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Objective: Home-based walking exercise is first-line therapy for peripheral artery disease (PAD), but benefits of home-based walking exercise are variable. This study evaluated whether specific clinical characteristics were associated with greater improvement after home-based walking exercise or with higher rates of serious adverse events (SAEs)., Methods: Data were combined from two randomized clinical trials comparing home-based walking exercise with control in PAD. The home-based exercise interventions used behavioral interventions to help participants adhere to exercise. The primary outcome was the proportion of PAD participants who improved 6-minute walk (6MW) by at least 20 meters. Serious adverse events consisted of overnight hospitalizations or death that occurred during the randomized clinical trial., Results: Of 376 participants with PAD (69.6 years; 54.5% Black; 49.5% women), 217 were randomized to exercise and 159 to control. Home-based exercise improved 6MW by at least 20 meters in 100 participants (54.9%), compared with 37 (28.0%) in control (odds ratio, 3.13; 95% confidence interval, 1.94-5.06; P < .001). Age, sex, race, comorbidities, baseline 6MW, and income did not significantly alter the effect of home-based exercise on improved 6MW. SAEs occurred in 28.1% and 23.3% of participants randomized to exercise and control, respectively (P = .29). There were statistically significant interactions, indicating that home-based exercise increased SAE rates, compared with control, in Black compared with non-Black participants (P interaction < .001), in those with vs without coronary artery disease (CAD) (P interaction < .001), and in people with vs without history of heart failure (P interaction = .005)., Conclusions: Among people with PAD, home-based exercise improved 6MW by at least 20 meters in 54.9% of people. Older age, female sex, Black race, and specific comorbidities were not associated with lower rates of attaining meaningful improvement in 6MW following home-based exercise. Further study is needed to establish whether certain patient characteristics, such as history of coronary artery disease, may affect SAE rates in patients with PAD participating in home-based exercise., Competing Interests: Disclosures M.M. reports grants from the National Heart, Lung, and Blood Institute and funding from the National Institute on Aging and the American Heart Association during the conduct of the study; research funding from Helixmith; and other research support from Mars and ArtAssist., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Among people with peripheral artery disease (PAD), perceived change in walking difficulty over time, compared with people without PAD, is unclear. Among people reporting no change in walking difficulty over time, differences in objectively measured change in walking performance between people with and without PAD are unknown., Methods: A total of 1289 participants were included. Eight hundred seventy-four participants with PAD (aged 71.1 ± 9.1 years) were identified from noninvasive vascular laboratories and 415 without PAD (aged 69.9 ± 7.6 years) were identified from people with normal vascular laboratory testing or general medical practices in Chicago. The Walking Impairment Questionnaire and 6-minute walk were completed at baseline and 1-year follow-up. The Walking Impairment Questionnaire assessed perceived difficulty walking due to symptoms in the calves or buttocks on a Likert scale (range, 0-4). Symptom change was determined by comparing difficulty reported at 1-year follow-up to difficulty reported at baseline., Results: At 1-year follow-up, 31.9% of participants with and 20.6% of participants without PAD reported walking difficulty that was improved (P < .01), whereas 41.2% vs 55%, respectively, reported walking difficulty that was unchanged (P < .01). Among all reporting no change in walking difficulty, participants with PAD declined in 6-minute walk, whereas participants without PAD improved (-10 vs +15 meters; mean difference, -25; 95% confidence interval, -38 to -13; P < .01)., Conclusions: Most people with PAD reported improvement or no change in walking difficulty from calf or buttock symptoms at one-year follow-up. Among all participants who perceived stable walking ability, those with PAD had significant greater declines in objectively measured walking performance, compared with people without PAD., Competing Interests: Disclosures M.M.M. reports other research support from ArtAssist, Helixmith, Mars, Chromadex, ReserveAge, and research funding from Regeneron and Helixmith., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This study identified barriers to participation in supervised exercise therapy covered by the Centers for Medicare and Medicaid Services (CMS), reported by people with lower extremity peripheral artery disease (PAD)., Methods: People with PAD participating