Transcript Smoking

Η σημασία του καπνίσματος στην
παθογένεση των καρδιαγγειακών
παθήσεων
Βασιλική Ν. Γιαννακοπούλου MD,
Phds, FESC, FEAS
Διευθ. ΕΣΥ Θριάσιο Νοσοκομείο
Συνεργάτης Λιπιδαιμικού Ιατρείου ΩΚΚ
History
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Rodrigo de Jerez was one of the Spanish crewmen who sailed to
the Americas on the Santa Maria as part of Christopher
Columbus's first voyage across the Atlantic Ocean in 1492. He is
credited being the 1st European smoker
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The Spanish introduced tobacco to Europeans in about 1518
Nicot, french ambassador in Lisbon, sent samples to Paris in
1559 ("sacred herb“referred by French, Spanish, & Portuguese )
in 1604 Stuart King James I wrote a famous polemic titled “A
Counterblaste to Tobacco”
Nazi Germany saw the first modern anti-smoking campaign and
in 1941 tobacco was banned in various public places as a health
hazard
This caused an enormous growth in the tobacco industry
until the scientific revelations discovering health
consequences of smoking, and tobacco companies adding
chemical additives were revealed in the mid-20th century,
as the Big Tobacco corporate crime and corruption expose
revealed, leading to the landmark corporate criminal case
Tobacco Master Settlement Agreement (MSA) of 1998 for
$206 billion, originally between the four largest original
participating manufacturers of United States tobacco
companies (Philip Morris Inc., R. J. Reynolds, Brown &
Williamson and Lorillard) and the Attorneys General of
46 States.
Many Diseases Are Directly Caused By Smoking
Cardiovascular
Cancer
Lung
Oral cavity/pharynx
Laryngeal
Esophageal
Stomach
Pancreatic
Kidney
Bladder
Cervical
Leukemia
Ischemic heart disease
Stroke – Vascular dementia2
Peripheral vascular disease3
Abdominal aortic aneurysm
Respiratory
COPD
Pneumonia
Poor asthma control
Active Smoking
Reproductive
Other
Adverse surgical outcomes/
wound healing
Hip fractures
Low bone density
Cataract
Peptic ulcer disease†
Low birthweight
Pregnancy complications
Reduced fertility
SIDS
† In patients who are Helicobacter pylori positive. COPD = chronic obstructive pulmonary disease; SIDS = sudden infant death syndrome.
1. Surgeon General’s Report. 2004. 2. Roman GC. Cerebrovasc Dis. 2005;20(Suppl 2):91-100. 3. Willigendael EM et al. J Vasc Surg. 2004;40:1158-1165.
Tobacco atlas 4th Edition 2011
World Lung Foundation,
American Cancer Society
Tobacco Kills More Americans/year Than
Alcohol, Cocaine, Crack, Heroin, Homicide,
Suicide, Car Accidents, Fires & AIDS
combined:
Cardiovascular diseases linked with smoking
Over 1/5 of deaths due to smoking-related
illness are caused by heart disease
European Cardiovascular Disease Statistics 2012 Edition
European Cardiovascular Disease Statistics 2012 Edition
Καπνός τσιγάρου:  4000 χημικές ουσίες,  250
ουσίες τοξικές ή καρκινογόνες
Χημική Ουσία στον Καπνό
του Τσιγάρου
Βρίσκεται επίσης σε…
Ακετόνη
Αποχρωστικά υλικά
Βουτάνιο
Υγρό αναπτήρων
Αρσενικό
Εντομοκτόνα
Κάδμιο
Μπαταρίες αυτοκινήτων
Μονοξείδιο του άνθρακα
Καυσαέρια αυτοκινήτων
Τολουένιο
Βιομηχανικά διαλυτικά μέσα
1. National Toxicology Program. 11th Report on Carcinogens; 2005. Διατίθεται στην ηλεκτρονική διεύθυνση: http://ntpserver.niehs.nih.gov. 2. Mackay J, Eriksen M. The Tobacco Atlas. World Health Organization; 2006. 3. Harvard Health Letter. May 2005. 4.
Surgeon General’s Report. The Health Consequences of Smoking; 2004.
