Effects of Long-Term Home Exercise in Participants With Peripheral Artery Disease.

Background This randomized controlled trial compared long-term changes in peak walking time (PWT) and exercise time-to-minimum calf muscle oxygen saturation (StO2) in symptomatic participants with peripheral artery disease following a long-term home exercise program (HEP), a short-term supervised exercise therapy (SET) program that transitioned to a long-term HEP (SET/HEP), and a control intervention. Methods and Results For the first 3 months, HEP and SET/HEP groups performed intermittent walking to mild-to-moderate claudication pain, whereas the control group performed light resistance training. For the subsequent 15 months, the HEP group continued their exercise program, the SET/HEP group transitioned from SET to the HEP program, and the control group transitioned to only receive walking advice. PWT increased significantly from baseline to month 18 in the HEP group (408±279 meters to 814±393 meters, P<0.001) and in the SET/HEP group (457±288 meters to 818±313 meters, P<0.001). Exercise time-to-minimum calf muscle StO2 increased significantly from baseline to month 18 in the HEP group (238±241 seconds to 497±485 seconds, P<0.05) and in the SET/HEP group (296±289 seconds to 620±450 seconds, P<0.001). These changes in PWT and exercise time-to-minimum calf muscle StO2 were greater than in the control group (P<0.001 and P<0.01, respectively). Additionally, the change in exercise time-to-minimum calf muscle StO2 was correlated with the change in PWT in both exercise groups combined (r=0.601, P=0.0015). Conclusions Long-term HEP and SET/HEP were efficacious in improving PWT and exercise time-to-minimum calf muscle StO2 in symptomatic participants with peripheral artery disease, and these changes were correlated with each other. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00618670.

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.

Diabetes Is Negatively Associated With Meeting Physical Activity Time-Intensity Guidelines in Patients With Claudication.

PURPOSES: We determined the percentage of patients with peripheral artery disease (PAD) and claudication who meet the 2018 physical activity (PA) time-intensity guidelines, and we identified the clinical characteristics associated with the status of meeting the guidelines. METHODS: Five hundred seventy-two patients were assessed on their daily ambulatory activity for 1 wk with a step activity monitor, and were evaluated on whether or not they achieved 150 min/wk of moderate-intensity PA. RESULTS: Thirty-one percent (n = 175) of the patients with PAD met the PA time-intensity guidelines and 69% (n = 397) did not. In a final multivariable logistic regression model identifying the independent predictors of meeting the PA time-intensity guidelines from clinical characteristics, diabetes was the only significant variable entered (OR = 0.310: 95% CI, 0.175-0.538; P < .001) and was associated with a 69% lower chance of meeting the guidelines. Patients with diabetes spent less daily time in moderate-intensity ambulatory PA than patients without diabetes (15 ± 13 vs 23 ± 20 min/d; P < .001). CONCLUSIONS: Thirty-one percent of patients with PAD and claudication met the PA time-intensity guidelines. Furthermore, patients with diabetes were least likely to meet the PA time-intensity guidelines, as they had a 69% lower chance than patients without diabetes. The clinical significance is that PAD patients who have diabetes are particularly susceptible to being physically sedentary, and are therefore prime patients who should be encouraged to increase their daily PA.

Increased pulse wave velocity is related to impaired working memory and executive function in older adults with metabolic syndrome.

Age-related vascular alterations promote the pathogenesis of vascular cognitive impairment (VCI). Cardiovascular risk factors that accelerate vascular aging exacerbate VCI. Metabolic syndrome (MetS) constitutes a cluster of critical cardiovascular risk factors (abdominal obesity, hypertension, elevated triglycerides, elevated fasting glucose, reduced HDL cholesterol), which affects nearly 37% of the adult US population. The present study was designed to test the hypotheses that MetS exacerbates cognitive impairment and that arterial stiffening moderates the association between cognitive dysfunction and MetS in older adults. MetS was defined by the NCEP ATP III guidelines. Cognitive function (digit span and trail-making tests) and brachial-ankle pulse wave velocity (baPWV; a non-invasive clinical measurement of arterial stiffness) were assessed in older adults with MetS and age- and sex-matched controls. Multiple linear regression models were applied to test for the main effects of MetS, baPWV, and their interaction on cognitive performance. Fifty-three participants with MetS (age: 68 ± 8 years) and 39 age-matched individuals without MetS (age: 66 ± 9 years) were enrolled into the study. In adjusted multivariable regression analyses of the digit span backward length score, both MetS (ß = 1.97, p = 0.048) and MetS by baPWV interaction (ß = - 0.001, p = 0.026) were significant predictors. In participants with MetS, higher baPWV was associated with poorer performance on digit span backward length score, a test of working memory (R = - 0.44, p = 0.0012), but there was no association in those without MetS (R = 0.035, p = 0.83). MetS was negatively associated with performance on the digit span backward length score, baPWV was negatively associated with multiple neuropsychological outcomes, and baPWV moderated the association between digit span backward length score and MetS, as individuals with both MetS and higher baPWV had the most impaired cognitive function. Our findings add to the growing body of evidence that individuals with MetS and higher baPWV may be prone to VCI.

