2 Declaración de Conflicto de InterésHe sido consultante y/o conferencista de: Pfizer Glaxo- Smithkline Johnson & Johnson

3 Objetivos Daño CV por consumo Exposición al Humo del Tabaco y daño CVMecanismos del daño

5 MORTALIDAD CV Y TABAQUISMOMundial: 10% de todas las muertes CV en adultos años son atribuibles al tabaco Varía según region: Africa: 4%, Americas: 15%, Sudeste Asiático: 9%, Europa: 15%, Mediterraneo Oriental: 8%, Pacifico Occidental: 6% ☼Note to international adaptations: Region and country specific data may be added Data by region, country, sex, and age is available at: World Health Organization. WHO Global Report: Mortality Attributable to Tobacco. World Health. Geneva; 2012. ¿Dedicamos los cardiólogo el tiempo adecuado a la magnitud del problema? WHO Global Report: Mortality Attributable to Tobacco. World Health. Geneva; 2012.

6 Tabaquismo : Rol en la Patogénesis de los Eventos CardiovascularesDisfunción endotelial Aumento de trombogenicidad Respuesta inflamatoria aumentada Aumento de estrés oxidativo Smoking has been implicated as a cause of both peripheral and coronary endothelial dysfunction and has been shown to be a predictor of long-term cardiovascular events, but its mechanism is not fully understood. Potential mechanisms by which smoking may play a role in cardiovascular events prior to the development of significant coronary artery disease (CAD) include induction of endothelial dysfunction, oxidative stress, increased blood thrombogenicity, and an enhanced inflammatory response. Atherosclerotic Disease Right Coronary Artery Lavi et al. Circulation. 2007;115: ; Accessed June 14, 2007. 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:

7 Tabaco : Disfunción endotelialLos fumadores (sin evidencia de coronariopatía) tienen más frecuentemente disfunción endotelial epicardica que los no fumadores 60 45 30 15 No fumadores Ex-fumadores Fumadores P=.03 46% 35% 34% Endothelial Dysfunction (%) 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:

8 Tabaquismo: Reduce la biosíntesis de Oxido Nitrico (NO)5000 P<.0001 4000 3613 3000 NO Concentration (nmol/L) 2000 1266 Key Point Smoking is associated with reduced nitric oxide (NO) biosynthesis. NO is the primary vasodilatory substance produced by endothelial cells. Smokers have been noted to have impaired endothelium-dependent vasodilation (EDV). Barua et al hypothesized that reduction in NO biosynthesis contributes to the impaired EDV noted in current smokers. Twenty-three male patients (15 current smokers, 8 nonsmokers) had fasting bloodwork drawn, while abstaining from smoking for a 6 to 8 hour period. Human umbilical vein endothelial cells (HUVECs) were incubated with serum from participants, and after 12 hours basal NO production in the supernatant was determined. NO production in the cell culture supernatant was evaluated by chemiluminscence. HUVECs incubated with current smoker’s serum showed significantly lower basal NO production compared with HUVECs incubated with nonsmoker’s serum (P<.0001). The authors concluded that smoking is associated with reduced basal NO production. 1000 No fumadores Fumadores Barua et al. Circulation. 2001;104: Reference Barua R, Ambrose JA, Eales-Reynolds LJ, DeVoe MC, Zervas JG, Saha DC. Dysfunctional endothelial nitric oxide biosynthesis in healthy smokers with impaired endothelium-dependent vasodilatation. Circulation. 2001;104:

