Η σημασία του καπνίσματος στην παθογένεση των καρδιαγγειακών παθήσεων

Παρουσίαση με θέμα: "Η σημασία του καπνίσματος στην παθογένεση των καρδιαγγειακών παθήσεων"— Μεταγράφημα παρουσίασης:

1 Η σημασία του καπνίσματος στην παθογένεση των καρδιαγγειακών παθήσεων
Βασιλική Ν. Γιαννακοπούλου MD, Phds, FESC, FEAS Διευθ. ΕΣΥ Θριάσιο Νοσοκομείο Συνεργάτης Λιπιδαιμικού 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 He is credited being the 1st European 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 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

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 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.

4 Many Diseases Are Directly Caused By Smoking
Cancer Lung Oral cavity/pharynx Laryngeal Esophageal Stomach Pancreatic Kidney Bladder Cervical Leukemia Cardiovascular Ischemic heart disease Stroke – Vascular dementia2 Peripheral vascular disease3 Abdominal aortic aneurysm Respiratory COPD Pneumonia Poor asthma control Reproductive Low birthweight Pregnancy complications Reduced fertility SIDS Other Adverse surgical outcomes/ wound healing Hip fractures Low bone density Cataract Peptic ulcer disease† Active Smoking Smoking is causally linked to a host of cardiovascular, respiratory, reproductive, and other conditions, as well as many types of cancer. Background In 2004, the US Surgeon General published a report on the health effects of active smoking, focusing specifically on the evidence for a causal relationship between smoking and disease and death. According to the research summarized in the report, many serious conditions are caused by smoking, including cardiovascular, respiratory, reproductive, and other conditions, as well as cancer affecting diverse areas and organs of the body. In addition to the widely-known consequences of lung cancer and respiratory disease, smoking has been causally linked to such diverse morbidities as low bone density, nuclear cataract, bladder cancer, and reduced fertility.1 Other studies have linked smoking to vascular dementia2 and peripheral arterial disease.3 These conditions can affect young and middle-aged smokers and, in general, as a smoker’s age increases, the frequency of smoking-caused diseases rises.1 References US Department of Health and Human Services. The Health Consequences of Smoking. A Report of the Surgeon General. Atlanta, Ga: Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2004. Roman GC. Vascular dementia prevention: a risk factor analysis. Cerebrovasc Dis. 2005;20 (Suppl 2):91–100. Willigendael EM, Teijink JA, Bartelink ML, et al. Influence of smoking on incidence and prevalence of peripheral arterial disease. J Vasc Surg. 2004;40:1158–1165. † In patients who are Helicobacter pylori positive. COPD = chronic obstructive pulmonary disease; SIDS = sudden infant death syndrome. 1. Surgeon General’s Report Roman GC. Cerebrovasc Dis. 2005;20(Suppl 2): Willigendael EM et al. J Vasc Surg. 2004;40:

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 Μπαταρίες αυτοκινήτων Καυσαέρια αυτοκινήτων Βιομηχανικά διαλυτικά μέσα
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; Διατίθεται στην ηλεκτρονική διεύθυνση: 2. Mackay J, Eriksen M. The Tobacco Atlas. World Health Organization; Harvard Health Letter. May Surgeon General’s Report. The Health Consequences of Smoking; 2004. 10

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 More than three-quarters of the world’s cardiovascular disease – the world’s leading cause of death – results from smoking, high blood pressure, cholesterol, or their combination. As the only risk factor, smoking is a major contributor to CV risk of death, however these effects multiply when other risk factors are also occurring. References: Kannel WB. In: Genest J. et al, eds. Hypertension: Physiopathology and Treatment. New York, NY: McGraw-Hill, Inc; 1977: 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 (nicotine increases the heart rate and transiently increases blood pressure (nitric oxide release and resultant vasodilation are impaired) smokers have on average higher low-density lipoprotein, more oxidized low-density lipoprotein, and lower high-density lipoprotein cholesterol than nonsmokers do evidenced by increased levels of C-reactive protein in the blood of smokers