Association Between Meeting Physical Activity Time-Intensity Guidelines With Ambulation, Quality of Life, and Inflammation in Claudication.

PURPOSE: The aim of this investigation was to determine if meeting the 2018 physical activity (PA) time-intensity guidelines was associated with better ambulatory function, health-related quality of life (HRQoL), vascular function, and inflammation than failing to meet the guidelines in patients with peripheral artery disease and claudication. Second, we determined the optimal number of total steps/d and steps taken at moderate cadence needed to meet the PA time-intensity guidelines. METHODS: Five hundred seventy-two patients were assessed on daily ambulatory activity for 1 wk with a step activity monitor, and were grouped according to whether they achieved <150 min/wk of moderate-intensity PA (group 1 = do not meet guidelines; n = 397) or whether they were above this threshold (group 2 = meet guidelines; n = 175). RESULTS: Treadmill peak walking time (mean ± SD) was higher ( P < .001) in group 2 (709 ± 359 sec) than in group 1 (427 ± 281 sec). The physical function HRQoL score was higher ( P < .001) in group 2 (61 ± 22%) than in group 1 (44 ± 21%). High-sensitivity C-reactive protein was lower ( P < .001) in group 2 (3.6 ± 4.5 mg/L) than in group 1 (5.9 ± 6.1 mg/L). Finally, ≥7675 total steps/d and ≥1660 steps/d at moderate cadence were optimal thresholds associated with meeting PA guidelines. CONCLUSIONS: Patients with claudication who meet the 2018 PA time-intensity guidelines for US adults had better ambulation, HRQoL, and vascular outcomes than those who failed to meet the PA guidelines. Patients with claudication best achieved the PA time-intensity guidelines by taking ≥7675 total steps/d, and ≥1660 steps/d at a moderate cadence.

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.

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.

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.

Association Between Daily Steps at Moderate Cadence and Vascular Outcomes in Patients With Claudication.

PURPOSE: We determined whether patients with peripheral artery disease (PAD) and claudication grouped according to tertiles of community-based daily steps taken at a moderate cadence had differences in vascular function and biomarkers and whether group differences in vascular function and biomarkers persisted after adjusting for demographic variables, comorbid conditions, and severity of PAD. METHODS: Two hundred sixty-three patients were evaluated for 1 wk on steps taken at a moderate cadence (exceeding 60 steps/min), and patients were placed into low (group 1), intermediate (group 2), and high (group 3) tertiles. RESULTS: Ankle/brachial index (ABI) at 1 min after exercise (mean ± SD) was significantly higher in groups 2 and 3 than in group 1 in unadjusted (P < .01) and adjusted (P < .01) analyses (group 1: 0.34 ± 0.25; group 2: 0.38 ± 0.27; and group 3: 0.44 ± 0.28). Exercise time to reach the minimum calf muscle oxygen saturation (StO2) value during treadmill exercise was significantly longer in groups 2 and 3 than in group 1 in unadjusted (P < .01) and adjusted (P < .01) analyses (group 1: 127 ± 127 sec; group 2: 251 ± 266 sec; and group 3: 310 ± 323 sec). Fibrinogen was significantly lower in group 3 than in group 1 in unadjusted (P = .02) and adjusted (P = .05) analyses (group 1: 3.5 ± 1.2 g/L; group 2: 3.6 ± 1.5 g/L; and group 3: 3.0 ± 1.1 g/L). CONCLUSIONS: Compared with patients with claudication in the lowest tertile of community-based daily steps taken at a moderate cadence, patients in the second and third tertiles had better calf muscle StO2 and ABI values during and immediately after exercise. Second, the most active group had lower fibrinogen levels than the least active group.

Cognitive decrement in older adults with symptomatic peripheral artery disease.

