Walking Training Increases microRNA-126 Expression and Muscle Capillarization in Patients with Peripheral Artery Disease.

Patients with peripheral artery disease (PAD) have reduced muscle capillary density. Walking training (WT) is recommended for PAD patients. The goal of the study was to verify whether WT promotes angiogenesis in PAD-affected muscle and to investigate the possible role of miRNA-126 and the vascular endothelium growth factor (VEGF) angiogenic pathways on this adaptation. Thirty-two men with PAD were randomly allocated to two groups: WT (n = 16, 2 sessions/week) and control (CO, n = 16). Maximal treadmill tests and gastrocnemius biopsies were performed at baseline and after 12 weeks. Histological and molecular analyses were performed by blinded researchers. Maximal walking capacity increased by 65% with WT. WT increased the gastrocnemius capillary-fiber ratio (WT = 109 ± 13 vs. 164 ± 21 and CO = 100 ± 8 vs. 106 ± 6%, p < 0.001). Muscular expression of miRNA-126 and VEGF increased with WT (WT = 101 ± 13 vs. 130 ± 5 and CO = 100 ± 14 vs. 77 ± 20%, p < 0.001; WT = 103 ± 28 vs. 153 ± 59 and CO = 100 ± 36 vs. 84 ± 41%, p = 0.001, respectively), while expression of PI3KR2 decreased (WT = 97 ± 23 vs. 75 ± 21 and CO = 100 ± 29 vs. 105 ± 39%, p = 0.021). WT promoted angiogenesis in the muscle affected by PAD, and miRNA-126 may have a role in this adaptation by inhibiting PI3KR2, enabling the progression of the VEGF signaling pathway.

Physiological Responses to Maximal and Submaximal Walking in Patients with Symptomatic Peripheral Artery Disease. / Respostas Fisiológicas à Caminhada Máxima e Submáxima em Pacientes com Doença Arterial Periférica Sintomática.

BACKGROUND: Although maximal and submaximal walking are recommended for patients with peripheral artery disease (PAD), performing these exercises may induce different physiological responses. OBJECTIVES: To compare the acute effects of maximal and submaximal walking on post-exercise cardiovascular function, regulation, and associated pathophysiological processes in patients with symptomatic PAD. METHODS: Thirty male patients underwent 2 sessions: maximal walking (Gardner's protocol) and submaximal walking (15 bouts of 2 minutes of walking separated by 2 minutes of upright rest). In each session, blood pressure (BP), heart rate (HR), cardiac autonomic modulation (HR variability), forearm and calf blood flows (BF), vasodilatory capacity (reactive hyperemia), nitric oxide (NO), oxidative stress (lipid peroxidation), and inflammation (four markers) were measured pre- and post-walking. ANOVAs were employed, and p < 0.05 was considered significant. RESULTS: Systolic and mean BP decreased after the submaximal session, but they increased after the maximal session (interactions, p < 0.001 for both). Diastolic BP did not change after the submaximal session (p > 0.05), and it increased after maximal walking (interaction, p < 0.001). HR, sympathovagal balance, and BF increased similarly after both sessions (moment, p < 0.001, p = 0.04, and p < 0.001, respectively), while vasodilatory capacity, NO, and oxidative stress remained unchanged (p > 0.05). Vascular and intercellular adhesion molecules increased similarly after both maximal and submaximal walking sessions (moment, p = 0.001). CONCLUSIONS: In patients with symptomatic PAD, submaximal, but not maximal walking reduced post-exercise BP, while maximal walking maintained elevated cardiac overload during the recovery period. On the other hand, maximal and submaximal walking sessions similarly increased post-exercise HR, cardiac sympathovagal balance, and inflammation, while they did not change post-exercise NO bioavailability and oxidative stress.

FUNDAMENTO: Embora a caminhada máxima e submáxima sejam recomendadas para pacientes com doença arterial periférica (DAP), a realização desses exercícios pode induzir diferentes respostas fisiológicas. OBJETIVOS: Comparar os efeitos agudos de caminhada máxima e submáxima na função cardiovascular, a regulação e os processos fisiopatológicos associados pós-exercício em pacientes com DAP sintomática. MÉTODOS: Trinta pacientes do sexo masculino foram submetidos a 2 sessões: caminhada máxima (protocolo de Gardner) e caminhada submáxima (15 períodos de 2 minutos de caminhada separados por 2 minutos de repouso ereto). Em cada sessão, foram medidos a pressão arterial (PA), a frequência cardíaca (FC), a modulação autonômica cardíaca (variabilidade da FC), os fluxos sanguíneos (FS) do antebraço e da panturrilha, a capacidade vasodilatadora (hiperemia reativa), o óxido nítrico (ON), o estresse oxidativo (a peroxidação lipídica) e a inflamação (quatro marcadores), pré e pós-caminhada. ANOVAs foram empregadas e p < 0,05 foi considerado significativo. RESULTADOS: A PA sistólica e a PA média diminuíram após a sessão submáxima, mas aumentaram após a sessão máxima (interações, p < 0,001 para ambas). A PA diastólica não foi alterada após a sessão submáxima (p > 0,05), mas aumentou após a caminhada máxima (interação, p < 0,001). A FC, o equilíbrio simpatovagal e os FS aumentaram de forma semelhante após as duas sessões (momento, p < 0,001, p = 0,04 e p < 0,001, respectivamente), enquanto a capacidade vasodilatadora, o ON e o estresse oxidativo permaneceram inalterados (p > 0,05). As moléculas de adesão vascular e intercelular aumentaram de forma semelhante após as sessões de caminhada máxima e submáxima (momento, p = 0,001). CONCLUSÕES: Nos pacientes com a DAP sintomática, a caminhada submáxima, mas não a máxima, reduziu a PA pós-exercício, enquanto a caminhada máxima manteve a sobrecarga cardíaca elevada durante o período de recuperação. Por outro lado, as sessões de caminhada máxima e submáxima aumentaram a FC, o equilíbrio simpatovagal cardíaco e a inflamação pós-exercício de forma semelhante, enquanto não alteraram a biodisponibilidade de ON e o estresse oxidativo pós-exercício.