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 (%) Key Point When evaluated by serial quantitative coronary arteriography, it is seen that smoking accelerates progression of existing coronary artery disease (CAD) and new lesion formation. Waters et al evaluated 331 participants (90 current smokers, 241 nonsmokers) with angiographically documented coronary atherosclerosis and fasting cholesterol levels between 220 and 300 mg/dL, enrolled in the randomized, double-blind, placebo-controlled Canadian Coronary Atherosclerosis Intervention Trial (CCAIT). Patients were randomized to receive either placebo or lovastatin 20 mg once daily. In an attempt to achieve a target low-density lipoprotein (LDL) cholesterol level 130 mg/dL, drug doses were increased over the initial 16 weeks of the trial to a maximum dose of 40 mg twice daily. Participants were evaluated over a 2-year period. Repeat angiography was performed at the conclusion of the study period (except in 21 patients in whom it was performed earlier). Baseline and follow-up coronary angiograms were compared, and a change in minimal lumen diameter 0.4 mm was considered a true change (either progression or regression). A new lesion was defined as a stenosis that was not apparent on the initial angiogram or was <25% in diameter stenosis but that narrowed by ≥0.4 mm in minimal lumen diameter at the second angiogram. Significantly more current smokers showed evidence of progression. Progression occurred in 41 of 72 (57%) current smokers and 83 of 227 (37%) nonsmokers, P=.002. Significantly more current smokers developed new atherosclerotic lesions, 36% vs 20%, P=.007. The authors therefore concluded that coronary atherosclerosis progresses more rapidly in current smokers than in nonsmokers. 20 Nonsmokers Current Smokers Nonsmokers Current Smokers Waters et al. Circulation. 1996;94: Reference Waters D, Lesperance J, Gladstone P, et al; the CCAIT Study Group. Effects of cigarette smoking on the angiographic evolution of coronary atherosclerosis: a Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) substudy. Circulation. 1996;94:

24 Smoking: Increased Risk of Angina
2.6 Relative Risk (95% CI)a 2.0 Key Point The risk of angina may be directly related to the amount smoked. Willett et al prospectively evaluated the incidence of coronary artery disease in a cohort of 119,404 female nurses enrolled in the Nurses’ Health Study. Participants completed questionnaires at baseline (1976) and were followed up over a 6-year period. Smoking status was identified. Criteria for confirmed angina was presence of one of the following: documented evidence of coronary artery bypass surgery, coronary angiography demonstrating more than 70% obstruction of any coronary artery, or ST-segment depression of more than 1 mm on exercise stress testing together with a positive response to a mailed version of the Rose questionnaire. Compared with nonsmokers, the age-adjusted RR of angina, increased with increasing daily cigarette use, 1.6, 2.0, and 2.6, for 1-14/day, 15-24/day, and 25/day, respectively. 1.6 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 References Willett WC, Green A, Stampfer MJ, et al. Relative and absolute excess risks of coronary heart disease among women who smoke cigarettes. N Engl J Med. 1987;317(21): Willigendael EM, Teijink JAW, Bartelink ML, Peter RJG, Büller HR, Prins MH. Smoking and the patency of lower extremity bypass grafts: a meta-analysis. J Vasc Surg. 2005;42(1):67-74.

25 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 Odds Ratio (95% CI)a 10 9 8 7 6 5 4 3 2 1 Age <40 y Age y Age y Age y Age >70 y 20 Nonsmokers Ex-smokers 1-19 Key Point Overall, current smoking was associated with a 3-fold increase in the odds of having a nonfatal acute myocardial infarction (MI) compared with nonsmokers. Teo et al evaluated 12,133 cases of first acute MI and 14,435 age-matched and sex-matched controls in the international, multicenter INTERHEART study. Trained staff administered a questionnaire to both cases and controls in which participants were asked detailed questions about their smoking status. Overall, current smoking was associated with a 3-fold increase in the odds of having a non-fatal acute MI, compared with nonsmokers (odds ratio [OR] 2.95; 95% CI ; P<.0001). Risk increased with the number of cigarettes smoked. The effect of current smoking was significantly greater in younger (OR, 3.53; 95% CI, ) than in older participants (OR, 2.55; 95% CI, ); P<.0001 for interaction. The effect of current smoking was markedly greater in younger subjects, particularly among the heaviest smokers (20 cigarettes per day) in whom ORs were 5.6 (95% CI, ) for younger smokers and 3.6 (95% CI, ) for older smokers (P<.0001 for interaction). aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Teo. Lancet Reference Teo KK, Ounpuu S, Hawken S, et al; on behalf of the INTERHEART Study Investigators. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006;368:

