EuroPRevent 2010 Prevention in Adults: Is it good to Know? Almir Sérgio Ferraz MD, PhD Cardiovascular Rehabilitation Center almirferraz@uol.com.br Institute Dante Pazzanese of Cardiology 1 No conflict of interest to be disclosured
Institute Dante Pazzanese of Cardiology São Paulo - Brazil What is this? 2
Exercise as a Mean to Control Low-Grade Systemic Inflammation Topics The Complexity of the Immune System The Inflammatory Pathways: Pathophysiology The Immune System and Prognosis Exercise intervention and the Immune System 3
Low-Grade Systemic Inflammation What is this? 4
Low-Grade Systemic Inflammation C Low- grade systemic inflammation is a chronic process that has been characterized by a 2 - to - 3 fold elevation in circulating levels of some pro-inflammatory and antiinflammatory cytokines, as well as the acute phase reactant C-reactive protein. These conditions are associated to many systemic chronic diseases 5
The Inflammatory Pathways: Pathophysiology 6
The Complexity of Immune System Low-Grade Systemic Inflammation C and Chronic Disease Insulin resistance Chronic Heart Failure Atherosclerosis Low Grade Inflammation CRP and Cytokines Obesity Dementia Alzheimer Diabetes Type II 7
The Immune System and Prognosis Cytokines in HF IDC and Chagas disease etiology C n =75 Control = 12 Chagas = 28 IDC = 35 8 Mocelin AO et al Eur J Heart Fail 2005;7:869-73
The Immune System and Prognosis Cytokines in HF IDC and Chagas disease etiology C 9 Mocelin AO et al Eur J Heart Fail 2005;7:869-73
Exercise intervention and the Immune System C IL-6 Production and Release in Contracting Muscle 10 Pedersen BK et al J Appl Physiol 2005 98:1154
Exercise intervention and the Immune System C Acute response of Cytokines Cascade during Exercise 11 Pedersen BK et al J Appl Physiol 2005 98:1154
e-selectin [ng/ml] Exercise intervention and the Immune System C Exercise Trainning and Inflammatory mediators 140 120 * e-selectin (Cell Adhesion Molecule) 100 # 80 60 40 20 0 CHF rest CHF training volunteers rest volunteers training *: p<0.05 vs. volunteers rest; #: p<0.08 (trend) vs CHF-rest 12 Niebauer J et al., Eur J Heart Fail 2005;7:183-188 & 189-193
Exercise intervention and the Immune System C Exercise Trainning and Inflammatory mediators [µm] 25 Hypoxathine (pro-oxidant) 20 15 * 10 5 0 CHF rest CHF training volunteers rest volunteers training *: p< 0.02 vs CHF rest; : p<0.05 vs CHF rest 13 Niebauer J et al., Eur J Heart Fail 2005;7:183-188 & 189-193
Exercise intervention and the Immune System Training and Immunomodulation in CHF c n = 44 12 weeks 14 Adamopoulus S et al. JACC 2002;39:653-63.
Exercise intervention and the Immune System Study Design C Referred 352 pts Selected 30 out-pts Inclusion / Exclusion Criteria 20 pts Exercise Randomization CPX, ECHO, hs-crp, TNF, IL-6, Adiponectin, BNP, QoL, 10 pts Control Exercise training program 6 months CPX, ECHO, hs-crp, TNF, IL-6, Adiponectin, BNP, QoL, 15 Ferraz AS et al Circulation 2004;17(suppl):793-4
Exercise intervention and the Immune System Exercise Training and Oxygen Consumption c 30. VO 2 ml/kg/min Before After - 6 month 25 p = 0.001 n = 30 p = ns 20 24 7% 15 p = 0.006 18 6% p = ns 10 5 0. VO 2 AT Exercise. Peak VO 2. VO 2 AT Control. Peak VO 2 16 Ferraz AS et al Circulation 2004;17(suppl):793-4
Exercise intervention and the Immune System Exercise Training and Immflamatory Markers c in CHF Circulating IL-6 and TNF- pg / ml 7.0 Before After - 6 month n = 30 6.0 p = ns 5.0 p = ns p = ns 4.0 p = ns 3.0 2.0 1.0 17 0.0 IL-6 TNF- IL-6 TNF- Exercise Control Ferraz AS et al Circulation 2004;17(suppl):793-4
Exercise intervention and the Immune System Effect of Exercise on Circulating and Local c Cytokines in CHF Vastus Lateralis - biopsy Ex Training - 6 month 18 Linke A et al Circulation 2005;111:1763-70
Exercise intervention and the Immune System Exercise Training and hs-crp cin CHF 10.0 Before After - 6 month 9.0 8.0 p = 0,002 n = 30 p = ns 7.0 6.0-52 7% 5.0 4.0 3.0 2.0 1.0 0.0 Exercise Control 19 Ferraz AS et al Circulation 2004;17(suppl):793-4
Exercise intervention and the Immune System Adiponectin: Inflammatory Mediator in CHF Adiponectin is an adipocyte-specific cytokine and its high plasma Level has been demonstrated to be a predictor of mortality in CHF n =449 follow up : 1.27-3.91 years 20 Tsutamoto T et al Eur Heart J 2007;28:1723-30 Kistorp et al Circulation 2005;112:1756-62
Adponectin (Median) Exercise intervention and the Immune System Exercise Training and Adiponectin in CHF 70 60 50 p time = 0.0001 n = 30 p interaction (group*time) = 0.0006 Control Exercise 40 30 20 10 0 Before Time After 21 Ferraz AS et al Eur Heart J 2009;30(suppl):74
Exercise intervention and the Immune System Adiponectin Difference Correlation between Adiponectin and Peak VO 2 (%) 50,00 25,00 r = -0.47 n = 30 p = 0.008 Grupo Control Exercise 0,00-25,00-50,00-75,00-5,00 0,00 5,00 10,00 15,00 Peak VO2 Difference (%) 22 Ferraz AS et al Eur Heart J 2009;30(suppl):74
Conclusions Exercise may reduce some inflammatory markers Exercise may protect against systemic low grade inflammation in chronic heart failure The link between effects of exercise and the long term benefits remain to be proven.
Conclusions Exercise may reduce some inflammatory markers Exercise may protect against systemic low grade inflammation in chronic heart failure The link between effects of exercise and the long term benefits remain to be proven.
Conclusions Exercise may reduce some inflammatory markers Exercise may protect against systemic low grade inflammation in chronic heart failure The link between effects of exercise and the long term benefits remain to be proven