9 Tabaquismo : Aumenta TrombogenicidadEl factor tisular (TF) está altamente presente en placas ateroscleroticas y puede jugar un rol en la trombosis TF fue evaluado por factor Xa (FXa) Los fumadores tienen significativos mayores niveles de actividad de TF circulante que los no fumadores P=.003 Factor Xa (FXa) pmol/L/min 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 Tabaco: Aumenta InflamaciónElevación de Leucocitos se ha asociado a mayor riesgo CV. Fumadores tienen leucocitosis más elevada que no fumadores P<.0001 No fumadores 8 6 4 2 Ex-fumadores Fumadores P=.03 Cell Counts (109/L) P<.0001 Key Point Current smokers without evidence of significant coronary artery disease have significantly increased WBC counts compared with nonsmokers. Elevated WBC counts have been associated with a greater long-term cardiovascular risk. 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 coronary artery disease 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 WBC count and other systemic markers of inflammation. Both total WBC count and leukocyte subtypes were higher in current smokers than in nonsmokers. P<.0001 GB Neutrofilos Linfocitos Monocitos Lavi et al. Circulation. 2007;115: ; Stewart et al. Circulation. 2005;111: References Stewart R, White H, Kirby A; et al; The Long-term Intervention With Pravastatin in Ischemic Disease (LIPID) Study Investigators. White blood cell count predicts reduction in coronary heart disease mortality with pravastatin. Circulation. 2005;111: Lavi S, Prasad A, Yang E, 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:

11 Tabaquismo: Aumenta estrés oxidativo640 1000 560 900 480 800 400 700 Free F2-Isoprostanesa (pmol/L) 320 Esterified F2-Isoprostanesa (pmol/L) 600 240 500 160 400 Key Point Current smokers have higher levels of oxidative modification in vivo than do nonsmokers. F2-isoprostane level is an accurate method of detecting lipid peroxidation, and thereby oxidant injury, in vivo. In this study Morrow et al determined whether smoking induces oxidative modification by evaluating whether production of F2-isoprostanes are increased in smokers. Twenty subjects (10 smokers, 10 nonsmokers) had fasting bloodwork drawn on 2 separate occasions. Participants were not allowed to smoke prior to venipuncture. The average of the 2 measurements of F2-isoprostanes are demonstrated above. Levels of free F2-isoprostanes in plasma from current smokers were significantly higher than those measured in age- and sex-matched nonsmokers (242147 and 10319 pmol/L, respectively) (P=.02). The levels of F2-isoprostanes esterified to lipids in plasma from smokers were also significantly higher than those measured in nonsmokers (574217 and 34565 pmol/L, respectively; P=.03). The authors concluded that elevated levels of F2-isoprostanes in current smokers indicate that smoking induces oxidative modification of biologic components in humans. 80 300 Nonsmokers Current Smokers Nonsmokers Current Smokers aF2-isoprostane level is an index of lipid peroxidation in vivo. The dots representing subjects who smoked are each connected to a dot representing a nonsmoker matched to the subject for age and sex. Adapted from Morrow et al. N Engl J Med. 1995;332(18): Reference Morrow JD, Frei B, Longmire AW, et al. Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers: smoking as a cause of oxidative damage. N Engl J Med. 1995;332(18):

12 MECANISMOS FISIOPATOLÓGICOS de la Enf CV relacionados al TABAQUISMOOXIDANT CHEMICALS OTHER COMBUSTION PRODUCTS Inflammation Reduced Oxygen Availability Platelet Activation/ Thrombosis Coronary Vasoconstriction Increased Myocardial Oxygen Demand Reduced Myocardial Oxygen Supply Myocardial Ischemia Myocardial Infarction Sudden Death CARBON MONOXIDE NICOTINE Increased heart rate Increased blood pressure Increased myocardial contractility PARTICULATES Sympathetic nervous system activation Endothelial dysfunction 12 12 12

13 Tabaquismo: Aumenta mortalidad coronaria- dosis dependiente (Estudio Nurses)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 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;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 Tabaquismo y riesgo de Muerte CVEl riesgo de muerte por coronariopatía es: 70% mayor en fumadores - 200% mayor en fumadores intensos Reference: 14. The Non-Smoker’s Movement of Australia. Accessed URL: The health consequences of smoking: cardiovascular disease. A report of the Surgeon General

15 Tabaquismo: Aumenta riesgo de muerte súbita cardíacaSeguimiento prospectivo, 8 años, hombres, 40-59 años 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;91: Reference Wannamethee G, Shaper AG, Macfarlane PW, Walker M. Risk factors for sudden cardiac death in middle-aged British men. Circulation. 1995;91:

16 Tabaquismo: Efecto sobre CoronariopatíaFormacion de nuevas Lesiones Progresion Lesiones 57 P=.002 P=.007 37 36 Patients (%) Patients (%) 20 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. No fumadores Fumadores No Fumadores Fumadores 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:

18 Unos pocos cigarrillos día ya incrementa el riesgo de IAMINTERHEART Aumento del riesgo 30% THE LANCET. Vol de Agosto 2006.

