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The aim of this meta-analysis was to investigate the effects of concurrent, aerobic, and resistance exercises on markers of inflammation and vascular adhesion molecules (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1], fibrinogen, IL-1 beta, IL-10, IL-18 and E-selectin) in patients with heart failure (HF).
Methods
PubMed, Scopus, Web of Science and Google-Scholar databases were searched until August 31, 2022. Randomized controlled trial (RCT) studies for exercise interventions on circulating inflammatory and vascular adhesion markers in patients with HF were included. Standardized mean difference (SMD) and 95% confidence intervals (95% CIs) were calculated.
Results
Forty-five articles were included. Exercise training significantly reduced hs-CRP [SMD -0.441 (95% CI:-0.642 to -0.240), p=0.001], IL-6 [SMD -0.158 (95%CI: -0.303 to -0.013), p=0.032], and sICAM-1 [SMD -0.282 (95% CI:-0.477 to -0.086), p=0.005] markers. Analysis of subgroup revealed that there was a significant reduction in hs-CRP for middle aged, elderly aged, overweight status, aerobic exercise, concurrent training, both high and moderate intensities, short-term, long-term, and very long-term follow-ups compared to control group (P<0.05). There was a significant reduction in IL-6 and sICAM-1 for middle aged, aerobic exercise, moderate intensity, short-term follow-up and as well as TNF-α for middle aged compared to control-group (P<0.05).
Conclusions
These exercise-related changes (improved inflammation and vascular adhesion markers) as clinical benefits in general and exercise-based cardiac rehabilitation, in a more specific format, improve clinical evolution and survival in patients with HF of different etiologies (registration number=CRD42021271423).
Committee on exercise physiology & training of the heart failure association of the European society of cardiology. Regional differences in exercise training implementation in heart failure: findings from the exercise training in heart failure(ExTraHF)survey.
). Regular exercise training can restore endothelial function and improved neo-angiogenesis, and reduce production of inflammatory cytokines, reactive oxygen species (ROS), and peripheral vascular resistance with improved cardiac output, maximal oxygen consumption (VO2max), maximal heart rate (HRmax), and systolic blood pressure in HF (
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Effect of 10-week supervised moderate-intensity-intermittent vs. continuous-aerobic-exercise programs on vascular adhesion molecules in patients with heart failure.
Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure:The Vent-HeFT trial:a European prospective multicentre randomized trial.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
), but these did not include patients with HF. Therefore, the purpose of this meta-analysis was to clarify the effects of concurrent, aerobic, and resistance exercises on inflammatory markers and VAMs in patients with HF.
Methods
Search strategy
Our meta-analysis protocol was registered in PROSPERO at the University of York (registration number = CRD42021271423) and designed based on the PRISMA guidelines (
). PubMed, Scopus, Web of Science, and Google Scholar databases were searched to identify original published full-text articles until August 31, 2022. The search strategy for exercises, inflammatory markers, VAMs and patients with HF included the keywords as follows: [concurrent AND resistance AND aerobic AND inflammation OR cytokines OR hs-CRP IL-6 OR TNF-α OR sVCAM-1 OR sICAM-1 OR fibrinogen OR IL-1 beta OR IL-10 OR IL-18 OR E-selectin AND heart failure AND randomized controlled trial (RCT)]. The abstracts and titles of articles after removing duplicate publications were screened and then articles were reviewed for eligibility by four reviewers (A-M, A-K, M-N and N-Gh).