26 Smoking: Increased CAD Mortality
Relative Risk (95% CI)a Key Point The risk of fatal CAD may be directly related to the amount smoked. Willett et al prospectively evaluated the incidence of CAD in a cohort of 119,404 female nurses enrolled in the Nurses’ Health Study. Participants completed questionnaires at baseline (1976) and were followed up over a 6-year period. Smoking status was identified. Deaths among nonrespondents were identified through searches of state records and the National Death Index or were reported by family members. More than 98% of the deaths were identified. Fatal CAD was defined as fatal myocardial infarction (MI) confirmed by hospital records or at autopsy, or as CAD recorded on the death certificate, if this was the only cause given and there was previous evidence of CAD. Compared with nonsmokers, the age-adjusted relative risk (RR) of fatal CAD, increased with increasing daily cigarette use: 1.7, 3.7, and 5.4, for 1-14/day, 15-24/day, and 25/day, respectively. Nonsmokers 1-14/Day 15-24/Day 25/Day Fatal CAD Cigarettes/Day Current Smokers 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 Reference Willett WC, Green A, Stampfer MJ, et al. Relative and absolute excess risks of coronary heart disease among women who smoke cigarettes. N Engl J Med. 1987;317(21):

27 Smoking: Increased Risk of Sudden Cardiac Death
Relative Risk (95% CI)a Key Point Current smoking is associated with an increased risk of sudden cardiac death. Wannamethee et al prospectively evaluated 7735 British men, aged 40 to 59 years from the British Regional Heart Study (BRHS). All participants completed questionnaires regarding their smoking habits, alcohol intake, and medical history. Subjects had complete physical exams that included fasting bloodwork, pulmonary function tests (PFTs), and ECG. Participants were followed up for 8 years. Fatal events were defined as death from ischemic heart disease. Sudden cardiac death was defined as an event in which death occurred within 1 hour after the onset of symptoms. Only those men for whom clear information was available about their death within 1 hour were included in the category of sudden death. A Cox proportional hazards model was used to evaluate contribution of risk factors to the risk of sudden cardiac death and to derive the age-adjusted RRs. When adjusted for age, current smokers had an increased risk of sudden cardiac death (RR, 2.3, 95% CI, ). 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 Reference Wannamethee G, Shaper AG, Macfarlane PW, Walker M. Risk factors for sudden cardiac death in middle-aged British men. Circulation. 1995;91:

28 Q-wave Myocardial Infarction (MI)
Smoking: Increased Risk of Q-Wave MI After Percutaneous Coronary Revascularization 2.08 Relative Risk (95% CI)a Key Point Current smokers have a higher risk of Q-wave MI after successful percutaneous transluminal coronary angioplasty (PTCA) than nonsmokers and ex-smokers. Patients (N=6600) who underwent PTCA at the Mayo Clinic from 1979 through 1995 were followed for up to 16 years by Hasdai et al. Patients were questioned about their smoking status at baseline and follow-up. Study population was divided into 4 groups on the basis of smoking status at baseline: nonsmokers, defined as patients who had never smoked cigarettes regularly; ex-smokers, who had quit smoking a minimum of 6 months before the procedure; quitters, those who had permanently quit smoking immediately after the procedure; and current smokers, who smoked before and after the procedure. The study end points were death from any cause, Q-wave acute MI or severe angina, and the need for coronary artery bypass grafting (CABG) or repeated PTCA. When adjusted for baseline variables significantly associated with each end point, current smokers had a greater risk of Q-wave MI (RR, 2.08 [ ]), than nonsmokers. 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 Reference Hasdai D, Garratt KN, Grill DE. Effect of smoking status on the long-term outcome after successful percutaneous coronary revascularization. N Engl J Med. 1997;336:

