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Modena, 6-7/8-9 Settembre 2011 CORSO DI FORMAZIONE PER PERSONALE MEDICO Nycomed

Modena, 6-7/8-9 Settembre 2011 CORSO DI FORMAZIONE PER PERSONALE MEDICO Nycomed. Malattie cardiovascolari e BPCO Pietro Roversi, Alessia Verduri e Fabrizio Luppi. Clinica di Malattie dell’Apparato Respiratorio Azienda Ospedaliero – Universitaria Policlinico di Modena.

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Modena, 6-7/8-9 Settembre 2011 CORSO DI FORMAZIONE PER PERSONALE MEDICO Nycomed

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  1. Modena, 6-7/8-9 Settembre 2011 CORSO DI FORMAZIONE PER PERSONALE MEDICO Nycomed Malattie cardiovascolari e BPCO Pietro Roversi, Alessia Verduri e Fabrizio Luppi Clinica di Malattie dell’Apparato Respiratorio Azienda Ospedaliero – Universitaria Policlinico di Modena

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

  3. Prevalence of Comorbid Diagnoses and Symptoms Among a National Sample of Patients with COPD The American Journal of Medicine (2009) 122, 348-355

  4. Frequency distribution of comorbid conditionsamong patients with COPD. Barr, The American Journal of Medicine, 2009

  5. The high prevalence of comorbidity in COPD is likely multifactorial and associated with age and multisystem impact of tobacco exposure COPD was less commonly treated than less symptomatic and less morbid conditions, such as hypertension and hypercholesterolemia, despite the increasing number of proven medications for the treatment of COPD Patients with COPD demonstrated better recall of their blood pressure and cholesterol than of their FEV1 This is not surprising in the context of the greater public education regarding hypertension and hypercholesterolemia Barr, The American Journal of Medicine, 2009

  6. Prevention of exacerbations of chronic obstructive pulmonary diseases with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. • Co-morbilità • Vascolari (compresa l’ipertensione) 64% • Cardiache 38% • Gastrointestinali 48% • Metaboliche o nutrizionali 47% • Muscolo scheletriche o connettivali 46% • Genito-urinarie 27% • Neurologiche 22% Niewoehner et al, Ann Intern Med 2005;143:317-326

  7. Role of co-morbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation • 51% of the patients reported at least one chronic • comorbidity added to COPD. • Metabolic (systemic hypertension, diabetes and/or • dyslipidaemia) and heart diseases (chronic heart • failure and/or coronary heart disease) were the most • frequently reported co-morbid combinations (61% and • 24%, respectively) Crisafulli E, et al.,Thorax 2008;63: 487-492.

  8. Screening della comorbilità: alcuni esempi GOLD Linee guida BPCO 2010

  9. Cause of death on treatment Deaths (%) Placebo SFC Cardio-vascular Pulmonary Cancer Other Unknown Calverley et al. NEJM 2007

  10. What do COPD Patients Die From? Mannino et al, ERJ, 2007

  11. Systemic Consequences of COPD Cardiovascular Morbidity 8 P=0.001 7 6 5 4 Cardiac infarction injury score 3 2 1 0 High CRP and severe obstruction High CRP Severe obstruction Sin and Man, Circulation. 2003

  12. . 450 population participants without CVD 52 population participants with CVD, 119 hospital patients with CAD Soriano , CHEST 2010

  13. . Soriano , CHEST 2010

  14. One of every three patients with CAD recruited from the hospital clinic, and one of every five patients with CVD in the general population, suffer AL compatible with COPD The majority of them are not diagnosed, and, therefore, they remain mostly untreated. These observations are clinically relevant because COPD is now considered a preventable and treatabledisease. Soriano , CHEST 2010

  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. RELATIONSHIP BETWEEN COPD AND CARDIOVASCULAR DISEASE CRP(FIBRINOGEN) Systemic Inflammation Cytokines Complement activation ENDOTELIN-1 IL-6 LDL uptake ICAM VCAM (adhesion molecules)

  18. The risk ratio of developing CHF in COPD patients is 4.5 (compared with age-matched controls without COPD after adjustments for cardiovascular risk factors ) (1) The rate-adjusted hospital prevalence of CHF is 3 times greater among patients discharged with a diagnosis of COPD compared with patients discharged without mention of COPD (2) (2) Holguin F, Folch E, Redd SC, Mannino DM. Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001. Chest 2005;128:2005–11. (1) Curkendall SM, DeLuise C, Jones JK, et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Ann Epidemiol 2006;16:63–70.

