Publications by authors named "Mary M McDermott"

206 Publications

Walking Exercise Therapy Effects on Lower Extremity Skeletal Muscle in Peripheral Artery Disease.

Circ Res 2021 Jun 10;128(12):1851-1867. Epub 2021 Jun 10.

Division of Intramural Research, National Institute on Aging (L.H., L.F.).

Walking exercise is the most effective noninvasive therapy that improves walking ability in peripheral artery disease (PAD). Biologic mechanisms by which exercise improves walking in PAD are unclear. This review summarizes evidence regarding effects of walking exercise on lower extremity skeletal muscle in PAD. In older people without PAD, aerobic exercise improves mitochondrial activity, muscle mass, capillary density, and insulin sensitivity in skeletal muscle. However, walking exercise increases lower extremity ischemia in people with PAD, and therefore, mechanisms by which this exercise improves walking may differ between people with and without PAD. Compared with people without PAD, gastrocnemius muscle in people with PAD has greater mitochondrial impairment, increased reactive oxygen species, and increased fibrosis. In multiple small trials, walking exercise therapy did not consistently improve mitochondrial activity in people with PAD. In one 12-week randomized trial of people with PAD randomized to supervised exercise or control, supervised treadmill exercise increased treadmill walking time from 9.3 to 15.1 minutes, but simultaneously increased the proportion of angular muscle fibers, consistent with muscle denervation (from 7.6% to 15.6%), while angular myofibers did not change in the control group (from 9.1% to 9.1%). These findings suggest an adaptive response to exercise in PAD that includes denervation and reinnervation, an adaptive process observed in skeletal muscle of people without PAD during aging. Small studies have not shown significant effects of exercise on increased capillary density in lower extremity skeletal muscle of participants with PAD, and there are no data showing that exercise improves microcirculatory delivery of oxygen and nutrients in patients with PAD. However, the effects of supervised exercise on increased plasma nitrite abundance after a treadmill walking test in people with PAD may be associated with improved lower extremity skeletal muscle perfusion and may contribute to improved walking performance in response to exercise in people with PAD. Randomized trials with serial, comprehensive measures of muscle biology, and physiology are needed to clarify mechanisms by which walking exercise interventions improve mobility in PAD.
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http://dx.doi.org/10.1161/CIRCRESAHA.121.318242DOI Listing
June 2021

Effects of supervised exercise therapy on blood pressure and heart rate during exercise, and associations with improved walking performance in peripheral artery disease: Results of a randomized clinical trial.

J Vasc Surg 2021 Jun 3. Epub 2021 Jun 3.

Deparment of Medicine, Feinberg School of Medicine, Northwestern Univeristy, Chicago. Electronic address:

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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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http://dx.doi.org/10.1016/j.jvs.2021.05.033DOI Listing
June 2021

In Memoriam: William R. Hiatt, MD, MSVM (1950-2020).

Vasc Med 2021 Jun 2:1358863X211012052. Epub 2021 Jun 2.

University Hospitals Cleveland Medical Center; Case Western Reserve University, Cleveland, OH, USA.

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http://dx.doi.org/10.1177/1358863X211012052DOI Listing
June 2021

Perceived Versus Objective Change in Walking Ability in Peripheral Artery Disease: Results from 3 Randomized Clinical Trials of Exercise Therapy.

J Am Heart Assoc 2021 Jun 2;10(12):e017609. Epub 2021 Jun 2.

Department of Medicine University of Chicago IL.

Background In people with lower-extremity peripheral artery disease, the effects of exercise on patient-reported outcomes remain unclear. Methods and Results Four hundred four people with peripheral artery disease in 3 clinical trials were randomized to exercise (N=205) or a control group (N=199) and completed the 6-minute walk and the Walking Impairment Questionnaire distance score (score 0-100, 100=best) at baseline and 6-month follow-up. Compared with the control group, exercise improved 6-minute walk distance by +39.8 m (95% CI, 26.8-52.8, <0.001) and the Walking Impairment Questionnaire distance score by +7.3 (95% CI, 2.4-12.1, =0.003). In all, 2828 individual Walking Impairment Questionnaire distance score questions were completed at baseline and follow-up. Among participants who perceived no change in ability to walk 1 or more distances between baseline and follow-up, 6-minute walk improved in the exercise group and declined in the control group (+26.8 versus -6.5 m, <0.001). Among participants who perceived that their walking ability worsened for 1 or more distances between baseline and follow-up, the 6-minute walk improved in the exercise group and declined in the control group (+18.4 versus -27.3 m, <0.001). Among participants who reported worsening calf symptoms at follow-up, the exercise group improved and the control group declined (+28.9 versus -12.5 m, <0.01). Conclusions In 3 randomized trials, exercise significantly improved the 6-minute walk distance in people with peripheral artery disease, but many participants randomized to exercise reported no change or decline in walking ability. These findings suggest a significant discrepancy in objectively measured walking improvement relative to perceived walking improvement in people with peripheral artery disease. Registration Information clinicaltrials.gov. Identifiers: NCT00106327, NCT01408901.
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http://dx.doi.org/10.1161/JAHA.120.017609DOI Listing
June 2021

Lower Extremity Peripheral Artery Disease Without Chronic Limb-Threatening Ischemia: A Review.

JAMA 2021 Jun;325(21):2188-2198

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Importance: Lower extremity peripheral artery disease (PAD) affects approximately 8.5 million people in the US and approximately 230 million worldwide.

