Η σημασία του καπνίσματος στην παθογένεση των καρδιαγγειακών παθήσεων

1. Η σημασία του καπνίσματος στην παθογένεση των καρδιαγγειακών παθήσεων Βασιλική Ν. Γιαννακοπούλου MD, Phds, FESC, FEAS Διευθ. ΕΣΥ Θριάσιο Νοσοκομείο ΣυνεργάτηςΛιπιδαιμικού Ιατρείου ΩΚΚ

2. History • 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 1stEuropean smoker • 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 1604Stuart 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

3. 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 crimeand 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.

4. Cardiovascular Ischemic heart disease Stroke – Vascular dementia2 Peripheral vascular disease3 Abdominal aortic aneurysm Respiratory COPD Pneumonia Poor asthma control Cancer Lung Oral cavity/pharynx Laryngeal Esophageal Stomach Pancreatic Kidney Bladder Cervical Leukemia Active Smoking Reproductive Low birthweight Pregnancy complications Reduced fertility SIDS Other Adverse surgical outcomes/ wound healing Hip fractures Low bone density Cataract Peptic ulcer disease† Many Diseases Are Directly Caused By Smoking † 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.

5. Tobacco atlas 4th Edition 2011 World Lung Foundation, American Cancer Society

6. Tobacco Kills More Americans/year Than Alcohol, Cocaine, Crack, Heroin, Homicide, Suicide, Car Accidents, Fires & AIDS combined:

7. Cardiovascular diseases linked with smoking Over 1/5 of deaths due to smoking-related illness are caused by heart disease

8. European Cardiovascular Disease Statistics 2012 Edition

9. European Cardiovascular Disease Statistics 2012 Edition

10. Καπνός τσιγάρου: 4000 χημικές ουσίες, 250 ουσίες τοξικές ή καρκινογόνες 1. National Toxicology Program. 11th Report on Carcinogens; 2005. Διατίθεται στην ηλεκτρονική διεύθυνση: http://ntp-server.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.

11. Multiplicative Effect on Risk of Death From Top Risk Factors of Cardiovascular Disease x3.5 x1.5 x2.3 x5.9 x2.7 x3.9 x1.7 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.

12. The mechanisms of the effects of smoking The mechanisms of the effects of smoking are not fully elucidated but are believed to include: • 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

13. JACC 2004

14. Platelet activation: A key factor in AMI and Sudden Death is thrombosis caused by platelet activation. • Tobacco smoke activates platelets through several mechanisms. Including: • Endothelial dysfunction, • Oxidative stress, • Decreased platelet derived nitric oxide (NO) production, • Increased fibrinogen and thromboxane.

15. 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

16. Endothelial Dysfunction & CAD Risk Factors • Endothelial dysfunction is strongly and independently associated with cardiovascular events • 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 • NO, secreted by the endothelium and responsible for vasodilatation, is decreased in active and passive smokers

17. Lipid profile in smokers • 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

18. Oxidation LDL is rapidly ingested by macrophages which, in turn, forms foam cells in atherosclerotic lesions • 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) • This Inflammatory state is reduced after smoking cessation.

19. Increased oxidative stress • Smokers and passive smokers have been found to have lower levels of anti-oxidants • 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 anti-oxidant levels that normally protect the body against oxidative damage

20. Genetic Predisposition • 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

21. Other Effects: • Smoking leads to higher levels of epinephrine and norepinephrine • These changes increase myocardial oxygen demand • In addition tobacco smoke has also been found to have arrythmogenic potential • Arterial stiffness is also increased in smokers and passive smokers

22. Cigarette smoking predisposes the individual to several different clinical atherosclerotic syndromes: • Stable angina • Acute coronary syndromes • Sudden death • Stroke • Aortic &peripheral atherosclerosis • Aortic aneurysm • Sexual impotence

23. Smoking: Effect on Coronary Artery Disease Progression of Existing Lesions Formation of New Lesions 57 P=.002 P=.007 37 36 Patients (%) Patients (%) 20 Nonsmokers Current Smokers Nonsmokers Current Smokers Waters et al. Circulation. 1996;94:614-621.

24. Smoking: Increased Risk of Angina 2.6 Relative Risk (95% CI)a 2.0 1.6 1.0 Nonsmokers 1-14/Day 15-24/Day 25/Day Cigarettes/DayCurrent 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.