Respostas fisiológicas à caminhada máxima e submáxima em pacientes com doença arterial periférica sintomática / Physiological responses to maximal and submaximal walking in patients with symptomatic peripheral artery disease

Resumo Fundamento: Embora a caminhada máxima e submáxima sejam recomendadas para pacientes com doença arterial periférica (DAP), a realização desses exercícios pode induzir diferentes respostas fisiológicas. Objetivos: Comparar os efeitos agudos de caminhada máxima e submáxima na função cardiovascular, a regulação e os processos fisiopatológicos associados pós-exercício em pacientes com DAP sintomática. Métodos: Trinta pacientes do sexo masculino foram submetidos a 2 sessões: caminhada máxima (protocolo de Gardner) e caminhada submáxima (15 períodos de 2 minutos de caminhada separados por 2 minutos de repouso ereto). Em cada sessão, foram medidos a pressão arterial (PA), a frequência cardíaca (FC), a modulação autonômica cardíaca (variabilidade da FC), os fluxos sanguíneos (FS) do antebraço e da panturrilha, a capacidade vasodilatadora (hiperemia reativa), o óxido nítrico (ON), o estresse oxidativo (a peroxidação lipídica) e a inflamação (quatro marcadores), pré e pós-caminhada. ANOVAs foram empregadas e p < 0,05 foi considerado significativo. Resultados: A PA sistólica e a PA média diminuíram após a sessão submáxima, mas aumentaram após a sessão máxima (interações, p < 0,001 para ambas). A PA diastólica não foi alterada após a sessão submáxima (p > 0,05), mas aumentou após a caminhada máxima (interação, p < 0,001). A FC, o equilíbrio simpatovagal e os FS aumentaram de forma semelhante após as duas sessões (momento, p < 0,001, p = 0,04 e p < 0,001, respectivamente), enquanto a capacidade vasodilatadora, o ON e o estresse oxidativo permaneceram inalterados (p > 0,05). As moléculas de adesão vascular e intercelular aumentaram de forma semelhante após as sessões de caminhada máxima e submáxima (momento, p = 0,001). Conclusões: Nos pacientes com a DAP sintomática, a caminhada submáxima, mas não a máxima, reduziu a PA pós-exercício, enquanto a caminhada máxima manteve a sobrecarga cardíaca elevada durante o período de recuperação. Por outro lado, as sessões de caminhada máxima e submáxima aumentaram a FC, o equilíbrio simpatovagal cardíaco e a inflamação pós-exercício de forma semelhante, enquanto não alteraram a biodisponibilidade de ON e o estresse oxidativo pós-exercício.

Abstract Background: Although maximal and submaximal walking are recommended for patients with peripheral artery disease (PAD), performing these exercises may induce different physiological responses. Objectives: To compare the acute effects of maximal and submaximal walking on post-exercise cardiovascular function, regulation, and associated pathophysiological processes in patients with symptomatic PAD. Methods: Thirty male patients underwent 2 sessions: maximal walking (Gardner's protocol) and submaximal walking (15 bouts of 2 minutes of walking separated by 2 minutes of upright rest). In each session, blood pressure (BP), heart rate (HR), cardiac autonomic modulation (HR variability), forearm and calf blood flows (BF), vasodilatory capacity (reactive hyperemia), nitric oxide (NO), oxidative stress (lipid peroxidation), and inflammation (four markers) were measured pre- and post-walking. ANOVAs were employed, and p < 0.05 was considered significant. Results: Systolic and mean BP decreased after the submaximal session, but they increased after the maximal session (interactions, p < 0.001 for both). Diastolic BP did not change after the submaximal session (p > 0.05), and it increased after maximal walking (interaction, p < 0.001). HR, sympathovagal balance, and BF increased similarly after both sessions (moment, p < 0.001, p = 0.04, and p < 0.001, respectively), while vasodilatory capacity, NO, and oxidative stress remained unchanged (p > 0.05). Vascular and intercellular adhesion molecules increased similarly after both maximal and submaximal walking sessions (moment, p = 0.001). Conclusions: In patients with symptomatic PAD, submaximal, but not maximal walking reduced post-exercise BP, while maximal walking maintained elevated cardiac overload during the recovery period. On the other hand, maximal and submaximal walking sessions similarly increased post-exercise HR, cardiac sympathovagal balance, and inflammation, while they did not change post-exercise NO bioavailability and oxidative stress.

Walking Training Improves Ambulatory Blood Pressure Variability in Claudication. / Treinamento de Caminhada Melhora a Variabilidade da Pressão Arterial Ambulatorial em Claudicantes.

