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Tools in the Battle Against Smoking and Tobacco

Tools in the Battle Against Smoking and Tobacco. 3-C CON, AHMEDABAD, FEBRUARY 2011. Chaim Lotan , MD. Heart Institute, Hadassah Hospital, Jerusalem, ISRAEL. Smoking and coronary artery disease. History Epidemiology CV Effects Importance of Cessation.

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Tools in the Battle Against Smoking and Tobacco

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  1. Tools in the Battle Against Smoking and Tobacco 3-C CON, AHMEDABAD, FEBRUARY 2011 ChaimLotan, MD Heart Institute, Hadassah Hospital, Jerusalem, ISRAEL

  2. Smoking and coronary artery disease History Epidemiology CV Effects Importance of Cessation

  3. Cigarette Smoking as a Risk Factor for Cardiovascular Disease was recognized in the results of the Framingham Heart Studyin 1960

  4. alcohol cocaine crack heroin homicide suicide car accidents fires AIDS Smoking kills more people each year than C O M B I N ED!!!

  5. Smoking and coronary artery disease History Epidemiology CV Effects Importance of Cessation

  6. Global Cigarette Consumption WHO World Health Report .Tobacco Atlas .2008.

  7. Section 2: The Hazards of Smoking

  8. Facts & Numbers • 1.25 billion smokers Worldwide • 30 million smokers added every year • 84% of smokers live in developing countries • Africa & Middle East (17% of World’s population) accounts for 7% of World’s total cigarette consumption 8 smokers die every minute Voute J, World Heart Foundation

  9. Gender-specific Smoking Prevalence Across the World 1.25 billion smokers worldwide1 Sweden 17% 18% Iceland 25% 20% Russian Federation 60% 16% Canada 22% 17% Belarus 53% 7% France 30% 21% Germany 37% 28% US 24% 19% China 67% 2% Portugal 33% 10% Spain 39% 25% Italy 33% 17% Iran 22% 2% Egypt 45% 12% Mexico 13% 5% India 47% 17% Philippines 41% 8% Brazil 22% 14% Kenya 21% 1% Men Women Australia 19% 16% South Africa 23% 8% Chile 48% 37% • Mackay J, Eriksen M. The Tobacco Atlas. Second Ed. American Cancer Society, 2006.

  10. 4 year-old addict to smoking in Indonesia

  11. Smoking and coronary artery disease History Epidemiology CV Effects Importance of Cessation

  12. Smoking: Leading Preventable Cause of Disease and Death1 Cancer Lung (#1) Leukemia (AML, ALL, CLL)2-4 Oral cavity/pharynx Laryngeal Esophageal Stomach Pancreatic Kidney Bladder Cervical Reproductive Low-birth weight Pregnancy complications Reduced fertility SIDS Other Adverse surgical outcomes/wound healing Hip fractures Low-bone density Cataract Peptic ulcer disease in Helicobacter pylori-positive patients Cardiovascular Ischemic heart disease (#2)Stroke – vascular dementia5 Peripheral vascular disease6 Abdominal aortic aneurysm Respiratory COPD (#3) Pneumonia Poor asthma control • AML = acute myeloid leukemia; ALL = acute lymphocytic leukemia; CLL = chronic lymphocytic leukemia; • COPD = chronic obstructive pulmonary disease; SIDS = sudden infant death syndrome. • Surgeon General’s Report. The Health Consequences of Smoking; 2004. • Sandler DP, et al. J Natl Cancer Inst. 1993;85:1994-2003. • Crane MM, et al. Cancer Epidemiol Biomarkers Prev. 1996;5:639-644. • Miligi L, et al. Am J Ind Med. 1999;36:60-69. • Roman GC. Cerebrovasc Dis. 2005;20:91-100. • Willigendael EM, et al. J Vasc Surg. 2004;40:1158-1165.

  13. 16 8 OR (99% CI) 4 2 0 1-5 6-10 11-15 16-20 21-25 26-30 31-40 >40 #cigarettes smoked per day INTERHEART: Smoking and MI Odds of myocardial infarction

  14. Smoking Is Related To 5 of the Top 10 Leading Causes of Death Worldwide1 • 1 in 10 adult deaths are smoking-related2 • 500,000,000 people alive today will die from smoking-related causes2 WHO top ten causes of death3 Causes Related to Smoking 1. Surgeon General’s Report, 2004. 2. World Bank, 1999. 3. World Health Organization, 2003.

