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Dott. Rodolfo Gentilini Dott. Silvia Maffei U.O. Cardiologia Ospedaliera - AOUS Siena

CARDIOLOGIA E’ PROGRESSO Montecatini Terme (PT) 14-15 Novembre 2007. OBESITA’, CACHESSIA E DISTURBI DELLA NUTRIZIONE. Dott. Rodolfo Gentilini Dott. Silvia Maffei U.O. Cardiologia Ospedaliera - AOUS Siena. “Sudden death is more common in those who are naturally fat than in the lean”.

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Dott. Rodolfo Gentilini Dott. Silvia Maffei U.O. Cardiologia Ospedaliera - AOUS Siena

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  1. CARDIOLOGIA E’ PROGRESSO Montecatini Terme (PT) 14-15 Novembre 2007 OBESITA’, CACHESSIA E DISTURBI DELLA NUTRIZIONE Dott. Rodolfo Gentilini Dott. Silvia Maffei U.O. Cardiologia Ospedaliera - AOUS Siena

  2. “Sudden death is more common in those who are naturally fat than in the lean” “The flesh is consumed and becomes water … The abdomen fills with water; the feet and legs swell; the shoulders, clavicles, chest and thighs melt away. This illness is fatal…”

  3. OBESITY IN HEART FAILURE

  4. Visceral Fat Diabetes Mellitus Hypertension Hyper-cholesterolemia Subcutaneous Fat Obesity and cardiovascular risk Després et al. BMJ. 2001;322:716-720

  5. ↑ Lipoprotein lipase Hypertension ↑ Angiotensinogen ↑ IL-6 Inflammation Atherogenicdyslipidaemia ↑ Insulin ↑ FFA Adiposetissue ↑ TNFα ↑ Resistin ↑ Leptin ↑ Adipsin(Complement D) ↑ Lactate Type2 diabetes ↑ Plasminogenactivator inhibitor-1(PAI-1) ↓ Adiponectin Atherosclerosis Thrombosis Adverse cardiometabolic effects of adipocytes Lyon 2003; Trayhurn et al 2004; Eckel et al 2005

  6. The Body Mass Index Poirier. Circulation 2006;113:898-918.

  7. Cumulative survival curves of four body mass index (BMI) categories at five years: reverse epidemiology? Horwich, Tillish. JACC 2001;38:789-95.

  8. The Obesity Paradox Curtis. Arch Intern Med 2005;165:55-61.

  9. Val-HeFT 5010 Pts with Chronic Heart Failure 42% of Pts NYHA III-IV 50% of Pts LVEF< 27% Cicoira, Maggioni.Eur J Heart Fail 2007;9:397-402.

  10. Prognostic importance of BMI in acute decompensated HF is independent of LVEF In hospital mortality of 108.927 pts with acute decompensated HF ADHERE. Am Heart J 2007;153:74-81.

  11. Osman, Milani. JACC 2000; 36:2126-31.

  12. Death Gruberg. JACC 2002;39:578-84.

  13. Beneficial effects of obesity in HF: The Obesity Paradox • Hemodinamic alterations in obesity♦Higher BP-> increased tolerance of ACE-I♦ Similar PCWP and Cardiac index - Lipoproteins♦Downregulation of inflammatory cytokines♦ Inhibition of endotoxin activity - Neurohormonal alterations♦Lower sympathetic nervous system activation level of epinephrine and renin♦ Increased production of soluble TNFa receptors which neutralize biologic effects of TNFa Horwich, Tillish. JACC 2001;38:789-95.

  14. No correlation of obesity and quality of life in HF KCCQ (Kansas City Cardiomyopathy Questionnaire): disease specific health status measure SF-12 PCS (Short Form 12 Physical Component Summary) : generic measure of physical health status SF-12 MCS (Short Form 12 Mental Component Summary) : generic measure of mental health status Conard. J Cardiac Fail 2006;12:700-6.

  15. Absence of difference in rate of hospitalization in the 3 BMI groups in chronic HF Bozkurt, Deswal. Am Heart J 2005;150:1233-9.

  16. CACHEXIA

  17. Rheumatoid arthritis Cancer Kwashiorkor Sepsis Renal failure AIDS Chronic liver disease Thyrotoxicosis COPD HF CACHEXIA

  18. Survival in HF patients with and without cachexia Anker, Coats. CHEST 1999;115:836-847.

  19. Cachexia • Reduction of fat and lean tissue mass Anorexia Malnutrition • Reversible once food is supplied • Fat mass is lost • Muscle mass is spared CACHEXIA Non edematous weight loss of >6% of the previous normal weight over a period of >6 months Anker. Cardiov Res 2007;73:298-309.

  20. Quantitative and qualitative modifications in muscles of cachectic pts with HF • Quadriceps muscle cross-sectional area Marker of muscle mass • Quadriceps strength per unit area of muscle Anker. Eur Heart J 1997;18:259-269.

  21. Body composition alterations in the wasting syndrome of chronic heart failure Total bone mineral density Total bone tissue content Total fat tissue content Total lean tissue content Coats. Eur Heart J 1999;20:683-693.

  22. 1964 Pittman and Cohen • Bowel edema - Malabsorption • Denutrition • Loss of nutrients NEUROHORMONAL AND IMMUNE MECHANISMS TNF-a MECHANISMS OF CACHEXIA Reduction of intermediary metabolism Anorexia Increased basal metabolism CELLULAR HYPOXIA Haehling, Anker. Cardiov Res 2007;73:298.