Study selection
Only RCT studies were considered for eligibility. Inclusion criteria as follows: a) English language original research, b) only human patients with HF aged ≥ 18 yrs, c) HF with maintaining routine medications, standard & usual care, home-based exercise, and optimal medical therapy d) measuring serum or plasma levels of hs-CRP, IL-6, TNF-α, sICAM-1, sVCAM-1, fibrinogen, IL-1-beta, IL-10, IL-18 and E-selectin at baseline and after intervention, e) duration of exercise ≥ 2 weeks, f) having at least one exercise group (aerobic, resistance, concurrent) with HF vs. control group with HF, g) usual care or routine medications for control group with and without exercise prescription and/or home-based exercise intervention. In this meta-analysis, the type of exercise included aerobic (aerobic training; endurance training; aerobic exercise-based cardiac rehabilitation; cardiac rehabilitation; low and moderate-intensity inspiratory; aerobic interval training; Tai Chi), resistance (resistance training; functional electrical stimulation; inspiratory muscle training; peripheral resistance training; power training), and concurrent (concurrent training; combined; aerobic plus resistance). Exclusion criteria as described previously (
Data extraction process was performed and any disagreement was resolved by discussion among all teamwork reviewers (A-M, A-K, M-N, N-Gh, and M-G). The parameters of each study were extracted as follows: a) study design, b) participant characteristics including age, sex, body mass index (BMI) and sample size, c) study characteristics including exercise (type, frequency, duration, training protocol, and supervised/unsupervised) and control group, d) outcome markers including hs-CRP, IL-6, TNF-α, sICAM-1, sVCAM-1, fibrinogen, IL-1-beta, IL-10, IL-18 and E-selectin. Pre & post-test values as mean ± standard deviation/SD and mean differences were considered to generate forest plots. Data of standard error, median, range and interquartile range were converted to mean ± SD (
). Data figures or graphs were extracted by Getdata Graph Digitizer software. Exercise studies with multiple arms vs. control group were included, as control group was divided by the number of intervention arms to avoid multiple sample size counting. In addition, for the studies with more than one evaluated post-test, only the last period of post-test was considered. To obtain additional information about the articles, the corresponding author was contacted.
Quality assessment and sensitivity analysis
The Pedro scale was used to assess the methodological quality of included-studies (Pedro scores ranged 7-15 with maximum 15 scores) and risk of bias [high risk of bias= Pedro score of less than 5, which were removed studies with a high risk of bias (
reporting of between group statistical comparison#
point measures and measures of variability reported for main effects
Activity monitoring in control group
Relative exercise intensity reviewed
Supervised /Non-supervised
Total PEDRO score
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Note: Total PEDRO score out of 15 points; (✓) = one point; (-) = not reported or unclear; *Three points possible—one point if adherence >85%, one point if adverse events reported, one point if exercise attendance is reported; #Two points possible—one point if primary outcome is reported, one point if all other outcomes reported. Pedro score less than 5=high risk of bias.
The comprehensive meta-analysis (CMA) software was used for data analysis and calculating the standardized mean difference (SMD) and 95% confidence intervals (CIs) by fixed and random effect models. Significance level was considered at a P < 0.05. The effect size was calculated to compare the effects of exercises vs. control group on circulating hs-CRP, IL-6, TNF-α, sICAM-1, sVCAM-1, fibrinogen, IL-1-beta, IL-10, IL-18 and E-selectin markers. The Cochrane guidelines for interpreting effect sizes were considered as follows: large (more than 0.8), medium (0.5-0.79), and small (0.2-0.49) effect sizes (
). Heterogeneity was assessed by using the I-squared (I2) statistic. Cochrane guidelines in the interpretation of I2 statistic were considered as follows: high heterogeneity (75%), medium heterogeneity (50%), and low heterogeneity (25%). The visual interpretation of funnel plots was considered to identify publication bias. In addition, Egger’s test was used as a secondary determinant test; significant publication bias was considered apparent if P < 0.1 (
The initial searches in PubMed, Scopus, Web of Science, and Google Scholar databases were identified including 278160, 1008, 4434264, and 174000 articles, respectively. After removing duplicates and screening articles based on the title/abstract, 426 full-text articles were included for final screening based on the inclusion and exclusion criteria. Forty-five full-text articles (of those 426 articles) met the inclusion criteria and 381 articles were excluded (Figure 1). In this meta-analysis, eight included articles were two arms of exercise interventions (
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Effect of 10-week supervised moderate-intensity-intermittent vs. continuous-aerobic-exercise programs on vascular adhesion molecules in patients with heart failure.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig exercise intervention in chronic heart failure and aging catabolism study.