BACKGROUND: Walking training (WT) improves walking capacity and reduces clinic blood pressure (BP) in patients with peripheral artery disease (PAD), but its effects on ambulatory BP remains unknown. OBJECTIVE: To investigate the effect of 12 weeks of WT on ambulatory BP and its variability in patients with PAD. METHODS: Thirty-five male patients with PAD and claudication symptoms were randomly allocated into two groups: control (n = 16, 30 min of stretching) and WT (n = 19, 15 bouts of 2 min of walking at the heart rate of leg pain threshold interspersed by 2 min of upright rest). Before and after 12 weeks, 24-hour ambulatory BP was assessed. Ambulatory BP variability indices assessed at both time points included the 24-hour standard deviation (SD24), the awake and asleep weighted standard deviation (SDdn), and the 24-hour average real variability (ARV24). Data were analyzed by mixed two-way ANOVAs, considering P<0.05 as significant. RESULTS: After 12 weeks, neither group had significant changes in 24-hour, awake and sleep BPs. The WT decreased systolic and mean BP variabilities (Systolic BP - 13.3±2.8 vs 11.8±2.3, 12.1±2.84 vs 10.7±2.5 and 9.4±2.3 vs 8.8±2.2 mmHg); Mean BP - 11.0±1.7 vs 10.4±1.9, 10.1±1.6 vs 9.1±1.7 and 8.0.±1.7 vs 7.2±1.5 mmHg) for SD24, SDdn and ARV24, respectively). Neither group had significant changes in diastolic BP variabilities after 12 weeks. CONCLUSIONS: The WT does not change ambulatory BP levels but decreases ambulatory BP variability in patients with PAD. This improvement may have a favorable impact on the cardiovascular risk of patients with symptomatic PAD. (Arq Bras Cardiol. 2021; 116(5):898-905).

FUNDAMENTO: O treinamento de caminhada (TC) melhora a capacidade de caminhar e reduz a pressão arterial (PA) clínica em pacientes com doença arterial periférica (DAP), mas seus efeitos na PA ambulatorial permanecem desconhecidos. OBJETIVO: Investigar o efeito de 12 semanas de TC na PA ambulatorial e sua variabilidade em pacientes com DAP. MÉTODOS: Trinta e cinco pacientes do sexo masculino com DAP e sintomas de claudicação foram alocados aleatoriamente em dois grupos: controle (n = 16, 30 min de alongamento) e TC (n = 19, 15 séries de 2 minutos de caminhada na frequência cardíaca em que ocorreu limiar de dor intercalados por 2 minutos de repouso em pé). Antes e depois de 12 semanas, a PA ambulatorial de 24 horas foi avaliada. Os índices de variabilidade da PA ambulatorial avaliados em ambos os momentos incluíram o desvio-padrão de 24 horas (DP24), o desvio-padrão ponderado de vigília e sono (DPvs) e a variabilidade real média de 24 horas (VRM24). Os dados foram analisados por ANOVAs mistas de dois fatores, considerando significativo P<0,05. RESULTADOS: Após 12 semanas, nenhum dos grupos apresentou alterações na PA de 24 horas, vigília e sono. O TC diminuiu as variabilidades da PA sistólica e média (PA sistólica ­ 13,3 ± 2,8 vs 11,8 ± 2,3; 12,1 ± 2,84 vs 10,7 ± 2,5; e 9,4 ± 2,3 vs 8,8 ± 2,2 mmHg; PA média ­ 11,0 ± 1,7 vs 10,4 ± 1,9; 10,1 ± 1,6 vs 9,1 ± 1,7; e 8,0 ± 1,7 vs 7,2 ± 1,5 mmHg para DP24, DPvs e VRM24, respectivamente). Nenhum dos grupos apresentou mudanças significantesnos índices de variabilidade da PA diastólica após 12 semanas. CONCLUSÕES: O TC não altera os níveis ambulatoriais da PA, mas diminui a sua variabilidade em pacientes com DAP. Essa melhora pode ter um impacto favorável no risco cardiovascular de pacientes com DAP sintomática. (Arq Bras Cardiol. 2021; 116(5):898-905).

Walking Training Improves Systemic and Local Pathophysiological Processes in Intermittent Claudication.

OBJECTIVE: This study examined the impact of submaximal walking training (WT) on local and systemic nitric oxide (NO) bioavailability, inflammation, and oxidative stress in patients with intermittent claudication (IC). METHODS: The study employed a randomised, controlled, parallel group design and was performed in a single centre. Thirty-two men with IC were randomly allocated to two groups: WT (n = 16, two sessions/week, 15 cycles of two minutes walking at an intensity corresponding to the heart rate obtained at the pain threshold interspersed by two minutes of upright rest) and control (CO, n = 16, two sessions/week, 30 minutes of stretching). NO bioavailability (blood NO and muscle nitric oxide synthase [eNOS]), redox homeostasis (catalase [CAT], superoxide dismutase [SOD], lipid peroxidation [LPO] measured in blood and muscle), and inflammation (interleukin-6 [IL-6], C-reactive protein [CRP], tumour necrosis factor α [TNF-α], intercellular adhesion molecules [ICAM], vascular adhesion molecules [VCAM] measured in blood and muscle) were assessed at baseline and after 12 weeks. RESULTS: WT statistically significantly increased blood NO, muscle eNOS, blood SOD and CAT, and muscle SOD and abolished the increase in circulating and muscle LPO observed in the CO group. WT decreased blood CRP, ICAM, and VCAM and muscle IL-6 and CRP and eliminated the increase in blood TNF-α and muscle TNF-α, ICAM and VCAM observed in the CO group. CONCLUSION: WT at an intensity of pain threshold improved NO bioavailability and decreased systemic and local oxidative stress and inflammation in patients with IC. The proposed WT protocol provides physiological adaptations that may contribute to cardiovascular health in these patients.

