Abstract
Purpose
This study investigated whether: 1) walking training (WT) changes cardiovascular load after walking until maximal intermittent claudication (IC) in patients with peripheral artery disease (PAD); and 2) acute and chronic cardiovascular responses to walking were related to each other.
Methods
A randomized, controlled, parallel-group design was employed. Thirty-two men with PAD and IC were randomly assigned to one of two groups: WT (n=16) or control (CO, n=16) twice a week for 12 weeks. The WT group completed 15, 2-min bouts of walking at moderate intensity interspersed with 2-min upright resting intervals per session. The CO group completed 30 minutes of stretching per session. At Baseline and after 12 weeks, both groups underwent a progressive walking session to maximal IC (3.2 km/h, 2% increase in grade every 2 min). Systolic blood pressure (BP), diastolic BP, heart rate (HR), and rate pressure product (RPP) were measured pre- and post-walking. Data were analyzed by three-way mixed ANOVAs. Pearson correlations were used to explore the association between the acute and chronic responses .
Results
WT significantly reduced pre- and post-walking systolic BP (p<0.001), diastolic BP (p<0.001), and RPP (p<0.001). No significant correlations were found between the acute and chronic changes observed for all variables (all p>0.05).
Conclusion
In patients with PAD, WT decreased cardiovascular load assessed before and after walking to maximal IC. Furthermore, the acute and chronic cardiovascular responses to walking were not associated. Thus, WT may reduce the risk of immediate post-walking cardiac events in susceptible patients.
Introduction
Peripheral arterial disease (PAD) affects over 200 million people worldwide and is characterized by the occlusion of peripheral arteries, reducing blood flow to the distal muscles The primary symptom of PAD is intermittent claudication (IC) that is characterized by pain in the affected leg triggered by walking and that decreases the patients’ functional capacity. , Additionally, patients with PAD and IC often exhibit impaired cardiac autonomic modulation and high blood pressure (BP), contributing to increased cardiovascular overload and, consequently, higher cardiovascular mortality. ,
Walking training (WT) is the first-line treatment for improving functional capacity in patients with PAD and IC. , Additionally, WT has been shown to ameliorate cardiovascular function in this population by reducing resting BP, heart rate (HR) and rate-pressure product (RPP). , However, each session of walking can acutely increase the cardiovascular risk of these patients. Previous studies reported elevated BP and HR after an acute session of walking to maximal IC, leading to increased post-exercise cardiovascular load, , which enhances the risk of ischemia and/or arrhythmias in susceptible patients While the benefits of chronic WT for reducing resting cardiovascular load are well-established, , its impact on cardiovascular load immediately following walking has not yet been studied in this population.
Furthermore, it has been suggested that the acute and chronic cardiovascular responses to exercise are related for a range of populations with acute post-exercise responses able to predict chronic training effects and identify individuals who are likely to benefit more from chronic training Along this line, strong positive correlations have been reported between the decrease in BP after a session of exercise and the BP-lowering effect of chronic training in healthy women, pre-hypertensives, , hypertensives , and patients with coronary artery disease Similar correlations have been reported for HR and RPP in medicated hypertensives elderly women However, given that patients with PAD and IC have numerous pathophysiological alterations that affect cardiovascular function, and cardiovascular mortality, , it is important to identify associations between cardiovascular responses resulting from acute and chronic exercise to aid appropriate exercise prescription in this specific population.
Therefore, the present study aimed to determine, in patients with PAD and IC: a) the effect of chronic exercise (i.e. WT) on cardiovascular load after walking to maximal IC; and b) the relationships between cardiovascular responses following acute and chronic exercise.
Materials and methods
The study’s protocol followed the Declaration of Helsinki, was registered at the Brazilian Clinical Trials database ( http://www.ensaiosclinicos.gov.br , RBR-3pq58k), and was approved by an Ethics Committee of Human Research at the University of São Paulo (process 667.382). Written informed consent from all participants was obtained prior to participation. This study was part of a larger, randomized clinical trial where the primary outcomes of the effects of WT on resting physiological parameters were published
Participants
Patients with PAD and IC enrolled at a tertiary center specialized in the treatment of vascular disease were invited to participate. Patients were included if they met the following criteria: (i) male; (ii) aged ≥ 50 years; (iii) graded at Fontaine stage II and Rutherford stages 1 – 3 of PAD; (iv) ankle brachial index (ABI) at rest < 0.90 in at least one lower limb; (v) absence of non-compressible arteries; (vi) resting systolic and diastolic BPs lower than 160 and 105 mmHg, respectively; (vii) absence of revascularization surgery or angioplasty in the last year; (viii) not taking betablockers, non-dihydropyridine calcium channel antagonists, anticoagulant clopidogrel, and insulin; (ix) ability to walk at least 2 minutes at 3.2 km/h on a treadmill; (x) ability to undertake an incremental treadmill test limited by symptoms of IC; (xi) absence of myocardial ischemia or complex dysrhythmias during a treadmill test; (x) absence of diabetes with clinical autonomic neuropathy; and (xi) absence of medical comorbidities (such as cardiomyopathies, neurodegenerative conditions, orthopedic diseases and others) that prevent exercise execution. Patients were also excluded if they changed their medications during the study period.
