Maximal calf conductance is associated with 6-minute walk distance in participants with and without peripheral artery disease.

INTRODUCTION: The aims were (a) to compare the maximal calf conductance and 6-minute walk distance of participants with and without peripheral artery disease (PAD) and claudication, (b) to determine whether maximal calf conductance was more strongly associated with 6-minute walk distance in participants with PAD than in the controls, and (c) to determine whether this association was significant in participants with PAD after adjusting for ABI, as well as for demographic, anthropometric, and comorbid variables. METHODS: Participants with PAD (n = 633) and without PAD (n = 327) were assessed on maximal calf conductance using venous occlusion plethysmography, and on 6-minute walk distance. Participants were further characterized on ABI, and on demographic, anthropometric, and comorbid variables. RESULTS: The PAD group had lower maximal calf conductance than the control group (0.136 ± 0.071 vs 0.201 ± 0.113 mL/100 mL/min/mmHg, p < 0.001). Additionally, the PAD group had a lower 6-minute walk distance (375 ± 98 m vs 480 ± 107 m, p < 0.001). Maximal calf conductance was positively associated with 6-minute walk distance in both groups (p < 0.001) and was more strongly associated in the PAD group (p < 0.001). In adjusted analyses, maximal calf conductance remained positively associated with 6-minute walk distance in the PAD group (p < 0.001) and in the control group (p < 0.001). CONCLUSIONS: Participants with PAD and claudication had impaired maximal calf conductance and a lower 6-minute walk distance than those without PAD, and maximal calf conductance was positively and independently associated with 6-minute walk distance within each group before and after adjusting for ABI, and for demographic, anthropometric, and comorbid variables.

Microvascular dysfunction and neurovascular uncoupling are exacerbated in peripheral artery disease, increasing the risk of cognitive decline in older adults.

Peripheral artery disease (PAD) is a vascular pathology with high prevalence among the aging population. PAD is associated with decreased cognitive performance, but the underlying mechanisms remain obscure. Normal brain function critically depends on an adequate adjustment of cerebral blood supply to match the needs of active brain regions via neurovascular coupling (NVC). NVC responses depend on healthy microvascular endothelial function. PAD is associated with significant endothelial dysfunction in peripheral arteries, but its effect on NVC responses has not been investigated. This study was designed to test the hypothesis that NVC and peripheral microvascular endothelial function are impaired in PAD. We enrolled 11 symptomatic patients with PAD and 11 age- and sex-matched controls. Participants were evaluated for cognitive performance using the Cambridge Neuropsychological Test Automated Battery and functional near-infrared spectroscopy to assess NVC responses during the cognitive n-back task. Peripheral microvascular endothelial function was evaluated using laser speckle contrast imaging. We found that cognitive performance was compromised in patients with PAD, evidenced by reduced visual memory, short-term memory, and sustained attention. We found that NVC responses and peripheral microvascular endothelial function were significantly impaired in patients with PAD. A positive correlation was observed between microvascular endothelial function, NVC responses, and cognitive performance in the study participants. Our findings support the concept that microvascular endothelial dysfunction and neurovascular uncoupling contribute to the genesis of cognitive impairment in older PAD patients with claudication. Longitudinal studies are warranted to test whether the targeted improvement of NVC responses can prevent or delay the onset of PAD-associated cognitive decline.NEW & NOTEWORTHY Peripheral artery disease (PAD) was associated with significantly decreased cognitive performance, impaired neurovascular coupling (NVC) responses in the prefrontal cortex (PFC), left and right dorsolateral prefrontal cortices (LDLPFC and RDLPFC), and impaired peripheral microvascular endothelial function. A positive correlation between microvascular endothelial function, NVC responses, and cognitive performance may suggest that PAD-related cognitive decrement is mechanistically linked, at least in part, to generalized microvascular endothelial dysfunction and subsequent impairment of NVC responses.

Light and moderate intensity physical activity are associated with better ambulation, quality of life, and vascular measurements in patients with claudication.