Observations: Peripheral artery disease is uncommon before aged 50 years but affects up to 20% of people aged 80 years and older. It can be noninvasively diagnosed with the ankle-brachial index (ABI), a ratio of Doppler-recorded pressures in the dorsalis pedis and/or posterior tibial artery in each leg to brachial artery pressures. An ABI value less than 0.90 is 57% to 79% sensitive and 83% to 99% specific for arterial stenosis of at least 50%. Intermittent claudication, consisting of exertional calf pain that does not begin at rest and that resolves within 10 minutes of rest, is considered the classic symptom of PAD. However, 70% to 90% of people with an ABI value less than 0.90 either report no exertional leg symptoms (ie, asymptomatic) or report leg symptoms with walking that are not consistent with classic claudication. Over time, people with PAD restrict walking activity or slow walking speed to avoid leg symptoms. Thus, although approximately 75% of people with PAD report no change in leg symptoms over time, those with PAD have significantly greater annual declines in 6-minute walk performance compared with those without it. Approximately 11% of people with PAD develop chronic limb-threatening ischemia, the most severe form of PAD. Compared with people without PAD, those with the disease have approximately twice the rate of all-cause mortality, cardiovascular mortality, and major coronary events at 10-year follow-up. High-dose statins and antiplatelet therapy with or without antithrombotic therapy reduced rates of coronary events and stroke in people with PAD. Supervised treadmill exercise improved 6-minute walk distance by 30 to 35 m, consistent with a clinically meaningful change, whereas effective home-based walking exercise interventions improved 6-minute walk by 42 to 53 m. Effective home-based exercise programs require behavioral methods, including monitoring by a coach.

Conclusions And Relevance: Peripheral artery disease affects approximately 230 million people worldwide and is associated with increased rates of cardiovascular events, lower extremity events, and functional decline compared with that of people without PAD. People with PAD should be treated with the highest dose of statin tolerated, antithrombotic and/or antiplatelet therapy, and exercise.
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http://dx.doi.org/10.1001/jama.2021.2126DOI Listing
June 2021

High Mortality Rates in Medicare Patients After Peripheral Artery Disease Revascularization.

JAMA Intern Med 2021 May 16. Epub 2021 May 16.

Northwestern University Feinberg School of Medicine, Chicago, Illinois.

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http://dx.doi.org/10.1001/jamainternmed.2021.2782DOI Listing
May 2021

Remote Research and Clinical Trial Integrity During and After the Coronavirus Pandemic.

JAMA 2021 05;325(19):1935-1936

Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.

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http://dx.doi.org/10.1001/jama.2021.4609DOI Listing
May 2021

Sustained physical activity in peripheral artery disease: Associations with disease severity, functional performance, health-related quality of life, and subsequent serious adverse events in the LITE randomized clinical trial.

Vasc Med 2021 Apr 8:1358863X21989430. Epub 2021 Apr 8.

Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

This study investigated cross-sectional associations of peripheral artery disease (PAD) severity (defined by the ankle-brachial index (ABI)) and amounts of daily sustained physical activity (PA) (defined as > 100 activity counts per minute lasting 5 consecutive minutes or more). This study also investigated associations of amounts of daily sustained PA with 6-minute walk (6MW) distance and the Short Form-36 physical functioning domain (SF-36 PF) score in cross-sectional analyses and with serious adverse events (SAEs) in longitudinal analyses of people with PAD. PA was measured continuously for 10 days using a tri-axial accelerometer at baseline in 277 participants with PAD randomized to the LITE clinical trial. In regression analyses, each 0.15 lower ABI value was associated with a 5.67% decrease in the number of daily bouts of sustained PA (95% CI: 3.85-6.54; < 0.001). Every additional bout of sustained PA per day was associated with a 4.56-meter greater 6MW distance (95% CI: 2.67-6.46; < 0.0001), and a 0.81-point improvement in SF-36 PF score (95% CI: 0.34-1.28; < 0.001). Participants with values of daily bouts of sustained PA below the median had higher rates of SAEs during follow-up, compared to participants above the median (41% vs 24%; = 0.002). In conclusion, among participants with PAD, lower ABI values were associated with fewer bouts of daily sustained PA. A greater number of bouts of daily sustained PA were associated with better 6MW performance and SF-36 PF score, and, in longitudinal analyses, lower rates of SAEs.
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http://dx.doi.org/10.1177/1358863X21989430DOI Listing
April 2021

Elevated IL-6 and CRP levels are associated with incident self-reported major mobility disability: A pooled analysis of older adults with slow gait speed.

J Gerontol A Biol Sci Med Sci 2021 Apr 5. Epub 2021 Apr 5.

University of Florida, Gainesville, FL.

Background: Elevated Interleukine-6 (IL-6) and C-reactive protein (CRP) are associated with aging-related reductions in physical function, but little is known about their independent and combined relationships with major mobility disability (MMD), defined as the self-reported inability to walk a quarter-mile.

Methods: We estimated the absolute and relative effect of elevated baseline IL-6, CRP, and their combination on self-reported MMD risk among older adults (≥68 years; 59% female) with slow gait speed (<1.0m/s). Participants were MMD-free at baseline. IL-6 and CRP were assessed using a central laboratory. The study combined a cohort of community dwelling high-functioning older adults (Health ABC) with two trials of low-functioning adults at risk of MMD (LIFE-P, LIFE). Analyses utilized Poisson regression for absolute MMD incidence and proportional hazards models for relative risk.

Results: We found higher MMD risk per unit increase in log IL-6 [HR=1.26 (95% CI 1.13 to 1.41)]. IL-6 meeting pre-determined threshold considered to be high (>2.5 pg/mL) was similarly associated with higher risk of MMD [HR=1.31 (95% CI: 1.12 to 1.54)]. Elevated CRP (CRP >3.0 mg/L) was also associated with increased MMD risk [HR=1.38 (95% CI: 1.10 to 1.74)]. The CRP effect was more pronounced among participants with elevated IL-6 [HR=1.62 (95% CI: 1.12 to 2.33)] compared to lower IL-6 levels [HR=1.19 (95% CI: 0.85 to 1.66)].