Multiplicative Effect on Risk of Death From Top
Risk Factors of Cardiovascular Disease
Hypertension
x3.5
x1.5
x2.3
Dyslipidemia
x5.9
x2.7
x3.9
x1.7
Smoking
Hypertension defined as systolic blood pressure = 150 mm Hg; Dyslipidemia defined as total cholesterol=260 mg/ dL; Smoking defined as current smoking.
Kannel WB, 1977.
The mechanisms of the effects of smoking
The mechanisms of the effects of smoking are not fully
elucidated but are believed to include:
1.
2.
3.
4.
5.
6.
7.
8.
Hemodynamic stress
Endothelial injury and dysfunction
Development of an atherogenic lipid profile
Enhanced coagulability
Arrhythmogenesis
Relative hypoxemia because of the effects of carbon
monoxide
Cigarette smoking also induces a chronic inflammatory state
Genetic predisposition
JACC 2004
Platelet activation:
A key factor in AMI and Sudden Death is thrombosis
caused by platelet activation.
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Tobacco smoke activates platelets through several
mechanisms. Including:
Endothelial dysfunction,
Oxidative stress,
Decreased platelet derived nitric oxide (NO)
production,
Increased fibrinogen and thromboxane.
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Platelet activation occurs soon after exposure
Platelet activation has been observed after smoking
for 5 minutes, and 20 minutes of breathing second
hand smoking
Despite the much lower dose of tobacco smoke
inhaled by passive smokers, the effects of platelet
activation is 96% of that observed in active smokers
The increased platelet agreeability resulting from
smoking is an ameliorated as nearly as 2 weeks after
smoking cessation, suggesting that the effects of
tobacco smoke on platelet agreeability are transient
and partially reversible
Endothelial Dysfunction
& CAD Risk Factors

Endothelial dysfunction is strongly and independently
associated with cardiovascular events
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Endothelial Dysfunction results in atherosclerosis, plaque
rupture, and decreases blood flow owing to thrombosis and
vasospasm
Tobacco smoke exposure leads to endothelial dysfunction,
which is manifest clinically in 15 to 30 min
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NO, secreted by the endothelium and responsible for
vasodilatation, is decreased in active and passive smokers
Lipid profile in smokers
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Lipid levels are altered in smokers and passive
smokers
Tobacco smoke ↑LDL and ↓HDL
In addition to altering lipid levels, cigarette
smoking renders LDL more prone to oxidation
Active and passive smoking have higher
levels of products of lipid peroxidation and
oxidation LDL

Oxidation LDL is rapidly ingested by macrophages
which, in turn, forms foam cells in atherosclerotic
lesions
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Active & Passive smokers also show evidence of
increased inflammatory markers. Inflammation is
now recognized as a key step in the atherosclerosis
process. (e.g.: leukocyte count, acute phase reactants,
IL-6, and TNF)
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This Inflammatory state is reduced after smoking
cessation.
Increased oxidative stress
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Smokers and passive smokers have been found to
have lower levels of anti-oxidants
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Therefore, the harmful effect of tobacco smoke are
two-fold. First, tobacco smoke is a source of free
radicals. Second, it leads to a decrease in antioxidant levels that normally protect the body
against oxidative damage
Genetic Predisposition
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The atherosclerotic process in smokers may be partially
mediated by genetic variants
CYP1A1 MSP polymorphism or certain endothelial NO
synthase intron 4 polymorphisms increased the
susceptibility to cigarette smoke exposure-related
atherosclerotic diseases including multi-vessel CAD & MI
The importance of these genetic variants is unknown as
their prevalence in the entire population of cigarette
smokers has not been determined
Other Effects:
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Smoking leads to higher levels of epinephrine and
norepinephrine
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These changes increase myocardial oxygen demand
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In addition tobacco smoke has also been found to
have arrythmogenic potential
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Arterial stiffness is also increased in smokers and
passive smokers
Cigarette smoking predisposes the
individual to several different clinical
atherosclerotic syndromes:
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Stable angina
Acute coronary syndromes
Sudden death
Stroke
Aortic & peripheral atherosclerosis
Aortic aneurysm
Sexual impotence
Smoking: Effect on Coronary Artery Disease
Progression of
Existing Lesions
60
57
Patients (%)
40
Patients (%)
P=.002
50
37
30
20
60
Formation of New
Lesions
50
P=.007
40
30
20
10
10
0
0
Nonsmokers
Current
Smokers
36
20
Nonsmokers
Current
Smokers
Waters et al. Circulation. 1996;94:614-621.