in research studies of walking impairment due to PAD in the Chicagoland area were asked to complete a questionnaire between March 15, 2019, and July 12, 2022, assessing their experience and attitudes about supervised exercise therapy. Participants were identified using mailed postcards to people aged 50 and older in Chicagoland, from medical centers in Chicago, and using bus and train advertisements. The questionnaire was developed based on focus group feedback from people with PAD., Results: Of 516 participants with PAD approached, 489 (94.8%) completed the questionnaire (mean age: 71.0 years [standard deviation: 8.7], mean ankle-brachial index: 0.71 [standard deviation: 0.25]; 204 [41.7%] women and 261 [53.4%] Black). Of the 489 participants, 416 (85.1%) reported that their physician had never prescribed or recommended supervised exercise therapy. Overall, 357 (73.2%) reported willingness to travel three times weekly to the medical center for supervised exercise participation. However, of these, 214 (59.9%) reported that they were unwilling or unable to pay the $11 per exercise session copay required for supervised exercise covered by CMS. Of 51 people with PAD who reported prior participation in supervised exercise, only 5 (9.8%) completed the 12 weeks of supervised exercise therapy covered by CMS and 29 (56.9%) completed 6 or fewer weeks. Of 131 (26.8%) unwilling to travel three times weekly to a center for supervised exercise, the most common reasons for unwillingness to participate were "too time-consuming" (55.0%), "too inconvenient" (45.8%), and "lack of interest in treadmill exercise" (28.2%)., Conclusions: Approximately 2 to 4 years after CMS began covering supervised exercise for PAD, most people with PAD in this study from a large urban area had not participated in supervised exercise therapy. Of those who participated, most completed fewer than half of the sessions covered by CMS. The required CMS copayment was a common barrier to supervised exercise participation by people with PAD., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: An individual's understanding of disease risk factors and outcomes is important for the ability to make healthy lifestyle choices and decisions about disease treatment. Peripheral artery disease (PAD) is a condition with increasing global prevalence and high risk of adverse patient outcomes. This study seeks to understand the adequacy of disease understanding in patients with PAD., Methods: This was an observational study of patients with PAD recruited from vascular surgery outpatient clinic and PAD clinical studies at a single academic medical center over an 8-month period. A 44-item paper survey assessed demographic and socioeconomic information, knowledge of personal medical history, PAD risk factors, consequences of PAD, and health education preferences. Patients with documented presence of PAD were offered the survey. Patients unable to complete the survey or provide informed consent were not considered eligible. Disease "awareness" was defined as correct acknowledgement of the presence or absence of a disease, including PAD, in the personal medical history. "PAD knowledge score" was the percentage of correct responses to questions on general PAD risk factors and consequences. Of 126 eligible patients, 109 participated. Bivariate analysis was used to study factors associated with awareness of PAD diagnosis. Factors associated with the PAD knowledge score were studied using the Pearson correlation coefficient, two-sample t test, or one-way analysis of variance. P value < .05 was considered statistically significant., Results: The mean participant age was 69.4 ± 11.0 years, and 39.4% (n = 43) were female. Most participants (78.9%; n = 86) had critical limb-threatening ischemia. Only 65.4% (n = 70) of participants were aware of a diagnosis of PAD, which was less than their awareness of related comorbidities. Factors positively associated with PAD diagnosis awareness were female sex (81.4% vs 54.7%; P = .004) and history of percutaneous leg revascularization (78.6% vs 47.9%; P = .001). Among 17 patients who had undergone major leg amputation, 35% (n = 6) were unaware of a diagnosis of PAD. PAD knowledge scores correlated positively with an awareness of PAD diagnosis (59.1% vs 48.7%; P = .02) and negatively with a history of hypertension (53.4% vs 68.1%; P = .001). Most participants (86.5%; n = 90) expressed a desire to be further educated on PAD. The most popular education topics were dietary recommendations, causes, and treatment for PAD., Conclusions: Patients with PAD have deficits in their awareness of this diagnosis and general knowledge about PAD. Future research priorities should further define these deficits and their causes in order to inform new strategies that foster information-seeking behavior and effective educational programs for PAD., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021. Published by Elsevier Inc.)

