Malefícios cardio-pulmonares do tabagismo

Apresentação em tema: "Malefícios cardio-pulmonares do tabagismo"— Transcrição da apresentação:

1 Malefícios cardio-pulmonares do tabagismo
Oliver Nascimento Disciplina de Pneumologia Centro de Reabilitação Pulmonar Universidade Federal de São Paulo Lar Escola São Francisco

2 Funcionário público federal (Unifesp) Consultoria e pesquisa clínica:
Conflitos de interesse Conselho Federal de Medicina 1595/00 de 18/5/2000 ANVISA n 120/2000 de 30/11/2000 Funcionário público federal (Unifesp) Consultoria e pesquisa clínica: Pfizer Pesquisa clínica: Boehringer Ingelheim Novartis Aché Aztra Zeneca

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4 Doenças respiratórias mais frequentes
Doenças das vias aéreas/obstrutivas Bronquiolite DPOC Doenças Intersticiais Bronquiolite respir. Assoc. à doença intersticial Pneumonia Intersticial Descamativa Granuloma Eosinofílico/células de Langerhan Câncer: cavidade nasal, laringe, pulmão

5 Outros efeitos Aumenta risco de tuberculose e pneumonia.
Exacerba doenças pré-existentes como asma e DPOC. Doença do refluxo gastresofágico – DRGE. Sinergismo com outros cancerígenos. Fibrose intersticial idiopática e hipertensão pulmonar.

6 Declínio do VEF1 com idade
Nunca fumou ou não suscetível ao tabagismo 100 Gold 0 + 1 75 Gold 2 FEV1 (% do previsto) 50 Gold 3 Parou de fumar aos 50 anos 25 Incapacidade Gold 4 Parou de fumar aos 65 anos Morte 25 50 75 100 Idade (anos) Fletcher C, 1976

7 Prevalência de comorbidade por gravidade em pacientes com DPOC
São Paulo – Projeto Platino 2003 Grave e muito grave Leve Moderado n = 90 n = 43 n = 11 Comorbidades % % % Asma ou alergia 12,2 14,0 18,2 Doença do coração 15,6 11,6 27,3 Hipertensão arterial sistêmica 43,3 27,9 63,6 Diabetes 13,3 11,6 9,1 Câncer no pulmão 1,1 0,0 0,0 Acidente vascular encefálico 4,4 4,7 0,0 Gastrite ou úlcera 30,0 44,1 27,3 Obesidade, IMC > 25Kg/m 60,7 64,3 81,8 Carvalho, AK et al, Submmited Braz J Med Biol Res 2009

8 Epidemiologia do tabagismo
O uso de tabaco é fator de risco para 6 das 8 principais causas de morte no mundo WHO Report on the Global Tobacco Epidemic, 2008:The MPOWER package. Geneva, World Health Organization, 2008

9 Tabagismo Aumenta risco trombogenicidade
Fator Xa pmol/L/min P=0,003 400 300 200 100 Antes de fumar 2 cigarros Após fumar 2 cigarros 217 283 Fator tissular está presente nas placas ateroscleróticas e pode participar da trombose O Fator tissular foi avaliado pelo acréscimo do fator Xa Fumantes tem maiores níveis de fator tissular circulante que não fumantes Key Point Current smokers have elevated levels of tissue factor (TF), which may be one of the mechanisms by which smoking is associated with increased atherothrombotic complications. TF is highly expressed in atherosclerotic plaques and its presence has been related to plaque thrombogenicity. TF may be present in the blood as well, and plays a role in the propagation of thrombosis. Acute coronary syndromes are associated with atherosclerotic lesion disruption and thrombus formation. Smoking has been implicated in both atherosclerotic progression and atherothrombotic complications. The objective of this study was to evaluate whether the increased rate of atherothrombotic complications observed in current smokers, is mediated through increased circulating levels of TF. Levels of TF were assessed by adding factor X, factor VIIa, and calcium to plasma, and then quantifying the concentration of factor Xa (FXa). Circulating TF was reported as changes in factor FXa per unit time (pmol/L/min). Subjects who smoke 10 cigarettes per day with a smoking history of 10 years were evaluated before and 2 hours after smoking 2 cigarettes. Baseline levels of circulating TF were significantly increased 2 hours after smoking 2 cigarettes (21772 pmol/L [before] and 283106 pmol/L/min FXa [after]; P=.003). The authors concluded that smoking has significant modulatory effects on plasma levels of circulating TF. Sambola et al. Circulation. 2003;107: Reference Sambola A, Osende J, Hathcock J, et al. Role of risk factors in the modulation of tissue factor activity and blood thrombogenicity. Circulation. 2003;107:

10 Alteração da vasodilatação endotelial Fumantes x Não fumantes
Não fumantes angiograficamente normais Fumantes angiograficamente normais Fumantes angiograficamente irregulares Não fumantes angiograficamente irregulares P<0,01 P<0,001 20 30 40 60 50 10 –10 P<0,01 P<0,01 Key Point Flow-dependent dilation was significantly blunted in current smokers compared with nonsmokers. Zeiher et al evaluated whether long-term smoking is associated with impaired endothelial vasodilator function, irrespective of preexisting atherosclerotic disease. Blood vessels were distinguished as either normal or irregular, according to their angiographic appearance. Ninety-six long-term current smokers (at least 2 pack/years of cigarette smoking immediately before the study) underwent diagnostic cardiac catheterization. Patients were excluded from the study if they had evidence of >30% stenosis in the left anterior descending (LAD) coronary artery or a history of variant angina, valvular heart disease, clinical evidence of heart failure, or diabetes. Intracoronary ultrasound examination was performed in 24 patients. LAD diameter was evaluated angiographically before and after a 7-mg papaverine infusion. Papaverine maximally increases coronary blood flow without affecting global hemo-dynamics. Changes in LAD diameter were utilized to assess flow-dependent dilation. Flow-dependent dilation was significantly blunted in current smokers compared with nonsmokers (P<.0001). When vessel segments were divided into normal and irregular segments based upon their angiographic appearance, both smoking groups demonstrated significantly blunted response in flow-dependent vasodilation compared with the nonsmoking groups (P<.01). The authors concluded that long-term cigarette smoking is associated with a reduction in endothelium-dependent vasodilation, regardless of the presence or absence of coronary atherosclerotic lesions. P<0,01 Dilatação fluxo-dependente (%) Não fumantes Fumantes Zeiher et al. Circulation. 1995;92: Reference Zeiher AM, Schächinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation. 1995;92:

11 Disfunção endotelial epicárdica História de tabagismo
Dor precordial Angiografia com vasorreatividade coronariana Infusão de nitroglicerina 60 45 30 15 Não fumantess Ex-fumantes Fumantes P=0,03 46% 35% 34% Disfunção endothelial epicárdica (%) Key Point Current smokers, without evidence of significant coronary artery disease (CAD), are more likely to have epicardial endothelial dysfunction than nonsmokers. In an attempt to establish whether or not smoking is associated with coronary endothelial dysfunction and inflammation, Lavi et al evaluated 881 patients referred for evaluation of chest pain, who did not have evidence of significant CAD on diagnostic coronary angiography. Patients consisted of 115 current smokers (smoking within the last month) and 766 ex-smokers and nonsmokers. Nonsmokers included both previous and never smokers. All patients underwent diagnostic coronary angiography. Microvascular coronary flow reserve was assessed after infusion with incremental doses of adenosine. Coronary vasoreactivity was assessed after infusion of incremental doses of acetylcholine. Endothelium-independent epicardial coronary artery function was assessed by the change in coronary artery diameter in response to an intracoronary bolus of nitroglycerine. All patients had baseline bloodwork prior to angiography to evaluate white blood cell (WBC) count and other systemic markers of inflammation. Significantly more current smokers were found to have epicardial endothelial dysfunction, 46%, than ex-smokers, and nonsmokers, 34% and 35%, respectively. Lavi et al. Circulation. 2007;115: Reference Lavi S, Prasad A, Yang EH, et al. Smoking is associated with epicardial coronary endothelial dysfunction and elevated white blood cell count in patients with chest pain and early coronary artery disease. Circulation. 2007; 115:

12 Papel multiplicador dos fatores de risco para doença coronariana
250 189 200 150 Taxa por 1000 103 92 100 54 50 Key Point Smoking has a multiplicative interaction with the major risk factors for coronary artery disease (CAD), to increase disease risk. For example, if the presence of smoking alone doubles the level of risk for CAD, the presence of another major risk factor in conjunction with smoking results in approximately a 4-fold (22) increase in risk, and the presence of 2 other risk factors together with smoking results in approximately an 8-fold increase in risk (222). As shown above, baseline risk of a new cardiac event is 23/1000 (without risk factors present). Presence of any one of the major risk factors increases the risk for a new cardiac event over a 10-year interval to 31/1000. If the presence of each additional risk factor acted independently, then the risk would increase by 31 for 1, by 62 for 2, and by 93 for 3 risk factors. However, as noted above, adding smoking to another risk factor results in markedly higher risk than would have resulted from simply adding together independent risks. This indicates that smoking interacts with other risk factors to produce a level of risk greater than that of independent risk factors alone. 23 Sem fatores de risco Tabagismo, hipercolesterolemia ou hipertensão isolados Tabagismo + hipercolesterolemia ou hipertensão Hipercolesterolemia + hipertensão Todos os 3 fatores de risco Fatores de risco ao entrarem no estudo Burns. Prog Cardiovasc Dis. 2003;46(1): 11-29 Reference Burns DM. Epidemiology of smoking-induced cardiovascular disease. Prog Cardiovasc Dis. 2003;46(1):11-29.

