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SINDROME METABOLICA E BPCO A lessia Verduri - Leonardo M. Fabbri

Clinica di Malattie dell’Apparato Respiratorio Università degli Studi di Modena e Reggio Emilia Direttore Prof. Leonardo M. Fabbri. SINDROME METABOLICA E BPCO A lessia Verduri - Leonardo M. Fabbri. CORSO DI FORMAZIONE PER PERSONALE MEDICO DI NYCOMED Modena, 6-7/8-9 Settembre 2011.

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SINDROME METABOLICA E BPCO A lessia Verduri - Leonardo M. Fabbri

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  1. Clinica di Malattie dell’Apparato Respiratorio Università degli Studi di Modena e Reggio Emilia Direttore Prof. Leonardo M. Fabbri SINDROME METABOLICA E BPCO AlessiaVerduri - Leonardo M. Fabbri CORSO DI FORMAZIONE PER PERSONALE MEDICO DI NYCOMED Modena, 6-7/8-9 Settembre 2011

  2. DEFINITIONS

  3. Definition of COPD • COPD is a preventable and treatable disease with some significant extrapulmonary effectsthat may contribute to the severity in individual patients. • Its pulmonary component is characterized by airflow limitation • that is not fully reversible. • The airflow limitation is usually progressive and associated • with an abnormal inflammatory response of the lung to • noxious particles or gases.

  4. METABOLIC SYNDROME …is a complex disorder and an emerging clinical challenge, recognised clinically by the findings of abdominal obesity, atherogenic dyslipidaemia, hypertension and insulin resistance… Grundy SM, et al. Circulation 2005; 112: 2735-52

  5. The Metabolic Syndrome IDF 2006

  6. Obesity and Body Mass Index (BMI) BMI = (kg)/(m)2 Body Mass Index (BMI) provides a more accurate measure of obesity than does weight alone

  7. EPIDEMIOLOGY

  8. Courtesy of M. Porta

  9. Obesity Trends* Among U.S. AdultsBRFSS, 1985 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman) No Data <10% 10%–14% 15%–19% 20%-24% 25%

  10. Obesity Trends* Among U.S. AdultsBRFSS, 1995 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman) No Data <10% 10%–14% 15%–19% 20%-24% 25%

  11. Obesity Trends* Among U.S. AdultsBRFSS, 2000 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman) No Data <10% 10%–14% 15%–19% 20%-24% 25%

  12. Obesity Trends* Among U.S. AdultsBRFSS, 2003 (*BMI 30, or about 30 lbs overweight for 5’4” person) No Data <10% 10%–14% 15%–19% 20%-24% 25% Source: Behavioral Risk Factor Surveillance System, CDC

  13. The present study analysed data from 20,296 subjects aged >45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). 5-yrs mortality 5-yrs mortality and presence of no, 1 ,2 or 3 comorbidities (diabetes, hypertension, CVD) The present study analysed data from 20,296 subjects aged >45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS).

  14. Cause of death on treatment Deaths (%) 7.0 Placebo SFC 6.0 5.0 4.0 3.0 2.0 1.0 0.0 Cardio-vascular Pulmonary Cancer Other Unknown Calverley et al. NEJM 2007

  15. Cardiovascular mortality in COPD For every 10% decrease in FEV1, cardiovascular mortality increases by approximately 28% and non-fatal coronary event increases by approximately 20% in mild to moderate COPD Anthonisen et al. Am J Respir Crit Care Med 2002

  16. ARTERIAL STIFFNESS IS INDEPENDENTLY ASSOCIATED WITH EMPHYSEMA SEVERITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Emphysema severity is associated with arterial stiffness in patients with COPD Similar pathophysiological processes may be involved in both lung and arterial tissue Further studies are now required to identify the mechanism underlying this newly described association MacNee W et al. AJRCCM 2007; 176:1208-1214

  17. Lancet 2007; 370:797-99

  18. PHYSIOPATHOLOGY: • link between MS and COPD

  19. Martinis M et al. Exp. Mol. Pathol. 2006;80(3):219-227.

  20. Metabolic Syndrome Type 2 diabetes Muscle Weakness / Wasting TNFa IL-6 ? Local Inflammation Osteoporosis Cardiovascular Events Liver CRP Fabbri LM et al. Eur Respir J 2008