Conclusions: High baseline IL-6 and CRP were associated with increased risk of MMD among older adults with slow gait speed. A combined biomarker model suggests CRP was associated with MMD when IL-6 was elevated.
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http://dx.doi.org/10.1093/gerona/glab093DOI Listing
April 2021

Effect of Low-Intensity vs High-Intensity Home-Based Walking Exercise on Walk Distance in Patients With Peripheral Artery Disease: The LITE Randomized Clinical Trial.

JAMA 2021 04;325(13):1266-1276

Wake Forest University, Winston-Salem, North Carolina.

Importance: Supervised high-intensity walking exercise that induces ischemic leg symptoms is the first-line therapy for people with lower-extremity peripheral artery disease (PAD), but adherence is poor.

Objective: To determine whether low-intensity home-based walking exercise at a comfortable pace significantly improves walking ability in people with PAD vs high-intensity home-based walking exercise that induces ischemic leg symptoms and vs a nonexercise control.

Design, Setting, And Participants: Multicenter randomized clinical trial conducted at 4 US centers and including 305 participants. Enrollment occurred between September 25, 2015, and December 11, 2019; final follow-up was October 7, 2020.

Interventions: Participants with PAD were randomized to low-intensity walking exercise (n = 116), high-intensity walking exercise (n = 124), or nonexercise control (n = 65) for 12 months. Both exercise groups were asked to walk for exercise in an unsupervised setting 5 times per week for up to 50 minutes per session wearing an accelerometer to document exercise intensity and time. The low-intensity group walked at a pace without ischemic leg symptoms. The high-intensity group walked at a pace eliciting moderate to severe ischemic leg symptoms. Accelerometer data were viewable to a coach who telephoned participants weekly for 12 months and helped them adhere to their prescribed exercise. The nonexercise control group received weekly educational telephone calls for 12 months.

Main Outcomes And Measures: The primary outcome was mean change in 6-minute walk distance at 12 months (minimum clinically important difference, 8-20 m).

Results: Among 305 randomized patients (mean age, 69.3 [SD, 9.5] years, 146 [47.9%] women, 181 [59.3%] Black patients), 250 (82%) completed 12-month follow-up. The 6-minute walk distance changed from 332.1 m at baseline to 327.5 m at 12-month follow-up in the low-intensity exercise group (within-group mean change, -6.4 m [95% CI, -21.5 to 8.8 m]; P = .34) and from 338.1 m to 371.2 m in the high-intensity exercise group (within-group mean change, 34.5 m [95% CI, 20.1 to 48.9 m]; P < .001) and the mean change for the between-group comparison was -40.9 m (97.5% CI, -61.7 to -20.0 m; P < .001). The 6-minute walk distance changed from 328.1 m at baseline to 317.5 m at 12-month follow-up in the nonexercise control group (within-group mean change, -15.1 m [95% CI, -35.8 to 5.7 m]; P = .10), which was not significantly different from the change in the low-intensity exercise group (between-group mean change, 8.7 m [97.5% CI, -17.0 to 34.4 m]; P = .44). Of 184 serious adverse events, the event rate per participant was 0.64 in the low-intensity group, 0.65 in the high-intensity group, and 0.46 in the nonexercise control group. One serious adverse event in each exercise group was related to study participation.

Conclusions And Relevance: Among patients with PAD, low-intensity home-based exercise was significantly less effective than high-intensity home-based exercise and was not significantly different from the nonexercise control for improving 6-minute walk distance. These results do not support the use of low-intensity home-based walking exercise for improving objectively measured walking performance in patients with PAD.

Trial Registration: ClinicalTrials.gov Identifier: NCT02538900.
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http://dx.doi.org/10.1001/jama.2021.2536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025122PMC
April 2021

Exercise Training and Revascularization in the Management of Symptomatic Peripheral Artery Disease.

JACC Basic Transl Sci 2021 Feb 22;6(2):174-188. Epub 2021 Feb 22.

Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Exercise therapy and lower extremity revascularization both improve walking performance in symptomatic patients with peripheral artery disease. The combination of therapies provides greater benefit than either alone and may reduce the need for subsequent revascularization procedures, but further trials with longer follow-up are needed for the outcome of subsequent revascularization.
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http://dx.doi.org/10.1016/j.jacbts.2020.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907537PMC
February 2021

Safety of paclitaxel-coated devices in peripheral artery disease.

Nat Rev Cardiol 2021 May;18(5):311-312

Department of Surgery and Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA.

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http://dx.doi.org/10.1038/s41569-021-00531-6DOI Listing
May 2021

Associations Between Systolic Interarm Differences in Blood Pressure and Cardiovascular Disease Outcomes and Mortality: Individual Participant Data Meta-Analysis, Development and Validation of a Prognostic Algorithm: The INTERPRESS-IPD Collaboration.

Hypertension 2021 Feb 21;77(2):650-661. Epub 2020 Dec 21.

NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Hospital and University of Exeter College of Medicine & Health, England (A.C.S.).

Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We undertook individual participant data meta-analyses to (1) quantify independent associations of systolic interarm difference with mortality and cardiovascular events; (2) develop and validate prognostic models incorporating interarm difference, and (3) determine whether interarm difference remains associated with risk after adjustment for common cardiovascular risk scores. We searched for studies recording bilateral blood pressure and outcomes, established agreements with collaborating authors, and created a single international dataset: the Inter-arm Blood Pressure Difference - Individual Participant Data (INTERPRESS-IPD) Collaboration. Data were merged from 24 studies (53 827 participants). Systolic interarm difference was associated with all-cause and cardiovascular mortality: continuous hazard ratios 1.05 (95% CI, 1.02-1.08) and 1.06 (95% CI, 1.02-1.11), respectively, per 5 mm Hg systolic interarm difference. Hazard ratios for all-cause mortality increased with interarm difference magnitude from a ≥5 mm Hg threshold (hazard ratio, 1.07 [95% CI, 1.01-1.14]). Systolic interarm differences per 5 mm Hg were associated with cardiovascular events in people without preexisting disease, after adjustment for Atherosclerotic Cardiovascular Disease (hazard ratio, 1.04 [95% CI, 1.00-1.08]), Framingham (hazard ratio, 1.04 [95% CI, 1.01-1.08]), or QRISK cardiovascular disease risk algorithm version 2 (QRISK2) (hazard ratio, 1.12 [95% CI, 1.06-1.18]) cardiovascular risk scores. Our findings confirm that systolic interarm difference is associated with increased all-cause mortality, cardiovascular mortality, and cardiovascular events. Blood pressure should be measured in both arms during cardiovascular assessment. A systolic interarm difference of 10 mm Hg is proposed as the upper limit of normal. Registration: URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42015031227.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803446PMC
February 2021

