Acute Myocardial Infarction
Conditions
Keywords
Cardiac Rehabilitation, High Mobility Group Box proteins, Inflammatory markers, Cardiopulmonary Functional Capacity, Maximal Oxygen Consumption, Echocardiography, Left Ventricular Ejection Fraction, Left Ventricular Chambers Dilation, Left Ventricular Remodeling, Left Atrium Remodeling, Cardiac Remodeling, Exercise Training
Brief summary
This purpose of this study is to examine the relationship between HMGB-1 and postinfarction predictors of outcome such as cardiopulmonary and echocardiographic parameters before and after a 6-month exercise-based cardiac rehabilitation program.
Detailed description
Exercise-based Cardiac Rehabilitation after acute myocardial infarction (AMI) has beneficial effects on cardiovascular functional capacity, quality of life, risk factors modification, and morbidity and mortality. Mounting evidences suggest that inflammation plays a key role both on initiation and progression of atherosclerosis. Several markers of systemic inflammation appear to be active effectors in the pathophysiology of athero-thrombotic disease leading to the occurrence of AMI. The high mobility group box 1 (HMGB-1) is a ubiquitous nuclear protein constitutively expressed in quiescent cells, and it has been implicated in several cellular functions, including determination of nucleosomal structure and stability, and binding of transcription factors to DNA sequences. HMGB-1 has been recently recognized as a critical mediator of inflammatory diseases. In fact, the passive release of this protein from necrotic or damaged cells represents an effective stimulus triggering the inflammatory response. Specifically, HMGB-1 binds to the receptor for advanced glycation end products (RAGE) and, in turns, it activates mitogen-activated protein-kinase (MAPK) and nuclear factor-κB (NF-κB). This intracellular pathway leads to the production of several pro-inflammatory cytokines. Interestingly, increased levels of HMGB-1 have been observed in atherosclerotic lesions, suggesting that HMGB-1 might be involved in the pathophysiology of atherosclerosis. This study was designed to investigate the relationship between HMGB-1 and strong postinfarction predictors of outcome such as cardiopulmonary and echocardiographic parameters before and after a 6-month exercise-based Cardiac Rehabilitation program.
Interventions
Trained patients attend the exercise training protocol for 6 months on hospital ambulatory-based regimen 3 times/week. Training sessions are supervised under continuous electrocardiography monitoring by a cardiologist, a physiotherapist and a graduate nurse. Each session is preceded by a 5-min warming-up and followed by a 5-min cooling-down. Exercise is performed for 30 min on a bicycle ergometer with the target of 60-70% of the peak oxygen consumption achieved at the initial symptom-limited cardiopulmonary exercise test. Exercise protocol is performed with a gradual increase in exercise workload until the achievement of the predefined target.
Sponsors
Federico II University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Acute Myocardial Infarction
Exclusion criteria
* BMI higher than 30 and lower than 18 * Residual myocardial ischemia * Severe ventricular arrhythmias * IIb or III degree atrio-ventricular block * Valvular disease requiring surgery * Pericarditis * Severe renal dysfunction (i.e. creatinine \>2.5 mg/dl) * Severe concomitant non-cardiac disease such as cancer * Liver dysfunction (alanine aminotransferase/aspartate aminotransferase level \>1.5 times the upper normal limit) * Dementia * Any systemic disease limiting exercise * Inability to participate in a prospective study for any logistic reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months | baseline and 6-month follow-up | High mobility group box-1 (HMGB1) is a ubiquitous nuclear protein, constitutively expressed in quiescent cells, where it is involved in several cellular functions, including determination of nucleosomal structure and stability, and binding of transcription factors to DNA sequences. HMGB1 has been recently recognized as a critical mediator of inflammatory processes: the passive release of this protein from necrotic or damaged cells represents an effective stimulus triggering the inflammatory response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months | Baseline and 6-month follow-up | Oxygen consumption at peak exercise stress testing (VO2peak) was obtained breath-by-breath with use of a computerized metabolic cart. VO2peak was recorded as the mean value of VO2 during the last 20 s of the test and expressed in millilitres per kilogram per minute. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate Recovery at Baseline and 6 Months | baseline and 6 month follow-up | The autonomic nervous system (ANS) is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. It is subdivided into two subsystems: the parasympathetic (vagal) and sympathetic nervous system. Sympatho-vagal imbalance is evaluated by post-exercise Heart Rate Recovery (HRR), defined as the fall in heart rate during the first minute after exercise (beats/min). HRR is a marker of vagal tone which is a powerful predictor of all-cause mortality in patients with coronary artery disease. |
Countries
Italy
Participant flow
Recruitment details
This study was a single-center, randomized, controlled study carried out from October 2008 to January 2009 at the Department of Clinical Medicine, Cardiovascular and Immunological Sciences, University of Naples Federico II.