OBJECTIVE: We sought to determine whether patients with claudication who reported performing either light intensity physical activity (LPA) or moderate-to-vigorous intensity physical activity (MVPA) would have higher levels of objectively determined physical activity and better physical function, health-related quality of life (HRQoL), and vascular measures, consisting of exercise time to minimum calf muscle oxygen saturation (StO2) and high-sensitivity C-reactive protein, than patients who reported being physically sedentary. METHODS: A total of 269 patients were assessed using the Johnson Space Center physical activity scale. The patients were grouped according to whether they performed no physical activities (n = 75), LPAs (n = 140), or MVPAs (n = 54). The primary measurements were the total daily steps obtained from a step activity monitor worn for 1 week, peak walking time obtained from a treadmill test, physical function score on the Medical Outcomes Study short-form 36-item survey to assess HRQoL, and high-sensitivity C-reactive protein. RESULTS: The total daily steps was significantly different among the groups. Both the LPA group (mean ± standard deviation, 7878 ± 2808 steps/d) and the MVPA group (mean, 8551 ± 3365 steps/d) had taken more daily steps (P < .01) than had the sedentary group (mean, 3323 ± 986 steps/d). The treadmill peak walking time was significantly different among the three groups. Both the LPA group (433 ± 296 seconds) and the MVPA group (548 ± 300 seconds) had had a greater peak walking time (P < .01) than that of the sedentary group (302 ± 210 seconds). The physical function score was also significantly different among the groups. The LPA group (44% ± 20%) and MVPA group (58% ± 19%) both had had higher scores (P < .01) than the sedentary group (36% ± 20%). In addition, the exercise time to the minimum calf muscle StO2 was significantly different among the groups. Both the LPA group (215 ± 238 seconds) and the MVPA group (377 ± 351 seconds) had had greater values (P < .05 and P < .01, respectively) than the sedentary group (147 ± 172 seconds). Finally, the high-sensitivity C-reactive protein level was significantly different among the groups. Both the LPA group (4.8 ± 5.5 mg/L) and the MVPA group (3.5 ± 3.6 mg/L) had had lower values (P < .01) than the sedentary group (8.6 ± 8.4 mg/L). CONCLUSIONS: Patients with claudication who reported performing LPA had greater amounts of objectively determined physical activity levels and better physical function, HRQoL, and vascular measures than those who reported being physically sedentary. Furthermore, these favorable results associated with LPA were even more pronounced for the patients who performed MVPA compared with those who were sedentary. The clinical significance is that our results have shown that engaging in any physical activity, even at relatively light intensity, is associated with favorable health and vascular measures for patients with claudication.

Minimal clinically important differences in daily physical activity outcomes following supervised and home-based exercise in peripheral artery disease.

Introduction: We estimated minimal clinically important differences (MCID) for small, moderate, and large changes in daily step counts and time spent in moderate-to-vigorous physical activity (MVPA) following both supervised and home-based exercise programs in symptomatic patients with peripheral artery disease (PAD). Methods: Patients were randomized to either 12 weeks of a supervised exercise program (n = 60), a home-based exercise program (n = 60), or an attention-control group (n = 60). Results: Using the anchor-based method to determine MCID, the MCID value for a large change in health-related quality of life (HRQoL) was an increase of 1211 total daily steps and an increase in 11 minutes in the time spent in MVPA following 12 weeks of exercise intervention. Using the distribution-based method, the MCID values for small, moderate, and large changes in total daily steps in the home-based exercise group were 558, 1396, and 2233 steps/d, respectively, and the corresponding changes in the time spent in MVPA were 6, 15, and 23 minutes. Similar distribution-based MCID scores were noted for the supervised exercise group. Conclusion: Following 3 months of home-based and supervised exercise programs for patients with PAD and claudication, increases of 11 minutes in time spent in MVPA and 1211 total daily steps were associated with large anchor-based MCID increases in HRQoL. The clinical implication is that patients with PAD and claudication should be encouraged to increase daily steps, particularly by walking an additional 11 minutes each day in MVPA, which is associated with a large meaningful increase in HRQoL.

Association between meeting daily step count goals with ambulatory function and quality of life in patients with claudication.

