-adjusted P = .02). CONCLUSIONS AND RELEVANCE: Among patients with PAD, supervised treadmill exercise significantly improved 6-minute walk distance compared with attention control + placebo, whereas GM-CSF did not significantly improve walking performance, either when used alone or when combined with supervised treadmill exercise. These results confirm the benefits of exercise but do not support using GM-CSF to treat walking impairment in patients with PAD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01408901
Patients with lower-extremity peripheral artery disease (PAD) have greater functional impairment, faster functional decline, increased rates of mobility loss, and poorer quality of life than people ...without PAD. Supervised exercise therapy (SET) improves walking ability, overall functional status, and health-related quality of life in patients with symptomatic PAD. In 2017, the Centers for Medicare & Medicaid Services released a National Coverage Determination (CAG-00449N) for SET programs for patients with symptomatic PAD. This advisory provides a practical guide for delivering SET programs to patients with PAD according to Centers for Medicare & Medicaid Services criteria. It summarizes the Centers for Medicare & Medicaid Services process and requirements for referral and coverage of SET and provides guidance on how to implement SET for patients with PAD, including the SET protocol, options for outcome measurement, and transition to home-based exercise. This advisory is based on the guidelines established by the Centers for Medicare & Medicaid Services for Medicare beneficiaries in the United States and is intended to assist clinicians and administrators who are implementing SET programs for patients with PAD.
Abstract People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and ...is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. −10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed.
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