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

Acute Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00755131
• Other study ID #: UNINA-15775
• Status: Completed
• Phase: N/A
• First received: September 17, 2008
• Last updated: January 25, 2010
• Start date: September 2008
• Est. completion date: October 2009

Study information

• Verified date: December 2009
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Institute of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: October 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

Other:
• Exercise-based Cardiac Rehabilitation program
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.

Locations

Country	Name	City	State
Italy	University of Naples "Federico II"	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

References & Publications (11)

Cirillo P, Calì G, Golino P, Calabrò P, Forte L, De Rosa S, Pacileo M, Ragni M, Scopacasa F, Nitsch L, Chiariello M. Tissue factor binding of activated factor VII triggers smooth muscle cell proliferation via extracellular signal-regulated kinase activation. Circulation. 2004 Jun 15;109(23):2911-6. Epub 2004 Jun 1. — View Citation

Cirillo P, Golino P, Calabrò P, Calì G, Ragni M, De Rosa S, Cimmino G, Pacileo M, De Palma R, Forte L, Gargiulo A, Corigliano FG, Angri V, Spagnuolo R, Nitsch L, Chiariello M. C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation. Cardiovasc Res. 2005 Oct 1;68(1):47-55. — View Citation

Giallauria F, Cirillo P, Lucci R, Pacileo M, D'Agostino M, Maietta P, Vitelli A, Chiariello M, Vigorito C. Autonomic dysfunction is associated with high mobility group box-1 levels in patients after acute myocardial infarction. Atherosclerosis. 2010 Jan;208(1):280-4. doi: 10.1016/j.atherosclerosis.2009.07.025. Epub 2009 Jul 14. — View Citation

Giallauria F, Cirillo P, Lucci R, Pacileo M, D'agostino M, Maietta P, Vitelli A, Chiariello M, Vigorito C. Effects of exercise-based cardiac rehabilitation on high mobility group box-1 levels after acute myocardial infarction: rationale and design. J Cardiovasc Med (Hagerstown). 2009 Aug;10(8):659-63. doi: 10.2459/JCM.0b013e32832d4979. — View Citation

Giallauria F, Cirillo P, Lucci R, Pacileo M, De Lorenzo A, D'Agostino M, Moschella S, Psaroudaki M, Del Forno D, Orio F, Vitale DF, Chiariello M, Vigorito C. Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide. Eur J Cardiovasc Prev Rehabil. 2008 Feb;15(1):113-8. doi: 10.1097/HJR.0b013e3282f00990. — View Citation

Giallauria F, De Lorenzo A, Pilerci F, Manakos A, Lucci R, Psaroudaki M, D'Agostino M, Del Forno D, Vigorito C. Long-term effects of cardiac rehabilitation on end-exercise heart rate recovery after myocardial infarction. Eur J Cardiovasc Prev Rehabil. 2006 Aug;13(4):544-50. — View Citation

Giallauria F, De Lorenzo A, Pilerci F, Manakos A, Lucci R, Psaroudaki M, D'Agostino M, Del Forno D, Vigorito C. Reduction of N terminal-pro-brain (B-type) natriuretic peptide levels with exercise-based cardiac rehabilitation in patients with left ventricular dysfunction after myocardial infarction. Eur J Cardiovasc Prev Rehabil. 2006 Aug;13(4):625-32. — View Citation

Giallauria F, Galizia G, Lucci R, D'Agostino M, Vitelli A, Maresca L, Orio F, Vigorito C. Favourable effects of exercise-based Cardiac Rehabilitation after acute myocardial infarction on left atrial remodeling. Int J Cardiol. 2009 Aug 21;136(3):300-6. doi: 10.1016/j.ijcard.2008.05.026. Epub 2008 Aug 3. — View Citation

Giallauria F, Lucci R, Pietrosante M, Gargiulo G, De Lorenzo A, D'Agostino M, Gerundo G, Abete P, Rengo F, Vigorito C. Exercise-based cardiac rehabilitation improves heart rate recovery in elderly patients after acute myocardial infarction. J Gerontol A Biol Sci Med Sci. 2006 Jul;61(7):713-7. — View Citation

Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002 Mar 5;105(9):1135-43. Review. — View Citation

Yamada S, Maruyama I. HMGB1, a novel inflammatory cytokine. Clin Chim Acta. 2007 Jan;375(1-2):36-42. Epub 2006 Jul 25. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	High Mobility Group Box-1 (HMGB1)Levels at Baseline and 6 Months		baseline and 6-month follow-up	No
Secondary	Peak Oxygen Consumption (VO2peak) at Baseline and 6 Months		Baseline and 6-month follow-up	No