Chronic heart failure and aging-effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig exercise intervention in chronic heart failure and aging (LEICA) study.
). Forty-five full-text articles (intervention arms=55), 41 aerobic intervention arms, 10 concurrent intervention arms, and 4 resistance intervention arms were included. A total of 3403 participants (exercise=1868 and control=1535) were included. The study flowchart is shown in Figure 1.
Figure 1Flowchart of study selection. Note. HF= Heart failure.
The participant characteristics of included articles are presented in Table 2. The sample size, mean age and BMI for each article were ranged between 7 and 477 participants (
Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig exercise intervention in chronic heart failure and aging catabolism study.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
), respectively. A total of 45 included articles, 36 articles were included both male and female genders, six articles were included only male gender (
Exercise training in patients with advanced chronic heart failure(NYHA-IIIb) promotes restoration of peripheral vasomotor function, induction of endogenous regeneration, and improvement of left ventricular function.
Regular exercise training compared with percutaneous intervention leads to a reduction of inflammatory markers and cardiovascular events in patients with coronary artery disease.
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Effect of 10-week supervised moderate-intensity-intermittent vs. continuous-aerobic-exercise programs on vascular adhesion molecules in patients with heart failure.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig exercise intervention in chronic heart failure and aging catabolism study.
Chronic heart failure and aging-effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig exercise intervention in chronic heart failure and aging (LEICA) study.
Exercise training in patients with advanced chronic heart failure(NYHA-IIIb) promotes restoration of peripheral vasomotor function, induction of endogenous regeneration, and improvement of left ventricular function.
Regular exercise training compared with percutaneous intervention leads to a reduction of inflammatory markers and cardiovascular events in patients with coronary artery disease.
Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris.
Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients.
Short-term walking physical training and changes in body hydration status, B-type natriuretic peptide and C-reactive protein levels in compensated congestive heart failure.
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure:The Vent-HeFT trial:a European prospective multicentre randomized trial.
Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex-DHF pilot study.
Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients with combined coronary artery disease and type-2 diabetes mellitus: Sub-study of a randomized control trial.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris.
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Effect of 10-week supervised moderate-intensity-intermittent vs. continuous-aerobic-exercise programs on vascular adhesion molecules in patients with heart failure.
Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig exercise intervention in chronic heart failure and aging catabolism study.
Chronic heart failure and aging-effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig exercise intervention in chronic heart failure and aging (LEICA) study.
Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Regular exercise training compared with percutaneous intervention leads to a reduction of inflammatory markers and cardiovascular events in patients with coronary artery disease.
Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure:The Vent-HeFT trial:a European prospective multicentre randomized trial.
Exercise training in patients with advanced chronic heart failure(NYHA-IIIb) promotes restoration of peripheral vasomotor function, induction of endogenous regeneration, and improvement of left ventricular function.
Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris.
Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex-DHF pilot study.
Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig exercise intervention in chronic heart failure and aging catabolism study.
Chronic heart failure and aging-effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig exercise intervention in chronic heart failure and aging (LEICA) study.
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Effect of 10-week supervised moderate-intensity-intermittent vs. continuous-aerobic-exercise programs on vascular adhesion molecules in patients with heart failure.
Short-term walking physical training and changes in body hydration status, B-type natriuretic peptide and C-reactive protein levels in compensated congestive heart failure.
Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients with combined coronary artery disease and type-2 diabetes mellitus: Sub-study of a randomized control trial.
Regular exercise training compared with percutaneous intervention leads to a reduction of inflammatory markers and cardiovascular events in patients with coronary artery disease.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris.
Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients.
Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients with combined coronary artery disease and type-2 diabetes mellitus: Sub-study of a randomized control trial.
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Effect of 10-week supervised moderate-intensity-intermittent vs. continuous-aerobic-exercise programs on vascular adhesion molecules in patients with heart failure.
Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure:The Vent-HeFT trial:a European prospective multicentre randomized trial.
Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig exercise intervention in chronic heart failure and aging catabolism study.
Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig exercise intervention in chronic heart failure and aging catabolism study.
Chronic heart failure and aging-effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig exercise intervention in chronic heart failure and aging (LEICA) study.
Short-term walking physical training and changes in body hydration status, B-type natriuretic peptide and C-reactive protein levels in compensated congestive heart failure.
Exercise training in patients with advanced chronic heart failure(NYHA-IIIb) promotes restoration of peripheral vasomotor function, induction of endogenous regeneration, and improvement of left ventricular function.
Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig exercise intervention in chronic heart failure and aging catabolism study.
Chronic heart failure and aging-effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig exercise intervention in chronic heart failure and aging (LEICA) study.
Exercise training in patients with advanced chronic heart failure(NYHA-IIIb) promotes restoration of peripheral vasomotor function, induction of endogenous regeneration, and improvement of left ventricular function.
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Effect of 10-week supervised moderate-intensity-intermittent vs. continuous-aerobic-exercise programs on vascular adhesion molecules in patients with heart failure.
Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris.
Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients.
Short-term walking physical training and changes in body hydration status, B-type natriuretic peptide and C-reactive protein levels in compensated congestive heart failure.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure:The Vent-HeFT trial:a European prospective multicentre randomized trial.
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Regular exercise training compared with percutaneous intervention leads to a reduction of inflammatory markers and cardiovascular events in patients with coronary artery disease.
Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients with combined coronary artery disease and type-2 diabetes mellitus: Sub-study of a randomized control trial.
Table 3Study characteristics in patients with heart failure.
Source, yr
Exercise intervention
Control group
Type
Frequency (days/week)
Follow-up (Duration)
Training protocol
Supervised or Unsupervised
Abolahrari-Shirazi et al., 2018-a
Combined (cycle+weight training)
3
7 weeks
Endurance= 45 min, 40%–70% peak VO2; 20 min cycle ergometer, 10 min arm ergometer, 15 min treadmill; Resistance= knee extension, knee flexion, elbow flexion, and shoulder abduction. 40% one repetition maximum (1RM)-60% 1RM and duration of 15 min.
Supervised
Pamphlet for daily exercising at home lasted 15–20.
Abolahrari-Shirazi et al., 2018-b
Endurance (cycle)
3
7 weeks
Endurance= 45 min, 40%–70% peak VO2; 20 min cycle ergometer, 10 min arm ergometer, 15 min treadmill;
Supervised
Pamphlet for daily exercising at home lasted 15–20.
Adamopoulos et al., 2001
Aerobic (bicycle)
5
12 weeks
30 min bicycle, 5 days/week at 50 rpm with 70%–80% of HRmax.
Unknown
Home-based bicycle exercise similar to the aerobic group.
Adamopoulos et al., 2002
Aerobic (bicycle)
5
12 weeks
30 min home-based bicycle, 5 days/week at 50 rpm with 60%–80% of HRmax.
Unknown
Home-based bicycle similar to the aerobic group.
Adamopoulos et al., 2014
Concurrent (cycle+ inspiratory muscle training)
3
12 weeks
Aerobic= 45 min ergometer at 70–80% HRmax with 5 min warm-up and cool down periods. Resistance= 30 min inspiratory-incremental resistive loading device at 60% of individual sustained maximal inspiratory pressure (SPImax) with six inspiratory efforts at each level. Initially, 60 s rest intervals over its six inspiratory efforts, but at the second level through to the sixth level, this rest period was reduced to 45, 30, 15, 10, and 5 sec. After the sixth level, the rest period was kept at 5 sec.
Supervised
Control group was exercised at only 10% of their SPImax.
Ahmad et al., 2014
Aerobic (walking, treadmill or cycling)
3
12 weeks
15-30 min per session at 60% of HRmax reserve.