Skeletal Muscle Pathology in Peripheral Artery Disease: A Brief Review.

Arterioscler Thromb Vasc Biol 2020 11 17;40(11):2577-2585. Epub 2020 Sep 17.

Department of Neurology (R.S.), Northwestern University Feinberg School of Medicine, Chicago, IL.

This brief review summarizes current evidence regarding lower extremity peripheral artery disease (PAD) and lower extremity skeletal muscle pathology. Lower extremity ischemia is associated with reduced calf skeletal muscle area and increased calf muscle fat infiltration and fibrosis on computed tomography or magnetic resonance imaging. Even within the same individual, the leg with more severe ischemia has more adverse calf muscle characteristics than the leg with less severe ischemia. More adverse computed tomography-measured calf muscle characteristics, such as reduced calf muscle density, are associated with higher rates of mobility loss in people with PAD. Calf muscle in people with PAD may also have reduced mitochondrial activity compared with those without PAD, although evidence is inconsistent. Muscle biopsy document increased oxidative stress in PAD. Reduced calf muscle perfusion, impaired mitochondrial activity, and smaller myofibers are associated with greater walking impairment in PAD. Preliminary evidence suggests that calf muscle pathology in PAD may be reversible. In a small uncontrolled trial, revascularization improved both the ankle-brachial index and mitochondrial activity, measured by calf muscle phosphocreatine recovery time. A pilot clinical trial showed that cocoa flavanols increased measures of myofiber health, mitochondrial activity, and capillary density while simultaneously improving 6-minute walk distance in PAD. Calf muscle pathological changes are associated with impaired walking performance in people with PAD, and interventions that both increase calf perfusion and improve calf muscle health are promising therapies to improve walking performance in PAD.
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http://dx.doi.org/10.1161/ATVBAHA.120.313831DOI Listing
November 2020

Mitochondrial DNA damage in calf skeletal muscle and walking performance in people with peripheral artery disease.

Free Radic Biol Med 2020 11 8;160:680-689. Epub 2020 Sep 8.

University of Florida, Institute on Aging, Department of Aging and Geriatric Research, Gainesville, FL, USA. Electronic address:

Background: Peripheral artery disease (PAD) is associated with mitochondrial dysfunction in calf skeletal muscle and a greater abundance of mitochondrial DNA (mtDNA) heteroplasmy. However, it is unknown whether calf skeletal muscle mtDNA of PAD participants harbors a greater abundance of mitochondrial DNA 4977-bp common deletion (mtDNA), strand breaks and oxidative damage (i.e., oxidized purines) compared to non-PAD participants and whether these mtDNA abnormalities are associated with poor walking performance in participants with PAD.

Methods: Calf muscle biopsies were obtained from 50 PAD participants (ankle-brachial index (ABI) < 0.95) and 25 non-PAD participants (ABI = 0.99-1.40) matched by age, sex, and race. The abundance of mtDNA copy number, mtDNA deletion, strand breaks, and oxidized purines in selected mtDNA regions coding for electron transport chain (ETC) constituents and the non-coding D-Loop region was determined in calf muscle. All participants completed measurement of 6-min walk and usual and fast-paced 4-m walking velocity test.

Results: Participants with PAD (mean age = 65.4 years, SD = 6.9; 14 (28%) women, 38 (76%) black) and without PAD (mean age = 65.2 years, SD = 6.7; 7 (28%) women, 16 (64%) black) did not differ in the abundance of calf muscle mtDNA deletion, mtDNA strand breaks, and oxidized purines. Though, a greater abundance of mtDNA strand breaks within ND4/5 genes was significantly associated with poorer 6-min walk distance, lower usual-paced 4-m walking velocity, and lower fast-paced 4-m walking velocity in non-PAD participants. Significant associations were also found in the density of strand break damage (i.e., damage per mtDNA copy) within ND1/2, ND4/5 and COII/ATPase 6/8 region with 6-min walk distance, usual-paced 4-m walking velocity and fast-paced 4-m walking velocity in non-PAD participants. Significant interactions were found between PAD presence vs. absence and density of strand break damage within ND1/2, ND4/5, COII/ATPase 6/8 regions for the associations with 6-min walk distance, usual-paced 4-m walking velocity, fast-paced 4-m walking velocity. Conversely, of the three walking performance measures only the usual-paced 4-m walking velocity showed a significant, although modest, negative association with the abundance of oxidized purines in the D-Loop (P = 0.031) and ND4/5 (P = 0.033) regions in the calf skeletal muscle of people with PAD.

Conclusion: Overall, these data suggest that the abundance of calf muscle mtDNA strand breaks and mtDNA common deletion are not associated with walking performance in people with PAD and may not be directly involved in the pathophysiology of PAD. Conversely, strand breaks in specific mtDNA regions may contribute to poor walking performance in people without PAD. Further study is needed to confirm whether usual-paced 4-m walking velocity is associated significantly with a greater abundance of oxidized purines in the D-loop, a "mutational hotspot" for oxidative damage, and why this association may differ from the association with 6-min walk distance and fast-paced 4-m walking velocity.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.09.004DOI Listing
November 2020

Associations of Poly (ADP-Ribose) Polymerase1 abundance in calf skeletal muscle with walking performance in peripheral artery disease.