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., (Copyright © 2020 Society for Vascular Surgery. All rights reserved.)

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., (Copyright © 2020 Society for Vascular Surgery. All rights reserved.)

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., (Copyright © 2019 Society for Vascular Surgery. All rights reserved.)

Objective: Multiple studies have shown that gut microbes contribute to atherosclerosis, and there is mounting evidence that microbial metabolism of dietary nutrients influences pathophysiology. We hypothesized that indole- and phenyl-derived metabolites that originate solely or in part from bacterial sources would differ between patients with advanced atherosclerosis and age- and sex-matched controls without clinically apparent atherosclerosis., Methods: Plasma from the advanced atherosclerosis cohort (n = 100) was from patients who underwent carotid endarterectomy, open infrainguinal leg revascularization, or major leg amputation for critical limb ischemia. The controls (n = 22) were age- and sex-matched participants who had no peripheral arterial disease or history of stroke or myocardial infarction. Patients with chronic kidney disease were excluded. Metabolites and internal standards were measured using high-performance liquid chromatography and tandem mass spectrometry., Results: Plasma metabolite concentrations differed significantly between the advanced atherosclerosis and control cohorts. After adjustment for traditional atherosclerosis risk factors, indole (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75-0.95; P = .004), tryptophan (OR, <0.001; 95% CI, <0.001-0.003; P < .001), indole-3-propionic acid (OR, 0.27; 95% CI, 0.019-0.91; P = .02), and indole-3-aldehyde (OR, 0.12; 95% CI, 0.014-0.92; P = .04) concentrations negatively associated with advanced atherosclerosis, whereas the kynurenine/tryptophan ratio (OR, 61.7; 95% CI, 1.9->999; P = .02) was positively associated. Furthermore, tryptophan and indole-3-propionic acid concentrations (Spearman coefficients of 0.63 and 0.56, respectively; P < .001) correlated with the ankle-brachial index, a surrogate for overall atherosclerotic disease burden. Fourteen patients experienced a major postoperative cardiac complication within 30 days in the advanced atherosclerosis cohort, which was associated with baseline kynurenine/tryptophan ratio (P = .001) and hippuric acid (P = .03). In a multivariate analysis, only the kynurenine/tryptophan ratio remained significantly associated with a postoperative cardiac complication (OR, 44.1; 95% CI, 3.3-587.1; P = .004). Twenty patients in the advanced atherosclerosis cohort experienced a major adverse cardiac event during the follow-up period, which was associated with hippuric acid (P = .002) and the kynurenine/tryptophan ratio (P < .001) at baseline. Both hippuric acid and the kynurenine/tryptophan ratio were independently associated with a major adverse cardiac event in multivariate analyses that included diabetes mellitus., Conclusions: Specific microbe-derived metabolite signatures associate with advanced human atherosclerosis and postoperative cardiac complications. We suggest that these metabolites are potential novel biomarkers for atherosclerotic disease burden and that further investigation into mechanistic links between defined microbial metabolic pathways and cardiovascular disease is warranted., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to provide an overview of evidence regarding exercise therapies for patients with lower extremity peripheral artery disease (PAD)., Methods: This manuscript summarizes the content of a lecture delivered as part of the 2016 Crawford Critical Issues Symposium., Results: Multiple randomized clinical trials demonstrate that supervised treadmill exercise significantly improves treadmill walking performance in people with PAD and intermittent claudication symptoms. A meta-analysis of 25 randomized trials demonstrated a 180-meter increase in treadmill walking distance in response to supervised exercise interventions compared with a nonexercising control group. Supervised treadmill exercise has been inaccessible to many patients with PAD because of lack of medical insurance coverage. However, in 2017, the Centers for Medicare and Medicaid Services issued a decision memorandum to support health insurance coverage of 12 weeks of supervised treadmill exercise for patients with walking impairment due to PAD. Recent evidence also supports home-based walking exercise to improve walking performance in people with PAD. Effective home-exercise programs incorporate behavioral change interventions such as a remote coach, goal setting, and self-monitoring. Supervised treadmill exercise programs preferentially improve treadmill walking performance, whereas home-based walking exercise programs preferentially improve corridor walking, such as the 6-minute walk test. Clinical trial evidence also supports arm or leg ergometry exercise to improve walking endurance in people with PAD. Treadmill walking exercise appears superior to resistance training alone for improving walking endurance., Conclusions: Supervised treadmill exercise significantly improves treadmill walking performance in people with PAD by approximately 180 meters compared with no exercise. Recent evidence suggests that home-based exercise is also effective and preferentially improves over-ground walking performance, such as the 6-minute walk test., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to determine whether blacks with lower extremity peripheral artery disease (PAD) have faster functional decline than whites with PAD., Methods: Participants with ankle-brachial index <0.90 were identified from Chicago medical centers and observed longitudinally. Mobility impairment and the 6-minute walk were assessed at baseline and every 6 to 12 months. Mobility loss was defined as becoming unable to walk up and down a flight of stairs or to walk ¼ mile without assistance., Results: Of 1162 PAD participants, 305 (26%) were black. Median follow-up was 46.0 months. Among 711 PAD participants who walked 6 minutes continuously at baseline, black participants were more likely to become unable to walk 6 minutes continuously during follow-up (64/171 [37.4%] vs 156/540 [28.9%]; log-rank, P = .006). Black race was associated with becoming unable to walk 6 minutes continuously, adjusting for age, sex, ankle-brachial index, comorbidities, and other confounders (hazard ratio, 1.45; 95% confidence interval, 1.05-1.99; P = .022). This association was attenuated after adjustment for income and education (P = .229). Among 844 participants without baseline mobility impairment, black participants had a higher rate of mobility loss (64/209 [30.6%] vs 164/635 [25.8%]; log-rank, P = .009). Black race was associated with increased mobility loss, adjusting for potential confounders (hazard ratio, 1.42; 95% confidence interval, 1.04-1.94; P = .028). This association was attenuated after additional adjustment for income and education (P = .392) and physical activity (P = .113). There were no racial differences in average annual declines in 6-minute walk, usual-paced 4-meter walking velocity, or fast-paced 4-meter walking velocity., Conclusions: Black PAD patients have higher rates of mobility loss and becoming unable to walk for 6 minutes continuously. These differences appear related to racial differences in socioeconomic status and physical activity., (Copyright © 2017 Society for Vascular Surgery. All rights reserved.)

