systemic inflammation leading to comorbidities associated with copd leonardo m. fabbri
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SYSTEMIC INFLAMMATION LEADING TO COMORBIDITIES ASSOCIATED WITH COPD Leonardo M. Fabbri. Comorbidities and systemic effects of COPD Cardiovascular diseases in COPD COPD in Chronic Heart Failure Cardiovascular drugs in COPD. CHRONIC DISEASE IN THE ELDERLY: - PowerPoint PPT PresentationTRANSCRIPT
SYSTEMIC INFLAMMATION LEADING TO SYSTEMIC INFLAMMATION LEADING TO COMORBIDITIES ASSOCIATED WITH COPDCOMORBIDITIES ASSOCIATED WITH COPD
Leonardo M. Fabbri
Comorbidities and systemic effects of COPD
Cardiovascular diseases in COPD
COPD in Chronic Heart Failure
Cardiovascular drugs in COPD
CHRONIC DISEASE IN THE ELDERLY:
Back to the Future of Internal Medicine
LM Fabbri and R Ferrari, Breathe, 2006, in press
Two or more chronic diseases almost invariably develop together in the same patient, particularly in the elderly, often making it difficult to
establish a proper diagnosis and assessment of severity
Patient-oriented approach that takes into account the several coexisting components of chronic disease is required
This “change of concept” implies the need for medical specialists to extend their expertise to broader diagnostic and treatment
approaches that are traditionally the purview of internal medicine
Leading Causes of Death in U.S.
#1. MI#2. CA#3. CVA#4. COPD
Cigarette Related DiseasesLeading Causes of
Death Worldwide 2010
0% 20% 40% 60% 80% 100%
GOLD 3/4
GOLD 2
Restricted
Normal
COPD ASCVD Lung Cancer Other
What do COPD Patients Die From?
Mannino D.M., Mannino D.M., et al. et al. Respiratory Medicine 2006; 100:115Respiratory Medicine 2006; 100:115
Chronic diseases represent a huge proportion of human illness
58 million deaths in 2005:
Cardiovascular disease 30%
Cancer 13%
chronic respiratory diseases 7%
Diabetes 2%
Horton R. Lancet, 2006
COPD AS A SYSTEMIC DISEASECOPD AS A SYSTEMIC DISEASECOPD A COMPONENT OF THE CHRONIC DISEASECOPD A COMPONENT OF THE CHRONIC DISEASE
COPD A SYSTEMIC DISEASE
•Systemic inflammation•Cachexia
•Skeletal muscle wasting•Osteoporosis
COPD A COMORBIDITY OFChronic heart failure
Coronary and peripheral arterial diseasesLung cancer
Metabolic syndrome
?
=
?
?
Inhaled particles:pulmonary and heart co-morbidity
Comorbidities and systemic effects of COPD
Cardiovascular diseases in COPD
COPD in Chronic Heart Failure
Cardiovascular drugs in COPD
SYSTEMIC INFLAMMATION LEADING TO SYSTEMIC INFLAMMATION LEADING TO COMORBIDITIES ASSOCIATED WITH COPDCOMORBIDITIES ASSOCIATED WITH COPD
Leonardo M. Fabbri
Cardiovascular mortality in Cardiovascular mortality in COPDCOPD
For every 10% decrease in FEVFor every 10% decrease in FEV11, ,
cardiovascular mortality increases by cardiovascular mortality increases by approximately 28% and non-fatal coronary approximately 28% and non-fatal coronary event increases by approximately 20% in event increases by approximately 20% in
mild to moderate COPD.mild to moderate COPD.
Anthonisen et al, Am J Respir Crit Care Med 2002Anthonisen et al, Am J Respir Crit Care Med 2002
Curkendall et al. Ann Epidemiol
2006;16:63–70.