Supervised
Usual care
Aksoy et al., 2015
Aerobic (cycle)
3
10 weeks
35 min of aerobic exercise (bicycle ergometer at a constant pedal rate of 50 revolutions per min) including 10 min of warm-up and cool down at 50-75% peak VO2. Intermittent: 60-sec bouts of cycling, 30-sec intervals of low intensity cycling at 30 W, 17 cycles of low- and high-intensity bouts. Continuous: worked without any change in the intensity.
Supervised
Optimal medical therapy without any particular regular physical activity before.
Balen et al., 2008
Aerobic (cycle)
3
3 weeks
45 min cycle-ergometer with 50–60% VO2peak plus 30-min organized program of supervised walking on a standardized track.
Supervised
Standard care
Butts et al., 2018
Aerobic (walking)
3
3 months
30 min at 60% HRmax for the first two weeks, 45 minutes 3 times per week at 60% Hrmax for weeks three and four, and 45 min at 70% HRmax for the remaining eight weeks.
Supervised
Education and flexibility and stretching exercises
Byrkjeland et al., 2011
Aerobic (walking)
2
4 months
Three intervals of high intensity (15-18 on the Borg scale) and two periods of moderate intensity (11-13 on the Borg scale), in addition to warm-up and cool-down periods, 50 min walking per session.
Supervised
Standard follow-up care by their primary physician.
de Meirelles et al., 2014
Concurrent (walking+weight training)
3
6 months
90 min aerobic, resistance, and stretching exercises; 30 min of treadmill with 5–15% above the ventilator threshold, whole body skeletal muscle strength with 2-3 sets of 10–15 repetition maximum of 8-10 exercises for the major muscle groups, and Stretching or cool-down period for the major muscle groups.
Supervised
Optimal medical therapy and usual care.
Eleuteri et al., 2013
Aerobic (cycle)
5
3 months
30-min cycle ergometer (60 rev/min) at a power and heart rate corresponding to ventilatory anaerobic threshold (VAT), preceded and followed by a 5-min warm-up and cool-down unloaded period, respectively.
Supervised
Normal activities without exercise intervention.
Erbs et al., 2010
Aerobic (bicycle)
3-6
12 weeks
During the first 3 weeks, patients exercised 3 to 6 times daily for 5 to 20 minutes on a bicycle ergometer at 50% of VO2max in-hospital and 60% of VO2max On discharge.
Supervised
Without exercise intervention.
Feiereisen et al., 2013-a
Concurrent (bicycle+ weight training)
3
14 weeks (40 sessions)
20 min of bicycle and 20 min of strength training on 5 different weight machines by a warm-up period of 5 minutes of bicycle training at 30% of VO2 peak.
Supervised
Without exercise intervention.
Feiereisen et al., 2013-b
Resistance (weight training)
3
14 weeks (40 sessions)
10 different strength exercises on weight machines during 40 min, starting at 60% of 1RM, and progressively increasing to 75% of 1RM; by a warm-up period of 5 minutes of bicycle training at 30% of VO2 peak.
Supervised
Lifestyle activities without exercise intervention.
Feiereisen et al., 2013-c
Aerobic (bicycle)
3
14 weeks (40 sessions)
40 min of bicycle and treadmill, starting at 60% of VO2peak, which they progressively adapted to reach 75% of the V˙O2 peak; by a warm-up period of 5 minutes of bicycle training at 30% of VO2 peak.
Supervised
Without exercise activities.
Fernandes-Silva et al., 2017
Aerobic (cycle)
3
12 weeks
30 min cycle ergometer, 11-14 Borg scales, and 5-min warming and cool-down.
Supervised
Medical therapy without exercise activities.
Fu et al., 2013
Aerobic (cycle)
3
12 weeks
Aerobic interval training (AIT)= 3 min at 30% of VO2peak and five 3-min intervals at 80% of VO2peak; Each interval was separated by 3-min exercise at 40% of VO2peak and 3-min cool-down at 30% of VO2peak. Moderate continuous training (MCI)= warm-up at 30% of VO2peak for 3 min, 60% of VO2peak for 30 min, then a cool-down at 30% of VO2peak for 3 min.