Exp Gerontol 2020 10 2;140:111048. Epub 2020 Aug 2.

Northwestern University Feinberg School of Medicine, Department of Preventive Medicine, Chicago, IL, United States of America; Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, IL, United States of America. Electronic address:

Objective: This study investigated associations of markers of oxidative stress and mitochondrial function in calf muscle biopsies with walking performance in people with and without lower extremity peripheral artery disease (PAD).

Methods: Participants with PAD (ankle-brachial index (ABI) <0.90) and without PAD (ABI: 0.90-1.50) underwent calf muscle biopsy and measurement of 6-min walk and four-meter walking velocity. PARP1 (Poly (ADP-Ribose) Polymerase 1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), silent information regulator 1 (SIRT1) and 4-hydroxynonenal (4HNE) expression were measured in calf muscle using western blot.

Results: Among 15 participants with PAD mean age: 66.8 years (standard deviation (SD): 6.4) and six without PAD (age: 64.4 years, SD: 5.9), mean PARP1-abundance in calf muscle was 1.16 ± 0.92 AU and 0.96 ± 0.38 AU, respectively (P = 0.61). Among participants with PAD after adjustment with ABI, a greater abundance of PARP1 was associated with poorer 6-min walking distance (r = -0.65, P = 0.01), usual-paced 4-m walking velocity (r = -0.73, P = 0.003) and slower fast-paced four-meter walking velocity (r = -0.51, P = 0.07). Among participants with PAD, ABI was not associated with PARP1 abundance in calf muscle (r = 0.02, P = 0.93). Among participants without PAD, skeletal muscle PARP1 abundance was not significantly associated with 6-min walk distance (r = -0.58; P = 0.22), usual-paced walking velocity (r = -0.26; P = 0.62), or fast-paced walking velocity (r = -0.21; P = 0.69), perhaps due to lack of statistical power. There were no associations of remaining calf muscle measures with walking performance.

Conclusions: These findings are consistent with the hypothesis that calf skeletal muscle characteristics are related to walking performance, independently of severity of lower extremity arterial obstruction in people with PAD.
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http://dx.doi.org/10.1016/j.exger.2020.111048DOI Listing
October 2020

The relationship between interleukin-6 levels and physical performance in mobility-limited older adults with chronic low-grade inflammation: The ENRGISE Pilot study.

Arch Gerontol Geriatr 2020 Sep - Oct;90:104131. Epub 2020 May 30.

Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, United States. Electronic address:

Previous studies have found an inverse relation between serum concentrations of interleukin (IL)-6 and physical performance in seniors, however this was limited to higher functioning older adults with low to moderate levels of inflammation. We explored the consistency of this association in a cohort of mobility limited older adults with chronic low-grade inflammation. This study included 289 participants (≥ 70 years old) with IL-6 level between 2.5 and 30 pg/mL and a walking speed < 1.0 m/sec from the ENRGISE Pilot study. Physical performance was assessed using the short physical performance battery (SPPB), usual gait speed over 400 m, grip strength, and knee extensor and flexor strength measured by isokinetic dynamometry at 60 and 180°/sec. There was a significant inverse correlation between log IL-6 and knee extensor strength at 60°/sec (r= -0.20, p = 0.002), at 180°/sec (r = -0.14, p = 0.037), and knee flexor strength at 60°/sec (r = -0.15, p = 0.021). After adjustment for potential confounders, the values of knee extensor strength at 60°/sec showed a trend toward a progressive reduction across IL-6 tertiles as IL-6 levels increased (p = 0.024). No significant association was found between IL-6 and other objectively measured physical performance. The findings were generally of smaller magnitude and less consistent than previously reported, which suggests that the associations are attenuated in those with both elevated inflammation and mobility limitations. These results have implications for planning and interpreting future intervention studies in older adults with low-grade inflammation and mobility limitations.
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http://dx.doi.org/10.1016/j.archger.2020.104131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434645PMC
December 2020

Nicotinamide riboside-A missing piece in the puzzle of exercise therapy for older adults?

Exp Gerontol 2020 08 22;137:110972. Epub 2020 May 22.

Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA.. Electronic address:

Maintaining physical mobility is important for preventing age-related comorbidities in older adults. Endurance and resistance training prevent mobility loss in aging, but exercise alone does not always achieve the expected improvements in physical and cardiopulmonary function. Recent preclinical evidence suggests that a reason for the variability in exercise training responses may be the age-related dysregulation of the nicotinamide adenine dinucleotide (NAD+) metabolome. NAD+ is an essential enzymatic cofactor in energetic and signaling pathways. Endogenous NAD+ pool is lower in several chronic and degenerative diseases (e.g., cardiovascular diseases, Alzheimer's and Parkinson's diseases, muscular dystrophies), and also in aging. Exercise requires a higher energy expenditure than a resting state, thus a state of NAD+ insufficiency with reduced energy metabolism, could result in an inadequate exercise response. Recently, the NAD+ precursor nicotinamide riboside (NR), a vitamin B3 derivate, showed an ability to improve NAD+ metabolome homeostasis, restoring energy metabolism and cellular function in various organs in animals. NR has also been tested in older humans and is considered safe, but the effects of NR supplementation alone on physical performance are unclear. The purpose of this review is to examine the preclinical and clinical evidence on the effect of NR supplementation strategies alone and in combination with physical activity on mobility and skeletal muscle and cardiovascular function.
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http://dx.doi.org/10.1016/j.exger.2020.110972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204261PMC
August 2020

Clinical characteristics and response to supervised exercise therapy of people with lower extremity peripheral artery disease.