Local and Systemic Inflammation and Oxidative Stress After a Single Bout of Maximal Walking in Patients With Symptomatic Peripheral Artery Disease.

OBJECTIVE: The aim of this study was to assess the effects of a single bout of maximal walking on blood and muscle nitric oxide (NO) bioavailability, oxidative stress, and inflammation in symptomatic peripheral artery disease (PAD) patients. METHODS: A total of 35 men with symptomatic PAD performed a graded maximal exercise test on a treadmill (3.2 km/h, 2% increase in grade every 2 minutes). Plasma samples and gastrocnemius muscle biopsies were collected preexercise and postexercise for assessment of NO bioavailability (plasma NO and muscle, endothelial NO synthase), oxidative stress and antioxidant function (lipid peroxidation [LPO], catalase [CAT], and superoxide dismutase), and inflammation (interleukin-6, C-reactive protein, tumor necrosis factor-α, intercellular adhesion molecules, and vascular adhesion molecules). The effects of the walking exercise were assessed using paired t tests or Wilcoxon tests. RESULTS: After maximal walking, plasma NO and LPO were unchanged (P > .05), plasma CAT decreased, and all blood inflammatory markers increased (all P ≤ .05). In the disease-affected skeletal muscle, endothelial NO synthase, CAT, LPO, and all inflammatory markers increased, whereas superoxide dismutase decreased (all P ≤ .05). CONCLUSION: In patients with symptomatic PAD, maximal exercise induces local and systemic impairments, which may play a key role in atherogenesis. Exercise strategies that avoid maximal effort may be important to reduce local and systemic damage and enhance clinical benefits.

Reproducibility of Hemodynamic, Cardiac Autonomic Modulation, and Blood Flow Assessments in Patients with Intermittent Claudication.

BACKGROUND: The aim of this study is to identify, in patients with peripheral artery disease and intermittent claudication (IC), the reproducibility of heart rate (HR), blood pressure (BP), rate pressure product, heart rate variability (HRV), and forearm and calf blood flow (BF) and vasodilatory assessments. METHODS: Twenty-nine patients with IC underwent test and retest sessions, 8-12 days apart. During each session, HR, BP, HRV, BF, and vasodilatory responses were measured by electrocardiogram, auscultation, spectral analysis of HRV (low frequency, LFR-R; high frequency, HFR-R), and strain gauge plethysmography (baseline BF, post-occlusion BF, post-occlusion area under the curve). Reproducibility was determined by intra-class correlation coefficient (ICC), typical error, coefficient of variation (CV), and limits of agreement. RESULTS: The ICC for HR and BP was >0.8 with CV <9%. For most HRV measures, ICC was >0.9 while CV was <7%, except for LF/HF (ICC = 0.737, CV = 93.8%). The ICC for forearm and calf baseline BF assessments was >0.9 while CV was <19%; variable ICC and CV for vasodilatory responses were exhibited for calf (0.653-0.770, 35.2-37.7%) and forearm (0.169-0.265, 46.2-55.5%). CONCLUSIONS: In male patients with IC, systemic hemodynamics (HR and BP), cardiac autonomic modulation (LFR-R and HFR-R), and forearm and calf baseline BF assessments exhibited excellent reproducibility, whereas the level of reproducibility for vasodilatory responses were moderate to poor. Assessment reproducibility has highlighted appropriate clinical tools for the regular monitoring of disease/intervention progression in patients with IC.

Reproducibility of heart rate recovery in patients with intermittent claudication.

BACKGROUND: Postexercise heart rate recovery (HRR) is a non-invasive tool for cardiac autonomic function assessment. Reproducibility of HRR has been established in healthy subjects; however, no study has evaluated this reproducibility in clinical populations who may present autonomic dysfunction. Patients with peripheral artery disease and intermittent claudication (IC) often present altered cardiac autonomic function and HRR could be an interesting tool for evaluating autonomic responses to interventions in this population. Therefore, the reproducibility of HRR should be determined in this specific population. OBJECTIVE: To determine the reproducibility of HRR indices in patients with IC. METHODS: Nineteen men with IC underwent two repeated maximal treadmill tests. Raw HR and relative HRR (difference to exercise peak) indices measured at 30, 60, 120, 180, 240 and 300s of recovery were evaluated. The presence of systematic bias was assessed by comparing test and retest mean values via paired t-test. Reliability was assessed by intraclass correlation coefficient (ICC), and agreement by typical error (TE), coefficient of variation (CV) and minimal detectable difference (MDD). RESULTS: There were no significant differences between the test and retest values of all raw HR and relative HRR indices (P ≥ 0·05), except for HR120s (P = 0·032). All indices exhibited excellent reliability (ICC ≥ 0·78). Raw HR and relative HRR indices showed TEs ≤ 6·4 bpm and MDDs ≤ 17·8 bpm. In addition, all indices showed CVs ≤ 13·2%, except HRR30s (CV = 45·6%). CONCLUSIONS: The current results demonstrated that most HRR indices were highly reproducible with no systematic error, excellent reliability and good agreement in patients with IC following maximal graded exercise.