OBJECTIVE: To determine (a) whether patients with peripheral artery disease (PAD) who walked at least 7000 and 10,000 steps/day had better ambulatory function and health-related quality of life (HRQoL) than patients who walked less than 7000 steps/day, and (b) whether differences in ambulatory function and HRQoL in patients grouped according to these daily step count criteria persisted after adjusting for covariates. METHODS: Two hundred forty-eight patients were assessed on their daily ambulatory activity for 1 week with a step activity monitor, and were grouped according to daily step count targets. Patients who took fewer than 7000 steps/day were included in group 1 (n = 153), those who took 7000 to 9999 steps/day were included in group 2 (n = 57), and patients who took at least 10,000 steps/day were included in group 3 (n = 38). Primary outcomes were the 6-minute walk distance (6MWD) and Walking Impairment Questionnaire (WIQ) distance score, which is a disease-specific measurement of HRQoL. Patients were further characterized on demographic variables, comorbid conditions, and cardiovascular risk factors. RESULTS: The groups were significantly different on ankle-brachial index (P = .02), and on the prevalence of hypertension (P = .04), diabetes (P < .01), abdominal obesity (P < .01), arthritis (P = .04), and chronic obstructive pulmonary disease (P < .01). Thus, these variables served as covariates in adjusted analyses, along with age, weight, and sex. The 6MWD (mean ± standard deviation) was significantly different among the groups in unadjusted (P < .01) and adjusted (P < .01) analyses (group 1, 313 ± 90 m; group 2, 378 ± 84 m; and group 3, 414 ± 77 m), with groups 2 and 3 having a higher 6MWD than group 1 (P < .01). The WIQ distance score was significantly different among the groups in unadjusted (P < .01) and adjusted (P < .01) analyses (group 1, 30 ± 30%; group 2, 45 ± 35%; and group 3, 47 ± 34%), with groups 2 and 3 having higher WIQ distance scores than group 1 (P < .01). CONCLUSIONS: Patients with PAD who walked more than 7000 and 10,000 steps/day had greater ambulatory function and HRQoL than patients who walked fewer than 7000 steps/day. Second, the greater ambulatory function and HRQoL associated with walking 7000 and 10,000 steps/day persisted after adjusting for covariates. This study provides preliminary evidence that patients with PAD who walk more than 7000 steps/day have better ambulatory function and HRQoL than patients below this threshold.

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

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.

Association between calf muscle oxygen saturation with ambulatory function and quality of life in symptomatic patients with peripheral artery disease.

OBJECTIVE: The objective of this study was to determine whether calf muscle hemoglobin oxygen saturation (Sto2) obtained during a standardized treadmill test is associated with ambulatory function and health-related quality of life (HRQoL) in patients with symptomatic peripheral artery disease (PAD). We hypothesized that a rapid decline in calf muscle Sto2 during walking is associated with impaired ambulatory function and HRQoL and that these associations are independent of ankle-brachial index (ABI). METHODS: Calf muscle Sto2, peak walking time, and claudication onset time were obtained during a treadmill test in 151 symptomatic men and women with PAD. Patients were further characterized by demographic variables, comorbid conditions, cardiovascular risk factors, ABI, 6-minute walk distance, daily ambulatory activity, Walking Impairment Questionnaire (WIQ) score, and Medical Outcomes Study 36-Item Short Form Health Survey physical function score to assess HRQoL. RESULTS: The median calf muscle Sto2 value at rest was 52%, which declined to 22% after only 1 minute of walking during the treadmill test and reached a minimum value of 9% after a median time of 87 seconds of walking. Of the various calf muscle Sto2 measurements obtained during the treadmill test, the exercise time to the minimum calf muscle Sto2 value (log transformed) had the strongest univariate associations with peak walking time (r = 0.56; P < .001), claudication onset time (r = 0.49; P < .001), 6-minute walk distance (r = 0.31; P < .001), WIQ distance score (r = 0.33; P < .001), WIQ speed score (r = 0.39; P < .001), WIQ stair-climbing score (r = 0.37; P < .001), and Medical Outcomes Study 36-Item Short Form Health Survey physical function score (r = 0.32; P < .001). In adjusted multiple regression models, these associations persisted (P < .001) after adjustment for demographic measures, cardiovascular risk factors, comorbid conditions, and ABI. CONCLUSIONS: More rapid decline in oxygen saturation of the calf musculature during walking, indicative of impaired microcirculation, is predictive of impaired ambulatory function and HRQoL in patients with symptomatic PAD. Of particular importance, these associations are independent of ABI and other common health burdens, highlighting the clinical relevance that the microcirculation has on ambulatory function and HRQoL in patients with symptomatic PAD.

Diet is associated with ankle-brachial index, inflammation, and ambulation in patients with intermittent claudication.