Peripheral artery disease (PAD) is highly prevalent, affecting up to 20% of people over 70 years of age. To test the hypothesis that PAD promotes the pathogenesis of vascular cognitive impairment (VCI), we compared cognitive function in older adults with symptomatic PAD and in participants without PAD who had a burden of comorbid conditions. Furthermore, we compared the cognitive function of these groups after adjusting for demographic and clinical characteristics, comorbid conditions, and cardiovascular risk factors. Participants with PAD (age: 69 ± 8 years; n = 58) and those without PAD (age: 62 ± 8 years; n = 30) were assessed on a battery of eight neuropsychological tests. The tests assessed attention and working memory, verbal memory, non-verbal memory, perceptuo-motor speed, and executive function. Participants were further characterized on demographic and clinical characteristics, comorbid conditions, cardiovascular risk factors, and ankle-brachial index. The PAD group had significantly lower neuropsychological scores than the non-PAD control group on all eight tests (P < .01). After adjusting for covariates, significantly worse scores in the PAD group persisted for verbal memory, measured by tests on logical memory-immediate recall (P = .022), and logical memory-delayed recall (P < .001), and for attention and working memory, measured by tests on digits forward (P < .001), and digits backward (P = .003). Participants with symptomatic PAD have substantially lower levels of performance on tests of attention, working memory, and verbal memory than participants without PAD independent of demographic characteristics and comorbid health burdens. These findings provide additional evidence in support of the concept that generalized accelerated vascular aging manifesting as symptomatic PAD in the peripheral circulation also affects the brain promoting the pathogenesis of VCI. These cognitive difficulties may also negatively impact symptomatic patient's ability to understand and adhere to behavioral and medical therapies, creating a vicious cycle. We speculate that more intensive follow-up may be needed to promote adherence to therapies and monitor cognitive decline that may affect care.

Association between Physical Activity and Mortality in Patients with Claudication.

PURPOSE: This study aimed to determine the association between light-intensity physical activity and the incidence of all-cause and cardiovascular mortality in patients with peripheral artery disease (PAD) limited by claudication followed for up to 18.7 yr. METHODS: A total of 528 patients with PAD and claudication were screened in Baltimore between 1994 and 2002, and 386 were deemed eligible for the study. At baseline, patients were classified into three physical activity groups: 1) physically sedentary, 2) light intensity, and 3) moderate to vigorous intensity based on a questionnaire. All-cause and cardiovascular mortality of patients through December 2014 was determined using the National Death Index and the U.S. Department of Veterans Affairs and the U.S. Department of Defense Suicide Data Repository. RESULTS: Median survival time was 9.9 yr (interquartile range, 4.9-15.7 yr; range, 0.38-18.7 yr). During follow-up, 257 patients (66.6%) died, consisting of 40/48 (83.3%) from the sedentary group, 135/210 (64.3%) from the light-intensity group, and 82/128 (64.0%) from the moderate- to vigorous-intensity group. For all-cause mortality, light-intensity activity status (hazard ratio [HR] = 0.523, P = 0.0007) and moderate- to vigorous-intensity status (HR = 0.425, P < 0.0001) were significant predictors. During follow-up, 125 patients died because of cardiovascular causes (32.4%), in which light-intensity activity status (HR = 0.511, P = 0.0113) and moderate- to vigorous-intensity activity status (HR = 0.341, P = 0.0003) were significant predictors. CONCLUSIONS: Light-intensity physical activity is associated with nearly 50% lower risk of all-cause and cardiovascular mortality in high-risk patients with PAD and claudication. Furthermore, moderate- to vigorous-intensity physical activity performed regularly is associated with 58% and 66% lower risk of all-cause and cardiovascular mortality, respectively. The survival benefits associated with light-intensity physical activity make it a compelling behavioral intervention that extends beyond improving ambulation.

Daily Step Counts in Participants With and Without Peripheral Artery Disease.

PURPOSE: We compared the prevalence of participants with and without symptomatic peripheral artery disease (PAD) who met the goals of attaining >7000 and 10 000 steps/d, and we determined whether PAD status was significantly associated with meeting the daily step count goals before and after adjusting for demographic variables, comorbid conditions, and cardiovascular risk factors. METHODS: Participants with PAD (n = 396) and without PAD (n = 396) were assessed on their walking for 7 consecutive days with a step activity monitor. RESULTS: The PAD group took significantly fewer steps/d than the non-PAD control group (6722 ± 3393 vs. 9475 ± 4110 steps/d; P < .001). Only 37.6% and 15.7% of the PAD group attained the goals of walking >7000 and 10 000 steps/d, respectively, whereas 67.9% and 37.4% of the control group attained these goals (P < .001 for each goal). Having PAD was associated with a 62% lower chance of attaining 7000 steps/d than compared with the control group (OR = 0.383; 95% CI, 0.259-0.565; P < .001), and a 55% lower chance of attaining 10 000 steps/d (OR = 0.449; 95% CI, 0.282-0.709; P < .001). Significant covariates (P < .01) included age, current smoking, diabetes, and body mass index. CONCLUSIONS: Participants with symptomatic PAD had a 29% lower daily step count compared with age- and sex-matched controls, and were less likely to attain the 7000 and 10 000 steps/d goals. Additionally, participants who were least likely to meet the 7000 and 10 000 daily step count recommendations included those who were older, currently smoked, had diabetes, and had higher body mass index.