J Vasc Surg 2021 Feb 19;73(2):608-625. Epub 2020 May 19.

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

Background: Among people with lower extremity peripheral artery disease (PAD), little is known about variation in response to supervised exercise therapy (SET). Clinical characteristics associated with greater responsiveness to SET have not been identified.

Methods: Data from participants with PAD in two randomized clinical trials comparing SET vs nonexercising control were combined. The exercise intervention consisted of three times weekly supervised treadmill exercise. The control groups received lectures on health-related topics.

Results: Of 309 unique participants randomized (mean age, 67.9 years [standard deviation, 9.3 years]; 132 [42.7%] women; 185 [59.9%] black), 285 (92%) completed 6-month follow-up. Compared with control, those randomized to SET improved 6-minute walk distance by 35.6 meters (95% confidence interval, 21.4-49.8; P < .001). In the 95 (62.1%) participants who attended at least 70% of SET sessions, change in 6-minute walk distance varied from -149.4 to +356.0 meters. Thirty-four (35.8%) had no 6-minute walk distance improvement. Among all participants, age, sex, race, body mass index, prior lower extremity revascularization, and other clinical characteristics did not affect the degree of improvement in 6-minute walk distance after SET relative to the control group. Participants with 6-minute walk distance less than the median of 334 meters at baseline had greater percentage improvement in 6-minute walk distance compared with those with baseline 6-minute walk distance above the median (+20.5% vs +5.3%; P for interaction = .0107).

Conclusions: Among people with PAD, substantial variability exists in walking improvement after SET. Shorter 6-minute walk distance at baseline was associated with greater improvement after SET, but other clinical characteristics, including age, sex, prior lower extremity revascularization, and disease severity, did not affect responsiveness to exercise therapy.
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http://dx.doi.org/10.1016/j.jvs.2020.04.498DOI Listing
February 2021

Correlations of Calf Muscle Macrophage Content With Muscle Properties and Walking Performance in Peripheral Artery Disease.

J Am Heart Assoc 2020 05 9;9(10):e015929. Epub 2020 May 9.

College of Health Sciences and Center for Muscle Biology University of Kentucky Lexington KY.

Background Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD. Methods and Results Macrophages, satellite cells, and extracellular matrix in gastrocnemius muscles from 25 patients with PAD and 7 patients without PAD were quantified using immunohistochemistry. Among patients with PAD, both the absolute number and percentage of cluster of differentiation (CD) 11b+CD206+ M2-like macrophages positively correlated to satellite cell number (=0.461 [=0.023] and =0.416 [=0.042], respectively) but not capillary density or extracellular matrix. The number of CD11b+CD206- macrophages negatively correlated to 4-meter walk tests at normal (=-0.447, =0.036) and fast pace (=-0.510, =0.014). Extracellular matrix occupied more muscle area in PAD compared with non-PAD (8.72±2.19% versus 5.30±1.03%, <0.001) and positively correlated with capillary density (=0.656, <0.001). Conclusions Among people with PAD, higher CD206+ M2-like macrophage abundance was associated with greater satellite cell numbers and muscle fiber size. Lower CD206- macrophage abundance was associated with better walking performance. Further study is needed to determine whether CD206+ macrophages are associated with ongoing reparative processes enabling skeletal muscle adaptation to damage with PAD. Registration URL: https://www.clini​caltr​ials.gov; Unique identifiers: NCT00693940, NCT01408901, NCT0224660.
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http://dx.doi.org/10.1161/JAHA.118.015929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660852PMC
May 2020

Association of six-minute walk distance with subsequent lower extremity events in peripheral artery disease.

Vasc Med 2020 08 27;25(4):319-327. Epub 2020 Apr 27.

Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

The prognostic significance of the six-minute walk distance for lower extremity events in people with peripheral artery disease (PAD) is unknown. This longitudinal study assessed whether a poorer six-minute walk distance at baseline was associated with higher rates of subsequent lower extremity atherosclerotic disease events in PAD. A total of 369 patients (mean age 69.4 ± 10.0 years; mean ankle-brachial index (ABI) 0.67 ± 0.17; 31% women; 30% black individuals) from Chicago-area medical centers with PAD were enrolled. Participants underwent baseline six-minute walk testing and returned for annual study visits. Lower extremity events consisted of one or more of the following: ABI decline greater than 15% or medical record adjudicated lower extremity revascularization, critical limb ischemia, or amputation. At a mean follow-up of 33.3 months, lower extremity events occurred in 66/123 (53.7%) people in the first (worst) tertile of six-minute walk performance, 55/124 (44.4%) in the second tertile, and 56/122 (45.9%) in the third (best) tertile. After adjusting for age, sex, race, ABI, comorbidities, and other confounders, participants in the first (worst) tertile of six-minute walk distance at baseline had higher rates of lower extremity events during follow-up, compared to those in the best tertile at baseline (HR = 1.74, 95% CI 1.17-2.60, = 0.0067). Among people with PAD, a poorer six-minute walk distance was associated with higher rates of subsequent lower extremity PAD-related events after adjusting for confounders. Further study is needed to determine whether interventions that improve six-minute walk distance can reduce lower extremity adverse events in people with PAD.
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http://dx.doi.org/10.1177/1358863X20901599DOI Listing
August 2020

Meaningful change in 6-minute walk in people with peripheral artery disease.

J Vasc Surg 2021 01 23;73(1):267-276.e1. Epub 2020 Apr 23.

Department of Epidemiology, University of Maryland, College Park, Md.

Objective: The 6-minute walk test is a common outcome measure in clinical trials of people with lower extremity peripheral artery disease (PAD). However, what constitutes a meaningful change in the 6-minute walk distance has not been well defined for people with PAD. The present study related the change in the 6-minute walk distance to the degree of participant-reported improvement or decline in the 6-minute walk distance to define a meaningful change in the 6-minute walk distance for those with PAD.