Background: Individuals with peripheral arterial disease (PAD) have a nearly two-fold increased risk of all-cause and cardiovascular disease mortality compared to those without PAD. This pilot study determined whether metabolomic profiling can accurately identify patients with PAD who are at increased risk of near-term mortality., Methods: We completed a case-control study using (1)H NMR metabolomic profiling of plasma from 20 decedents with PAD, without critical limb ischemia, who had blood drawn within 8 months prior to death (index blood draw) and within 10 to 28 months prior to death (preindex blood draw). Twenty-one PAD participants who survived more than 30 months after their index blood draw served as a control population., Results: Results showed distinct metabolomic patterns between preindex decedent, index decedent, and survivor samples. The major chemical signals contributing to the differential pattern (between survivors and decedents) arose from the fatty acyl chain protons of lipoproteins and the choline head group protons of phospholipids. Using the top 40 chemical signals for which the intensity was most distinct between survivor and preindex decedent samples, classification models predicted near-term all-cause death with overall accuracy of 78% (32/41), a sensitivity of 85% (17/20), and a specificity of 71% (15/21). When comparing survivor with index decedent samples, the overall classification accuracy was optimal at 83% (34/41) with a sensitivity of 80% (16/20) and a specificity of 86% (18/21), using as few as the top 10 to 20 chemical signals., Conclusions: Our results suggest that metabolomic profiling of plasma may be useful for identifying PAD patients at increased risk for near-term death. Larger studies using more sensitive metabolomic techniques are needed to identify specific metabolic pathways associated with increased risk of near-term all-cause mortality among PAD patients., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Among individuals with peripheral artery disease (PAD), we compared annual change in 6-minute walk performance between participants who neither underwent lower extremity revascularization nor walked for exercise (group 1, reference), those who walked regularly for exercise (group 2), and those who underwent lower extremity revascularization (group 3)., Methods: Participants were recruited from Chicago-area vascular laboratories and followed annually. Change in 6-minute walk was calculated beginning at the study visit preceding lower extremity revascularization or exercise behavior and continuing for 1 additional year after the therapy was reported. Results are adjusted for age, sex, race, comorbidities, and other confounders., Results: Of 348 PAD participants, 43 underwent revascularization during median follow-up of 84 months. Adjusted annual declines in 6-minute walk were -96.6 feet/year for group 1, -49.9 feet/year for group 2, and -32.6 feet/year for group 3 (P < .001). Forty-one percent of revascularizations were not associated with ankle-brachial index (ABI) improvement. When group 3 was limited to participants with ABI improvement ≥0.15 after revascularization, annual adjusted changes in 6-minute walk were -97.7 feet/year for group 1, -46.5 feet/year for group 2, and +68.1 feet/year for group 3 (P < .001). When group 3 was limited to participants without ABI improvement ≥0.15 after revascularization, annual adjusted changes in 6-minute walk were -99.2 feet/year for group 1, -48.0 feet/year for group 2, and -61.7 feet/year for group 3 (P < .001)., Conclusions: A large proportion of PAD participants did not have ABI improvement of at least 0.15 at follow-up study visit after revascularization. The benefits of lower extremity revascularization in patients with PAD appear closely tied to improvements in the ABI after revascularization., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The Walking Impairment Questionnaire (WIQ) measures self-reported walking distance, walking speed, and stair-climbing ability in men and women with lower extremity peripheral arterial disease (PAD). We determined whether poorer WIQ scores are associated with higher all-cause and cardiovascular disease (CVD) mortality in individuals with and without PAD., Methods: We identified 1048 men and women with and without PAD from Chicago-area medical centers. Participants completed the WIQ at baseline and were monitored for a median of 4.5 years. Cox proportional hazards models were used to relate baseline WIQ scores with death, adjusting for age, sex, race, the ankle-brachial index (ABI), comorbidities, and other covariates., Results: During follow-up, 461 participants (44.0%) died, including 158 deaths from CVD. PAD participants in the lowest baseline quartile of the WIQ stair-climbing scores had higher all-cause mortality (hazard ratio, 1.70; 95% confidence interval, 1.08-2.66, P = .02) and higher CVD mortality (hazard ratio, 3.11; 95% confidence interval, 1.30-7.47, P = .01) compared with those with the highest baseline WIQ stair-climbing score. Among PAD participants, there were no significant associations of lower baseline WIQ distance or speed scores with rates of all-cause mortality (P = .20 and P = .07 for trend, respectively) or CVD mortality (P = .51 and P = .33 for trend, respectively). Among non-PAD participants there were no significant associations of lower baseline WIQ stair-climbing, distance, or speed score with rates of all-cause mortality (P = .94, P = .69, and P = .26, for trend, respectively) or CVD mortality (P = .28, P = .68, and P = .78, for trend, respectively)., Conclusions: Among participants with PAD, lower WIQ stair-climbing scores are associated with higher all-cause and CVD mortality, independently of the ABI and other covariates., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: This study investigated whether higher body mass index (BMI) is associated with more adverse lower extremity muscle characteristics at baseline and more adverse changes in muscle over time among participants with lower extremity peripheral arterial disease (PAD)., Methods: This was a longitudinal, observational study of 425 men and women with PAD and 261 without PAD. Computed tomography was used to measure calf muscle characteristics at baseline and every 2 years. Knee extension isometric strength, power, and 6-minute walk distance were measured at baseline and annually. Baseline BMI (kg/m(2)) categories were ideal (20-25), overweight (>25-30), and obese (>30). Analyses adjust for age, race, sex, ankle brachial index, comorbidities, and other covariates., Results: At baseline, higher BMI among participants with PAD was associated with greater calf muscle area (ideal BMI: 5181 mm(2); overweight: 5513 mm(2); obese: 5695 mm(2); P = .0009 for trend), higher calf muscle percentage of fat (6.38%, 10.28%, 17.44%, respectively, P < .0001 for trend), lower calf muscle density (P < .0001 for trend), and higher isometric knee extension strength (P = .015 for trend). Among participants with PAD, higher BMI was associated with greater declines in calf muscle area (P = .030 for trend) and greater increases in calf muscle percentage of fat (P = .023 for trend). Among participants without PAD, there were no significant associations of baseline BMI with changes in lower extremity muscle outcomes over time., Conclusions: Among PAD participants, higher BMI is associated with greater calf muscle area at baseline. However, higher BMI is associated with more adverse calf muscle density and calf muscle percentage of fat at baseline and greater declines in calf muscle area over time., (Copyright © 2012 Society for Vascular Surgery. All rights reserved.)