OBJECTIVE: The aims of this investigation were to determine whether the daily dietary intake of nutrients by patients with peripheral artery disease (PAD) and intermittent claudication (IC) met recommended levels for adults older than 50 years and to determine whether meeting recommended levels of nutrients was associated with ankle-brachial index (ABI), inflammation, and ambulation of patients with PAD and IC. METHODS: A total of 48 patients were assessed on their dietary intake of 20 nutrients during a 3-day period. Patients were further characterized on demographic variables, comorbid conditions, cardiovascular risk factors, ABI, 6-minute walk distance (6MWD), and high-sensitivity C-reactive protein (hsCRP) concentration. RESULTS: Few patients met the daily recommended intakes for calcium (4%), fiber (6%), vitamin E (6%), trans fatty acids (13%), vitamin A (15%), total sugars (19%), potassium (23%), sodium (29%), saturated fat (29%), and vitamin C (31%), and none of the patients met the daily recommended intake of vitamin D (0%). Overall, patients met few of the 20 dietary recommendations as the median score was seven recommendations. Only 17 of 48 patients met more than seven of the recommendations. For the ABI regression model adjusted for age, sex, race, smoking, hypertension, dyslipidemia, body mass index, and percentage body fat, the only significant predictor was total sugars (P < .001); patients who did not meet the recommendation had lower ABI values. For the hsCRP-adjusted regression model, the strongest significant predictor was omega-3 polyunsaturated fatty acids (P = .001), indicating that those who did not meet the recommendation had higher hsCRP values. Finally, for the 6MWD-adjusted regression model, folate (P = .011) and dietary score index (P = .014) were significant predictors; those who did not meet the recommendation for folate and those who met 5 or fewer of the 20 recommendations had shorter 6MWD. CONCLUSIONS: Patients with PAD and IC consume a low-nutrient-dense diet that is deficient in many vitamins, calcium, fruits, and vegetables and contains too much added sugar, saturated and trans fats, and processed foods. In addition, more severe PAD, greater inflammation, and ambulatory dysfunction are independently associated with aspects of a low-nutrient-dense diet, such as too much intake of added sugars, low intake of omega-3 polyunsaturated fatty acids and folate, and meeting the recommended intakes of only five or fewer nutrients.

Changes in vascular and inflammatory biomarkers after exercise rehabilitation in patients with symptomatic peripheral artery disease.

OBJECTIVE: Home-based exercise is an alternative exercise mode to a structured supervised program to improve symptoms in patients with peripheral artery disease (PAD), but little is known about whether the slow-paced and less intense home program also elicits changes in vascular and inflammatory biomarkers. In an exploratory analysis from a randomized controlled trial, we compared changes in vascular and inflammatory biomarkers in patients with symptomatic PAD (typical and atypical of claudication) after home-based exercise and supervised exercise programs and in an attention-control group. METHODS: A total of 114 patients were randomized into one of the three groups (n = 38 per group). Two groups performed exercise interventions, consisting of home-based and supervised programs of intermittent walking to mild to moderate claudication pain for 12 weeks; a third group performed light resistance training as a nonwalking attention-control group. Before and after intervention, patients were characterized on treadmill performance and endothelial effects of circulating factors present in sera by a cell culture-based bioassay on primary human arterial endothelial cells, and they were further evaluated on circulating vascular and inflammatory biomarkers. RESULTS: Treadmill peak walking time increased (P = .008) in the two exercise groups but not in the control group (P > .05). Cultured endothelial cell apoptosis decreased after home-based exercise (P < .001) and supervised exercise (P = .007), and the change in the exercise groups combined was different from that in the control group (P = .005). For circulating biomarkers, increases were found in hydroxyl radical antioxidant capacity (P = .003) and vascular endothelial growth factor A (P = .037), and decreases were observed in E-selectin (P = .007) and blood glucose concentration (P = .012) after home-based exercise only. The changes in hydroxyl radical antioxidant capacity (P = .005), vascular endothelial growth factor A (P = .008), and E-selectin (P = .034) in the exercise groups combined were different from those in the control group. CONCLUSIONS: This exploratory analysis found that both home-based and supervised exercise programs are efficacious to decrease cultured endothelial cell apoptosis in patients with symptomatic PAD. Furthermore, a monitored home-based exercise program elicits additional vascular benefits by improving circulating markers of endogenous antioxidant capacity, angiogenesis, endothelium-derived inflammation, and blood glucose concentration in patients with symptomatic PAD. The novel clinical significance is that important trends were found in this exploratory analysis that a contemporary home-based exercise program and a traditional supervised exercise program may favorably improve vascular and inflammatory biomarkers in addition to the well-described ambulatory improvements in symptomatic patients with PAD.

Predictors of health-related quality of life in patients with symptomatic peripheral artery disease.