Methods: Participants with PAD from three observational longitudinal studies completed the walking impairment questionnaire (WIQ) distance score and 6-minute walk at baseline and 1 year later. The WIQ distance score measures participants' perceived difficulty walking seven different distances without stopping (ranging from walking around the home to walking 5 blocks) on a 0 to 4 Likert scale, with 0 representing an inability to walk the distance and 4 representing no difficulty. The mean changes in the 6-minute walk distance corresponding to the participants' report of no change, 1-unit change, or 2-unit change, respectively, in the Likert scale score between the baseline and 1-year follow-up measures were calculated for each WIQ distance.

Results: A total of 777 participants with PAD (mean age, 71.2 ± 8.8 years; mean baseline 6-minute walk distance, 350.1 ± 118.1 meters) completed 5439 questions about their difficulty walking each WIQ distance at baseline and follow-up. Participants with PAD who reported no change in their difficulty in walking each WIQ distance between baseline and follow-up had a decline of 7.2 meters (95% confidence interval [CI], -11.6 to -2.8 meters) in the 6-minute walk test. Relative to those reporting no change in difficulty walking, the participants reporting 1- and 2-point improvements in walking ability showed 6-minute walk distance improvements of 7.8 meters (95% CI, -0.3 to 15.9 meters) and 20.1 meters (95% CI, 1.1-39.2 meters), respectively. Relative to those reporting no change in walking difficulty, those reporting 1- and 2-point declines in perceived walking difficulty showed declines of -11.2 meters (95% CI, -19.0 to -3.4 meters) and -23.8 meters (95% CI, -37.4 to -10.3 meters) in the 6-minute walk distance.

Conclusions: Among people with PAD, ∼8- and ∼20-meter improvements in the 6-minute walk distance represent small and large improvements in walking ability, respectively. People with PAD who reported no change in their ability to walk distances over 1 year simultaneously declined by a mean of 7 meters in the 6-minute walk test. These findings will be useful for interpreting the results from randomized trials of interventions to improve the walking performance of people with PAD.
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http://dx.doi.org/10.1016/j.jvs.2020.03.052DOI Listing
January 2021

Preserving Clinical Trial Integrity During the Coronavirus Pandemic.

JAMA 2020 Jun;323(21):2135-2136

Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.

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http://dx.doi.org/10.1001/jama.2020.4689DOI Listing
June 2020

Associations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmy.

J Am Heart Assoc 2020 04 21;9(7):e015197. Epub 2020 Mar 21.

National Institutes on Health National Institute on Aging Baltimore MD.

Background Patients with peripheral artery disease (PAD) undergo frequent episodes of ischemia-reperfusion in lower extremity muscles that may negatively affect mitochondrial health and are associated with impaired mobility. We hypothesized that skeletal muscle from PAD patients will show high mitochondrial DNA heteroplasmy, especially in regions more susceptible to oxidative damage, such as the displacement loop, and that the degree of heteroplasmy will be correlated with the severity of ischemia and mobility impairment. Methods and Results Mitochondrial mutations and deletions and their relative abundance were identified by targeted mitochondrial DNA sequencing in biopsy specimens of gastrocnemius muscle from 33 PAD (ankle brachial index <0.9) and 9 non-PAD (ankle brachial index >0.9) subjects aged ≥60 years. The probability of heteroplasmy per DNA base was significantly higher for PAD subjects than non-PAD within each region. In adjusted models, PAD was associated with higher heteroplasmy than non-PAD (=0.003), but the association was limited to microheteroplasmy, that is heteroplasmy found in 1% to 5% of all mitochondrial genomes (=0.004). Heteroplasmy in the displacement loop and coding regions were significantly higher for PAD than non-PAD subjects after adjustment for age, sex, race, and diabetes mellitus (=0.037 and 0.004, respectively). Low mitochondrial damage, defined by both low mitochondrial DNA copy number and low microheteroplasmy, was associated with better walking performance. Conclusions People with PAD have higher "low frequency" heteroplasmy in gastrocnemius muscle compared with people without PAD. Among people with PAD, those who had evidence of least mitochondrial damage, had better walking performance than those with more mitochondrial damage. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02246660.
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http://dx.doi.org/10.1161/JAHA.119.015197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428597PMC
April 2020

Impact and Lessons From the Lifestyle Interventions and Independence for Elders (LIFE) Clinical Trials of Physical Activity to Prevent Mobility Disability.

J Am Geriatr Soc 2020 04 27;68(4):872-881. Epub 2020 Feb 27.

Department of Internal Medicine and the Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: Walking independently is basic to human functioning. The Lifestyle Interventions and Independence for Elders (LIFE) studies were developed to assess whether initiating physical activity could prevent major mobility disability (MMD) in sedentary older adults.

Methods: We review the development and selected findings of the LIFE studies from 2000 through 2019, including the planning phase, the LIFE-Pilot Study, and the LIFE Study.

Results: The planning phase and the LIFE-Pilot provided key information for the successful implementation of the LIFE Study. The LIFE Study, involving 1635 participants randomized at eight sites throughout the United States, showed that compared with health education, the physical activity program reduced the risk of the primary outcome of MMD (inability to walk 400 m: hazard ratio = 0.82; 95% confidence interval = 0.69-0.98; P = .03), and that the intervention was cost-effective. There were no significant effects on cognitive outcomes, cardiovascular events, or serious fall injuries. In addition, the LIFE studies provided relevant findings on a broad range of other outcomes, including health, frailty, behavioral outcomes, biomarkers, and imaging. To date, the LIFE studies have generated a legacy of 109 peer-reviewed publications, 19 ancillary studies, and 38 independently funded grants and clinical trials, and advanced the development of 59 early career scientists. Data and biological samples of the LIFE Study are now publicly available from a repository sponsored by the National Institute on Aging (https://agingresearchbiobank.nia.nih.gov).