  19. How common is HF in COPD? Prevalence (%) Prevalence (%) Italian Health Search Database n=341,329 7.9% prevalence HF in COPD overall Scottish Continuous Morbidity Record n=377,439 11.9% prevalence HF in COPD overall Cazzola M. Respiration 2010; epub; Hawkins NM. Data on file.

  20. How common is LVSD in COPD? • high prevalence • selected populations • severe COPD • suspected LVSD • coronary disease Prevalence (%) Rutten FH. Eur J Heart Fail 2006: 8(7):706-711.

  21. Kaplan–Meier event-free survival curves according to chronic obstructive pulmonary disease coexistence Mascarenhas, Am Heart J 2008

  22. Why is heart failure important? 1.0 • primary care patients with COPD ≥ 65 years (n=404) • follow up for a mean duration of 4.2 (SD 1.4) years. • HF doubles mortality of patients with COPD: adjusted HR 2.1 (1.2–3.6 C.I.) 0.9 0.8 Survival 0.7 COPD COPD GOLD COPD + Heart failure 0.6 COPD GOLD + Heart Failure 0.5 0 12 24 36 48 60 72 Time (Months) Boudestein LC. Eur J Heart Fail 2009; 11(12):1182-1188.

  23. Mechanisms of Skeletal Muscle Atrophy in Patients With CHF or COPD M. Padeletti- LeJemtel : International Journal of Cardiology, 2008

  24. PROGRESSION OF CHF AND COPD M. Padeletti- LeJemtel : International Journal of Cardiology, 2008

  25. 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

  26. 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 Jun ;4(2):121-6

  27. 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).

  28. diabetes, • b) hypertension • c) cardiovascular disease Results from Cox proportional hazard models (presented as hazard ratio with 95% confidence interval) that predict death within 5 yrs by modified Global Initiative for Obstructive Lung Disease (GOLD) category and the presence of a) diabetes, b) hypertension or c) cardiovascular disease

  29. diabetes, • b) hypertension • c) cardiovascular disease Results from Cox proportional hazard models (presented as hazard ratio with 95% confidence interval) that predict time to first hospitalisation within 5 yrs by modified Global Initiative for Obstructive Lung Disease (GOLD) category and the presence of a) diabetes b) hypertension or c) cardiovascular

  30. REDUCTION OF MORBIDITY AND MORTALITY BY STATINS, ANGIOTENSIN-CONVERTING ENZYME INHIBITORS, AND ANGIOTENSIN RECEPTOR BLOCKERS IN COPD The combination of statins and either ACE inhibitors or ARBs is associated with a reduction in COPD hospitalization and total mortality not only in the high CV risk cohort but also in the low CV risk cohort Mancini JB, et al. J Am CollCardiol. 2006 Jun 20;47(12):2554-60

  31. Challenges in patients with coexistent COPD and CHF COPD is the one that most delays the diagnosis of CHF COPD is most often advocated for nonadherence to therapeutic guidelines, especially betablockade(BB) safety and efficacyof BB and bronchodilators in patientswith COPD and HF M. Padeletti-LeJemtel : International Journal ofCardiology, 2008

  32. restrizione polmonare gabbia toracica congestione ematica versamento pleurico Ridotta compliance Aumento del lavoro respiratorio cardiomegalia

  33. Limitazione del flusso espiratorio edema peribronchiale espirazione bassi volumi polmonari bronchi alveoli occlusione forze radiali ridotte

  34. Caution diagnosing COPD in HF Airwaycompression Bronchial hyperresponsiveness overestimate severity misdiagnosis always perform Spirometry… and always when euvolaemic inappropriate avoidance of β-blockers inappropriate bronchodilators

  35. COPD masks or mimics heart failure pulmonary vascular remodeling masks alveolar shadowing radiology hyperinflation reduces cardiothoracic ratio vascular bed loss causes upper lobe venous diversion asymmetric and regional patterns Gehlbach BK. Chest 2004; 125:669-682.