Supervised
General home-based health care
Giallauria et al., 2011
Aerobic (bicycle)
3
6 months
30 min bicycle ergometer, 60-70% of peak VO2, 5-min warming-up and 5-min cool-down.
Supervised
Generic instructions for maintaining physical activity and a correct lifestyle.
Gielen et al., 2012
Aerobic (bicycle)
4
4 weeks
20 min of bicycle ergometer (excluding 5 min of warming-up and cooling down) at 70% of VO2max.
Supervised
Usual clinical care.
Jalaly et al., 2015
Aerobic (walking or jogging)
2
12 weeks
20–30 min walking or jogging on treadmill at 40–60% of heart rate reserve (HRR) and a rating of perceived exertion (RPE) of 11–13 (on 6–20 Borg scale).
Supervised
Without exercise intervention.
Karavidas et al., 2006
Resistance (electrical stimulation)
5
6 weeks
30 min/day at 25 Hz for 5 s followed by 5 s of rest. When the muscles of the right leg were contracted, the muscles of the left leg were relaxing and vice versa.
Supervised
Control group was exposed to the same regimen as the functional electrical stimulation group.
Kim et al., 2008
Aerobic (treadmill or bicycle)
2
14 weeks
A warm-up, 30-40-min of treadmill or bicycle ergometer at 50-85% of VO2max, and a cool-down.
Supervised
Standard care.
Kobayashi et al., 2003
Aerobic (cycle)
2-3
12 weeks
15-min of cycle, adjusted to maintain the heart rate equivalent to the ventilatory threshold level.
Supervised
Normal lifestyle without exercise intervention.
Lara Fernandes et al., 2010
Aerobic (cycling)
3
4 months
60-min including 5 min stretching, 40 min of cycling with a target heart rate between anaerobic threshold and respiratory compensation point, 10 min of local strengthening and 5 min of cool down.
Supervised
Recommendations for lifestyle modification.
Larsen et al., 2001
Aerobic (walking and jogging)
3
12 weeks
10 min of warmup, 25 min of walking and jogging at 80% of maximum capacity, and 10 min of cooling down and stretching.
Supervised
Without exercise intervention.
Linke et al., 2005
Aerobic (walking and bicycle)
3
6 months
20 min of walking, noncompetitive ball games, and calisthenics at 70% of VO2max; during the first 2 weeks, aerobic group exercised in hospital 4 to 6 times daily for 10 minutes each on a bicycle ergometer at 70% of VO2max.
20 min of high-intensity inspiratory muscle training with 10 consecutive maximal repetitions (10RM), five sets of 10 repetitions followed by 1–2 min of unloaded recovery breathing off the device and with 100% of their 10RM twice a day.
Supervised
Sham- inspiratory muscle training at an initial workload of 10 cmH2O which was increased 2.5 cmH2O every/wk.
Masterson-Creber et al., 2015
Aerobic (walking or cycling)
3
12 months
30-35 min of walking or cycling at 60-70% HRmax reserve.
Supervised
Usual care
Mc Dermott et al., 2004
Aerobic (walking)
3
12 weeks
50 min of step back on the treadmill and walk continuously, speed 0.5 miles/hour and grade 2%, and 11-12 RPE.
Supervised
Usual clinical care.
Melo et al., 2019
Aerobic (walking)
2
6 months
60 min, 4 interval training periods, 90–95% HRmax with 3 lower-intensity active periods (60–70% of HRmax) between interval training periods as well as a 10-min warm-up and a 5–7 min cool-down.
Supervised
Usual care.
Munk et al., 2011
Aerobic (bicycle or running)
3
6 months
60 min, warm-up period, followed by four 4-minute intervals at 80–90% of HRmax, intervals were interrupted by 3 min of active recovery at 60–70% of HRmax, 5 min cool-down, 10 min abdominal- and spine-resistance exercises, and 5 min of stretching and relaxing.
Supervised
Usual care.
Myers et al., 2010
Concurrent (treadmill, cycling, stair climbing, elliptical training and rowing)
3
12 months
45 min of treadmill, cycle ergometry, stair climbing, elliptical training, and rowing by 10 min of resistance exercise at 60-80% of HRmax reserve.
