1. SINDROME METABOLICA E BPCO Alessia Verduri - Leonardo M. Fabbri Clinica Clinica di Malattie dell’Apparato Respiratorio Università degli Studi di Modena e Reggio Emilia Direttore Prof. 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 effects that 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) Body Mass Index (BMI) provides a more accurate measure of obesity than does weight alone BMI = (kg)/(m)2

7. EPIDEMIOLOGY

8. Courtesy of M. Porta

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

12. Source: Behavioral Risk Factor Surveillance System, CDC (*BMI 30, or about 30 lbs overweight for 5’4” person) Obesity Trends* Among U.S. Adults BRFSS, 2003

13. 5-yrs mortality 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). 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 and presence of no, 1,2 or 3 comorbidities (diabetes, hypertension, CVD)

14. Cause of death on treatment 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 Cardio- vascular PulmonaryCancerOtherUnknown Deaths (%) PlaceboSFC Calverley et al. NEJM 2007

15. For every 10% decrease in FEV 1, 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 Cardiovascular mortality in COPD

16. 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 ARTERIAL STIFFNESS IS INDEPENDENTLY ASSOCIATED WITH EMPHYSEMA SEVERITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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. Muscle Weakness / Wasting Metabolic Syndrome Type 2 diabetes Osteoporosis CRP Cardiovascular Events Liver ? Local Inflammation TNF  IL-6 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 Bolton CE et al. COPD. 2007;4:121-6 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.

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

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

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

32. PHYSICAL ACTIVITIES IN DAILY LIFE IN COPD

34. Malnutrition and COPD: phenotypes

36. BMI > 29 Kg/m 2 BMI 24-29 Kg/m 2 BMI 20-24 Kg/m 2 BMI < 20 Kg/m 2 Weight loss is a prognostic factor in COPD Schols et al. AJRCCM 1998; 157: 1791-7

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

38. Mechanisms of Skeletal Muscle Atrophy in Patients with COPD or CHF Padeletti- LeJemtel. International Journal of Cardiology, 2008 LeJemtel et al. JACC, 2007

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

40. THERAPY

41. 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 MS should be treated.

43. Pulmonary rehabilitation in chronic obstructive pulmonary disease Troosters et al Am J Respir Crit Care Med. 2005 Jul 1;172(1):19-38 Today the question is no longer "should patients with chronic obstructive lung disease receive pulmonary rehabilitation?" but rather "how should pulmonary rehabilitation be delivered to patients with COPD?"

44. 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.

45. Fighting Sloth, Start Walking