Smoking: Increased Risk of Angina
Relative Risk (95% CI)a
5
4
3
2.6
2.0
2
1.6
1.0
1
0
Nonsmokers
1-14/Day
15-24/Day
25/Day
Cigarettes/Day
Current Smokers
aThe
probability of an event (developing a disease) occurring in exposed people compared
with the probability of the event in nonexposed people. Adjusted for age.
Willett et al. N Engl J Med. 1987.
Smoking: Increased Risk of Acute
Nonfatal Myocardial Infarction
Odds Ratio (95% CI)a
Current smoking was associated with a 3-fold increase
in odds of a nonfatal acute MI compared with nonsmokers
10
9
8
7
6
5
4
3
2
1
0
Age <40 y
Age 40-49 y
Nonsmokers
Age 50-59 y
Ex-smokers
aThe
Age 60-69 y
1-19
Age >70 y
20
ratio of the odds of development of disease in exposed persons
to the odds of development of disease in nonexposed persons.
Teo. Lancet. 2006.
Smoking: Increased CAD Mortality
Relative Risk (95% CI)a
12
10
8
5,4
6
3,7
4
2
1,7
1.0
0
Nonsmokers
1-14/Day
15-24/Day
25/Day
Cigarettes/Day
Current Smokers
Fatal CAD
a The
probability of an event (developing a disease) occurring in exposed people
compared with the probability of the event in nonexposed people. Adjusted for age.
Willett et al. N Engl J Med. 1987
Smoking: Increased Risk of Sudden Cardiac Death
Relative Risk (95% CI)a
4,0
3,0
2,3
2,0
1,0
1,0
0,0
Nonsmokers
aThe
Current Smokers
probability of an event (developing a disease) occurring in exposed people
compared with the probability of the event in nonexposed people. Adjusted for age.
Wannamethee et al. Circulation. 1995
Smoking: Increased Risk of Q-Wave MI After
Percutaneous Coronary Revascularization
Relative Risk (95% CI)a
4,0
3,0
2.08
2,0
1.28
1.0
1,0
0,0
Nonsmokers
Ex-smokers
Current Smokers
Q-wave Myocardial Infarction (MI)
aThe
probability of an event (developing a disease) occurring in exposed people compared with the probability
of the event in nonexposed people. Adjusted for the baseline variables significantly associated with each end point.
Hasdai et al. N Engl J Med. 1997
Κάπνισμα και ΑΕΕ
Στο κάπνισμα οφείλεται το
12% to 14% όλων των
θανάτων από ΑΕΕ
Το κάπνισμα αυξάνει τον
κίνδυνο για ΑΕΕ
 oξέως: ευνοεί το
σχηματισμό θρόμβων
 χρονίως: ευνοεί την
αθηρωματική νόσο
Progression of Intima-Medial
Thickness, µm/3 y (95% CI)a
Smoking: Increased Progression of Carotid
Atherosclerosis
50
43.0
38.8
40
31.6
30
32.8
25.9
20
aAdjusted
Nonsmokers
without
Exposureb
Nonsmokers
with
Exposureb
Ex-smokers
without
Exposureb
Ex-smokers
with
Exposureb
Current
Smokers
for demographic characteristics, cardiovascular risk factors, and lifestyle variables (risk factor model and
Keys score, education, leisure activity, body mass index, and alcohol use). bTo environmental tobacco smoke.
Howard et al. JAMA. 1998
Smoking: Increased Risk of Fatal
& Nonfatal Stroke in Women
Relative Risk (95% CI)a
6
5
3,8
4
3
2,5
2,9
2
1,0
1
0
Nonsmokers
1-14
15-24
≥25
Cigarettes/Day
Current Smokers
aThe
probability of an event (developing a disease) occurring in exposed people compared with the probability of
the event in nonexposed people. Adjusted for age, follow-up period, history of diabetes, hypertension, high
cholesterol levels, and relative weight (in 5 categories).
