Diapositiva 1

1
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
Fisiopatologia e Diagnosi Precoce dei Danni da
Fumo di Tabacco alla Funzione Cardiovascolare
Prof.ssa Maria Grazia Modena
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
2
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
Prevalence While the prevalence of tobacco use
has declined among men in some high-income
countries, it is still increasing among young
people and women. About 47.5 of men and 10.3
of women are current smokers
Chest 20071311557-1566
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
3
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
OMS
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
4
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
OMS
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
5
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
OMS
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
6
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
OMS
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
7
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
Physiopathology While the adverse effects of
cigarette smoke on lung health are well
established, it is becoming more evident that
smoke has an important extrapulmonary toxicity.
Injury in the lung, primary target of inhaled
smoke, can be explained by the direct chemical
exposure to cigarette smoke, but effects causing
chronic diseases in other organ systems are
likely to be the result of indirect consequences
of the exposure.
Chest 20071311557-1566
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
8
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009

• Cigarette smoking represents an indipendent
• risk factor for cardiovascular disease (CVD).
• Potential mechanisms by which smoking increases
  the risk of CVD include
• Systemic oxydative stress
• vascular endothelial dysfunction
• lipid abnormalities
• Inflammatory mechanisms
• haemostatic disturbances

Eur Heart J 2005261765-73 Chest
20071311557-1566
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
9
(No Transcript)
10
Noninvasive evaluation of endothelial function
Like systemic index of inflammation (eg,
hs-PCR), endothelial dysfunction, as measured by
impaired FMD in the brachial artery, can aid in
the detection of pan-arterial vulnerability, and
may serve as a screening tool
Circulation, October 2003 108 1664-1672
11
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
Cigarette smoke has been shown to contain large
amounts of free radicals such as superoxide anion
and hydroxyl radicals. Exposure to oxidant
chemicals in smoke is associated with depletion
of endogenous levels of antioxidants in the
systemic compartment. Numerous studies have
reported that smoking results in low antioxidant
concentrations in plasma.

JACC 200035277-83
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
12
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009

Oral supplementation of vitamin E can attenuate
transient impairment of endothelial function
after heavy smoking due to an improvement of the
oxidative status but cannot restore chronic
endothelial dysfunction within four weeks in
healthy male smokers
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
13
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
It is hypothesized that endothelial
dysfunction plays a major role in cardiovascular
events in smokers.

Oxidative Stress Endotelial dysfunction
Cigarette smoke contains large amounts of free
radicals such as superoxide anion and hydroxyl
radicals that degrade nitric oxide (NO) released
from the endothelium and produce highly reactive
intermediates, resulting in endothelial injury.
JACC 200239251-6
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
14
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009

Other constituents of cigarette smoke may
contribute to acute endothelial dysfunction after
cigarette smoking, since nicotine nasal spray
caused less impairment of FMD than smoking a
cigarette containing the same amount of nicotine
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
15
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
The development of dysfunctional endothelium at
the level of the epicardial vessels may lead to
thrombus formation and plaque erosion, which have
been implicated in the acute coronary syndromes
and in sudden death in young smokers.
Circulation 20071152621-2627
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
16
(No Transcript)
17
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
3) Lipid abnormalities ROS and Reactive
nitrogen species LDL oxidation limite the
bioactivity of take up by macrophage
endothelium-derived NO
scavenger receptors, promoting
cholesterol increase inflammatory cell ester
accumulation, entry into the arterial
wall foam ester accumulation
Chest 20071311557-1566
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
foam cell formation
18
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
4) Inflammatory mechanisms Activation and
release of inflammatory cells into the
circulation, and an increase in circulating
inflammatory mediators such as acute phase
proteins and proinflammatory cytokines,
characterize the systemic inflammation. risk
factor and predictor for myocardial infarction,
coronary heart disease and stroke

Eur Heart J 2005261765-73
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
19
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009

• Acute phase proteins
• C-reactive protein
• while cell count (polymorphonuclear neutrophil)
• fibrinogen
• Proinflammatory cytokines
• IL-6
• endothelin-1
• TNF-a

Eur Heart J 2005261765-73
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
20
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
Increased levels of CRP and fibrinogen have been
associated with risk for subsequent
cardiovascular events in several large
prospective studies. CRP may have direct effects
on the pathogenesis of atherosclerosis and
endothelial dysfunction CRP
IL-6 endothelin-1 clot formation
upregulates adhesion molecules

Eur Heart J 2005261765-73 Chest
20071311557-1566
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
21
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009

High fibrinogen levels may promote CVD through
arterial wall infiltration and effects on blood
viscosity, platelet aggregation, and fibrin
formation. Smoking also increases viscosity by
increasing haematocrit Smoking is positively
associated with fibrin D-dimer, a measure of
ongoing fibrin formation and degradation that is
related to CHD risk. The increased D-dimer in
smokers probably reflects increased coagulation
activation.

Eur Heart J 2005261765-73
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
22
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009

• 5) Haemostatic disturbance
• Several studies revealed that current smokers
  have increased blood viscosity, associated with
  increased hematocrit or/and plasma viscosity
  resulting in a procoagulant condition. Increased
  plasma viscosity may be caused by higher levels
  of fibrinogen reported in plasma of smokers
• blood and plasma viscosity
• haematocrit associated with
• fibrin D-dimer cardiovascular
• factor VIII mortality

Eur Heart J 2005261765-73
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
23
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
Passive smoking has been linked to an increased
risk of dying from atherosclerotic heart disease
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
24
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
N Engl J Med 1996334150- 4
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
25
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
Am J Hypertens 200114942949
Impact of Smoking Cessation on Ambulatory Blood
Pressure and Heart Rate in Postmenopausal Women
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
26
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009

Cessation from smoking results in a rapid
reduction in haemostatic and inflammatory
markers, but levels remained significantly raised
after 1019 years and did not revert to
that of never smokers until after 20
years. Smoking cessation is
associated with a significant
reduction in risk of MI and stroke

Eur Heart J 2005261765-73
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
27
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009

• Diagnosis
• Systemic oxydative stress
• bioumoral
• Inflammation exam
• haemostatic disturbance
• vascular endothelial dysfunction

World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
28
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
endothelial function

• Smokers
• ? urinary NO metabolites
• ?homocysteine
• ?antioxidant (ascorbid acid, alpha- and
  beta-carotene)

FMD
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
29
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
All studies of smoking and intima media thickness
(IMT) have established a strong correlation
between smoking and an accelerated progression of
carotid atherosclerosis. Smoking is associated
with an increased intima-media thickness in the
carotid and femoral arteries as assessed by
ultrasound method. The occurrence of
atherosclerotic plaques both in the carotid and
femoral arteries were associated with the total
number of cigarette-years.
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
30
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings
31
Il fumo e la salute una sfida professionale a
tutto campo, Assistenza Didattica Ricerca Modena
- 25 Maggio 2009
Systemic oxydative stress
Chest 20071311557-1566
World Health Organization (WHO) World No Tobacco
Day 2009 Theme Tobacco Health Warnings