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 Progression of Intima-Medial Thickness, µm/3 y (95% CI)a 31.6 32.8 Key Point Both active smoking and environmental tobacco smoke exposure are associated with increased progression of carotid atherosclerosis. Howard et al evaluated 10,914 participants enrolled in the Atherosclerosis Risk in Communities (ARIC) study, a prospective study that assessed atherosclerotic disease and its clinical consequences in a cohort of approximately 16,000 US adults. Subjects underwent carotid ultrasound to evaluate carotid intima-medial thickness, a surrogate of atherosclerotic progression. Assessments were made at baseline and at a follow-up visit 3 years later. All participants completed self-administered questionnaires based upon which they were classified as current smokers, ex-smokers, nonsmokers, and exposed to environmental tobacco smoke. Current smokers demonstrated the highest rate of atherosclerotic progression (41 µm per 3 years). Rates of progression followed, in descending order, ex-smokers with environmental tobacco smoke exposure, nonsmokers with environmental tobacco smoke exposure, ex-smokers without environmental tobacco smoke exposure, followed by nonsmokers without environmental tobacco smoke exposure, 39.6 µm, 33.2 µm,32.5 µm; and 27.0 µm, respectively. The authors therefore concluded that both active smoking and environmental tobacco smoke exposure are associated with increased progression of carotid atherosclerosis. 25.9 Nonsmokers without Exposureb Nonsmokers with Exposureb Ex-smokers without Exposureb Ex-smokers with Exposureb Current Smokers 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 Reference Howard G, Wagenknecht LE, Burke GL, et al; the ARIC Investigators.. Cigarette smoking and progression of atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. JAMA. 1998;279(2):

31 Smoking: Increased Risk of Fatal & Nonfatal Stroke in Women
Relative Risk (95% CI)a Key Point In young and middle-aged women, the risk of stroke may be related to the amount smoked. Colditz et al evaluated 118,539 women from the Nurses’ Health Study in the United States. The Nurses’ Health Study consisted of a cohort of 121,700 female nurses, aged 30 to 55 who completed baseline and follow-up self-administered questionnaires evaluating social and past medical history. Subjects were followed up for a period of 8 years ( ). Primary end points were incidence of nonfatal and fatal stroke. Stroke was defined as a clinical syndrome consisting of a constellation of neurologic findings of sudden or rapid onset, persisting for more than 24 hours, with vascular origins limited to thrombosis of a cerebral artery resulting in infarction or vessel rupture resulting in hemorrhage. There were 274 incidents of stroke in the 8-year follow-up period. Current smokers had a significantly higher rate of stroke, both nonfatal and fatal. Risk of stroke increased with the number of cigarettes smoked daily. The adjusted RR of fatal and nonfatal stroke increased from 2.5 ( ) to 2.9 ( ) to 3.8 ( ) in 25 cigarettes, respectively. Relative risk was adjusted for age in 5-year intervals, history of diabetes, history of hypertension, history of high cholesterol, and relative weight. 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): Reference Colditz GA, Bonita R, Stampfer MJ, et al.. Cigarette smoking and risk of stoke in middle-aged women. N Engl J Med. 1988;318(15):

