Effects of Cardiac Rehabilitation on High Mobility Group Box-1 Levels After Acute Myocardial Infarction

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Cardiac Rehabilitation on High Mobility Group Box-1 Levels After Acute Myocardial Infarction

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Other: Exercise-based Cardiac Rehabilitation program


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Training Group<br>Postinfarction patients undergo 6-month exercise-based Cardiac Rehabilitation Program | Other: Exercise-based Cardiac Rehabilitation program<br>* 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.<br>* Other names: Cardiac Rehabilitation;|
| No Intervention: Control Group<br>Postinfarction patients NOT undergoing 6-months exercise-based Cardiac Rehabilitation program | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline and 6-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 6-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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