OBJECTIVE: The aim of this study was to identify predictors of baseline measures of health-related quality of life (HRQoL) in symptomatic patients with peripheral artery disease (PAD) from objective markers of severity of PAD, clinical and demographic characteristics, comorbid conditions, cardiovascular risk factors, objectively measured physical activity, and patient-based measures of physical function. METHODS: HRQoL measurements of 216 symptomatic men and women with PAD were assessed with the Medical Outcomes Study 36-Item Short Form Health Survey. Patients were further characterized on demographic variables, comorbid conditions, cardiovascular risk factors, ankle-brachial index, peak walking time during a maximal treadmill test, 6-minute walk distance, gait speed, ambulatory activity monitored during 1 week, activities of daily living (ADLs), Mini-Mental State Examination questionnaire, and Walking Impairment Questionnaire (WIQ). RESULTS: For the physical function HRQoL subscale, the significant predictors included WIQ speed score (P < .001), history of stumbling (P < .001), WIQ stair climbing score (P < .001), ADL associated with bathing (P = .001), 6-minute walk distance (P = .004), and daily walking cadence (P = .043). For the role emotional function HRQoL subscale, the significant predictors included a history of stumbling (P < .001), the ADL associated with transferring from a bed to a chair (P < .001), and the WIQ distance score (P = .022). CONCLUSIONS: Physical and mental subscales of HRQoL in symptomatic patients with PAD are primarily predicted by patient-based physical function rather than by more specific markers of PAD severity and comorbid conditions. The clinical significance is that interventions designed to improve HRQoL should focus on improving the quality of executing functional tasks, such as walking more steadily without stumbling; completing ADLs that are not specific to walking, such as bathing and transferring; and improving patient-based ability to walk various distances and speeds and to climb stairs.

Minimal clinically important differences in treadmill, 6-minute walk, and patient-based outcomes following supervised and home-based exercise in peripheral artery disease.

We estimated minimal clinically important differences (MCIDs) for small, moderate, and large changes in measures obtained from a standardized treadmill test, a 6-minute walk test, and patient-based outcomes following supervised and home-based exercise programs in symptomatic patients with peripheral artery disease (PAD). Patients were randomized to either 12 weeks of a supervised exercise program ( n=60), a home-based exercise program ( n=60), or an attention-control group ( n=60). Using the distribution-based method to determine MCIDs, the MCIDs for small, moderate, and large changes in peak walking time (PWT) in the supervised exercise group were 38, 95, and 152 seconds, respectively, and the changes in claudication onset time (COT) were 35, 87, and 138 seconds. Similar MCID scores were noted for the home-based exercise group. An anchor-based method to determine MCIDs yielded similar patterns of small, moderate, and large change scores in PWT and COT, but values were 1-2 minutes longer than the distribution approach. In conclusion, 3 months of supervised and home-based exercise programs for symptomatic patients with PAD results in distribution-based MCID small, moderate, and large changes ranging from 0.5 and 2.5 minutes for PWT and COT. An anchor-based approach yields higher MCID values, ranging from a minimum of 73 seconds for COT to a maximum of 4 minutes for PWT. The clinical implication is that a goal for eliciting MCIDs in symptomatic PAD patients through a walking exercise intervention is to increase PWT and COT by up to 4 minutes, which corresponds to two work stages during the standardized progressive treadmill test.

Sarcopenia in Peripheral Arterial Disease: Prevalence and Effect on Functional Status.

OBJECTIVES: (1) To determine the prevalence of sarcopenia in older men with peripheral arterial disease (PAD); (2) to compare a subgroup of the group with age-, race-, sex-, and body mass index (BMI)-matched non-PAD control counterparts, and (3) to compare the functional status of those with PAD with and without sarcopenia. DESIGN: Cohort study. SETTING: Medical center. PARTICIPANTS: Sedentary community-dwelling men (N=108; age, >50y) with a confirmed diagnosis of PAD (44% blacks; BMI, 27.8±0.4kg/m2; ankle-brachial index, .62±.01). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry scans were used to assess appendicular lean mass and determine the prevalence of sarcopenia by/height2. Treadmill tests were used to determine claudication onset time, peak walking time, and claudication recovery time. 6-Minute walk distance was also measured. RESULTS: Sarcopenia prevalence in our PAD cohort was 25%. The PAD subgroup (n=42) matched with control counterparts in terms of race, sex, age, and BMI had higher prevalence rates than did their non-PAD counterparts (23.8% vs 2.4%; P<.05). Individuals with sarcopenia (n=28) had a shorter 6-minute walk distance (326±18.8m vs 380±9.7m; P<.05) and higher claudication recovery time (592±98s vs 395±29s; P<.05) than did individuals with PAD but without sarcopenia (n=80). There was no difference in claudication onset time or peak walking time between the PAD groups. CONCLUSIONS: Men with PAD demonstrate a high prevalence of sarcopenia. Those with sarcopenia and PAD demonstrate decreased mobility function.