Study design
This was a randomized, controlled, parallel group study performed in a single center. Adherence to the study criteria was checked by preliminary evaluations, and patients who fulfilled all criteria were randomly assigned, via a computer random number generator ( https://www.randomizer.org ), to one of two groups: Control (CO) or 12- weeks of regular WT. Prior to (i.e. baseline) and after the 12-week intervention period, participants from both groups completed an experimental session in which they underwent a progressive walking test to maximal IC while the study’s outcomes were assessed pre- and post-walking test.
Preliminary evaluations
All participants were interviewed to identify age, PAD characteristics, presence of cardiovascular disease and risk factors, comorbid conditions, and current medication. ABI was measured as previously described Body mass and height were assessed to calculate body mass index (BMI). Auscultatory BP was measured in triplicate after five minutes of seated rest during two visits and the mean value was calculated. Afterwards, participants completed a graded maximal walking test on a treadmill (Imbrasport, ATL, Porto Alegre, Brazil) with the speed set at 3.2 km/h and grade increased by 2% every two minutes until maximal IC pain Participants were monitored by a 12-lead ECG (Welch Allyn, Inc., Cardio Perfect MD, New York, USA), and the HR at the initial onset of pain was recorded .
Experimental sessions
For both experimental sessions, participants were instructed to maintain similar routines in the prior 24 hours and to avoid physical exercise for the previous 48 hours, alcoholic beverages for 24 hours, and smoking on the day of the sessions. Medication consumption, as recommended by their physicians, was followed by all participants and all attended the laboratory in a fasted state at the same time of the day (07:00). The laboratory temperature was kept between 20 and 22°C.
Upon arrival at the laboratory, participants rested in the supine position for 20 minutes before the beginning of the assessments. HR and auscultatory BP were measured in triplicate with the mean value calculated. After this pre-walking assessment, participants moved to the treadmill and underwent a graded maximal walking test using the same protocol as in the preliminary evaluations (i.e., 3.2 km/h with grade increased by 2% every 2 minutes) until maximal IC (i.e., when leg pain could not be tolerated). Thereafter, participants returned to the supine position and rested for 30 minutes when post-walking assessments were conducted. Participants were randomized and informed about their allocated group after the baseline experimental session.
Measurements
Cardiovascular load was assessed as HR, BP and RPP. HR was determined from the ECG (EMG System do Brazil, EMG 030110/00B, Brazil) while auscultatory systolic and diastolic BPs were measured using a mercury sphygmomanometer (Unitec, São Paulo, Brazil). RPP was calculated as HR x systolic BP.
Interventions
Both groups completed an intervention consisting of two sessions per week for 12 weeks. The WT group followed a training protocol detailed elsewhere , , that has been shown to produce health benefits for PAD and IC patients. Each training session was supervised by a researcher and consisted of 15 bouts of 2-minutes walking on a treadmill interspersed by 2-minutes upright rest, resulting in a 60-minute training session with 30-minutes of active walking. During the walking bouts, the speed was kept at 3.2 km/h and the grade was adjusted to maintain the patient’s HR at the HR obtained at the onset of pain threshold evaluated in the graded maximal walking test executed in the preliminary procedures.
The CO group also performed supervised sessions consisting of stretching for 30 minutes. During each session, approximately 20 passive stretching exercises were performed for all body segments with each exercise executed two to three times for 20-seconds. This CO intervention was applied instead of a non-walking group as active commuting within the study could induce cardiovascular benefits. In previous studies, this stretching training protocol induced no change in cardiovascular function in patients with PAD and IC. , ,
Statistical analyses
Normality of data distribution and homogeneity of variance were evaluated, respectively, by Shapiro-Wilk and Levene tests. Between group characteristics at Baseline were compared by t- or chi-squared tests. To analyze the chronic training effects on post-walking responses, the values obtained in both groups (CO and WT) at both timepoints of the study (i.e. Baseline and 12 weeks), and before and after the walking test (i.e. pre- and post-walking) were compared by three-way mixed ANOVAs (group vs. study timepoint vs. session timepoint) (Statsoft, Statistic for Windows 4.3, Oklahoma, USA). Newman-Keuls post-hoc tests were used, when necessary. Additionally, Pearson correlations were used to explore the relationship between the acute cardiovascular responses (BP, HR and RPP) after maximal walking at Baseline (Δ = post – pre-walking) and the pre-walking responses to chronic WT (Δ = 12-weeks – Baseline). A P value of < 0.05 was considered significant and data were presented as mean ± standard error (SE).
Results
As previously described, 78 participants were recruited with 54 providing informed consent, and 32 completing both Baseline and 12-weeks assessments (16 in each group). The Baseline characteristics for age, BMI, ABI, systolic and diastolic BP, frequency of comorbidities and medication use were similar between the groups as previously reported (7).
All cardiovascular variables, except HR at Baseline for the WT group, increased significantly from pre- to post-walking at Baseline and after 12 weeks of intervention for both groups ( Fig. 1 ). Pre- and post-walking systolic BP, diastolic BP and RPP were significantly lower at both, Baseline and 12-weeks, in the WT group ( Fig. 1 ), while pre-walking HR was significantly greater at Baseline than 12-weeks in the WT group ( Fig. 1 ). The pre- and post-walking RPP values at 12-weeks for the WT group were significantly lower compared to those of the CO group ( Fig. 1 ).