Supervised
Usual care.
Niebauer et al., 2005
Concurrent (calisthenics and bicycle)
5
8 weeks
Exercise training consisted of at least 5 days a week of a 20 min/daily of calisthenics and bicycle ergometer at home, first nine exercises in the Canadian airforce XBX program with 25W at 50 rev/min, resistance 70-80% HRmax, and 2-3 min cool down.
Supervised
Without exercise intervention.
Parrinello et al., 2010
Aerobic (walking)
5
10 weeks
30 min of mild–moderate walking exercise over the usual physical activity.
Supervised
Medical therapy and dietary recommendations with routine activities.
Pierce et al., 2008
Aerobic (walking)
7
12 weeks
30 min of continuous treadmill walking and progressed to 35–40 min as tolerated after the initial 4 weeks, and exercise intensity 12–14 Borg scale.
Supervised
Standard medical care.
Prescott et al., 2009
Concurrent walking, cycling, step machine, and step board+ weight training)
2
8 weeks
1.5-h including 20 min warm-up, four 6-min series of aerobic training (walking, cycling, step machine, and step board) and two posts of resistance endurance exercises (leg press and exercises with rubber bands for quadriceps, gluteus/ hamstring region, and arms; three sets of 20 repetitions with each arm/leg), 70–80% of peak VO2 (4–5 modified Borg Scale.
Supervised
Usual care.
Pullen et al., 2008
Aerobic (yoga)
2
8 weeks
10-min warm-up, 40-min standing or seated yoga postures (Asanas), and finally 20-min relaxation including breathing exercises (pranayama) and meditation.
Supervised
Standard medical therapy.
Ranković et al., 2009
Aerobic (treadmill, bicycle or walking)
3
6 weeks
45 min of treadmill, room bicycle or walking at 70-80% of HRmax.
Supervised
Without exercise intervention.
Redwine et al., 2019-a
Aerobic (Tai Chi)
2
16 weeks
60 min of Tai Chi Chuan movements (Yang–Style Short Form–First Third) with 11–13 Borg scale, and warm-up; 10–20 min per day on non-class days at home.
Supervised
Usual care.
Redwine et al., 2019-b
Resistance (resistance band)
2
16 weeks
Resistance band (Upper back, Tricep extension, Bicep curl, Chest press, Internal obliques, Standing hip abduction, Standing hip extension, Seated leg extension, Bent over rows, Lateral rows) with 8- 10 repetitions on each side), with 11–13 Borg scale, and warm-up; 10–20 min per day on non-class days at home.
Supervised
Usual care.
Sandri et al., 2016
Aerobic (bicycle)
4
4 weeks
15-20 min cycle ergometer at 70% VO2max, 5 min of warm up and cool down.
Supervised
Usual clinical care.
Tisi et al., 1997
Aerobic (active and passive leg exercises+walking)
7
12 months
45 min of active and passive leg exercises performed to the limit of claudication pain with daily walks of at least 1 mile.
Supervised
Normal volunteers and/or at least 5 months following elective minor or intermediate non-arterial elective general surgery.
Trippel et al., 2017
Concurrent (bicycle+weight training)
3
12 weeks
30-60 min, the first 4 weeks of bicycle ergometer at 50% peakVO2 in the first 2 weeks and 70% peak VO2 after 1-month, 10 min warm-up and cool-down. After the initial 4 weeks, seven resistance training for major muscle groups; 12–15 repetitions at 60% of 1-RM with one repetition lasting 3 s; After 3 months, increase to two sets, allowing 90 s of rest between set.
Supervised
Usual care.
Tsarouhas et al., 2011
Aerobic (walking)
5
12 weeks
40 min of walking at 40% of HRmax for 10 min progressing to reach at 60% of HRmax.
Unsupervised
Control group received usual care.
Walther et al., 2008
Aerobic (bicycling)
Unknown
24 months
Daily bicycling.
Unsupervised
Control group received usual care and PCI.