Reproducibility (Reliability and Agreement) of Post-exercise Hypotension.

This study determined the reproducibility of post-exercise hypotension (PEH) calculated by the following methods: PEH_I=post-exercise BP - pre-exercise BP; PEH_II=post-exercise BP - post-control BP; and PEH_III=[(post-exercise BP - pre-exercise BP)-(post-control BP - pre-control BP)]. Twenty-five participants underwent four sessions divided in two blocks (test and retest). Each block consisted of one exercise and one control session. BP pressure was measured before and after the interventions. The presence of systematic error (paired t-tests), reliability [intraclass coefficient correlation (ICC)], and agreement [typical error (TE) and minimal detectable difference (MDD)] were evaluated. PEHs calculated by the three methods were similar between test and retest. For systolic PEH, ICC was>0.74, TE ranged from 2.6 to 4.6 mmHg and MDD from 7.2 to 12.8 mmHg for the three methods. For diastolic PEH, ICC was<0.48, TE ranged from 3.5 to 5.6 mmHg and MDD from 9.8 to 15.4 mmHg for the three methods. Thus, systolic PEH calculated by the three methods has good/excellent reliability, while diastolic PEH has fair/poor reliability. Regarding agreement, TE and MDD varied among the methods, which implies that the specific parameters given for each method should be used to estimate sample sizes for studies and the minimal individual difference considered real when comparing PEHs.

Walking training at the heart rate of pain threshold improves cardiovascular function and autonomic regulation in intermittent claudication: A randomized controlled trial.

OBJECTIVES: This study investigated the effects of walking training (WT) on cardiovascular function and autonomic regulation in patents with intermittent claudication (IC). DESIGN: Randomized controlled trial. METHODS: Forty-two male patients with IC (≥50years) were randomly allocated into two groups: control (CG, n=20, 30min of stretching exercises) and WT (WTG, n=22, 15 bouts of 2min of walking interpolated by 2min of upright rest-walking intensity was set at the heart rate of pain threshold). Both interventions were performed twice/week for 12 weeks. Walking capacity (maximal treadmill test), blood pressure (auscultatory), cardiac output (CO2 rebreathing), heart rate (ECG), stroke volume, systemic vascular resistance, forearm and calf vascular resistance (plethysmography), and low (LF) and high frequency (HF) components of heart rate variability and spontaneous baroreflex sensitivity were measured at baseline and after 12 weeks of the study. RESULTS: WT increased total walking distance (+302±85m, p=0.001) and spontaneous baroreflex sensitivity (+2.13±1.07ms/mmHg, p=0.02). Additionally, at rest, WT decreased systolic and mean blood pressures (-10±3 and -5±2mmHg, p=0.001 and p=0.01, respectively), cardiac output (-0.37±0.24l/min, p=0.03), heart rate (-4±2bpm, p=0.001), forearm vascular resistance (-8.5±2.8U, p=0.02) and LF/HF (-1.24±0.99, p=0.001). No change was observed in the CG. CONCLUSIONS: In addition to increasing walking capacity, WT improved cardiovascular function and autonomic regulation in patients with IC.

Relationship between walking capacity and ambulatory blood pressure in patients with intermittent claudication.

OBJECTIVE: Patients with intermittent claudication (IC) often have high blood pressure (BP), which increases their cardiovascular risk. However, whether walking capacity is associated with BP levels in patients with IC remains unknown. Therefore, this study was designed to investigate whether the total walking distance is associated with ambulatory BP in patients with IC. PARTICIPANTS AND METHODS: This was a cross-sectional study of 75 patients with IC (58 men; 17 women). A maximal treadmill test (Gardner protocol) was performed to assess total walking distance in these patients. Furthermore, ambulatory BP, heart rate, rate-pressure product, and BP load were obtained over a 24-h period. One-way analysis of variance and multiple linear regression were carried out. RESULTS: Walking capacity was correlated negatively with the following: (i) asleep systolic BP, diastolic BP, mean BP and heart rate; (ii) 24-h, awake and asleep RPP; and (iii) awake and asleep systolic BP load (all P<0.05). These associations occurred irrespective of confounders such as age, sex, BMI, smoking status, and number of antihypertensive medications. CONCLUSION: A better walking capacity is associated with lower ambulatory BP parameters in patients with IC.

Reproducibility of Anaerobic and Pain Thresholds in Male Patients With Intermittent Claudication.

