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BENEFITS OF TOBACCO CESSATION ON CARDIOVASCULAR HEALTH

BENEFITS OF TOBACCO CESSATION ON CARDIOVASCULAR HEALTH. PROF. G.C. ONYEMELUKWE MON MEMBER, SMOKING CESSATION ADVISORY BOARD. DEPARTMENT OF MEDICINE, AHMADU BELLO UNIVERSITY TEACHING HOSPITAL, ZARIA. Introduction. 1. Increasing tobacco use in developing countries of Africa

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BENEFITS OF TOBACCO CESSATION ON CARDIOVASCULAR HEALTH

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  1. BENEFITS OF TOBACCO CESSATION ON CARDIOVASCULAR HEALTH PROF. G.C. ONYEMELUKWE MON MEMBER, SMOKING CESSATION ADVISORY BOARD DEPARTMENT OF MEDICINE, AHMADU BELLO UNIVERSITY TEACHING HOSPITAL, ZARIA

  2. Introduction 1.Increasing tobacco use in developing countries of Africa • More than 150million adolescents use tobacco and 80% of this started before the age of 18years 2.National Global Youth Tobacco Survey 2008 Nigeria- Abuja, Cross River, Ibadan, Kano and Lagos. Ekanem I et al 2008 • Current use of tobacco by youths: Cross River =26.1%, Lagos = 14.6% • Exposure to second hand smoke: Home=14.5% in Ibadan to 31.3% in Cross River • Public places: Kano= 55.5%, Ibadan =35%. 3. Platelets Low Reaction to Aggregators and spontaneous disaggregation of normal Nigerians reduced by diabetes and tobacco – Onyemelukwe et al 2006

  3. USE OF TOBACCO - NCD EXPERT COMMITTEE LAGOS SURVEY 2003 SMOKING STATUS-- ONYEMELUKWE et al

  4. Metabolic Syndrome in adolescents associated with cotinine from tobacco smoke exposure Weiztman M at al Circulation 2005: 112:862-869 • Maternal smoking associated with low birth weight syndromeleading to later cardiovascular disease in adult (Baker Thrifty Phenotype Hypothesis) • Nicotine Induces New Vessel formation and tumour Growth(Cooke et al 2009 Nat. Med) • Nicotine Depresses Endothelial progenitor Cells(Heiss C et al 2008)

  5. Cigarette Smoking to Cardiovascular Disease and Its Risk Factors

  6. Pathophysiology of nicotine on CVS

  7. MRI of BrainWith an Acute Ischemic Stroke Build-up of atherosclerotic plaque in arterial wall

  8. Prefrontal cortex Ventral tegmental area Nucleus Accumbens (reward centre) nAChRs Stimulated by Nicotine & Acetylcholine Hippocampus Simplified diagram of the brain showing the anatomic locations of the ventral tegmental area and the nucleus accumbens α4 β2 β2 Surface of dopamine neuron α4 β2 Simplified structure of α4β2nicotinic receptor located on surface of a dopamine cell body

  9. VARENICLINE BLOCKS NICOTINE RECEPTORS AND PARTIALLY STIMULATES MODERATE DOPAMINE RELEASE A B C Nicotine receptors Varenicline ( ) blocks nicotine receptors Nicotine Cell body of dopamine neuron in ventral tegmental area Rapid/burst firing Partial agonist effects stimulate moderate dopamine release Dopamine ( ) release from dopamine terminal in the nucleus accumbens Bupropion reduces dopamine reuptake and blocks nicotine receptors Highly simplified scheme showing effects of (A) nicotine from cigarettes (B) nicotine withdrawal and (C) varenicline on nicotinic receptors and dopamine release

  10. PHARMACOTHERAPY

  11. NICE: Smoking Cessation Guidelines. (U.K)(NATIONAL INSTITUTE FOR HEALTH AND CLINICAL GUIDANCE) • Targeted at all professionals, councils, community, NGO, governments to achieve smoking cessation. • Urgent need to establish Cessation clinics and guidelines in all African Countries with available pharmacotherapy • Tobacco use is a chronic disease

  12. 5 A’s-Model for tobacco Treatment in Medical Care • ASK patients about smoking at every visit. • ADVISE all tobacco users to quit. • ASSESS patients willingness to try to quit. • ASSIST patient’s quitting effort (Provide smoking cessation treatment or referral). • ARRANGE follow up (Supportive Contacts). * Note Fagerstrom Screening of Smokers. * Note that CS consist of • Psychological (Behavioral Support). • Pharmacological Support for Nicotine Dependence.

  13. BEHAVIOR CHANGE MODEL- STAGES • PRE-CONTEMPLATION. • CONTEMPLATION. • PREPARATION • ACTION • MAINTENANCE • RELAPSE. Requires devotion persistence and understanding

  14. IMMEDIATE EFFECTS OF SMOKING CESSATION • At 20 minutes after quitting – Blood pressure decreases – Pulse rate drops – Body temperature of hands and feet increases • At 8 hours – Carbon monoxide level in blood drops to • normal • – Oxygen level in blood increases to normal

  15. At 24 hours • – Chance of a heart attack decreases • At 48 hours • – Ability to smell and taste is enhanced • At 2 weeks to 3 months • – Circulation improves • – Walking becomes easier • – Lung function increases

  16. Cardiovascular Benefits of Cessation: Fibrinogen • After 2 weeks of cessationby formerly chronic smokers, both fibrinogen concentration and the rate of fibrinogen synthesis are reduced P<.001 P<.001 3.06 24.1 2.49 16.1 Plasma FibrinogenConcentration (g/L) Fibrinogen ASR mg/kg Smoking Abstentiona Smoking Abstentiona ASR=absolute rate of fibrinogen synthesis. aAbstention period of 2 weeks. Hunter et al. Clin Sci (Lond). 2001;100(4):459-465.

