Clinica di Malattie dell’Apparato Respiratorio
Università degli Studi di Modena e Reggio Emilia
Direttore Prof. Leonardo M. Fabbri
SINDROME METABOLICA E BPCO
Alessia Verduri - Leonardo M. Fabbri
CORSO DI FORMAZIONE PER PERSONALE MEDICO DI NYCOMED
Modena, 6-7/8-9 Settembre 2011
DEFINITIONS
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.
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
The Metabolic Syndrome
IDF 2006
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
EPIDEMIOLOGY
Courtesy of M. Porta
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%
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%
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%
Obesity Trends* Among U.S. Adults
BRFSS,
2003
(*BMI 30, or about 30 lbs overweight for 5’4” person)
No Data
<10%
10%–14%
15%–19%
Source: Behavioral Risk Factor Surveillance System, CDC
20%-24%
25%
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).
Cause of death on treatment
Deaths (%)
7.0
Placebo
SFC
6.0
5.0
4.0
3.0
2.0
1.0
0.0
Cardiovascular
Pulmonary
Cancer
Other
Unknown
Calverley et al. NEJM 2007
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
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
Lancet 2007; 370:797-99
PHYSIOPATHOLOGY:
link between MS and COPD
Martinis M et al. Exp. Mol. Pathol. 2006;80(3):219-227.
Muscle
Weakness / Wasting
Metabolic Syndrome
Type 2 diabetes
TNFa
IL-6
?
Local
Inflammation
Cardiovascular
Events
CRP
Osteoporosis
Liver
Fabbri LM et al. Eur Respir J 2008
Courtesy of M. Porta
Pathogenesis of MS
Grundy SM. J Clin Endocrinol Metab 2007;92:399-404
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
Sindrome Metabolica
Sindrome delle
apnee ostruttive
del sonno
Diabete mellito tipo 2
Obesità
Genetica
Resistenza
insulinica
BMI >30mg/kg2
Girovita:
M>102
F>88cm
Sindrome disfunzionale
restrittiva
Fumo
Ipertensione
Aumento di
colesterolo e
trigliceridi
Ipossiemia
SEDENTARIETA‘
Complicazioni secondarie
Courtesy of Muller B
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
RESULTS: 43% of COPD pts and 21% of control participants
presented 3 or more determinants of the metabolic syndrome.
Gifford AH et al. CHEST 2010;138;704-15
Peppard PE et al. JAMA 2000;284:3015-21
• 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
Eterogeneità della BPCO
FEV1=33%
MRC=2/4
PaO2=57
6MWT=400
FEV1=35%
MRC=3/4
PaO2=66
6MWT=230
BMI = 21
BMI = 34
SCORE=6
SCORE=7
PHYSICAL ACTIVITIES IN DAILY LIFE IN COPD
Malnutrition and COPD:
phenotypes
Weight loss is a prognostic
factor in COPD
1.0
0.8
Survival
BMI > 29 Kg/m2
0.6
BMI 24-29 Kg/m2
0.4
BMI 20-24 Kg/m2
BMI < 20 Kg/m2
0.2
0.0
0
6
12
18
24
30
36
42
Follow-up, months
Schols et al. AJRCCM 1998; 157: 1791-7
48
Mechanism of inflammatory bone loss
Takayanagi , J Mol Medicine 2005; 83:170-9
Mechanisms of Skeletal Muscle
Atrophy in Patients with COPD or CHF
LeJemtel et al. JACC, 2007
Padeletti- LeJemtel . International Journal of Cardiology, 2008
PROGRESSION OF CHF AND COPD
LeJemtel et al. JACC, 2007
THERAPY
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.
Pulmonary rehabilitation in chronic
obstructive pulmonary disease
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?"
Troosters et al Am J Respir Crit Care Med. 2005 Jul 1;172(1):19-38
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.
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