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 1.74 4.04 3.43 2.39 2.89 Key Point Female smokers have an increased risk of total hemorrhagic stroke as well as intracerebral hemorrhage and subarachnoid hemorrhage. In an attempt to evaluate the impact of smoking on the risk of hemorrhagic stroke, Kurth et al evaluated data obtained from the Women’s Health Study. The Women’s Health Study is a randomized, double-blind, placebo-controlled trial ( ) in which 39,876 healthy women were followed up to determine the benefits of low-dose aspirin and vitamin E for the prevention of cardiovascular disease (CVD). Kurth et al determined subjects’ smoking habits from responses to baseline self-administered questionnaires. Stroke was defined as a focal neurologic deficit of sudden onset and vascular mechanism that lasted more than 24 hours. Hemorrhagic stroke was further classified into intracerebral hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage. During a mean of 9 years of follow-up, a total of 70 hemorrhagic strokes occurred. Analysis was adjusted for age, exercise (<4 times per week vs 4 times per week), alcohol consumption (<1 drink per week, 1-6 drinks per week, and 1 drink per day), body mass index (continuous), history of hypertension (self-reported systolic pressure 140 mm Hg, or diastolic blood pressure 90 mm Hg, or current treatment of hypertension, regardless of blood pressure), and history of diabetes. Risk of total hemorrhagic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage increased with quantity of cigarettes smoked. 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: Reference Kurth T, Kase CS, Berger K, Gaziano JM, Cook NR, Buring JE. Smoking and risk of hemorrhagic stroke in women. Stroke. 2003;34:

33 Smoking: Increased Stroke Mortality
Mortality Ratea Key Point Cigarette smoking increases the risk of mortality from stroke. Hart et al evaluated data derived from the Renfrew/Paisley study, a prospective cohort study initiated in the 1970s in West Scotland. Residents (7052 male and 8354 female) of Renfrew and Paisley, Scotland, aged 45 to 64 years were evaluated prospectively over a period of 20 years. Subjects underwent a thorough baseline physical exam, which included fasting bloodwork, ECG and pulmonary function tests, and responded to a self-administered questionnaire in which smoking habits and other cardiovascular risk factors were assessed. The age-adjusted 20-year stroke mortality rate was similar for men and women. There was a dose-related increase in stroke-related mortality in men. Cigarette smoking increased the risk of mortality from stroke in women as well; however, the dose-related increase was not as pronounced as in men. 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: Reference Hart CL, Hole DJ, Smith GD. Risk factors and 20-year stroke mortality in men and women in the Renfrew/Paisley Study in Scotland. Stroke. 1999;30:

34 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 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% Build-up of atherosclerotic plaque in arterial wall Peripheral vascular disease (PVD) affects approximately 20% of adults older than age 55. Approximately half of patients with PVD are asymptomatic. Five to ten percent of asymptomatic patients will progress to symptomatic PVD over 5 years. Patients with symptomatic PVD are at higher risk for concomitant cardiovascular disease as well as cardiovascular mortality. JAMA. 2006 lAm J Epidemiol. 2001 Gen Pract. 1999; Scand J Prim Health Care. 1998 Accessed October 8, 2007. References Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA. 2006;295(5): Hooi JD, Kester ADM, Stoffers HEJH, Overdijk M, van Ree JW, Knottnerus JA. Incidence of and risk factors for asymptomatic peripheral arterial occlusive disease: a longitudinal study. Am J Epidemiol. 2001;153(7): Hooi JD, Stoffers HEJH, Knottnerus JA, van Ree JW. The prognosis of non-critical limb ischaemia: a systematic review of population-based evidence. Br J Gen Pract. 1999;49:49-55. Hooi JD, Stoffers HEJH, Kester ADM, et al. Risk factors and cardiovascular diseases associated with asymptomatic peripheral arterial occlusive disease: the Limburg PAOD study. Scand J Prim Health Care. 1998;16:

35 Asymptomatic Peripheral Vascular Disease: Increased Risk
Odds Ratio (95% CI)a Key Point Smoking is associated with a significantly increased risk of asymptomatic peripheral vascular disease (PVD). Hooi et al evaluated 3650 residents of the province of Limburg, The Netherlands, in the Limburg Peripheral Arterial Occlusive Disease (PAOD) study. Participants answered a self-administered questionnaire at their doctor’s office, and ankle-brachial pressure index (ABPI) was assessed by means of a pocket Doppler device and a sphygmomanometer. ABPI was calculated as a ratio of the ankle systolic blood pressure to the highest arm systolic blood pressure. Subjects were considered as having evidence of PVD when a minimum of 1 leg’s resting ABPI was <0.95 on 2 evaluations within a 1-week interval. Asymptomatic PVD was defined as the combination of an ABPI <0.95 without symptoms of intermittent claudication. Among study participants, 458 subjects had PVD. One hundred thirty-eight were symptomatic, 314 were asymptomatic, and 6 had unspecified PVD. Current and ex-smoking were significantly associated with asymptomatic PVD, OR 2.8 ( ) and 1.6 ( ), respectively. 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: Reference Hooi J, Stoffers HEJH, Kester A, et al. Risk factors and cardiovascular diseases associated with asymptomatic peripheral arterial occlusive disease: the Limburg PAOD study. Scand J Prim Health Care. 1998;16:

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 36

37 Risk of Peripheral Vascular Disease vs Coronary Artery Disease
Relative Risk (95% CI)a Key Point Although smoking increases the risk of both CAD and PVD, the risk of PVD is greater than the risk of CAD. Participants (N=1592) aged years from 11 general practices in Edinburgh, Scotland, were followed up in the Edinburgh Artery Study over a period of 5 years to monitor for cardiovascular events and mortality. At baseline, subjects had a complete physical exam, along with an ECG, fasting bloodwork, and completed a questionnaire in which subjects were asked detailed questions about their cardiovascular and smoking history. Subjects had a 5-year follow-up examination in which they completed a self-administered questionnaire about cardiovascular symptomatology. Moderate smokers were defined as those participants who had 25 pack/year history. Heavy smokers were defined as those participants who had >25 pack/year history. Although both CAD and PVD were more common in moderate and heavy smokers than in nonsmokers, cigarette smoking was a stronger risk factor for PVD than for CAD. The age- and sex-adjusted RRs of PVD associated with smoking were 1.87 (95% CI, ) for moderate smokers and 3.94 (95% CI, ) for heavy smokers. The age- and sex-adjusted RRs of CAD were 1.59 (95% CI, ) and 1.66 (95% CI, ), respectively. 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): Reference Price JF, Mowbray PI, Lee AJ, Rumley A, Lowe GDO, Fowkes F. Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study. Eur Heart J. 1999;20(5):

38 Κάπνισμα και ανεύρυσμα κοιλιακής αορτής
Odds Ratio (95% CI)a Key Point Smoking is the most important modifiable risk factor for development of abdominal aortic aneurysm (AAA). Vardulakai et al performed a randomized, controlled trial on 5356 men and women in Chichester, UK, between 1988 and Anteroposterior measurements of the aorta were obtained with an ultrasound, and aneurysm was defined as an aortic diameter of 30 mm or more. Personal and social history were obtained prior to the baseline physical via a self-administered questionnaire. Men were 5.6 times more likely to have an AAA than women. The chart above depicts that the level of risk for AAA increases with the number of cigarettes smoked daily. Risk of AAA ranges from 0.7, 3.0, 2.9, 5.5 for current smokers who smoked 1-9, 10-19, 20-24, and 25 cigarettes daily, respectively. Nonsmokers 1 to 9 10 to 19 20 to 24 25 Cigarettes/Day Current Smokers Vardulaki et al. Br J Surg. 2000;87(2): Reference Vardulaki KA, Walker NM, Day NE, Duffy SW, Ashton AH, Scott RAP. Quantifying the risks of hypertension, age, sex and smoking in patients with abdominal aortic aneurysm. Br J Surg. 2000;87(2): 38

39 Smoking: Increased Progression of Aortic Atherosclerosis
Relative Risk (95% CI)a Key Point Risk of aortic atherosclerotic progression increases with number of cigarettes smoked. Witteman et al evaluated the association between smoking and progression of abdominal aortic atherosclerosis in a population-based cohort of 758 women aged 45 to 64. Women were clinically evaluated at baseline and followed up for a mean of 8.90.8 years. Women underwent a second physical evaluation at follow-up. Aortic atherosclerosis was diagnosed by radiographic detection of calcific deposits in the abdominal aorta. Atherosclerotic change was defined as the occurrence (disappearance) of calcifications or enlargement (reduction) of the calcified area present at baseline. All women completed self-administered questionnaires regarding their smoking status at baseline and follow-up. At follow-up, atherosclerotic changes were noted in 284 women. The risk of aortic atherosclerotic progression increased with number of cigarettes smoked per day. 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): Reference Witteman JCM, Grobbee DE, Valkenburg HA, van Herwert AM, Stijnen T, Hofman A. Cigarette smoking and the development and progression of aortic atherosclerosis: a 9-year population-based follow-up study in women. Circulation. 1993;88(part 1):