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.

Patients With Peripheral Arterial Disease With Exaggerated Pressor Response Have Greater Ambulatory Dysfunction Than Patients With Lower Pressor Response.

We determined whether patients with peripheral arterial disease (PAD) who have either an exaggerated or a negative pressor response during treadmill walking have shorter peak walking time (PWT) and claudication onset time (COT) than patients with a normal pressor response, independent of comorbid conditions. A total of 249 patients were categorized to 1 of 3 groups based on systolic blood pressure (SBP) responses at 2 minutes of treadmill walking (speed = 2 mph, grade = 0%): group 1 (negative pressor response, SBP < 0 mm Hg), group 2 (normal pressor response, SBP 18 mm Hg), and group 3 (exaggerated pressor response, SBP > 18 mm Hg). After adjusting for comorbid conditions, group 3 (exaggerated) had significantly reduced COT (P = .011) and PWT (P = .002) compared to group 2 (normal), while group 1 (negative) and group 2 (normal) were not different. Patients with symptomatic PAD with an increase in SBP > 18 mm Hg after 2 minutes of treadmill walking experience claudication earlier and thus have greater ambulatory dysfunction, compared to patients with PAD with a normal pressor response, whereas patients with PAD with negative pressor response had a similar walking performance. The implication is that the magnitude of pressor response to only 2 minutes of treadmill walking can partially explain the degree of ambulatory dysfunction in patients with 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.

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.

Vascular Inflammation, Calf Muscle Oxygen Saturation, and Blood Glucose are Associated With Exercise Pressor Response in Symptomatic Peripheral Artery Disease.

We determined whether calf muscle oxygen saturation (StO2) and vascular biomarkers of inflammation and oxidative stress were associated with an exercise pressor response during treadmill walking in 179 patients with symptomatic peripheral artery disease (PAD). The exercise pressor response was measured as the change in blood pressure from rest to the end of the first 2-minute treadmill stage (2 mph, 0% grade). There was a wide range in the change in systolic blood pressure (-46 to 50 mm Hg) and in diastolic blood pressure (-23 to 38 mm Hg), with mean increases of 4.3 and 1.4 mm Hg, respectively. In multiple regression analyses, significant predictors of systolic pressure included glucose (P < .001) and insulin (P = .039). Significant predictors of diastolic pressure included cultured endothelial cell apoptosis (P = .019), the percentage drop in exercise calf muscle (StO2; P = .023), high-sensitivity C-reactive protein (P = .032), and glucose (P = .033). Higher levels in pro-inflammatory vascular biomarkers, impaired calf muscle StO2 during exercise, and elevated blood glucose were independently associated with greater exercise pressor response in patients with symptomatic PAD. The clinical implication is that exercise and nutritional interventions designed to improve inflammation, microcirculation, and glucose metabolism may also lower blood pressure during exercise in patients with symptomatic PAD.

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.

Greater Exercise Pressor Response Is Associated With Impaired Claudication Outcomes in Symptomatic Peripheral Artery Disease.

We determined whether a greater exercise pressor response during a constant-load treadmill test was associated with lower peak walking time (PWT) and claudication onset time (COT) measured during a graded maximal treadmill test in 304 patients with symptomatic peripheral artery disease (PAD). The exercise pressor response was assessed by measuring heart rate and blood pressure (BP) at rest and during a constant-load treadmill test (speed = 2 mph, grade = 0%). After only 2 minutes of walking, mean heart rate increased by 26 beats/min from rest and mean systolic BP increased by 16 mm Hg. In adjusted analyses, increases in systolic BP (P = .021), heart rate (P = .002), mean arterial pressure (P = .034), and rate-pressure product (P < .001) from rest to 2 minutes of constant-load exercise were negatively associated with COT. Similarly, increases in heart rate (P = .012) and rate-pressure product (P = .018) from rest to 2 minutes of constant-load exercise were negatively associated with PWT. A greater exercise pressor response observed after only 2 minutes of walking at no incline was independently associated with impaired claudication outcomes in patients with symptomatic PAD. The implication is that the exercise pressor response is an important and easily obtained clinical measurement that partially explains differences in PWT and COT.

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.