COPD
CAUSES OF HOSPITAL ADMISSION
CAUSES OF DEATH
Prevention of Exacerbations of Chronic Obstructive Pulmonary Disease with Tiotropium, a Once-Daily
Inhaled Anticholinergic Bronchodilator
Niewoehner,et al, Ann Intern Med. 2005;143:317-326
COEXISTING ILLNESSES
Vascular (including hypertension) 64%Cardiac 38%
Gastrointestinal 48%Musculoskeletal or connective tissue 46%
Metabolic or nutritional 47%Reproductive or urinary 27%
Neurologic 22%
Coronary Artery Calcification in Older Adults
Newman AB et al Circulation 2001
Occurrence and Prognostic Significance of Ventricular Arrhythmia Is Related to Pulmonary Function
Engstrom G et al Circulation 2001
402 men, 68 yrs old – 14 yrs follow-up
Carotid Plaque, Intima Media Thickness, Cardiovascular Risk Factors, and Prevalent Cardiovascular Disease in Men and Women
65.4 %
59.2%
50.4%
Perc
en
tuale
di sog
gett
i (m
asch
i) c
on
u
na p
lacca c
aro
tid
ea
50%
FEV1 terzilies
800 soggetti, età media 66 anni
Ebrahim S et al Stroke 1999
FEV1 e risk of stroke:the Copenhagen Stroke Study
≥100% 90-99% 80-89% 70-79% 60-69% 50-59% <50%
Percentuale FEV1 rispetto al previsto
Ris
ch
io R
ela
tivo
4
2
1.5
0.5
1
RR per maschi e femmine RR per maschi RR per femmine
Truelsen T et al Int J Epidemiol 2001
PULMONARY EMBOLISM IN PATIENTS WITH UNEXPLAINED EXACERBATION OF CHRONIC
OBSTRUCTIVE PULMONARY DISEASE: PREVALENCE AND RISK FACTORS
Tillie-Leblond et al, Ann Intern Med. 2006;144:390-396.
25% pulmonary embolism in patientswith COPD hospitalized for severe
exacerbation of unknown origin
Previous TEP, malignancy, low PaCO2
Cardiovascular morbidity in Cardiovascular morbidity in COPDCOPD
0
1
2
3
4
5
6
7
8
High CRPHigh CRP Severe Severe obstructionobstruction
High CRP High CRP and severe and severe obstructionobstruction
Car
dia
c in
farc
tio
n in
jury
sco
reC
ard
iac
infa
rcti
on
inju
ry s
core
P=0,001P=0,001
Sin and Man, Circulation 2003Sin and Man, Circulation 2003
Inflammation, atherosclerosis and coronary artery disease Inflammation, atherosclerosis and coronary artery disease Hansson GK, N Engl J Med. 2005;352(16):1685-95Hansson GK, N Engl J Med. 2005;352(16):1685-95
Activation of a type 1 immune response in atheroma formationActivation of a type 1 immune response in atheroma formation
Cross-sectional study, patients 65 years of age
Of 405 participating patients with a diagnosis of chronic obstructive pulmonary disease, 83 (20.5%, 95% CI 16.7–24.8) had previously unrecognized heart failure
RECOGNISING HEART FAILURE IN ELDERLY PATIENTS WITH STABLE CHRONIC OBSTRUCTIVE PULMONARY
DISEASE IN PRIMARY CARE
F H Rutten et al, BMJ 2005, Dec;331(4):1379-81
A limited number of items easilyavailable from history and physical examination,withaddition of NT-proBNP and electrocardiography, can
help general practitioners to identify concomitantheart failure in individual patients with stable COPD
Peptidi natriuretici come marker dello scompenso cardiaco cronico
ANP
Cuore normaleCuore normale Cuore scompensatoCuore scompensato
ANP
BNP
ANPANPPeptide natriuretico atrialePeptide natriuretico atriale
BNP
Peptidi natriureticiPeptidi natriuretici
BNPBNPPeptide natriuretico cerebralePeptide natriuretico cerebrale
Breathing Not Properly Multinational Study
McCullough et al. Circ 2002
1586 participants who presented with acute dyspnea
1538 (97%) had clinical certainty of CHF determined by the attending physician in the emergency department
Participants underwent routine care and had BNP measured in a blinded fashion
~ 37 % COPD comorbidity
Breathing Not Properly (BNP) Multinational Study
McCullough et al. Circ 2002
Utility of BNP in Differentiating Heart Failure from Lung Disease in Patients Presenting
with Dyspnea
Morrison et al. JACC 2002
Utility of BNP in Differentiating Heart Failure from Lung Disease in Patients Presenting
with Dyspnea
Morrison et al. JACC 2002
Comorbidities and systemic effects of COPD
Cardiovascular diseases in COPD
COPD in Chronic Heart Failure
Cardiovascular drugs in COPD
SYSTEMIC INFLAMMATION LEADING TO SYSTEMIC INFLAMMATION LEADING TO COMORBIDITIES ASSOCIATED WITH COPDCOMORBIDITIES ASSOCIATED WITH COPD