PURPOSE: Maximal and submaximal parameters assessed during treadmill tests are used to prescribe exercise training and assess exercise-induced adaptations in patients with intermittent claudication (IC). Although reproducibility of maximal parameters is well documented, the reproducibility of submaximal is not clear. The aim of this study was to identify the reproducibility (reliability and agreement) of heart rate (HR) and oxygen uptake ((Equation is included in full-text article.)O2) measured at the anaerobic (AT) and the pain (PT) thresholds assessed during a maximal test in patients with IC. METHODS: Twenty male patients with IC underwent 2 cardiopulmonary treadmill tests to maximal pain. The HR and (Equation is included in full-text article.)O2 at the AT and PT were identified, and differences between repeat tests were compared. Reliability was determined by intraclass coefficient correlation (ICC). Agreement was assessed by coefficient of variation (CV), standard error of measurement (SEM), smallest detectable difference (SDD), and limits of agreement (LOA). RESULTS: The (Equation is included in full-text article.)O2 at AT and PT exhibited moderate reliability and moderate/good agreement (ICC = 0.73 and 0.70; CV = 9.6% and 11.1%, respectively). The HR at the AT and PT exhibited high reliability and good agreement (ICC = 0.87 and 0.92; SEM = 3.9 and 3.2 bpm; SDD = 10.8 and 8.8 bpm, respectively). The LOA for (Equation is included in full-text article.)O2 at AT and PT were ≤20% and for HR ≤11 bpm. CONCLUSIONS: The (Equation is included in full-text article.)O2 and HR measured at the AT and PT were moderately to highly reproducible in male patients with IC. The HR and (Equation is included in full-text article.)O2 at AT and PT may be used to establish training intensity and evaluate training effectiveness for these patients in clinical practice and research.

Effects of oral N-acetylcysteine on walking capacity, leg reactive hyperemia, and inflammatory and angiogenic mediators in patients with intermittent claudication.

Increased oxidative stress and inflammation contribute to impaired walking capacity and endothelial dysfunction in patients with intermittent claudication (IC). The goal of the study was to determine the effects of oral treatment with the antioxidant N-acetylcysteine (NAC) on walking capacity, leg postocclusive reactive hyperemia, circulating levels of inflammatory mediators, and whole blood expression of angiogenic mediators in patients with IC. Following a double-blinded randomized crossover design, 10 patients with IC received NAC (1,800 mg/day for 4 days plus 2,700 mg before the experimental session) and placebo (PLA) before undergoing a graded treadmill exercise test. Leg postocclusive reactive hyperemia was assessed before and after the test. Blood samples were taken before and after NAC or PLA ingestions and 5 and 30 min after the exercise test for the analysis of circulating inflammatory and angiogenic markers. Although NAC increased the plasma ratio of reduced to oxidized glutathione, there were no differences between experimental sessions for walking tolerance and postocclusive reactive hyperemia. Plasma concentrations of soluble vascular cell adhesion protein-1, monocyte chemotactic protein-1, and endothelin-1 increased similarly following maximal exercise after PLA and NAC (P < 0.001). Whole blood expression of pro-angiogenic microRNA-126 increased after maximal exercise in the PLA session, but treatment with NAC prevented this response. Similarly, exercise-induced changes in whole blood expression of VEGF, endothelial nitric oxide synthase and phosphatidylinositol 3-kinase R2 were blunted after NAC. In conclusion, oral NAC does not increase walking tolerance or leg blood flow in patients with IC. In addition, oral NAC prevents maximal exercise-induced increase in the expression of circulating microRNA-126 and other angiogenic mediators in patients with IC.

Barriers to physical activity in patients with intermittent claudication.

BACKGROUND: The main barriers reported by the patients with claudication are related to claudication symptoms. However, it remains unclear whether these barriers are associated with physical activity levels in these patients. PURPOSE: The aim of this study was to analyze the barriers to and the factors associated with physical activity (PA) in intermittent claudication (IC) patients. METHODS: The sample included 150 IC Brazilian patients and mean age 64 ± 9 years old. Sociodemographic factors, comorbid conditions and cardiovascular risk factors, personal and environmental barriers to PA, and walking capacity (claudication onset distance-COD and peak walking distance-PWD) were obtained. PA was assessed using a pedometer over seven consecutive days. RESULTS: Patients performed 6,041 ± 3,166 steps/day. The most prevalent personal and environmental barriers to PAs were exercise-induced pain and the presence of obstacles that aggravate the leg pain. Multiple linear regression showed that level of PA was inversely associated with age (ß = -81.13; p < 0.001), lack of green areas (ß = -1363.54; p < 0.001), and positively associated with PWD (ß = 3.07; p < 0.001). CONCLUSION: Older IC patients who live in neighborhoods that lack green areas to walk in, and who have poor walking capacity present lower levels of PA.

Post-walking exercise hypotension in patients with intermittent claudication.

PURPOSE: This study aimed to investigate the acute effect of intermittent walking exercise (WE) on blood pressure (BP) responses in patients with intermittent claudication (IC). Secondly, this study aimed to gain improved insight into the physiological mechanisms controlling BP regulation after intermittent WE in this patient group. METHODS: Twenty patients with IC participated in two experimental sessions in a random order, as follows: WE (15 × 2-min bouts of WE interpolated with 2-min rest intervals) and control (standing rest on a treadmill for 60 min). BP, cardiac output (CO: CO2 rebreathing), and cardiovascular autonomic modulation (spectral analysis of HR variability) were assessed before and after both experimental sessions during supine rest, and stroke volume (SV) and systemic vascular resistance (SVR) were calculated. Data were analyzed using two-way ANOVA. RESULTS: WE decreased systolic, diastolic, and mean BP, with net effects of -13 ± 2, -5 ± 2, and -7 ± 2 mm Hg versus control, respectively (all P < 0.05). WE also decreased SV (-5.62 ± 1.97 mL, P < 0.05) and CO (-0.05 ± 0.13 L·min(-1), P < 0.05) versus preintervention and prevented the observed increase in SVR in the control condition (+4.2 ± 1.4 U, P < 0.05). HR showed a decrease (P < 0.05), consistent with evidence of increased vagal modulation, in the control condition. BP measurements over the subsequent 24 h were similar between experimental conditions. CONCLUSIONS: In patients with IC, WE induced a postexercise hypotension response that had a significant magnitude versus control but was not maintained over the next 24 h of daily activities. The acute postexercise hypotension response was mediated by a decrease in CO and SV, which was not compensated by an augmentation of SVR, as observed in the control arm of the study.