25. 10 9 8 7 6 5 Odds Ratio (95% CI)a 4 3 2 1 0 Age <40 y Age 40-49 y Age 50-59 y Age 60-69 y Age >70 y Nonsmokers Ex-smokers 1-19 20 Smoking: Increased Risk of Acute Nonfatal Myocardial Infarction Current smoking was associated with a 3-fold increase in odds of a nonfatal acute MI compared with nonsmokers aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons.Teo. Lancet. 2006.

26. Smoking: Increased CAD Mortality Relative Risk (95% CI)a Nonsmokers 1-14/Day 15-24/Day 25/Day Cigarettes/DayCurrent 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

27. Smoking: Increased Risk of Sudden Cardiac Death Relative Risk (95% CI)a 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.Wannamethee et al. Circulation. 1995

28. Smoking: Increased Risk of Q-Wave MI After Percutaneous Coronary Revascularization 2.08 Relative Risk (95% CI)a 1.28 1.0 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

29. 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

30. Smoking: Increased Progression of Carotid Atherosclerosis 43.0 38.8 31.6 Progression of Intima-Medial Thickness, µm/3 y (95% CI)a 32.8 25.9 NonsmokerswithoutExposureb NonsmokerswithExposureb Ex-smokers withoutExposureb Ex-smokers with Exposureb CurrentSmokers aAdjusted 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

31. Smoking: Increased Risk of Fatal & Nonfatal Stroke in Women Relative Risk (95% CI)a 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.

32. Smoking: Increased risk of hemorrhagic stroke Nonsmokers (n=20,339) <15 Cigarettes/day (n=1914) 15 Cigarettes/day (n=3265) Relative Risk (95% CI)a 2.06 4.04 1.74 3.43 2.39 2.89 Total Hemorrhagic Stroke Intracerebral Hemorrhage Subarachnoid Hemorrhage 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, exercise, alcohol consumption, body mass index, history of hypertension, and history of diabetes. Kurth et al. Stroke. 2003;34:2792-2795.

33. Smoking: Increased Stroke Mortality Mortality Ratea 1-15 15-24 ≥25 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.

34. Η ΠΑΑ προσβάλει το 20% των καπνιστών > 55 ετών 50% των ασθενών με ΠΑΑ είναι ασυμπτωματικοί 5% to 10% των ασυμπτωματικών θα αναπτύξουν συμπτωματική ΠΑΑεντός 5 ετών Οι ασθενείς με συμπτωματική ΠΑΑείναι 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% Περιφερική αποφρακτική αγγειοπάθεια & κάπνισμα Build-up of atherosclerotic plaque in arterial wall JAMA. 2006 lAm J Epidemiol. 2001 Gen Pract. 1999; Scand J Prim Health Care. 1998 Accessed October 8, 2007.

35. Asymptomatic Peripheral Vascular Disease: Increased Risk Odds Ratio (95% CI)a Nonsmokers Ex-smokers Current Smokers aThe 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.

36. 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

37. Risk of Peripheral Vascular Disease vs Coronary Artery Disease Relative Risk (95% CI)a Moderate Smokers Heavy 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 and sex. Price et al. Eur Heart J. 1999;20(5):344-353.

38. Κάπνισμα και ανεύρυσμα κοιλιακής αορτής Odds Ratio(95% CI)a 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

39. Smoking: Increased Progression of Aortic Atherosclerosis Relative Risk (95% CI)a 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.

40. Smoking-women • Tobacco is responsible for 17% of all female deaths in the US • Smoking is the most preventable risk factor for heart attack • 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

41. “The Nurses' Health Study Cohort” Kawachi I et al. Circulation 1997;95:2374-2379

42. “The Nurses' Health Study Cohort” Kawachi I et al. Circulation 1997;95:2374-2379

43. Secondhand smoke: • 20%–30% κίνδυνος εμφάνισης Ca πνεύμονα •  25%–30% κίνδυνος εμφάνισης καρδιοπάθειας • Προκαλεί / επιδεινώνει νοσήματα όπως το άσθμα, η ΧΑΠ και το εμφύσημα

44. Παθητικό κάπνισμακαι καρδιαγγειακό 0.20 0.15 0.10 0.05 0 0 5 10 15 20 Light activea Heavy passiveb Proportion With Major CAD Light passivec Years of Follow up

45. 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.

46. 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 4 Nonsmokers 2 Odds Ratio (95% CI)a 1 Never 1-7 8-14 15-21 22 0.75 Environmental Tobacco Smoke Exposure (Hours per Week) aThe 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.

47. 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. • ΜεγάληΒρετανία 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.