Leonardo M. Fabbri
Primary Endpoint: All-Cause MortalitySecondary Endpoints: CV Death, MI, or HFOther Endpoints: Safety and Tolerability
Captopril 50 mg tid(n = 4909)
Valsartan 160 mg bid(n = 4909)
Captopril 50 mg tid + Valsartan 80 mg bid
(n = 4885)
Acute MI (0.5–10 days)—SAVE, AIRE or TRACE eligible(either clinical/radiologic signs of HF or LV systolic dysfunction)
Major Exclusion Criteria:— BP 100 mm Hg— Serum creatinine 2.5 mg/dL— Prior intolerance of an ARB or ACEI— Nonconsent
double-blind active-controlled
median duration: 24.7 monthsevent-driven
VALIANT Trial:Prevalence of COPD
• 14703 patients included in the trial
• 1258 clinical diagnosis of COPD (8.6%)
Valsartan Heart Failure Trial
Study Design
J. N. Cohn et. al, J. Card. Fail. 1999; 5: 155-160
HF patients 18 yr; NYHA II–IV
LVIDD> 2.9 cm/m² BSA; EF<40%
Valsartan40 mg bid titrated
to160 mg bid
906 deaths (events reported)
Randomized to
Receiving Standard Therapyincluding ACE inhibitors , diuretics digoxin , -blockers
Placebo
Val-HeFT Trial:Prevalence of COPD
• 5010 patients included in the trial
• 628 clinical disgnosis of COPD (12.5%)
0
5
10
15
20
25
30
Mortalità totale Ospedal per HF
No COPD COPD
Val-HeFT TrialClinical events at 2 year follow-up
<0.0001 <0.0001P value
Mortality Hospitalization
Contributors to exercise intolerance in
COPD and CHF
Gosker et al. AJCN 1999
Comorbidities and systemic effects of COPD
Cardiovascular diseases in COPD
COPD in Chronic Heart Failure
Cardiovascular drugs in COPD
SYSTEMIC INFLAMMATION LEADING TO SYSTEMIC INFLAMMATION LEADING TO COMORBIDITIES ASSOCIATED WITH COPDCOMORBIDITIES ASSOCIATED WITH COPD
Leonardo M. Fabbri
METHODS
Case-control study of two population-based retrospective cohorts
1) COPD patients having undergone coronary revascularization (high CV risk cohort)
2) COPD patients without previous myocardial infarction (MI) and newly treated with nonsteroidal anti-inflammatory drugs (low CV
risk cohort)
Outcomes: COPD hospitalization, MI, and total mortality
Mancini GB, et al. J Am Coll Cardiol. 2006 Jun 20;47(12):2554-60Mancini GB, et al. J Am Coll Cardiol. 2006 Jun 20;47(12):2554-60
REDUCTION OF MORBIDITY AND MORTALITY BY STATINS, ANGIOTENSIN-REDUCTION OF MORBIDITY AND MORTALITY BY STATINS, ANGIOTENSIN-CONVERTING ENZYME INHIBITORS, AND ANGIOTENSIN RECEPTOR CONVERTING ENZYME INHIBITORS, AND ANGIOTENSIN RECEPTOR
BLOCKERS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY BLOCKERS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASEDISEASE
These drugs reduced both CV and pulmonary outcomes
Largest benefits with statins combined with ACEin or ARBs
This combination reduces COPD hospitalization and mortality in the high and low CV risk cohort
The combination also reduced MI in the high CV risk cohort
Benefits were similar when steroid users were included
Mancini GB, et al. J Am Coll Cardiol. 2006 Jun 20;47(12):2554-60Mancini GB, et al. J Am Coll Cardiol. 2006 Jun 20;47(12):2554-60
REDUCTION OF MORBIDITY AND MORTALITY BY STATINS, REDUCTION OF MORBIDITY AND MORTALITY BY STATINS, ANGIOTENSIN-CONVERTING ENZYME INHIBITORS, AND ANGIOTENSIN-CONVERTING ENZYME INHIBITORS, AND
ANGIOTENSIN RECEPTOR BLOCKERS IN PATIENTS WITH ANGIOTENSIN RECEPTOR BLOCKERS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASECHRONIC OBSTRUCTIVE PULMONARY DISEASE
These agents may have dual cardiopulmonary These agents may have dual cardiopulmonary protective properties, thereby substantially protective properties, thereby substantially altering prognosis of patients with COPDaltering prognosis of patients with COPD
These findings need confirmation in randomized These findings need confirmation in randomized clinical trialsclinical trials
Mancini GB, et al. J Am Coll Cardiol. 2006 Jun 20;47(12):2554-60Mancini GB, et al. J Am Coll Cardiol. 2006 Jun 20;47(12):2554-60
Comorbidities and systemic effects of COPD
Cardiovascular diseases in COPD
COPD in Chronic Heart Failure
Cardiovascular drugs in COPD
SYSTEMIC INFLAMMATION LEADING TO SYSTEMIC INFLAMMATION LEADING TO COMORBIDITIES ASSOCIATED WITH COPDCOMORBIDITIES ASSOCIATED WITH COPD
Leonardo M. Fabbri