Colditz et al. N Engl J Med. 1988;318(15):937-941.
Smoking: Increased risk of hemorrhagic stroke
Relative Risk (95% CI)a
12
<15 Cigarettes/day
(n=1914)
15 Cigarettes/day
(n=3265)
10
8
6
4
2.06
3.43
1.74
2.39
4.04
2.89
2
0
aThe
Nonsmokers
(n=20,339)
Total Hemorrhagic
Stroke
Intracerebral
Hemorrhage
Subarachnoid
Hemorrhage
probability of an event (developing a disease) occurring in exposed people compared with the probability
of the event in nonexposed people.
Adjusted for age, exercise, alcohol consumption, body mass index, history of hypertension, and history of
diabetes.
Kurth et al. Stroke. 2003;34:2792-2795.
Smoking: Increased Stroke Mortality
60
50,6
Mortality Ratea
50
39,0
40
30,9
30
20
10
0
1-15
15-24
Cigarettes/Day
Current Smokers
aTwenty-year
age-adjusted mortality per 10,000 person-years for men. P<.014 for trend.
Hart et al. Stroke. 1999;30:1999-2007.
≥25
Περιφερική αποφρακτική αγγειοπάθεια & κάπνισμα
Η ΠΑΑ προσβάλει το 20% των καπνιστών
> 55 ετών
50% των ασθενών με ΠΑΑ είναι
ασυμπτωματικοί
5% to 10% των ασυμπτωματικών θα
αναπτύξουν συμπτωματική ΠΑΑ εντός
5 ετών
Build-up of
atherosclerotic
plaque in
arterial wall
Οι ασθενείς με συμπτωματική ΠΑΑ είναι
σε υψηλό κίνδυνο για άλλα
καρδιαγγειακά επεισόδια και θάνατο
Η 5ετής θνησιμότητα για τους ασθενείς με
διαλείπουσα χωλότητα που συνεχίζουν
να καπνίζουν είναι 40%-50%
JAMA. 2006
lAm J Epidemiol. 2001
Gen Pract. 1999;
Scand J Prim Health Care. 1998
Accessed October 8, 2007.
Asymptomatic Peripheral Vascular
Disease: Increased Risk
Odds Ratio (95% CI)a
4,0
2,8
3,0
2,0
1,6
1,0
1,0
0,0
Nonsmokers
aThe
Ex-smokers
Current Smokers
ratio of the odds of development of disease in exposed persons to the odds of development of disease in
nonexposed persons. Adjusted for other cardiovascular risk factors.
Hooi et al. Scand J Prim Health Care. 1998;16:177-182.
Περιφερική αποφρακτική αγγειοπάθεια και
κάπνισμα
4 φορές πιο συχνή η διαλείπουσα χωλότητα
Οι καπνιστές κινδυνεύουν περισσότερο να
αναπτύξουν ΠΑΑ παρά ΣΝ
Ο κίνδυνος αυξάνει με την ένταση του
καπνίσματος
Αυξημένος κίνδυνος μετά από αγγειακά
χειρουργεία
Risk of Peripheral Vascular Disease
vs Coronary Artery Disease
Relative Risk (95% CI)a
8
PVD
CAD
6
3,94
4
1,87
2
1,59
1,66
0
Moderate Smokers
aThe
Heavy Smokers
probability of an event (developing a disease) occurring in exposed people compared with the probability of
the event in nonexposed people. Adjusted for age and sex.
Price et al. Eur Heart J. 1999;20(5):344-353.