Participants by arm
| Arm | Count |
|---|---|
| Exercise Training Group Postinfarction patients undergoing 6-month exercise-based Cardiac Rehabilitation Program | 37 |
| Control Group Postinfarction patients NOT enrolled in exercise-based Cardiac Rehabilitation program. | 38 |
| Total | 75 |
Baseline characteristics
| Characteristic | Control Group | Exercise Training Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 9 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 28 Participants | 57 Participants |
| Age Continuous | 59.5 years STANDARD_DEVIATION 7.7 | 60.8 years STANDARD_DEVIATION 7 | 60.4 years STANDARD_DEVIATION 7.5 |
| Region of Enrollment Italy | 38 participants | 37 participants | 75 participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 32 Participants | 28 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 37 | 0 / 38 |
| serious Total, serious adverse events | 0 / 37 | 0 / 38 |
Outcome results
Primary
High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months
High mobility group box-1 (HMGB1) is a ubiquitous nuclear protein, constitutively expressed in quiescent cells, where it is involved in several cellular functions, including determination of nucleosomal structure and stability, and binding of transcription factors to DNA sequences. HMGB1 has been recently recognized as a critical mediator of inflammatory processes: the passive release of this protein from necrotic or damaged cells represents an effective stimulus triggering the inflammatory response.
Time frame: baseline and 6-month follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise Training Group | High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months | Baseline | 27.6 ng/ml | Standard Deviation 27.8 |
| Exercise Training Group | High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months | 6 months | 11.7 ng/ml | Standard Deviation 7 |
| Control Group | High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months | Baseline | 24.5 ng/ml | Standard Deviation 18.6 |
| Control Group | High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months | 6 months | 20.5 ng/ml | Standard Deviation 15.6 |
Comparison: Sample size determination was based on a t-test assuming a normal distribution with non-equal variance with the mean and standard deviation for the experimental group (postinfarction patients) of HMGB1 levels equal to 15 ± 7 and 2 ± 1 ng/dl for the control group derived from a previous study, respectively. The required sample size was calculated to be 30 subjects per group to detect on the size of one SD with α value of 0.05 (two-sided) and power (1 - β) of 0.8.p-value: <0.05t-test, 2 sided
Secondary
Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months
Oxygen consumption at peak exercise stress testing (VO2peak) was obtained breath-by-breath with use of a computerized metabolic cart. VO2peak was recorded as the mean value of VO2 during the last 20 s of the test and expressed in millilitres per kilogram per minute.
Time frame: Baseline and 6-month follow-up
Population: intention to treat (ITT) analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise Training Group | Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months | baseline | 16.4 ml/kg/min | Standard Deviation 1.5 |
| Exercise Training Group | Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months | 6 months | 21.0 ml/kg/min | Standard Deviation 2.4 |
| Control Group | Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months | baseline | 16.7 ml/kg/min | Standard Deviation 2.2 |
| Control Group | Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months | 6 months | 16.3 ml/kg/min | Standard Deviation 1.8 |
p-value: <0.05t-test, 2 sided
Other Pre-specified
Heart Rate Recovery at Baseline and 6 Months
The autonomic nervous system (ANS) is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. It is subdivided into two subsystems: the parasympathetic (vagal) and sympathetic nervous system. Sympatho-vagal imbalance is evaluated by post-exercise Heart Rate Recovery (HRR), defined as the fall in heart rate during the first minute after exercise (beats/min). HRR is a marker of vagal tone which is a powerful predictor of all-cause mortality in patients with coronary artery disease.
Time frame: baseline and 6 month follow-up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise Training Group | Heart Rate Recovery at Baseline and 6 Months | baseline | 13.4 beats/min | Standard Deviation 1.7 |
| Exercise Training Group | Heart Rate Recovery at Baseline and 6 Months | 6 months | 19.7 beats/min | Standard Deviation 3.4 |
| Control Group | Heart Rate Recovery at Baseline and 6 Months | baseline | 13.8 beats/min | Standard Deviation 2.7 |
| Control Group | Heart Rate Recovery at Baseline and 6 Months | 6 months | 12.4 beats/min | Standard Deviation 2.5 |
p-value: <0.05t-test, 2 sided