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:

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

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 κάπνισμα και καρδιαγγειακό
0.05 0.10 0.15 0.20 Light activea Heavy passiveb Proportion With Major CAD Key Point Exposure to environmental tobacco smoke increases the risk of heart disease among nonsmokers by 30%. Whincup et al prospectively evaluated the relationship between environmental tobacco smoke exposure (quantified by serum cotinine levels) and risk of coronary artery disease (CAD) and stroke in 4729 subjects enrolled in the British Regional Heart Study. Participants were male nonsmokers aged 40 to 59 years, initially evaluated from 1978 to Baseline examination included assessment of blood pressure and nonfasting cholesterol and cotinine levels in addition to a nurse-administered questionnaire, from which data on smoking and medical history were obtained. Men were classified as “current nonsmokers” at baseline if they reported that they did not smoke and had a cotinine concentration <14.1 ng/mL. Nonsmokers were further subclassified into light and heavy passive smokers. Light passive smokers were nonsmokers who had the lowest levels of cotinine concentration (0-0.7). Heavy passive smokers were nonsmokers who had the highest cotinine concentration (0.8 to 14.0). Light active smokers were men who reported smoking 1 to 9 cigarettes a day, irrespective of cotinine concentration. All men were followed up for all-cause mortality and cardiovascular mortality. The graph depicts the Kaplan-Meier plot showing the cumulative proportions of men with major CAD over time among the light active, heavy passive and light passive smokers. Age, systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, forced expiratory volume in 1 second (FEV1), height, preexisting CAD, body mass index, triglycerides, WBC, diabetes, physical activity (none, occasional, light, moderate, or more), alcohol intake (none/occasional, light/moderate, heavy), and social class (I, II, III non-manual, III manual, IV, V, and Armed Forces) were fitted as dichotomous variables. Heavy passive and light passive smokers had the highest incidence of major CAD. Although the groups diverged markedly in the early follow-up period, they remained almost parallel during later years. The authors concluded that environmental tobacco smoke exposure is associated with an increased risk of CAD of approximately 25% to 30%. Light passivec 5 10 15 20 Years of Follow up Reference Whincup PH, Gilg JA, Emberson JR, et al. Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement. BMJ. 2004;329: 44

45 Το ανθρώπινο κόστος του παθητικού καπνίσματος
 147 ως 251 θάνατοι μη καπνιστών ανά εργαζόμενους  ως 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. 45

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 Key Point Exposure to environmental tobacco smoke increased the risk of nonfatal acute (MI) in a graded manner. Teo et al evaluated 12,133 cases of first acute MI and 14,435 age-matched and sex-matched controls in the international, multicenter INTERHEART study. Trained staff administered a questionnaire to both cases and controls in which participants were asked detailed questions about their smoking status. After adjusting for age, sex, region, physical activity, and consumption of fruits, vegetables, and alcohol, nonsmokers who had no previous environmental tobacco smoke exposure showed increasing risk of nonfatal acute MI with increasing levels of exposure to environmental tobacco smoke. Although the etiology is unclear, this increase in risk was slightly attenuated in subjects with 22 hours per week of environmental tobacco smoke exposure. 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: Reference Teo KK, Ounpuu S, Hawken S, et al, on behalf of the INTERHEART Study Investigators. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006;368:

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. Μεγάλη Βρετανία  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 Mackay J, Eriksen M. The Tobacco Atlas. WHO; Fagerstrom K. Drugs. 2002; 4. Blizzard L, et al. Arch Pediatr Adolesc Med

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