Calf Muscle Oxygen Saturation during 6-Minute Walk Test and Its Relationship with Walking Impairment in Symptomatic Peripheral Artery Disease.

BACKGROUND: Impaired microcirculation is associated with poor walking capacity in symptomatic peripheral artery disease (PAD) patients during treadmill test; however, this test does not simulate the efforts of daily walking of these patients. Thus, the aim of the study was to describe the microcirculation responses during a 6-minute walk test (6MWT) and to analyze the relationship between microcirculation indicators and walking impairment in symptomatic PAD patients. METHODS: Thirty-four patients were included (mean age = 67.6 ± 11.2 years). Their clinical characteristics were collected, and they performed a 6MWT, in which the initial claudication distance (ICD) and total walking distance (TWD) were recorded. During and after the 6MWT, calf muscle oxygen saturation (StO2) parameters were monitored continuously to measure microcirculation behavior. The association between calf muscle StO2 parameters and walking impairment were analyzed by Pearson or Spearman correlations. RESULTS: Walking impairment was not associated with any StO2 parameters during exercise. In contrast, after 6MWT, recovery time of StO2 (r = -0.472, P = 0.008) and recovery time to maximal StO2 (r = -0.402, P = 0.019) were negatively correlated with ICD. Furthermore, the distance walked under claudication symptoms (ΔTWD-ICD) was positively correlated with recovery time to maximal StO2 (r = 0.347, P = 0.048). CONCLUSIONS: In symptomatic PAD patients, shorter ICD values during a 6MWT are associated with a delayed recovery in calf muscle StO2 after exercise. Calf muscle StO2 parameters decrease subtly during 6MWT, suggesting that the degree of ischemia in the calf muscle during ground walking, simulating efforts of the daily walking, is relatively low.

Association between daily walking and antioxidant capacity in patients with symptomatic peripheral artery disease.

OBJECTIVE: The primary aim of the study was to assess whether both the amount and pace of daily walking were associated with circulating antioxidant capacity in symptomatic patients with peripheral artery disease (PAD). METHODS: Community-based walking was measured in 244 men and women who were limited by symptomatic PAD during a 1-week period in which they wore an ankle-mounted step activity monitor. Patients were further characterized by circulating antioxidant capacity with the OxiSelect (Cell Biolabs Inc, San Diego, Calif) hydroxyl radical antioxidant capacity (HORAC) activity assay. RESULTS: To assess the amount of walking, patients were grouped into low (≤2440 strides/d), middle (2441-3835 strides/d), and high (>3835 strides/d) stride tertiles. HORAC was higher in the middle (P = .03) and high (P = .01) stride tertiles than in the low tertile, but there was no difference between middle and high tertiles (P = .44). To assess the pace of walking, patients were grouped into slow (<25.0 strides/min), middle (25.0-31.6 strides/min), and fast (>31.6 strides/min) cadence tertiles. HORAC was higher in the high cadence tertile than in the low (P < .01) and middle (P < .01) tertiles, but there was no difference between low and middle tertiles (P = .48). Similar findings were obtained on group differences in HORAC after adjusting for age, sex, race, and ankle-brachial index for both the amount and pace of daily walking. CONCLUSIONS: Walking >2440 strides each day and walking at a cadence faster than 31.6 strides/min for 30 minutes each day are both associated with greater circulating antioxidant capacity in symptomatic patients with PAD. The clinical significance is that a home-based walking program may be one approach to increase endogenous antioxidant capacity.

Prediction of 6-minute walk performance in patients with peripheral artery disease.