Objective: To establish associations between leg strength and mortality in men and women with lower extremity peripheral arterial disease (PAD)., Methods: This was an observational, prospective study of 410 men and women with PAD aged 55 and older recruited from Chicago-area medical centers and followed for a mean of 60 months. The participants were followed for a mean of 60.0 months. Isometric knee extension, knee flexion, hip extension, and hip flexion were measured at baseline. Primary outcomes were all-cause and cardiovascular disease mortality. Cox proportional hazards models were used to assess relations between leg strength and all-cause and cardiovascular disease mortality among men and women, adjusting for age, race, comorbidities, physical activity, smoking, body mass index, and the ankle brachial index., Results: Among the 246 male participants, poorer baseline strength for knee flexion (P trend = .029), knee extension (P trend =.010), and hip extension (P trend = .013) were each associated independently with higher all-cause mortality. Poorer strength for knee flexion (P trend = .042) and hip extension (P trend = .029) were associated with higher cardiovascular mortality. Compared with those in the fourth (best) baseline knee flexion quartile, hazard ratios for all-cause and cardiovascular disease mortality among men in the first (poorest) knee flexion quartile were 2.23 (95% confidence interval [CI], 1.02-4.87; P = .045) and 4.20 (95% CI, 1.12-15.79; P = .044), respectively. No significant associations of leg strength and all-cause mortality were identified among women., Conclusions: Poorer leg strength is associated with increased mortality in men, but not women, with PAD. Future study is needed to determine whether interventions that increase leg strength improve survival in men with PAD.

Background: Whether novel biomarkers improve risk prediction of mortality beyond standard cardiovascular disease (CVD) risk markers in peripheral arterial disease (PAD) patients, and whether any such prediction differs with length of follow-up, remains controversial. Our objective was to determine in patients with PAD whether novel biomarkers improve prediction of CVD mortality and total mortality., Methods: A cohort of 397 patients who were referred to a vascular lab had PAD diagnosed by noninvasive testing. Fifty-eight percent also had coronary or cerebrovascular disease at baseline. Predictors of total, CVD, and non-CVD mortality were assessed with Cox proportional hazards models, and the incremental value of predictors was evaluated with both the C-statistic and the integrated discrimination improvement (IDI) index., Results: Total mortality was 11% at 2-year follow-up and 65% at an average of 6.6-year of follow-up (maximum, 11.4 years). At 2 years, hs-CRP was a strong and significant predictor of mortality, with a hazard ratio (HR) of 1.56 per standard deviation (P = .006). However, at full follow up, standard CVD risk markers were significant (age, gender, ankle-brachial index, other CVD, and hypertension), but hs-CRP no longer showed a significant relationship (HR 1.12; P = .11). None of the other biomarkers studied showed a significant independent association with mortality. Hs-CRP improved the C-statistic and the IDI beyond standard risk markers at 2 years, but not at full follow-up., Conclusions: hs-CRP was a strong predictor of short-term mortality in this cohort of PAD patients, while standard risk markers were better at predicting longer-term mortality., (Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: The aim of this study was to determine the risk factors for conversion from a normal to either a low or high ankle-brachial index (ABI)., Methods: Participants in the Multi-Ethnic Study of Atherosclerosis who had two separate measurements of the ABI over a 3-year time period were assessed., Results: At baseline, the mean age was 62 years and 50% were women, 28% African American, 12% Chinese, 22% Hispanic and 38% non-Hispanic White. Of the 5514 participants with a baseline ABI between 0.90 and 1.40, 89 (1.6%) had an ABI < or = 0.90 ("low ABI group") and 71 (1.3%) had an ABI > or = 1.40 ("high ABI group") 3 years later. On multivariable analysis, the odds for having progressed into the low ABI group were significantly increased for higher baseline age, hypertension, diabetes, greater pack-years of cigarette smoking, and homocysteine levels. The odds for progression into the high ABI group were increased for male gender and higher body mass index. Compared with non-Hispanic Whites, African Americans had a significantly higher odds for progression to the low ABI group (odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.29-3.88) while having a reduced odds for progression to the high ABI group (OR: 0.50, 95% CI: 0.24-1.00). Neither Chinese nor Hispanic ethnicity was significantly associated with progression to either ABI group., Conclusions: The risk factors for progression to a low or high ABI were distinct and African Americans were at increased risk for progression to a low ABI but at decreased risk for progression into the high ABI group.