  15. How does smoking induce ACS ? Platelet Viscosity function Endothelial function Coagulation Collagen (PAI-1) Macrophages Inflammation (hs-CRP, cytokine, chemokine) MMPs Smooth LDL-C muscle cells HDL-C TG

  16. Role of AMI due to tobacco in India N=300 AMI, 300 Controls Pais P, Fay MP, Yusuf S Indian Heart J 2001; 53:731-5

  17. Tobacco associated mortality in Mumbai (Bombay) India. Results of the Bombay Cohort Study Gupta PC, Pednekar MS, Parkin DM, Sankaranarayanan R Background Little is known about the excess mortality from forms of tobacco use other than cigarette smoking that are widely prevalent in India, such as bidi smoking and the various forms of smokeless tobacco use. We report on absolute and relative risks of mortality among various kinds of ever tobacco users vs never-users in the city of Mumbai, India. (n=99570) Results The adjusted relative risk was 1.37 (95% CI 1.23–1.53) for (men) cigarette smokers and 1.64 (95% CI 1.47–1.81) for bidi smokers, with a significant dose–response relationship for number of bidis or cigarettes smoked. Women were essentially smokeless tobacco users; the adjusted relative risk was 1.25 (95% CI 1.15–1.35). ConclusionsBidi is no less hazardous than cigarette smoking, and smokeless tobacco use may also result in significantly increased mortality. Intl J Epidemiol 2005;43(6):1395-1402

  18. Tobacco consumption is a major source of mortality and morbidity in India. • Studies have shown contradictory results regarding smokeless tobacco use as a cardiovascular risk factor, but many show conclusive connection. • 2003 Study of adults males in a rural village in Haryana, northern India (chosen randomly)

  19. smokeless tobacco • With smoke-free laws, smokeless tobacco (ST) products are being marketed as smoking substitutes: snuff, chewing tobacco, spitless pouched moist snuff, compressed tobacco lozenges. • A recent US study found no reduction in smoking rates among people using ST as replacement, although a previous (2006) Swedish study showed an overall country reduction in smoking with increased overall ST consumption.

  20. Chemical Composition of ST Products • Similar to cigarettes, nicotine is the principal alkaloid • Amount of total and free nicotine varies substantially - generally, concentration similar in oral snuff and cigarette tobacco, somewhat lower in chewing tobacco • Minor alkaloids: nornicotine, anatabine, anabasine • Carcinogens: Combustion-derived Benzo[a]pyrene and other polycyclics lower than in cigarette smoking • Carcinogens: Nitrosamines - highest known nonoccupational exposure • Nitrite, nitrate, formate, chloride, sulfate, phosphate

  21. Impact of Smokeless Tobacco Products on Cardiovascular Disease: Implications for Policy, Prevention and Treatment: A Policy Statement From The American Heart Association 2010 • Long-term use of smokeless tobacco products increases the odds of fatal heart attack or fatal stroke (according to analysis of several studies). • The AHA advises against smokeless tobacco products for smoking cessation - they are not a “safe” alternative to smoking, and carry the risk of addiction and return to smoking.

  22. The Effects of Second-Hand Smoke Short-term effects of second-hand smoke: • Coughing • Headache • Eye irritation • Sore throat • Sneezing and runny nose • Feeling sick • Breathing problems (and possibly an asthma attack) • Irregular heartbeat (a particular problem for people with heart disease) Long-term effects of second-hand smoke: • Worsening of chest problems and allergies like asthma, hay fever, bronchitis and emphysema • Increased risk of heart disease • Increased risk of lung cancer • Pregnant women exposed to second hand smoke can pass on the harmful gases and chemicals onto their babies.

  23. The health consequences of smoking and second hand smoke evolve over a lifetime. Pregnancy Infant health Child Health and Smoking Physical Growth Behavior and cognitive development Respiratory infections More hospitalization Fetal growth Birth weight Abortions Premature Birth Fetal Death SIDS Adulthood Adolescence Chronic bronchitis Emphysema Lung cancer by 20%–30% Coronary heart disease Stroke COPD Small airway dysfunction Cough Wheezing Phlegm production other respiratory symptoms • News release, June 27, 2006; US Department of Health & Human Services. Available at: http://www.hhs.gov/news/press/2006pres/20060627.html. • Mackay J, et al. The Tobacco Atlas. World Health Organization, 2006. • Teo KK, et al. Lancet. 2006;368:647-658. • Fagerström K. Drugs. 2002;62:1-9. • Blizzard L, et al. Arch Pediatr Adolesc Med. 2004;158:687-693. • Leung GM, et al. Arch Pediatr Adolesc Med. 2004;158:687-693.