Κάπνισμα και ανεύρυσμα κοιλιακής αορτής
Odds Ratio (95% CI)a
12,0
9,0
5,5
6,0
3,0
2,9
3,0
1,0
0,7
0,0
Nonsmokers
1 to 9
10 to 19
20 to 24
25
Cigarettes/Day
Current Smokers
Vardulaki et al. Br J Surg. 2000;87(2):195-200
Relative Risk (95% CI)a
Smoking: Increased Progression of Aortic
Atherosclerosis
3
2,30
2,00
2
1,40
1,00
1
0
Never Smokers
1 to 9
10 to 19
20
Cigarettes/Day
Current Smokers
aThe
probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in
nonexposed people. Adjusted for age, systolic blood pressure, serum total cholesterol, Quetelet index, diabetes mellitus,
menopausal status, alcohol consumption, use of replacement estrogens, and duration of follow-up.
Witteman et al. Circulation. 1993;88(part 1):2156-2162.
Smoking-women

Tobacco is responsible for 17% of all
female deaths in the US

Smoking is the most preventable risk
factor for heart attack
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Women who smoke 1-4 cigarettes/day
are at almost twice as likely to develop
heart disease than nonsmokers
A woman who smokes is at risk for
heart attack 19 years earlier than one
who does not smoke
Women of all ages who quit smoking
greatly reduce their risk of dying
prematurely
“The Nurses' Health Study Cohort”
Kawachi I et al. Circulation 1997;95:2374-2379
“The Nurses' Health Study Cohort”
Kawachi I et al. Circulation 1997;95:2374-2379
Secondhand smoke:

 20%–30% κίνδυνος εμφάνισης Ca πνεύμονα

 25%–30% κίνδυνος εμφάνισης καρδιοπάθειας

Προκαλεί / επιδεινώνει νοσήματα όπως το άσθμα, η
ΧΑΠ και το εμφύσημα
Proportion With Major CAD
Παθητικό κάπνισμα και καρδιαγγειακό
0.20
Light activea
0.15
Heavy passiveb
0.10
0.05
Light passivec
0
0
5
10
Years of Follow up
15
20
Το ανθρώπινο κόστος του παθητικού καπνίσματος
 147 ως 251 θάνατοι μη
καπνιστών ανά 1.000.000
εργαζόμενους
 55.000 ως 94.000
θάνατοι το χρόνο στην
Ευρωπαϊκή Ένωση
Office of Environmental Health Hazard Assessment of the California Environmental
Protection Agency, Health Effects of Exposure to Environmental Tobacco Smoke, 1997.
Environmental Tobacco Smoke:
Risk of Acute Myocardial Infarction (MI)
Exposure to environmental tobacco smoke increased the risk
of non-fatal acute MI in a graded manner
Odds Ratio (95% CI)a
4
Nonsmokers
2
1
0.75
aThe
Never
1-7
8-14
15-21
22
Environmental Tobacco Smoke Exposure (Hours per Week)
ratio of the odds of development of disease in exposed persons to the odds of development of disease in
nonexposed persons. Adjusted for age, sex, region, physical activity, and consumption of fruits, vegetables, and
alcohol. Adapted from Teo et al. Lancet. 2006;368:647-658.
Συνέπειες παθητικού καπνίσματος σε νεογνά & παιδιά
60% των παιδιών στις ΗΠΑ εκτίθενται σε παθητικό κάπνισμα
Σε κάποιες χώρες  80% των νέων ζουν σε σπίτια όπου οι
άλλοι καπνίζουν όταν αυτοί είναι παρόντες
Η δευτερογενής έκθεση στον καπνό αυξάνει το φορτίο της
νόσου και τη νοσηλεία για τα νεογνά και τα παιδιά.
 Μεγάλη Βρετανία 17.000 παιδιά <5 ετών νοσηλεύονται
ετησίως
 Αυστραλία  56% μεγαλύτερος κίνδυνος για νοσηλεία εάν η
μητέρα κάπνιζε στο ίδιο δωμάτιο με το νεογνό,
73% εάν κάπνιζε ενώ κρατούσε το βρέφος στην
αγκαλιά της
95% εάν κάπνιζε ενώ τάιζε το βρέφος
1 Secondhand smoke; Fact sheet, June 2006. 2. Mackay J, Eriksen
M. The Tobacco Atlas. WHO; 2006. 3. Fagerstrom K. Drugs. 2002;
4. Blizzard L, et al. Arch Pediatr Adolesc Med. 2004.