Are the barriers for physical activity practice equal for all peripheral artery disease patients?

OBJECTIVE: To investigate barriers to physical activity related to the sociodemographic comorbidities and clinical variables of patients with intermittent claudication. DESIGN: Cross-sectional study. SETTING: Ambulatory care. PARTICIPANTS: The medical histories of patients (N=145) aged ≥50 years with intermittent claudication were examined. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sociodemographic data (sex, race, level of education, socioeconomic status, marital status), comorbidities (overweight, hypertension, dyslipidemia, diabetes, currently smoking, heart disease), and clinical variables (initial claudication distance, total walking distance, ankle-brachial index). Information on personal and environmental barriers was obtained by questionnaire. RESULTS: Low economic status was most associated with "being afraid of falling" (odd ratios [OR]=2.22; 95% confidence interval [CI], 1.08-4.54). Low education level was most associated with "lack of street pedestrian crossing" (OR=3.34; 95% CI, 1.48-7.52). Diabetes was associated with lack of energy (OR=3.38; 95% CI, 1.68-6.79) and other medical conditions (eg, arthritis, angina) (OR=3.44; 95% CI, 1.65-7.16). Ankle brachial index was associated with "some difficulty in getting to a place where physical activity can be performed" (OR=2.75; 95% CI, 1.22-6.21). Walking capacity was strongly associated with barriers relating to leg pain (OR=7.39; 95% CI, 1.66-32.88). CONCLUSIONS: Older patients, those with a low education level, patients with diabetes, low ankle brachial index, and those with a lower walking capacity are more likely to experience barriers to physical activity.

Effects of clustered comorbid conditions on walking capacity in patients with peripheral artery disease.

BACKGROUND: Comorbid conditions are known to increase cardiovascular risk in patients with peripheral artery disease (PAD). However, whether comorbid conditions affect walking capacity remains controversial. Previous studies have analyzed comorbidities separately, but they are known to occur in a clustered fashion in PAD patients. Therefore, the aim of this study was to analyze the influence of clustered comorbid conditions on walking capacity in PAD patients. METHODS: This cross-sectional study included 415 PAD patients (155 women and 260 men with an average age of 63 years). Claudication distance and total walking distance were assessed with the graded maximal treadmill test. Medical histories of hypertension, diabetes, cerebrovascular disease (CVD), coronary artery disease (CAD), and chronic obstructive pulmonary disease (COPD) were obtained. Binary logistic regression was carried out to analyze whether clustered comorbid conditions were associated with walking capacity. RESULTS: CVD was associated with lower total walking distance (odds ratio [OR] = 2.45; 95% confidence interval [CI]: 1.11-5.39). The cluster hypertension, diabetes, CVD, CAD, and COPD were associated with a lower claudication distance (OR = 7.63; 95% CI: 1.42-40.96). In addition, the clusters of CVD and hypertension (OR = 3.16; 95% CI: 1.38-7.23), CVD and CAD (OR = 3.46; 95% CI: 1.25-9.57), CVD, hypertension, and diabetes (OR = 11.38; 95% CI: 2.27-57.00) were associated with a lower total walking distance. CONCLUSIONS: CVD was associated with walking impairment of IC patients and in particular when CVD is clustered with other comorbid conditions.

Comparação entre os métodos subjetivo e objetivo para avaliação da capacidade funcional durante tratamento clínico em pacientes com claudicação intermitente / Comparison between subjective and objective methods to assess functional capacity during clinical treatment in patients with intermittent claudication

OBJETIVO: Verificar se há relação entre a medida da capacidade funcional avaliada subjetiva e objetivamente em relação ao estado atual e após tratamento clínico em pacientes com claudicação intermitente. MÉTODOS: Foram recrutados 500 pacientes com claudicação intermitente. Todos realizaram exame clínico e foram submetidos a uma avaliação funcional por meio do método subjetivo (consulta clínica) e objetivo (teste de esteira). Adicionalmente, 50 pacientes foram selecionados para se avaliar o efeito do tratamento clínico, pelos métodos subjetivo e objetivo, em relação à capacidade funcional. RESULTADOS: Dos 500 pacientes selecionados, somente 60 (12,0%) apresentaram valores referidos e observados similares. Os demais pacientes, ou seja, 440 (88,0%) apresentaram valores relatados discordantes em relação àqueles obtidos no teste de esforço. Com relação ao efeito do tratamento clínico em relação à capacidade funcional, os resultados foram similares entre ambos os métodos (χ²=1,7; p=0,427). CONCLUSÃO: Apesar de o método subjetivo superestimar os valores de capacidade funcional, quando comparados ao método objetivo, não foram observadas diferenças significantes entre ambos os métodos, quando se analisou o efeito do tratamento clínico. Assim, o método subjetivo fornece informações similares em comparação à medida objetiva no acompanhamento do tratamento clínico de pacientes com claudicação intermitente.