BACKGROUND: Peripheral artery disease (PAD) is a highly prevalent disease that impairs walking ability. Walking tests, such as the 6-minute walk test (6MWT) and 4-meter walk test, are commonly used to assess exercise endurance and ambulatory function over a short distance, respectively. The 6MWT performance is predictive of PAD severity and disease outcomes, but it is not feasible in many clinical settings because it requires a long walkway to serve as the test route and lengthens clinic visits. As an alternative, the 4-meter walk test is convenient, inexpensive, and repeatable, but whether it accurately predicts endurance performance in the long-distance 6MWT is not known. The goal of this study was to develop a statistical model to predict 6MWT gait speed from 4-meter walk test results and clinical characteristics among patients with PAD. METHODS: Measures of 6MWT gait speed were derived from 183 patients with symptomatic PAD who were evaluated at the University of Oklahoma Health Sciences Center (2004-2012). The testing procedures and research personnel remained constant throughout the duration of the study. Independent variables included demographic and clinical information and 4-meter walk test gait speed. Fivefold cross validation and manual backward selection were used for model selection. Adjusted R2 and corrected Akaike information criterion were applied to quantify the predictive performance of the regression models. RESULTS: A total of 183 people (54% male; mean age, 65 [standard deviation (SD), 10] years) with moderate PAD severity (ankle-brachial index [ABI]; mean, 0.72 [SD, 0.24]) performed the walking tests. Participants covered an average distance of 335 (SD, 97) m distance in the 6MWT. The 4-meter walk gait speed, ABI, and dyspnea were independent predictors of 6MWT speed in the multivariate model (adjusted R2 = 0.55). The model resulted in 95% prediction interval widths of 30 m for mean and 260 m for individual predicted 6MWT distance measures. CONCLUSIONS: Slower 4-meter walking speed, lower ABI, and presence of dyspnea all predict slower 6MWT gait speed, which corresponds to shorter 6MWT distance. Prediction of group means is reasonably precise; however, prediction of individual patient 6MWT performance is imprecise relative to between-group differences that are clinically important.

Effect of cognitive status on exercise performance and quality of life in patients with symptomatic peripheral artery disease.

BACKGROUND: We determined whether scores on a cognitive screening measure were associated with the primary outcome measure of peak walking time (PWT) and with secondary outcome measures related to mobility, community-based ambulation, health-related quality of life (QoL), and vascular function in patients with claudication and peripheral artery disease (PAD). METHODS: Gross cognitive status of 246 PAD patients was assessed with the Mini-Mental State Examination (MMSE) questionnaire. Patients were grouped according to whether they had a perfect MMSE score of 30 points (n = 123) or whether they missed one or more points (n = 123). Patients were characterized on numerous outcomes, including PWT during a treadmill test and QoL. RESULTS: Compared with the group with the higher MMSE scores, there was a trend for lower PWT in the group with the lower MMSE scores (P = .06) after adjusting for age, sex, race, and education level (model 1), which became significant (380 ± 250 seconds vs 460 ± 270 seconds; P < .05) after adjusting for model 1 plus coronary artery disease, chronic obstructive pulmonary disease, and arthritis (model 2). Multiple domains of QoL were lower (P < .05) in the group with the lower MMSE scores after adjusting for model 1, but only mental health remained lower (75 ± 20% vs 80 ± 5%; P = .02) after further adjustment with model 2. CONCLUSIONS: In symptomatic patients with PAD, lower cognitive screening scores were associated with greater ambulatory impairment than in patients with higher MMSE scores. Furthermore, worse cognitive status was associated with lower scores in multiple dimensions of health-related QoL, all of which except mental health were explained by the comorbid conditions of coronary artery disease, chronic obstructive pulmonary disease, and arthritis. The clinical significance is that there is a need for enhanced cognitive and mental health screening as potential indicators of poor outcome among symptomatic patients with PAD. Furthermore, patients identified as having worse cognitive status might be in greatest need of intervention to improve ambulation and QoL related to mental health.

Sedentary behavior is associated with impaired biomarkers in claudicants.

OBJECTIVE: Time spent in sedentary behavior has been associated with worse inflammation and cardiometabolic biomarkers in various populations. However, the association between time spent in sedentary behavior and biomarkers remains unknown in patients with intermittent claudication. The aim of the current study was to analyze the relationship between sedentary behavior and inflammatory and cardiometabolic biomarkers in patients with symptomatic peripheral arterial disease (PAD). METHODS: The sample included 297 patients with intermittent claudication. Sedentary behavior was assessed using a step activity monitor. Biomarkers of inflammation, oxidative stress, lipid profile, insulin resistance, and endogenous fibrinolysis were assessed. Demographic data, body mass index, physical activity status, and measures of severity of PAD (ankle-brachial index, peak walking time, and ischemic window) also were obtained. RESULTS: Time spent in sedentary behavior was related with high-sensitivity C-reactive protein (b = 0.187; P = .005), glucose (b = 0.238; P < .001), fibrinogen (b = 0.167; P = .017), plasminogen activator inhibitor 1 activity (b = 0.143; P = .036), and high-density lipoprotein cholesterol (b = -0.133; P = .029). After adjustment for sex, age, physical activity status, body mass index, and severity of PAD, sedentary behavior remained related with high-sensitivity C-reactive protein (b = 0.170; P = .015), glucose (b = 0.178; P = .004), fibrinogen (b = 0.189; P = .010), and high-density lipoprotein cholesterol (b = -0.128; P = .032). CONCLUSIONS: Time spent in sedentary activities was associated with worse inflammatory and cardiometabolic profile in patients with intermittent claudication.