19 Tabaquismo: Aumento de riesgo de IAM no fatalTabaquismo triplica el riesgo de IAM no fatal comparado con no fumadores. 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. 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:

20 Tabaquismo y riesgo vascular periféricoduplica el riesgo de claudicación intermitente vinculado a la progresión de la enfermedad vascular periférica. Eur J Cardiovasc Prev Rehabil 2006;13: Reference: 17. Tonstad S, Andrew Johnston J. Cardiovascular risks associated with smoking: a review for clinicians. Eur J Cardiovasc Prev Rehabil 2006;13(4): Enfermedad Vascular Periférica asintomática: Aumenta riesgo NO FUM EXFUM FUM 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

21 Tabaquismo y Aneurisma de AortaAumenta riesgo con una relación dosis-dependiente. Reference: 17. Tonstad S, Andrew Johnston J. Cardiovascular risks associated with smoking: a review for clinicians. Eur J Cardiovasc Prev Rehabil 2006;13(4): Eur J Cardiovasc Prev Rehabil 2006;13: Vardulaki et al. Br J Surg. 2000;87(2):

23 Tabaquismo: Aumenta riesgo de Stroke HemorrágicoNonsmokers (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 Stroke Hemorrágico Hemorragia Intracerebral Hemorragia Subaracnoidea 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:

24 Fumar disminuye los efectos beneficiosos de las estatinasPrevención Secundaria: riesgo eventos CV en Dislipémicos Fumadores tratados similar a dislipémicos no fumadores no tratados. ¿ Dejaríamos de tratar un dislipémico? ¿ Por qué no tratamos al fumador? Statin Reference: 19. Milionis HJ, Rizos E, Mikhailidis DP. Smoking diminishes the beneficial effect of statins: observations from the landmark trials. Angiology 2001;52(9): The risk of events in untreated nonsmokers was of a similar order to that seen in smokers taking statins Milionis HJ et al. Angiology 2001;52: 24

25 ¿ Qué pasa al dejar de fumar?

26 A las 24 horas : recuperación casi completa de vasodilatación x endotelio mediada por agonistasReference: 21. Moreno H, Jr., Chalon S, Urae A, Tangphao O, Abiose AK, Hoffman BB, Blaschke TF. Endothelial dysfunction in human hand veins is rapidly reversible after smoking cessation. Am J Physiol 1998;275(3 Pt 2):H Am J Physiol 1998;275:H1040-5

27 Dos semanas : mejora la agregación plaquetaria .Reference: 22. Morita H, Ikeda H, Haramaki N, Eguchi H, Imaizumi T. Only two-week smoking cessation improves platelet aggregability and intraplatelet redox imbalance of long-term smokers. J Am Coll Cardiol 2005;45(4): J Am Coll Cardiol 2005;45:589-94

28 4 SEMANAS: La relación HDL/LDL se incrementa significativamente.Reference: 23. Erguder IB, Erguder T, Ozkan C, Bozkurt N, Soylu K, Devrim E, Durak I. Short-term effects of smoking cessation on blood antioxidant parameters and paraoxonase activity in healthy asymptomatic long-term cigarette smokers. Inhal Toxicol 2006;18(8):575-9. Inhalation Toxicology 2006;18:

29 6 MESES: La disfunción coronaria endotelial mejora significativamente.Reference: 25. Hosokawa S, Hiasa Y, Miyazaki S, Ogura R, Miyajima H, Ohara Y, Yuba K, Suzuki N, Takahashi T, Kishi K and others. Effects of smoking cessation on coronary endothelial function in patients with recent myocardial infarction. Int J Cardiol 2008;128(1):48-52. International Journal of Cardiology 2008;128:48-52

31 Reduce el Riesgo de Paro Cardiorespiratorio RecurrenteRiesgo de PCR es menor entre los que abandonan . P=.038 Occurrence at 3 Years (%) Key Point Smoking cessation is associated with a significant reduction in risk of recurrent cardiac arrest. Hallstrom et al performed a life-table analysis of 310 survivors of out-of-hospital cardiac arrest who were current smokers at the time of the cardiac arrest to determine if immediate smoking cessation after hospitalization was associated with a decrease in risk of recurrent cardiac arrest. The life-table analysis included information about smoking cessation following hospital discharge, which was obtained through surveys of the families of the survivors and a review of medical records. Patients with coronary artery disease were stratified according to mortality risk into 5 prognostic strata on the basis of recognized clinical variables. Ninety-one patients quit smoking immediately following the sudden cardiac arrest, while 219 continued to smoke. At 3 years, the risk of recurrent cardiac arrest was significantly lower for ex-smokers than current smokers across all strata except the highest risk stratum (19% ex-smokers vs 27% smokers; P=.038). Total mortality due to recurrence of cardiac arrest was lower for ex-smokers (P=.062); however, there was no difference between mortality due to other causes (P=.91). Paro Cardíaco Recurrente aAbstention period of 3 years. Hallstrom et al. N Engl J Med. 1986;314: Reference Hallstrom AP, Cobb LA, Ray R. Smoking as a risk factor for recurrence of sudden cardiac arrest. N Engl J Med. 1986;314:

32 Prevención Primaria Intervención Vidas Salvadas NNTAbandono del Tabaco 9 Disminución de Lípidos 34 Control de la Presión Arterial 63.282 31 IECA (Control Insuf. Cardiaca) 11.000 ND Betabloqueantes (IAM) 17.023 120 Aspirina (IAM) 10.365 143 Anticoagulantes (ACxFA) 3418 2014 Woolf AH. JAMA 1999;282:

33 Prevención Secundaria: Dejar de fumar reduce : - riesgo de muerte 36%Aspirina = 15% Beta bloqueantes = 23% ACE inhibidores = 23% Estatinas = 29–35% Reference: 27. Critchley J, Capewell S. Smoking cessation for the secondary prevention of coronary heart disease. Cochrane Database Syst Rev 2003(4):CD Cochrane Database of Systematic Reviews 2003;4:CD003041

34

35 Efectos cardiovasculares de Exposición al Humo del TabacoCrónicos Agudos Disfunción endotelial Estrés oxidativo Activación plaquetaria Ateroesclerosis EC: Riesgo relativo mujeres no FUM expuestas 1,91 IC 95% 1,11 a 3,28 -Circulation 1997; 95: 2374-9 Acelera progresion de Aterosclerosis Carotídea. Howard et al. JAMA. 1998;279(2): Circulation 2005;111:

36 EXPOSICIÓN AL HUMO DEL TABACO Y ENF CVLa exposición al humo del tabaco (EHT) causa muerte y enfermedad CV prematura en no fumadores. No existe nivel mínimo seguro de exposición al humo del tabaco . Second-hand smoke (SHS) is the air pollution created by smoking cigarettes (and cigars and pipes) during the 90% of the time that the cigarette is not being smoked. Because the cigarette is burning at a lower temperature when it is not being smoked, the combustion is less complete and the smoke is richer in toxic chemicals than the mainstream smoke that the smoker inhales. Even though nonsmokers receive a much lower total dose of these chemicals (because the smoke is diluted in the air before nonsmokers inhale it), the effects on blood vessels, blood, and the heart are surprisingly large. Marriage to a smoker or working where smoking is permitted is associated with about a 30% increase in the risk of heart disease incidence or death (about one-third the effect of active smoking). Despite the tobacco industry’s efforts to cast doubt on the link between SHS and health risks (USDHHS, 2006), few scientists and clinicians would deny that SHS is harmful. Major conclusions of the 2006 Surgeon General’s report The Health Consequences of Involuntary Exposure to Tobacco Smoke (USDHHS, 2006) are listed below. The negative health consequences of most relevance to cardiology providers are presented on the slide. 1. SHS causes premature death and disease in children and in adults who do not smoke. 2. Children exposed to SHS are at an increased risk for sudden infant death syndrome, acute respiratory infections, ear problems, and more severe asthma. Smoking by parents causes respiratory symptoms and slows lung growth in their children. 3. Exposure of adults to SHS has immediate adverse effects on the cardiovascular system and causes coronary heart disease and lung cancer. 4. The scientific evidence indicates that there is no risk-free level of exposure to SHS. 5. Many millions of Americans, both children and adults, are still exposed to SHS in their homes and workplaces despite substantial progress in tobacco control. 6. Eliminating smoking in indoor spaces fully protects nonsmokers from exposure to SHS. Separating smokers from nonsmokers, cleaning the air, and ventilating buildings cannot eliminate exposures of nonsmokers to SHS. A comprehensive literature reviewed conducted by Barnoya and Glantz (2005) concluded that the cardiovascular effects of SHS are substantial and rapid. The effects of even brief exposure (minutes to hours) are often nearly as large (averaging 80–90%) as those of chronic active smoking. Barnoya J, Glantz SA. (2005). Cardiovascular effects of secondhand smoke: nearly as large as smoking. Circulation 11:2684–2698. U.S. Department of Health and Human Services (USDHHS). (2006). The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. - La única intervención eficaz para evitar el riesgo es la prohibición absoluta de fumar en lugares Públicos y de trabajo, cerrados. - CMCT: Art .8 – compromete a países a proteger a no fumadores USDHHS. (2006). The Health Consequences of Involuntary Exposure to Tobacco Smoke: Report of the Surgeon General. Institute of Medicine. Secondhand Smoke Exposure and Cardiovascular Effects : Making Sense of the Evidence. Exposure. Washington, D.C.: The National Academies Press; 2010. 36

37 Coronariopatía y exposición al humo del tabaco31% OR 1,31 IC 95% 1,20-1,41 0, , ,5 2,0 2, ,0

38 RIESGO CV por TABAQUISMO ACTIVO Y EXPOSICIÓN al Humo del TabacoN = 29 studies Overall RR = 1.78 para fumadores Overall RR = 1.31 para expuestos al humo del tabaco. Relative risk A review of the literature concluded that the cardiovascular effects of SHS are nearly as large as those of smoking. The relative risk of coronary heart disease (CHD) among active smokers was estimated at The relative risk of CHD among passive nonsmokers was 1.31, indicating that long-term SHS exposure in the work or at home is associated with a 30% increased risk for CHD in adult nonsmokers. This is the consensus effect (RR = 1.31), but most of the studies reviewed were based on questionnaires with the methodology containing a lot of error, which likely underestimates the effect of SHS exposure. Earlier epidemiologic studies that used marriage to a smoker as a surrogate for exposure did not capture exposure to SHS outside of the home (e.g., from workplaces and public places such as restaurants and bars). As a result, the earlier studies underestimated SHS exposure and simply compared more exposed people (nonsmokers married to a smoker but exposed to SHS elsewhere) to less exposed people (nonsmokers married to nonsmokers but exposed to SHS elsewhere). This comparison biases the risk estimate of the effect of SHS downward (Barnoya & Glantz, 2005). One study in the review (Whincup et al., 2004) used biomarker cotinine in a 20-year prospective study. Using a biomarker instead of self-report survey allowed for cleaner demarcation of the “exposed” group vs. a truly unexposed group. This study obtained higher estimates of passive smoke exposure (RRs = 1.45 and 1.57) depending on the level of SHS exposure (see next slide). Those exposed to high levels of passive smoke did not look much different from light smokers. Baronya J, Glantz, SA. (2005). Cardiovascular effects of secondhand smoke. Nearly as large as smoking. Circulation 111: Whincup PH, Gilg JA, Emberson JR, Jarvis MJ, Geyerabend C, Bryant A, Walker M, Cook DG. (2004) Passive smoking and risk of coronary heart disease and stroke: Prospective study with cotinine measurement. BMJ 329: Barnoya & Glantz. (2005). Circulation111:2684–2698.