Objective: To describe the success of diverse recruitment methods in a randomized controlled clinical trial of exercise in persons with peripheral arterial disease (PAD)., Methods: An analysis of recruitment sources conducted for the 746 men and women completing a baseline visit for the study to improve leg circulation (SILC), a randomized controlled trial of exercise for patients with PAD. For each recruitment source, we determined the number of randomized participants, the rate of randomization among those completing a baseline visit, and cost per randomized participant., Results: Of the 746 individuals who completed a baseline visit, 156 were eligible and randomized. The most frequent sources of randomized participants were newspaper advertising (n = 67), mailed recruitment letters to patients with PAD identified at the study medical center (n = 25), and radio advertising (n = 18). Costs per randomized participant were $2750 for television advertising, $2167 for Life Line Screening, $2369 for newspaper advertising, $3931 for mailed postcards to older community dwelling men and women, and $5691 for radio advertising. Among those completing a baseline visit, randomization rates ranged from 10% for those identified from radio advertising to 32% for those identified from the Chicago Veterans Administration and 33% for those identified from posted flyers., Conclusion: Most participants in a randomized controlled trial of exercise were recruited from newspaper advertising and mailed recruitment letters to patients with known PAD. The highest randomization rates after a baseline visit occurred among participants identified from posted flyers and mailed recruitment letters to PAD patients.

Objective: To compare associations of physical activity during daily life with treadmill walking performance and corridor-based functional performance measures in persons with lower extremity peripheral arterial disease (PAD)., Study Design: Cross-sectional., Subjects: One hundred fifty-six men and women with PAD who completed baseline measurements and were randomized into the study to improve leg circulation (SILC) exercise clinical trial., Main Outcome Measures: Participants completed a Gardner-Skinner treadmill protocol. Corridor-based functional performance measures were the 6-minute walk, walking velocity over four meters at usual and fastest pace, and the short physical performance battery (SPPB) (0-12 scale, 12 = best). Physical activity during daily life was measured continuously over 7 days with a Caltrac (Muscle Dynamics Fitness Network, Inc, Torrence, Calif) accelerometer., Results: Adjusting for age, gender, and race, higher levels of physical activity during daily life were associated with greater distance achieved in the 6-minute walk (P trend = .001), faster fast-paced four-meter walking velocity (P trend < .001), faster usual-paced four-meter walking speed (P trend = .027) and a higher SPPB (P trend = .005). The association of physical activity level with maximum treadmill walking distance did not reach statistical significance (P trend = .083). There were no associations of physical activity with treadmill distance to onset of leg symptoms (P trend = .795)., Conclusion: Functional performance measures are more strongly associated with physical activity levels during daily life than treadmill walking measures.

Objective: This cross-sectional study was set in an academic medical center and conducted to identify associations of physical activity level and walking exercise frequency with calf skeletal muscle characteristics in individuals with lower extremity peripheral arterial disease (PAD)., Methods: Calf muscle characteristics in 439 men and women with PAD were measured with computed tomography at 66.67% of the distance between the distal and proximal tibia. Physical activity was measured continuously during 7 days with a vertical accelerometer. Patient report was used to determine the number of blocks walked during the past week and walking exercise frequency. Results were adjusted for age, sex, race, comorbidities, ankle-brachial index, body mass index, smoking, and other confounders., Results: For both objective and subjective measures, more physically active PAD participants had higher calf muscle area and muscle density. Calf muscle area across tertiles of accelerometer-measured physical activity were first activity tertile, 5071 mm(2); second activity tertile: 5612 mm(2); and third activity tertile, 5869 mm(2) (P < .001). Calf muscle density across tertiles of patient-reported blocks walked during the past week were first activity tertile, 31.4 mg/cm(3); second activity tertile, 33.0 mg/cm(3); and third activity tertile, 33.8 mg/cm(3) (P < .001). No significant associations were found between walking exercise frequency and calf muscle characteristics., Conclusion: Among participants with PAD, higher physical activity levels, measured by accelerometer and by patient-reported blocks walked per week, were associated with more favorable calf muscle characteristics. In contrast, more frequent patient-reported walking exercise was not associated with more or less favorable calf muscle characteristics. Results suggest that clinicians should encourage their patients to increase their walking activity during daily life.