Differences in galectin-3, a biomarker of fibrosis, between participants with peripheral artery disease and participants with normal ankle-brachial index.

The aim of this study was to determine if galectin-3 levels were different between participants with peripheral artery disease (PAD) and controls, and to describe its relationship with markers of early atherosclerosis. Sixty participants were recruited into two groups: a PAD group (n=31), ankle-brachial index (ABI) ⩽0.90 and a normal ABI group (n=29), ABI 1.0-1.4. PAD participants were older (68.6 vs 61.8 years, p=0.037), more commonly men (68% vs 38%, p=0.02), and with more cardiovascular risk factors (p<0.001). Galectin-3 was 22% higher in PAD participants (mean±SD: 17.6±4.7 vs 14.4±4.1 ng/mL, p<0.01). The odds ratio for galectin-3 in PAD to be 1 ng/mL higher than the participants with normal ABI was 1.19, after adjusting by age and gender (p=0.014). High-sensitivity C-reactive protein (hs-CRP) and homeostatic model assessment (HOMA) were positively associated with galectin-3 in the age- and gender-adjusted model, while arterial elasticity and microalbuminuria were not. In conclusion, galectin-3 levels were higher in participants with PAD.

Gender and racial differences in endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease.

BACKGROUND: We compared (1) cellular reactive oxygen species (ROS) production, inflammation, and apoptosis of cultured endothelial cells treated with sera and (2) circulating inflammatory measures, antioxidant capacity, vascular biomarkers, and calf muscle hemoglobin oxygen saturation (StO2) in men and women with peripheral artery disease (PAD). A secondary aim was to compare exercise performance and daily ambulatory activity between men and women. We hypothesized that women would have more impaired endothelial cellular ROS, inflammation, and apoptosis than men as well as worse systemic inflammation, antioxidant capacity, vascular biomarkers, calf muscle StO2, exercise performance, and daily ambulatory activity. METHODS: The 148 symptomatic men and women with PAD were characterized on the endothelial effects of circulating factors present in the sera by a cell culture-based bioassay on primary human arterial endothelial cells. Patients were further evaluated by circulating inflammatory and vascular biomarkers, physical examination and medical history, exercise performance, and calf muscle StO2 during exercise, and ambulatory activity was monitored during 1 week. RESULTS: Cellular ROS production was higher in African American women than in men (P = .021), but there was no gender difference in white individuals (P = .537). Men and women were not significantly different on endothelial cell apoptosis (P = .833) and nuclear factor κB activity (P = .465). For circulating factors, additional gender differences were found when comparisons were made within each race. In African Americans, women had higher intercellular adhesion molecule 1 (P = .022) and leptin (P < .001); whereas in white individuals, women had higher matrix metallopeptidase 9 (P = .047), higher vascular cell adhesion molecule 1 (P = .047), and lower hepatocyte growth factor (P = .046). Overall, women had higher apolipoprotein CIII (P = .035), lower pain-free distance (P = .048) and total distance (P < .001) during the 6-minute walk test, shorter time for calf muscle StO2 to reach the minimum value during exercise (P = .027), and slower average cadence (P = .004) during daily ambulation. CONCLUSIONS: African American women with symptomatic PAD have a heightened oxidative status, likely resulting in increased endothelial oxidative stress, compared with men. Furthermore, women exhibit a more pronounced proinflammatory profile of circulating biomarkers as well as more limited peripheral microcirculation, exercise performance, and ambulatory activity than men do. The clinical significance is that women with symptomatic PAD are in greater need than men of clinical intervention to improve oxidative stress, inflammation, and microcirculation, which may in turn have a favorable impact on their lower exercise performance and daily activity.