Wosornu et al., 1992-a
Aerobic (running and bicycle)
3
6 months
12-60 min of modified Canadian Airforce PBX training; running on the spot, step ups, arm circling, star jumps, standing trunk curls, bridging, trunk rotation, side lying with hip abduction, arm raising, trunk side flexion, and crook lying with trunk rotation, and ended the session with a ride on a stationary bicycle.
Supervised
Control group had no formal exercise training but continued with their leisure time activities.
Wosornu et al., 1992-b
Resistance (weight training)
3
6 months
12-60 min of leg extensions, hamstrings curl, biceps curl, push down, pull down, press behind neck, bench press, pulley row, military press, and sit ups (rest periods of 45 s between each station from).
Supervised
Without formal exercise with their leisure time activities.
Yeh et al., 2011
Aerobic (Tai Chi)
2
12 weeks
1-hour tai chi exercises by standard protocol of a pilot trial.
Supervised
Time-matched education without exercise.
Zaidi et al., 2019
Concurrent (walking and bicycling+weight training)
2
12 months
10–15 min of warm-up and 5–10 min of cool down and concurrent program: 1) circuit training containing 10 aerobic and resistance exercises of large muscle groups(40s work, 20s break); 2) interval training (RPE⩾15) uphill walking (running) outdoors(20s on/off for 3–4min, 5–6 sets); 3) interval step training indoors (3-min series with basic steps, side steps and crossover steps, 4–5 sets) and resistance training; and 4) spinning on a bike (including pyramid intervals 6 × 20, 4 × 40 and 2 × 60 s) and resistance training of chest, biceps, shoulder, triceps, back and front, and 10–15 repetitions. Unsupervised home-based exercise session (e.g. walking, swimming, bicycling, cross-country skiing and resistance training in health studios).
Supervised and unsupervised
Normal follow-up by their general practitioner or without exercise intervention.
Exercise training in patients with advanced chronic heart failure(NYHA-IIIb) promotes restoration of peripheral vasomotor function, induction of endogenous regeneration, and improvement of left ventricular function.
Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris.
Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients with combined coronary artery disease and type-2 diabetes mellitus: Sub-study of a randomized control trial.
Effect of 10-week supervised moderate-intensity-intermittent vs. continuous-aerobic-exercise programs on vascular adhesion molecules in patients with heart failure.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
Exercise training attenuates MuRF-1 expression in the skeletal muscle of patients with chronic heart failure independent of age: the randomized Leipzig exercise intervention in chronic heart failure and aging catabolism study.
Chronic heart failure and aging-effects of exercise training on endothelial function and mechanisms of endothelial regeneration: Results from the Leipzig exercise intervention in chronic heart failure and aging (LEICA) study.
Regular exercise training compared with percutaneous intervention leads to a reduction of inflammatory markers and cardiovascular events in patients with coronary artery disease.
Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients.
Short-term walking physical training and changes in body hydration status, B-type natriuretic peptide and C-reactive protein levels in compensated congestive heart failure.
Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex-DHF pilot study.
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure:The Vent-HeFT trial:a European prospective multicentre randomized trial.
Inflammatory markers in patients with HF including serum/plasma hs-CRP, IL-6, TNF-α, sVCAM-1, sICAM-1, fibrinogen, IL-1-beta, IL-10, IL-18 and E-selectin levels were measured in 24 articles (
Efficacy of combined endurance-resistance training versus endurance training in patients with heart failure after percutaneous coronary intervention:A RCT.
Effect of 10-week supervised moderate-intensity-intermittent vs. continuous-aerobic-exercise programs on vascular adhesion molecules in patients with heart failure.
Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure:The Vent-HeFT trial:a European prospective multicentre randomized trial.
An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.
Regular exercise training compared with percutaneous intervention leads to a reduction of inflammatory markers and cardiovascular events in patients with coronary artery disease.
Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients.
Short-term walking physical training and changes in body hydration status, B-type natriuretic peptide and C-reactive protein levels in compensated congestive heart failure.
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