  24. Passive Smoking and CV Disability • Have a clear relationship to CV disability & mortality • ~ 37,000 to 40,000 people die from cardiovascular disease caused by other people’s smoke every year. Of these, 35,000 non-smokers die from coronary heart disease. American Heart Association 2007

  25. Smoking and coronary artery disease History Epidemiology CV Effects Importance of Cessation

  26. CHD risk is similar to never smokers Lung cancer risk is 30%–50% that of continuing smokers Stroke risk returns to the level of people who have never smoked at 5–15 years post-cessation Cardiovascular Heart Disease (CHD): excess risk is reduced by 50% among ex-smokers Lung function may start to improve with decreased cough, sinus congestion, fatigue, and shortness of breath 1 year 5 years 15 years 3 months 10 years Why Quit? Potential Health Benefits of Quitting Smoking Cessation • USDHHS. The Health Benefits of Smoking Cessation: A Report of the Surgeon General, 1990. Available at:http://profiles.nlm.nih.gov/NN/B/B/C/T/. • American Cancer Society. Guide to Quitting Smoking. Available at: http://www.cancer.org.

  27. Quitting at Any Age May Increase Life ExpectancyAge Stopped Smoking: 45–54 Years Old Results From a Study of Male Physician Smokers in the UK Nonsmokers Age Stopped: 45–54 Cigarette Smokers Percentage Survival from Age 50 Age (Years) • Even quitting smoking later in life can lead to longer life expectancy • Doll R, et al. BMJ. 2004;328:1519-1527.

  28. Smoking bans in public places and workplaces are significantly associated with a reduction in AMI incidence, particularly if enforced over several years.

  29. Countries Banning Smoking in Public Places • Nigeria • Norway 2004 • Paraguay • Peru • Philippines (partial) • Poland (partial) • Portugal 2007 • Puerto Rico • Singapore • Serbia • Slovenia • South Africa 2001 • Spain 2006-10 • Sweden (partial) • Syria 2009 • Thailand 2008and more! • Czech Rep.(partial) • Denmark 2007 • Estonia (partial) • Finland 2007 • France 2008 • Germany (contested) • Greece 1010 • Guatemala • Hong Kong 2007 • Hungary (partial) • Iceland • India (partial) • Indonesia (partial) • Ireland 2004 • Israel • Kazakhstan 2003-9 • Kenya 2007 • Latvia 2010 • Lithuania (partial) • Luxemburg (partial) • Macedonia 2010 • Malta • Malaysia • Mexico 2008 • Monaco (partial) • Montenegro • Morocco • Mozambique 2007 • Namibia 2010 • Netherlands • New Zealand 2004 • Albania 2007 • Andorra (partial) • Argentina-Buenos Aires 2006 • Armenia (partial) • Australia 2007-10 • Austria (partial) • Bahrain 2008 • Bosnia-Herzegv.2007 • Brazil 2009 • Bulgaria (partial) • Canada • Chile (partial) • China (partial) • Colombia 2009 • Croatia 2008-9 • Cyprus 2009 Source: Wikipedia

  30. 40 Symptoms among 67 barmen before and after ban dyspnea 30 morning cough cough sputum 20 eye irritation nose irritation throat irritation 10 0 Before ban After Ban Beneficial Effects of Smoking Ban for Employees Number of barmen with symptoms Eisner M et coll., JAMA 1998, 280, 1909-1914 Source:

  31. Smoking and coronary artery disease History Epidemiology CV Effects Importance of Cessation Nicotine addiction

  32. Nicotine Addictive or Just a Bad Habit??????

  33. b2 b2 a4 a4 b2 4b2 nicotinic acetylcholine receptor (nAChR) Mechanism of Action of Nicotine in the Central Nervous System • Nicotine binds preferentially to nAChRs in the central nervous system; one key area is the α4β2 nicotinic receptor in the VTA • After nicotine binds to the α4β2 nAChR in the VTA, dopamine is released in the nAcc which is believed to be linked to reward

  34. The Cycle of Nicotine Addiction Dopamine • Nicotine binding causes an increase in release of dopamine1,2 • Dopamine gives feelings of pleasure and calmness1 • competitive binding of nicotine to nicotinic acetylcholine receptors causes prolonged activation, desensitization, and upregulation2 Nicotine • Jarvis MJ. BMJ. 2004; 328:277-279. • Picciotto MR, et al. Nicotine and Tob Res. 1999:Suppl 2:S121-S125.