Objective: Several studies report a higher prevalence of peripheral arterial disease (PAD) in women and among blacks. These studies based their PAD definition on an ankle-brachial index (ABI) <0.90. We hypothesized that there is an inherent contribution of gender and ethnicity to normal ABI values, independent of biologic and social disparities that exist between gender and ethnic groups. Consequently, an ABI threshold that disregards these fundamental gender-related and ethnicity-related differences could partly contribute to reported prevalence differences., Methods: A cross-sectional study was designed as part of the Multi-Ethnic Study of Atherosclerosis (MESA), a multicenter United States population study. We selected a subgroup of participants with unequivocally normal ABIs (1.00 to 1.30), and additionally excluded participants with any major PAD risk factor (smoking, diabetes, dyslipidemia, hypertension). In a linear model with ABI as the dependent variable, demographic, clinical, biologic, and social variables were introduced as independent factors., Results: Among 1775 healthy participants, there was no association between ABI level and subclinical cardiovascular disease (coronary calcium or carotid plaque). Male gender, weight, and high education level were positively correlated with ABI, whereas black race, triglycerides, pack-years (in past smokers), and pulse pressure were negatively correlated. In the fully adjusted model, women had about 0.02 lower ABI values than men, and blacks showed ABI values about 0.02 lower than non-Hispanic whites., Conclusion: These data suggest intrinsic ethnic and gender differences in ABI. Such differences, although small in magnitude, are highly significant and can distort population estimates of disease burden.

Background: Our objectives were to determine whether obesity is associated with a greater functional decline compared with the ideal body mass index (BMI) among persons with peripheral arterial disease (PAD) and to determine the associations between weight gain and loss and functional declines in PAD. We hypothesized that baseline obesity and weight gain during follow-up would each be associated with functional declines in persons with PAD., Methods: The design was a prospective cohort study. The subjects were 389 men and women with PAD (mean ankle-brachial index, 0.65 +/- 0.14) who were followed up prospectively for a median of 48 months. The main outcome measures were functional assessments (6-minute walk, usual- and rapid-paced 4-m walking speed, and summary performance score). Weight and height were measured at baseline and annually. Results were adjusted for age, sex, race, comorbidities, ankle-brachial index, education, leg symptoms, exercise status, depressive symptoms, pack-years of cigarette smoking, prior-year functioning, and patterns of missing data., Results: Compared with those with a baseline BMI between 20 and 25 kg/m2, PAD participants with baseline BMI greater than 30 kg/m2 had a significantly greater average annual decline in 6-minute walk performance (-13.1 vs -26.5 m/y; P = .004), usual-paced 4-m walking velocity (-0.028 vs -0.055 m/s per year; P = .024), and fast-paced 4-m walking velocity (-0.053 vs -0.086 m/s per year; P = .012). Persons with weight gain between 5 and 10 pounds after baseline who walked for exercise regularly had significantly less decline in the 6-minute walk than persons without significant weight change who did not walk for exercise (P = .04)., Conclusions: Obesity is associated with functional decline in persons with PAD. Walking exercise may protect against functional decline in PAD persons with modest weight gain.

Purpose: To identify comorbidities associated with increased rates of functional decline in persons with lower-extremity peripheral arterial disease (PAD). We also determined whether female sex and black race were associated with greater functional decline than male sex and white race, respectively, in PAD., Methods: Three-hundred ninety-seven men and women with PAD were followed prospectively for a median of 36 months. The presence of comorbid illnesses was determined with medical record review, patient report, medications, laboratory values, and a primary care physician questionnaire. Functional outcomes, measured annually, included the 6-minute walk, usual-paced and fast-paced 4-meter walking speed, and summary performance score. The summary performance score is a composite measure of lower-extremity functioning (score range, 0 to 12; 12 = best)., Results: Adjusting for known and potential confounders, PAD patients with pulmonary disease had a significantly greater average annual decline in 6-minute walk performance of -34.02 ft/y (95% confidence interval [CI], -60.42 to -7.63; P = .012), rapid-paced 4-meter walk speed of -0.028 m/s/y (95% CI, -0.054 to -0.001; P = .042), and summary performance score of -0.460/y (95% CI, -0.762 to -0.157; P = .003) compared with those without pulmonary disease. PAD patients with spinal stenosis had a greater average annual decline in 6-minute walk performance of -77.4 ft/y (95% CI, -18.9 to -35.8; P < .001) and usual-paced 4-meter walking velocity of -0.045 m/s/y (95% CI, -0.081 to -0.009; P = .014) compared with participants without spinal stenosis., Conclusion: At 3-year follow-up, pulmonary disease and spinal stenosis were each associated with a significant decline in functioning among persons with PAD. In contrast, female sex and black race were not associated with functional decline among persons with PAD.