  21. Courtesy of M. Porta

  22. Pathogenesis of MS Grundy SM. J Clin Endocrinol Metab 2007;92:399-404

  23. INSULIN RESISTANCE AND INFLAMMATION - A FURTHER SYSTEMIC COMPLICATION OF COPD This study demonstrates greater insulin resistance in non-hypoxaemic patients with COPD compared with healthy subjects, which was related to systemic inflammation. This relationship may indicate a contributory factor in the excess risk of cardiovascular disease and type II diabetes in COPD. Bolton CE et al. COPD. 2007;4:121-6

  24. Sindrome Metabolica Diabete mellito tipo 2 Sindrome delle apnee ostruttive del sonno Genetica ObesitàBMI >30mg/kg2 Girovita:M>102 F>88cm Resistenza insulinica Sindrome disfunzionale restrittiva Fumo Aumento di colesterolo e trigliceridi Ipertensione IpossiemiaSEDENTARIETA‘ Complicazioni secondarie Courtesy of Muller B

  25. Schematic representaion of how smoking might add to several mechanisms linking obesity to CV disease. Red arrows indicate an effect of smoking. Fabbri ERJ 2008; 31:204-12

  26. RESULTS:43%of COPD pts and 21% of control participants presented 3 or more determinants of the metabolic syndrome.

  27. Gifford AH et al. CHEST 2010;138;704-15

  28. Peppard PE et al. JAMA 2000;284:3015-21

  29. The increasing prevalence of type 2 diabetes may be attributed to the epidemic of obesity • Excess weight is an important factor for OSA • OSA may be a novel risk factor for type 2 diabetes and/or the chronic hyperglycemia may promote OSA • Evidence links OSA to alterations in glucose tolerance, insulin resistance and type 2 diabetes (intermittent hypoxia, sleep fragmentation and sleep loss) • OSA has also been linked to metabolic syndrome • CPAP treatment has beneficial effect on visceral adiposity

  30. Eterogeneità della BPCO FEV1=33% MRC=2/4 PaO2=57 6MWT=400 BMI = 21 SCORE=6 FEV1=35% MRC=3/4 PaO2=66 6MWT=230 BMI = 34 SCORE=7

  31. PHYSICAL ACTIVITIES IN DAILY LIFE IN COPD

  32. Malnutrition and COPD: phenotypes

  33. Weight loss is a prognosticfactor in COPD BMI > 29 Kg/m2 BMI 24-29 Kg/m2 BMI 20-24 Kg/m2 BMI < 20 Kg/m2 Schols et al. AJRCCM 1998; 157: 1791-7

  34. Mechanism of inflammatory bone loss Takayanagi , J Mol Medicine 2005; 83:170-9

  35. MechanismsofSkeletalMuscle Atrophy in Patients with COPD or CHF LeJemtel et al. JACC, 2007 Padeletti-LeJemtel . International Journal ofCardiology, 2008

  36. PROGRESSION OF CHF AND COPD LeJemtel et al. JACC, 2007

  37. THERAPY

  38. Recommendations for treatment Primary intervention Healthy lifestyle that includes: • Calorie restriction (5-10% loss of body weight in the first year) • Moderate increase in physical activity (role of pulmonary rehabilitation) • Change in dietary composition Secondary intervention • In people for whom lifestyle change is not enough and who are considered to be at high risk for CVD, drug therapy may be required to treat the metabolic syndrome. • Individual components of MSshould be treated.

  39. Pulmonary rehabilitation in chronic obstructive pulmonary disease Today the questionis no longer "shouldpatientswithchronicobstructivelungdiseasereceivepulmonaryrehabilitation?" butrather "howshouldpulmonaryrehabilitationbedeliveredtopatientswith COPD?" Troosterset al Am J RespirCrit Care Med. 2005 Jul 1;172(1):19-38

  40. CONCLUSIONS • Metabolic syndrome (MS) and manifest diabetes are more frequent in COPD population. • A chronic systemic low-grade inflammation and a common complex pathogenetic pathway provide a link between COPD and MS. • The cluster of cardiometabolic abnormalities may confer an additional CV risk in COPD patients. • Physical activity and pulmonary rehabilitation along with change in dietary composition may be the way forward for effective management of these comorbidities.

  41. Fighting Sloth, Start Walking

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