39 Magnitud del riesgo: Exposición vs Consumo0,05 0,10 0,15 0,20 Fumador L-M HSM intenso 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%. Coronariopatía HSM leve 5 10 15 20 Años BMJ 2004;329:200-5 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:

40 Muertes a nivel Mundial por EXPOSICIÓN AL HUMO DEL TABACOHumo de Segunda Mano: 603,000 muertes prematuras cada año en el mundo 87% de las muertes por SHS en adultos : cardiopatía isquémica The harmful effects of smoking do not end with the smoker. Even brief exposure can be dangerous because nonsmokers inhale many of the same carcinogens and toxins in cigarette smoke as smokers. SHS exposure causes serious disease and death, including heart disease and lung cancer in nonsmoking adults and sudden infant death syndrome, acute respiratory infections, ear problems, and more frequent and severe asthma attacks in children. Second-hand smoke causes approx premature deaths worldwide each year. These deaths include deaths among children ( lower respiratory infections deaths and 1100 from asthma), and 435,800 adult deaths ( deaths from asthma deaths from lung cancer, deaths from ischaemic heart disease). 87% of adult SHS smoke deaths are CVD deaths. Oberg M, et al., Worldwide burden of disease from exposure to second-hand smoke: a retrospective analysis of data from 192 countries. Lancet Jan 8;377(9760):139–46. Also see: U.S. Department of Health and Human Services (USDHHS). (2006). The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. , Oberg M, et al., Lancet

41 Activación plaquetaria y ExposiciónThromb Res 1996;81:451-60

42 Activación plaquetaria y Exposición37 35 33 31 29 27 25 23 p=NS p=NS Fumadores 11-DH-TXB2 pg/ml No fumadores Día Thromb Res 1996;81:451-60

43 Exposición al humo de tabaco ambiental (Horas por semana)Exposición al Humo del Tabaco: Riesgo de Infarto Agudo de Miocardio (IAM) La exposición al humo de tabaco ambiental aumenta el riesgo de IAM no fatal de manera gradual 4 No fumadores 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 Exposición al humo de tabaco ambiental (Horas por semana) . 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:

44 Efecto agudo de la exposición: tiempoActivación plaquetaria Estrés oxidativo Inflamación vascular Disfunción endotelial 30 minutos Eur Heart J 2006;27:386-92

45 Impacto de la prohibición de fumar sobre ingresos hospitalarios por IAM (Uruguay, 2004-2008)22% Hospital admissions for acute myocardial infarction before and after implementation of a comprehensive smoke-free policy in Uruguay. E. Sebrie´, E.Sandoya, A. Hyland, E. Bianco, S. A Glantz, K M Cummings, Tobacco Control ,2011.

46 NO ES UNA RESPUESTA LINEAL .Asociación dosis-respuesta entre exposición al humo del tabaco y enfermedad isquémica cardíaca. NO ES UNA RESPUESTA LINEAL . Otros factores Agregación plaquetaria y trombosis . Pechacek, T. F et al. BMJ 2004;328: (Adapted from Law and Wald)

47 Conclusiones El tabaquismo y la exposición al humo del tabaco causan un serio daño CV. Dejar de fumar y de exponerse al humo del tabaco mejora el sistema CV. Las medicaciones para dejar de fumar son seguras en el paciente CV. Los Ambientes 100% libres de humo son una estrategia costo-efectiva para reducir enfermedad coronaria. LA EXPOSICIÓN AL HUMO DEL TABACO DEBERÍA SER CONSIDERADA COMO FACTOR DE RIESGO VASCULAR.