Conclusions: The LIFE studies generated a wealth of important scientific findings and accelerated research in geriatrics and gerontology, benefiting the research community, trainees, clinicians, policy makers, and the general public. J Am Geriatr Soc 68:872-881, 2020.
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http://dx.doi.org/10.1111/jgs.16365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187344PMC
April 2020

Cocoa to Improve Walking Performance in Older People With Peripheral Artery Disease: The COCOA-PAD Pilot Randomized Clinical Trial.

Circ Res 2020 02 14;126(5):589-599. Epub 2020 Feb 14.

Department of Health Research and Policy, Stanford University, CA (L.T.).

Rationale: Cocoa and its major flavanol component, epicatechin, have therapeutic properties that may improve limb perfusion and increase calf muscle mitochondrial activity in people with lower extremity peripheral artery disease (PAD).

Objective: In a phase II randomized clinical trial, to assess whether 6 months of cocoa improved walking performance in people with PAD, compared with placebo.

Methods And Results: Six-month double-blind, randomized clinical trial in which participants with PAD were randomized to either cocoa beverage versus placebo beverage. The cocoa beverage contained 15 g of cocoa and 75 mg of epicatechin daily. The identical appearing placebo contained neither cocoa nor epicatechin. The 2 primary outcomes were 6-month change in 6-minute walk distance measured 2.5 hours after a study beverage at 6-month follow-up and 24 hours after a study beverage at 6-month follow-up, respectively. A 1-sided <0.10 was considered statistically significant. Of 44 PAD participants randomized (mean age, 72.3 years [±7.1]; mean ankle brachial index, 0.66 [±0.15]), 40 (91%) completed follow-up. Adjusting for smoking, race, and body mass index, cocoa improved 6-minute walk distance at 6-month follow-up by 42.6 m ([90% CI, +22.2 to +∞] =0.005) at 2.5 hours after a final study beverage and by 18.0 m ([90% CI, -1.7 to +∞] =0.12) at 24 hours after a study beverage, compared with placebo. In calf muscle biopsies, cocoa improved mitochondrial COX (cytochrome c oxidase) activity (=0.013), increased capillary density (=0.014), improved calf muscle perfusion (=0.098), and reduced central nuclei (=0.033), compared with placebo.

Conclusions: These preliminary results suggest a therapeutic effect of cocoa on walking performance in people with PAD. Further study is needed to definitively determine whether cocoa significantly improves walking performance in people with PAD.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02876887. Visual Overview: An online visual overview is available for this article.
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http://dx.doi.org/10.1161/CIRCRESAHA.119.315600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141749PMC
February 2020

Comparing 6-minute walk versus treadmill walking distance as outcomes in randomized trials of peripheral artery disease.

J Vasc Surg 2020 03 23;71(3):988-1001. Epub 2019 Dec 23.

Intramural Research Program, National Institute on Aging, Baltimore, Md.

Background: Randomized trials of people with peripheral artery disease (PAD) and intermittent claudication have traditionally used maximal treadmill walking distance as the primary outcome, but the 6-minute walk test is increasingly used as a primary outcome in randomized trials of PAD. This study compared relative changes in maximal treadmill walking distance versus 6-minute walk distance in response to a therapeutic intervention or control in randomized trials of participants with PAD.

Methods: Data from four randomized trials of therapeutic interventions in participants with PAD that measured both 6-minute walk and treadmill walking performance at baseline and the 6-month follow-up were combined. Two trials studied supervised treadmill exercise, one studied home-based walking exercise, and one studied resveratrol.

Results: Of 467 participants (mean age, 69.8; standard deviation, 9.7), the mean ankle-brachial index was 0.66 (standard deviation, 0.17). At the 6-month follow-up, participants with PAD randomized to control or placebo significantly declined in 6-minute walk distance (-10.2 m; 95% confidence interval, -18.2 to -2.2; P = .013), but improved maximal treadmill walking distance (+25.7 m; 95% CI, +6.0 to +45.3 m; P = .010; difference between change in 6-minute walk versus maximal treadmill walking distance: -37.3 m; 95% CI, -56.4 to -18.2; P < .001). Home-based exercise improved the 6-minute walk distance by 43.2 m (95% CI, +28.4 to +57.9), and supervised treadmill exercise improved the 6-minute walk distance by 25.0 m (95% CI, +14.7 to +35.2; mean difference, +18.2 m favoring home-based exercise [95% CI, +0.2 to +36.2 m; P = .048]). Among all participants, the presence (vs absence) of treadmill exercise training was associated with a 141.3-m greater improvement in maximal treadmill walking distance compared to 6-minute walk distance (95% CI, 88.2-194.4; P < .001), suggesting a benefit from treadmill training on the treadmill outcome.

Conclusions: Maximal treadmill walking distance and the 6-minute walk distance are not interchangeable outcomes in participants with PAD. Participants with PAD randomized to control groups improved treadmill walking distance but simultaneously meaningfully declined in 6-minute walk distance. Supervised treadmill exercise training amplified improvement in treadmill walking distance because of a training to the outcome measure phenomenon.
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http://dx.doi.org/10.1016/j.jvs.2019.05.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141750PMC
March 2020

Implementation of Supervised Exercise Therapy for Patients With Symptomatic Peripheral Artery Disease: A Science Advisory From the American Heart Association.

Circulation 2019 09 26;140(13):e700-e710. Epub 2019 Aug 26.

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.
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http://dx.doi.org/10.1161/CIR.0000000000000727DOI Listing
September 2019

Smoking Cessation and Cardiovascular Disease: It's Never Too Early or Too Late for Action.

J Am Coll Cardiol 2019 07;74(4):508-511

Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.

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http://dx.doi.org/10.1016/j.jacc.2019.06.003DOI Listing
July 2019