  23. The pattern of cytokine activation and hormonal changes contribute to catabolism in chronic HF Berry. European Heart Journal (2000) 21, 521–532

  24. TNFa Berry. European Heart Journal 2000; 21, 521–532

  25. Levels of catabolic factors in patients with CHF and healthy controls Anker, S. D. et al. Circulation 1997;96:526-534

  26. Levels of anabolic factors in patients with CHF and healthy controls Anker, S. D. et al. Circulation 1997;96:526-534

  27. > Food intake Anabolic : Catabolic imbalance > Ghrelin > Cortisol:DHEA > Food intake Anabolic:catabolic imbalance + > GH:IGF-1 + > Neuropeptide Y Anabolic and lipolitic effects Acquired resistance < Leptin - Haehl, Doehner, Anker. Cardiovasc Res 2007;73:298-309

  28. NUTRITIONAL SUPPORT • Prefer enteral vs parenteral nutrition (integrated responses of digestive and cardiovascular system) • If parenteral nutrition is necessary • Avoid fluid overload • 35 Kcal/kg/day, 1.2 g of protein/kg/day • Glucose:Lipid ratio 70:30 • Amino-acid-enriched mixtures (leucine, isoleucine, valine, glutamate, aspartate) • Glucose, insulin and potassium (“polarizing solution”) • Feed the patient as soon as possiblewith frequent and small meals THERAPY Mustafa, Leverve. Nutrition 2001;17:756-760.

  29. NUTRITIONAL SUPPORT • Prefer enteral vs parenteral nutrition (integrated responses of digestive and cardiovascular system) • If parenteral nutrition is necessary • Avoid fluid overload • 35 Kcal/kg/day, 1.2 g of protein/kg/day • Glucose:Lipid ratio 70:30 • Amino-acid-enriched mixtures (leucine, isoleucine, valine, glutamate, aspartate) • Glucose, insulin and potassium (“polarizing solution”) • Feed the patient as soon as possiblewith frequent and small meals THERAPY PREVENT RATHER THAN CORRECT UNDERNUTRITION !!! Mustafa, Leverve. Nutriotion 2001;17:756-760.

  30. THERAPY • NUTRITIONAL SUPPORT • STYLE OF LIFE • Moderate excercise training in NYHA class I, II, III Anker, Sharma. Int J Cardiol 2002;85:51-66.

  31. THERAPY • NUTRITIONAL SUPPORT • STYLE OF LIFE • DRUGS • Beta-blockers :Inhibit lipolysis • (about 70% of weight increase is fat tissue) • - Carvedilol vs Placebo: COPERNICUS • - Bisoprolol vs Placebo: CIBIS II Anker, Sharma. Int J Cardiol 2002;85:51-66.

  32. THERAPY • NUTRITIONAL SUPPORT • STYLE OF LIFE • DRUGS • Beta-blockers :Inhibit lipolysis • (about 70% of weight increase is fat tissue) • ACE inhibitors and angiotensine receptor antagonists Anker, Sharma. Int J Cardiol 2002;85:51-66.

  33. SOLVD STUDY Enalapril vs Placebo Anker. Lancet 2003; 361:1077-83.

  34. THERAPY • NUTRITIONAL SUPPORT • STYLE OF LIFE • DRUGS • Beta-blockers :Inhibit lipolysis • (about 70% of weight increase is fat tissue) • ACE inhibitors and angiotensine receptor antagonists • Appetite stimulants: -Megestrol acetate • -Medroxyprogesterone acetate • Anabolic steroids (increase muscle mass and LV performance): • -Oxymetholone • -Testosterone Anker, Sharma. Int J Cardiol 2002;85:51-66.

  35. THERAPY • NUTRITIONAL SUPPORT • STYLE OF LIFE • DRUGS • Beta-blockers :Inhibit lipolysis • (about 70% of weight increase is fat tissue) • ACE inhibitors and angiotensine receptor antagonists • Appetite stimulants: -Megestrol acetate • -Medroxyprogesterone acetate • Anabolic steroids (increase muscle mass and LV performance): • -Oxymetholone • -Testosterone • Recombinant GH, GH-releasing peptide (ghrelin) • Monoclonal antibody or soluble TNFa receptors and IL-1 receptor antagonists Anker, Sharma. Int J Cardiol 2002;85:51-66.

  36. Ghrelin Growth hormone (GH)-releasing peptide, isolated from the stomach, which has been identified as an endogenous ligand for GH secretagogue receptor. The release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. Nagaja. Intern Med 2006

  37. THERAPY Etanercept Recombinant human TNFa receptor that binds to soluble (circulating) TNFa and functionally inactivates TNFa by preventing it from binding to its receptors on cell surface membranes

  38. THERAPY Mann. Circulation 2004;109:1594-1602.

  39. NUTRITIONAL SUPPORT • STYLE OF LIFE • DRUGS • Beta-blockers :Inhibit lipolysis • (about 70% of weight increase is fat tissue) • ACE inhibitors and angiotensine receptor antagonists • Appetite stimulants: -Megestrol acetate • -Medroxyprogesterone acetate • Anabolic steroids (increase muscle mass and LV performance): • -Oxymetholone • -Testosterone • Recombinant GH, GH-releasing peptide (ghrelin) • Monoclonal antibody or soluble TNFa receptors and IL-1 receptor antagonists THERAPY Haehling, Doehner, Anker, Cardiov Res 2007;73:298-309.

  40. Rheumatoid arthritis Sepsis AIDS Cancer Thyrotoxicosis CACHEXIA Kwashiorkior Chronic liver disease Renal failure COPD HF CONCLUSIONS

  41. ... the heavier the better?

  42. ... Grazie per l’attenzione!

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