13 Tabagismo Aumento da mortalidade por doença coronariana
Doença coronariana fatal 12 10 8 Risco Relativo (IC 95%) 5,4 6 3,7 4 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. 1,7 2 1,0 Não fumantes 1-14/dia 15-24/dia 25/dia Cigarros/dia Fumantes Willett et al. N Engl J Med. 1987;317(21): 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):

14 Tabagismo Efeitos na doença coronariana
Cateterismo com lesões, LDL > 130mg/dL Tratamento com estatina por 2 anos e repetiram Cate. Formação de novas lesões Progressão de lesões existentes Patcientes (%) Fumantes Não fumantes Pacientes (%) P=0,002 P=0,007 57 37 36 20 60 50 40 30 10 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. 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:

15 Tabagismo e mortalidade em portadores de cardiopatia isquêmica
Goldenberg I. Arch Intern Med 2003;163:

16 Tabagismo e mortalidade em portadores de cardiopatia isquêmica
Goldenberg I. Arch Intern Med 2003;163:

17 Sobrevida em portadores de cardiopatia isquêmica
Goldenberg I. Arch Intern Med 2003;163:

18 Tabagismo de doença arterial periférica e aneurisma de aorta abdominal

19 Doença vascular periférica
Doença vascular periférifa afeta 20% dos adultos maiores que 55 anos Metade dos pacientes com DVP são assintomáticos 5 - 10% dos pacientes assintomáticos podem progredir para DVP sintomática em 5 anos Pacientes com DVP sintomática tem maior para outras doenças cardiovasculares e maior mortalidade Placa aterosclerótica 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. Hankey et al. JAMA. 2006;295: Hooi et al. Am J Epidemiol. 2001;153: Hooi et al. Br J Gen Pract. 1999;49:49-55 Hooi et al. Scand J Prim Health Care. 1998;16: 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:

20 Doença vascular periférica assintomática
4,0 2,8 3,0 Risco Relativo (IC 95%) 2,0 1,6 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. 1,0 1,0 0,0 Não fumantes Ex-fumantes Fumantes 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:

21 Tabagismo e Risco de Aneurisma de Aorta Abdominal
12,0 9,0 5,5 Odds Ratio (IC 95%) 6,0 3,0 2,9 3,0 1,0 0,7 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. 0,0 Não fumantes 1 - 9  25 Cigarros/dia Fumantes 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):

22 Tabagismo e acidente vascular encefálico

23 Aterosclerose carotídea
Fumantes e tabagismo ocupacional estão associados com aumento da progressão da aterosclerose cartídea 50 43,0 38,8 40 Progressão do espessamento das camadas íntima e média (IC 95% CI) 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. 30 25,9 20 Não fumante sem exposição Não fumante com exposição Ex-fumantes sem exposição Ex-fumantes com exposição Fumantes Howard et al. JAMA. 1998;279(2): 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):

24 Aumento de risco de AVC fatal e não fatal em mulheres
6 5 3,8 4 2,9 3 2,5 Risco Relativo (IC 95%) 2 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. 1,0 1 Não fumantes 1-14 15-24 ≥25 Cigarros/dia Fumantes 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):

25 Tabagismo passivo e doença cardiovascular

26 Efeitos do tabagismo ocupacional na doença cardiovascular
 risco de doença cardíaca  função plaquetária e endotelial  aterosclerose  estresse oxidativo  inflamação  variabilidade cardíaca  metabolismo energético  tamanho do infarto Environmental tobacco smoke has multiple deleterious effects on the cardiovascular system, including increased risk of heart disease, diminished platelet and endothelial function and energy metabolism, increased arterial stiffness, oxidative stress and inflammation, and reduced heart rate variability. Environmental tobacco smoke contributes to the progression of atherosclerosis and is associated with increased infarct size in smokers who experience a myocardial infarction. American Heart Association. Scientific Position, Risk Factors and Coronary Heart Disease, Accessed February 2007; Barnoya et al. Circulation. 2005; 111: ; Accessed October 11, 2007. References American Heart Association. Scientific position, risk factors and coronary heart disease, Accessed February 2007. Barnoya J, Glantz SA. Cardiovascular effects of environmental tobacco smoke nearly as large as smoking. Circulation. 2005;111:

27 Tabagismo ocupacional Prevalência de doença cardíaca
Tabagismo passivo aumenta o risco de doença cardíaca em % nos não fumantes 0.05 0.10 0.15 0.20 Fumante 1-9 cig/dia Passivo intenso CO 0,8-14ng/mL 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%. Proporção com doença coronariana maior Passivo leve (0-0,07 ng/mL) 5 10 15 20 Anos de seguimento Whincup et al. BMJ. 2004;329: 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:

28 Conclusões Tabagismo está ssociado com diversas doenças pulmonares além da DPOC e câncer de pulmão Tabagismo tem grande associação com doenças cardiovasculares Disfunção vascular Estresse oxidativo Progressão aterosclerose Desenvolvimento de trombos Tabagismo está associado com aumento da mortalidade Tabagismo passivo também está associado com doenças cardiovasculares e aumento da mortalidade

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