OBJECTIVE: To analyze if there is any relation between functional capacity assessed by subjective and objective methods regarding the current state and after clinical treatment in patients with intermittent claudication. METHODS: A total of 500 patients with intermittent claudication were enrolled. All patients underwent clinical examination and a functional evaluation by subjective (clinical visit) and objective method (treadmill test). Additionally, 50 patients were selected to evaluate the effect of clinical treatment by subjective and objective methods in relation to functional capacity. RESULTS: Out of 500 patients, only 60 (12.0%) had similar results in both methods. The remaining, that is 440 patients (88.0%) had subject values in disagreement with stress test findings. Regarding the clinical effect of the treatment on the functional outcomes, results were similar in both methods (χ²=1.7; p=0.427). CONCLUSION: Although the subjective method overestimates the functional capacity when compared to the objective method, no significant differences were observed between both methods when analyzing the effect of clinical treatment. Thus, the subjective method provides similar information as compared with objective method, in monitoring the clinical treatment of patients with intermittent claudication.

Relacao entre o nivel de atividade fisica estimado pelo Baltimore Activity Scale for Intermittent Claudication e a pedometria em pacientes com claudicacao intermitente / Correlation between physical activity levels of patients with intermittent claudication estimated using the Baltimore Activity Scale for Intermittent Claudication and a pedometer

CONTEXTO: Os pacientes com claudicação intermitente apresentam níveis reduzidos de atividade física. A Baltimore Activity Scale for Intermittent Claudication (BASIC) foi validada para quantificar o nível de atividade física destes pacientes. No entanto, esta validação se baseou em apenas dois dias de monitoramento com acelerômetros, de modo que ainda permanece incerto se a BASIC fornece informações sobre os níveis de atividade física semanal. OBJETIVO: Analisar a correlação entre o nível de atividade física estimada pela BASIC e o nível obtido pelo pedômetro em uma semana, em pacientes com claudicação intermitente. MÉTODOS: Foram estudados 150 pacientes com claudicação intermitente, com idade entre 30 e 80 anos. Foram obtidos os dados sociodemográficos e verificada a presença de comorbidades e de fatores de risco cardiovascular, e a BASIC. O pedômetro foi utilizado por sete dias consecutivos, sendo a análise feita em três diferentes períodos de monitorização (todos os dias, dias da semana e do fim de semana). RESULTADOS: Foi observada correlação entre a BASIC e a média de passos de todos os dias (rho=0,343; p<0,001), dos dias de semana (rho=0,336; p<0,001) e dos dias do final de semana (rho=0,317; p<0,001). CONCLUSÃO: Em pacientes com claudicação intermitente, o nível de atividade física estimado pela BASIC se correlaciona com o nível de atividade física semanal. .

BACKGROUND: The levels of physical activity of patients with intermittent claudication (IC) are usually reduced. The Baltimore Activity Scale for Intermittent Claudication (BASIC) was designed to measure physical activity levels of patients with IC, but its validation was conducted against only two days of monitoring with an accelerometer, and it remains unclear whether BASIC provides information about weekly physical activity levels. OBJECTIVE: To analyze the correlation between physical activity levels of patients with IC estimated using BASIC or a pedometer for one week. METHODS: This study included 150 patients with IC aged 30 to 80 years. Sociodemographic data, comorbidities, cardiovascular risk factors and BASIC scores were recorded. Pedometers were used for seven consecutive days, and data were analyzed for three different periods (all days, weekdays and weekends). RESULTS: BASIC scores and mean number of steps were correlated on all days (rho=0.343, p<0.001), weekdays (rho=0.336, p<0.001) and weekends (rho=0.317, p<0.001). CONCLUSION: In patients with IC, physical activity levels estimated using BASIC correlate with weekly physical activity levels. .

Exercise prescription using the heart of claudication pain onset in patients with intermittent claudication.

OBJECTIVE: To assess the acute metabolic and cardiovascular responses to walking exercise at an intensity corresponding to the heart rate of claudication pain onset and to investigate the effects of a 12-week walking training program at this intensity on walking capacity. METHODS: Twenty-nine patients with intermittent claudication were randomly allocated to the walking training (n=17) or control (CO, n=12) group. The walking training group performed an acute exercise session comprising 15×2-min bouts of walking at the heart rate of claudication pain onset, with 2-min interpolated rest intervals. The claudication symptoms and cardiovascular and metabolic responses were evaluated. Walking training was then performed at the same intensity twice each week for 12 weeks, while the control group engaged in twice weekly stretching classes. The claudication onset distance and total walking distance were evaluated before and after the interventions. Brazilian Registry Clinical Trials: RBR-7M3D8W. RESULTS: During the acute exercise session, the heart rate was maintained within tight limits. The exercise intensity was above the anaerobic threshold and >80% of the heart rate peak and VO2peak. After the exercise training period, the walking exercise group (n=13) showed increased claudication onset distance (309±153 vs. 413±201m) and total walking distance (784±182 vs. 1,100±236m) compared to the control group (n=12) (p<0.05). CONCLUSION: Walking exercise prescribed at the heart rate of claudication pain onset enables patients with intermittent claudication to exercise with tolerable levels of pain and improves walking performance.