  35. Withdrawal Syndrome: A Combination of Physical and Psychological Conditions, Making Smoking Hard to Treat Decreased heart rate Irritability, frustration, or anger Insomnia/sleep disturbance Anxiety (may increase or decrease with quitting) Increased appetite or weight gain Restlessness or impatience Dysphoric or depressed mood Difficulty concentrating • DSM-IV-TR. APA; 2006: Available at:http://psychiatryonline.com

  36. The greatest risk of relapse is during the first three months after quitting. • 37% have their first lapse between 8:00pm and midnight • 50% are likely to relapse in the first month • 67% are likely to relapse in the first three months • DSM-IV-TR. APA; 2006: Available at:http://psychiatryonline.com

  37. “Nine out of ten ex-smokers who have a cigarette after quitting later return to smoking” (Brandon, 1990)

  38. Many Health Organizations Emphasise the Important Role Physicians Can Play in Helping Their Patients Quit Smoking • World Health Organization1 • Health Professionals Against Smoking2 • The American Academy of Family Physicians3 • American Medical Association2 • National Institute for Health and Clinical Excellence4 World Health Organization. Mayo report on addressing the worldwide tobacco epidemic through effective, evidence-based treatment. Report of an expert meeting, March 1999, Rochester (Minnesota) USA. Available at:http://www.who.int/tobacco/resources/publications/mayo/en/print.html. Accessed July 2006. American Cancer Society. Tobacco control strategy planning, companion guide #2: Engaging doctors in tobacco control. Available at: http://strategyguides.globalink.org/doctors.htm. The American Academy of Family Physicians. Tobacco use, prevention and cessation. Available at: http://www.aafp.org/online/en/home/policy/policies/t/tobacco.printerview.html. National Institute for Health and Clinical Excellence. Brief interventions and referral for smoking cessation in primary care and other settings. Available at: www.nice.org.uk/page.aspx?o=299611.

  39. ASK about tobacco USE ADVISE tobacco users to QUIT ASSESS READINESS to make a quit attempt ASSIST with the QUIT ATTEMPT ARRANGE FOLLOW-UP care US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update Tobacco Dependence Support – The “5 A’s”

  40. US PHS Guideline – Treating Tobacco Use and Dependence: 2008 UpdateFirst-line Pharmacotherapies for Tobacco Dependence1 • Nicotine replacement therapy (NRT) Patch Gum Inhaler Nasal spray Sublingual tablets/lozenges • Bupropion SR • Champix (Varenicline) • All decrease cravings, withdrawal • 20-25% quit rates at 1 year • Fiore MC, et al. Clinical Practice Guideline. Treating Tobacco Use and Dependence: 2008 Update. USDHHS. PHS. Rockville, MD. 2008.

  41. 21

  42. (varenicline)A Selective 42 Nicotinic Acetylcholine Receptor Partial Agonist

  43. Champix (varenicline): A Highly Selective 42 Receptor Partial Agonist Nicotine Varenicline Binding of nicotine at the 42 nicotinic receptor in the Ventral Tegmental Area (VTA) is believed to cause large amounts of dopamine to be released at the Nucleus Accumbens (nAcc) Varenicline is an 42 nicotinic receptor partial agonist, a compound with dual agonist and antagonist activities. This is believed to result in both a lesser amount of dopamine release from the VTA at the nAcc as well as the prevention of nicotine binding at the 42 receptors Binding of nicotine at the 42 nicotinic receptor in the Ventral Tegmental Area (VTA) is believed to cause release of dopamine at the Nucleus Accumbens (nAcc) 1. Coe JW et al. Presented at the 11th Annual Meeting and 7th European Conference of the Society for Research on Nicotine and Tobacco. 2005. Prague, Czech Republic. 2. Picciotto MR et al. Nicotine Tob Res. 1999; Suppl 2:S121-125.

  44. 100 60 40 43.9 44.0 29.8 29.5 20 17.7 17.6 0 n=344 n=342 n=341 n=352 n=329 n=344 Champix (varenicline) Efficacy Measurements: CO-Confirmed 4-Wk Continuous Abstinence Rates Wks 9–12 P < 0.001 P < 0.001 P < 0.001 P < 0.001 P = 0.001 P < 0.001 Continuous Abstinence Rate (%) Gonzales et al. Jorenby et al. Varenicline Bupropion SR Placebo The 9-12 week Continuous Abstinence Rate is defined as the percentage of subjects who abstained from smoking (not even a puff) from Week 9 through 12 of the study as confirmed by both subject self-report and by end-expiratory carbon monoxide (CO) measurement 1. Gonzalez D et al. JAMA. 2006;296:47-55. 2. Jorenby DE et al. JAMA. 2006;296:56-63.

  45. Prevention of smoking

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