  36. COPD masks or mimics heart failure

  37. Why is diagnosis important? Renin-angiotensin-aldosterone system inhibition bronchodilators beta-blockers OUTCOMES COPD heart failure beta-agonists devices smoking cessation

  38. THE IMPACT OF CARDIOSELECTIVE BETA-BLOCKERS ON MORTALITY IN PATIENTS WITH COPD AND ATHEROSCLEROSIS b-blockers are often withheld from patients with chronic obstructive pulmonary disease (COPD) because of fear of pulmonary worsening Beta1-blockers may reduce mortality in COPD patientsundergoingvascularsurgery(1) In some patientswith COPD selective beta1-blockers are safe and may reduce mortality(2) 1) Van Gestel , Am J Respir Crit Care Med . 2008 2) Salpeter S Cardioselective beta-blockers for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005;4:CD003566.

  39. Short PM et al., 2011 Baseline characteristics of 5977 patients at diagnosis of COPD, grouped according to final treatment.

  40. Short PM et al., 2011 Effect of different treatment regimens* on FEV1 of patients with COPD during study period

  41. Short PM et al., 2011 Adjusted hazard ratios for all cause mortality among patients with COPD in reference to the control group (who received only inhaled therapy with short acting β agonists or antimuscarinics)

  42. Short PM et al., 2011 Kaplan-Meier estimate of probability of survival among patients with COPD by use of β blockers Β-blocker use was associated with a 22% reduction in mortality: hazard ratio 0.78 (95% confidence interval 0.67 to 0.92)

  43. Short PM et al., 2011 Conclusions β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function.

  44. Use of beta blockers and the risk of death in hospitalised patients with acute exacerbations of COPD • In-hospitalmortalitywas 5.2% • Thosereceiving beta blockers (n = 142) wereolder and more frequentlyhadcardiovasculardiseasethanthosewhodidnot • Beta blockerusewasassociatedwithreducedmortality (OR = 0.39; 95% CI 0.14 to 0.99) • The useof beta blockersbyinpatientswithexacerbationsof COPD iswelltolerated and maybeassociatedwithreducedmortality Dransfield MT, Thorax. 2008 Apr;63(4):301-5.

  45. 1.0 0.9 SurvivalRate 0.8 No bronchodilator and beta-blocker No bronchodilator and no beta-blocker 0.7 Bronchodilator and beta-blocker Bronchodilator and no beta-blocker 0 1.0 2.5 0.5 1.5 2.0 3.0 3.5 Time (years) CHARMtrial: patients with HF receiving bronchodilators (n=674 of 7599) Hawkins NM. Eur J Heart Fail 2010

  46. Kaplan-Meier estimates of the probability of major and fatal CV events in the placebo and tiotropium groups from the 30-trial pooled analysis. 0,1 0,09 0,08 Placebo 0,07 0,06 Cumulative frequency of cardiovascular endpoint event 0,05 Tiotropium 0,04 0,03 0,02 0,01 Rate ratio = 0.83; 95% CI = (0.71-0.98) 0 0 6 12 18 24 30 36 42 48 Time to first event (months) Patients at risk Tiotropium Placebo 10846 8699 6889 5506 4698 3599 2420 2240 2274 2068 2133 1917 2022 1787 1911 1681 1785 1571 Celli B. et al., Chest 2010; 137: 20-30.

  47. Kaplan-Meier estimates of the probability of major and fatal CV events in the placebo and tiotropium groups from the 30-trial pooled analysis. 0,1 0,09 0,08 0,07 0,06 Cumulative frequency of cardiovascular death 0,05 0,04 Placebo 0,03 Tiotropium 0,02 0,01 Rate ratio = 0.77; 95% CI = (0.60-0.98) 0 0 6 12 18 24 30 36 42 48 Time to first event (months) Patients at risk Tiotropium Placebo 10846 8699 6933 5538 4737 3637 2456 2286 2322 2120 2193 1980 2087 1861 1986 1756 1863 1638 Celli B. et al., Chest 2010; 137: 20-30.

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