Objective: The purpose of this study was to determine relationships between lower-extremity arterial obstruction, leg strength, and lower-extremity functioning., Design: The study design was cross-sectional. A total of 514 outpatients (269 with ankle-brachial index [ABI] <0.90), aged 55 and older, were identified from three Chicago-area hospitals. Individuals with history of lower-extremity revascularization were excluded. Main outcome measures Strength in each leg, 6-minute walk, 4-meter walking velocity, accelerometer-measured physical activity, and a summary performance score were measured. The summary performance score is a composite measure of lower-extremity functioning, ranging from 0 to 12 (12 = best). The leg with the lower ABI was defined as the "index" leg, and the leg with higher ABI was defined as the "contralateral" leg., Results: Index leg ABI levels were associated linearly and significantly with strength for hip extension (P <.001), hip flexion (P <.001), knee extension (P =.066), and knee flexion (P =.003), adjusting for known and potential confounders. In adjusted analyses, the index ABI was also associated linearly and significantly with strength in the contralateral leg. Adjusting for confounders, including ABI, knee extension strength, was associated independently with functional measures., Conclusion: Among patients without prior leg revascularization, strength in each leg is highly correlated with the lower-leg ABI. Leg strength is associated independently with functional performance. Further study is needed to determine whether lower-extremity resistance training improves functioning in patients with peripheral arterial disease.

Objective: We compared three commonly used methods of ankle/brachial index (ABI) calculation to determine their relative association with objective measures of leg functioning in peripheral arterial disease., Method: The study design was cross-sectional; the setting was an academic medical center. The participants were 244 men and women, aged 55 years and older, with and without peripheral arterial disease, from a noninvasive vascular laboratory and a general medicine practice. The main outcome measures were walking velocity and endurance, measured with the 4-m walk and the 6-minute walk, respectively. Three methods of ABI calculation were assessed: using the highest arterial pressure within each leg (method #1), using the lowest pressure in each leg (method #2), and averaging the dorsalis pedis and posterior tibial pressures within each leg (method #3). For each method, we established the prevalence of peripheral arterial disease. We then used regression analyses to identify the ABI calculation method most closely associated with leg functioning. The ABI with the greatest statistical significance and largest regression coefficient was considered most closely associated with leg functioning., Results: Peripheral arterial disease prevalence ranged from 47% when method #1 was used to 59% when method #2 was used. When the right and left legs were compared, the leg with the lower ABI, as identified through use of method #3, was most associated with leg functioning. Within the leg with the lower ABI, method #3 was more closely associated with 6-minute walk distance (regression coefficient = 811.5 feet per 1 unit ABI; P<.001) and 4-m walking velocity (regression coefficient = 0.353 m/s per 1 unit ABI; P<.001) than method #1 or method #2., Conclusion: The lower ABI, determined by averaging the dorsalis pedis and posterior tibial arterial pressures in each leg, is most predictive of walking endurance and walking velocity in peripheral arterial disease.

Objectives: The Walking Impairment Questionnaire (WIQ) was designed to measure community walking ability in patients with peripheral arterial disease (PAD) and intermittent claudication. We compared the WIQ scores to objective measures of walking in a heterogeneous group of patients with and without PAD., Methods: The study was designed as a cross-sectional study, with the setting in an academic medical center. The subjects were patients with PAD (n = 145) who were identified from a noninvasive vascular laboratory at an academic medical center. The patients without PAD (n = 65) were identified from a general medicine practice. The average number of comorbidities was 2.03 for patients with PAD and 1.52 for patients without PAD. Among the patients with PAD, 28% had classical intermittent claudication symptoms and 55% had exertional leg symptoms other than claudication. The main outcome measures were the WIQ estimates of the patient-reported walking distance and walking speed on a scale of 0 to 100. Walking endurance was measured objectively with the 6-minute walk. Walking velocity was measured with a 4-m walk. PAD and PAD severity were defined with the ankle brachial index., Results: The Spearman rank correlation coefficients (rho) between the WIQ distance score and the 6-minute walk score were 0.557 among patients with PAD (P <.001) and 0.484 among patients without PAD (P <.001). The correlation coefficients between the WIQ speed score and the usual-paced 4-m walk score were 0.528 among patients with PAD (P <.001) and 0.524 among patients without PAD (P <.001). The correlations were not affected by the presence versus the absence of intermittent claudication, by PAD severity, or by the presence of 2 or more versus less than 2 comorbid illnesses. The WIQ scores in the highest and lowest quartiles were the most closely associated with the objective measures of function., Conclusion: The WIQ is a valid measure of community walking ability in a heterogeneous group of patients with and without PAD. The WIQ discriminates best among patients in the highest and the lowest quartiles of walking speed and endurance.