  17. Cardiovascular Benefits of Cessation: White Blood Cells (After 17 weeks) P<.026 White Blood Cells (×109/l) Smoking Abstentiona aAbstention period of 17 weeks. Eliasson et al. Nicotine Tob Res. 2001;3(3):249-255.

  18. Cardiovascular Benefits of Cessation: Improved Lipid Profile(After 17 weeks) P<.015 P<.001 LDL (mmol/L) HDL (mmol/L) Smoking Abstentiona Smoking Abstentiona P<.001 HDL/LDL Ratio Smoking Abstentiona HDL=high-density lipoprotein; LDL=low-density lipoprotein. aAbstention period of 17 weeks. Eliasson et al. Nicotine Tob Res. 2001;3(3):249-255.

  19. Cardiovascular Benefits of Cessation: Hemodynamic Profile (After 6 Months) • Smoking cessation is associated with an improvement in hemodynamic parameters. P<.05 P<.05 Mean Arterial Pressure (mm Hg) Heart Rate (Beats/min) Smoking Abstentiona Smoking Abstentiona a Abstention period of 6 months. Oren et al. Angiology. 2006;57(5):564-568.

  20. Cardiovascular Benefits of Cessation: Hemodynamic Profile (cont’d) (After 6 Months) • Smoking cessation is associated with an improvement in arterial compliance P<.01 P<.05 63.1 50.6 Oscillatory Compliance (mL/mm Hg × 100)a Augmentation Index (%)b Smoking Abstentionc Smoking Abstentionc aProvides an assessment of small arteriolar compliance. bThe amplitude of the reflected wave depends on the stiffness of the small vessels and large arteries and thus provides a measure of systolic arterial stiffness.cAbstention period of 6 months. Oren et al. Angiology. 2006;57(5):564-568.

  21. 9.0 12 8.8 10 8.6 8 8.4 6 8.2 4 0 0 1 1 2 2 1 1 4 4 8 8 9 9 1 1 4 4 8 8 9 9 12 12 Cardiovascular Benefits of Cessation: Platelet Effects • Smoking cessation is associated with reduced platelet volume and enhanced platelet cAMPc response to stimulation of adenylatecyclase with prostaglandin E1 Smoking NicotineChewingGum Nonsmoking/Nonchewing Smoking NicotineChewingGum Nonsmoking/Nonchewing P=.02 P<.001 cAMP After PGE (nmol/L) (95% CI)a MPV (fL) (95% CI)b Weeks Weeks aPGE=prostaglandin E1; bMPV=mean platelet volume; ccAMP= cyclic adenosine monophosphate. Terres et al. Am J Med. 1994;97:242-249.

  22. 100 80 60 40 20 0 0 7 14 21 28 Cardiovascular Benefits of Cessation: Platelet Effects (cont’d) • Smoking abstinence is associated with reduced platelet aggregability ADP=5.0 µmol/L Group Aa Group Bb NS P<.01 P<.01 NS Platelet Aggregation (%) NS Time (Days) aQuit smoking for 28 days. bResumed smoking after quitting for 14 days. ADP=adenosine diphosphate. ADP is a platelet aggregation agonist. Morita et al. J Am Coll Cardiol. 2005;45:589-594.

  23. National Health And Nutrition Examination Survey (NHNES III) Smoking cessation and cardiovascular Risks Factors. Results From (NHNES III): Bakru, A and Erlinger, T.P 2005: • Markers of inflammation which include C-reactive protein, plasma fibrinogen and white blood Cell Count ↓↓ with cessation of smoking . • Smoking Associated Inflammatory response subsides within 5 years.

  24. National Health And Nutrition Examination Survey (NHNES III) 3. Total Cholesterol -↓↓. 4. Serum Triglyceride- ↓↓. 5. Serum LDL Cholesterol - ↓↓. 6. Serum HDL Cholesterol -↑↑. Other studies confirming this are the MONICA study ,1999; and NORTHWICK PARK HEART Study, 1987. Helena, Montana, - Sargent RP at al 2004 BMJ 2004 328,977-80 6 months clean air ordinance with 40% reduction in acute myocardial infarction with rebound after the ordinance was suspended.

  25. LONG TERM BENEFITS OF SMOKING CESSATION (CS) • Risk of Coronary Heart Disease ↓ by 50% after one year. • Risk of Stroke similar to that of Non Smoker within 5-15 years. • Within 15 years, relative risk of dying from coronary Heart Disease for an ex smoker approaches that of a life time of non smokers. These are due to endothelial cell regeneration by endothelial progenitor cells, recovery of NO function, Cytokines ↓, ↓reduced activation of neutrophils, platelets, etc. 4 Insulin resistance ↓

  26. 100 80 60 40 20 0 0 2 3 1 Cardiovascular Benefits of Cessation: Reduced Risk of Arrhythmic Death • Cessation of cigarette smoking is associated with a reduction in arrhythmic death for patients with post-myocardial infarction left ventricular dysfunction P=.040 Survival (%) Smokers Ex-smokers Survival in Years Peters et al. J Am Coll Cardiol. 1995;26(5):1287-1292.

  27. Cardiovascular Benefits of Cessation: Reduced Risk of Acute Myocardial Infarction (MI) P<.0001 4 2 Odds Ratio (95% CI)a 1 Current >1-3 >3-5 >5-10 >10-15 >15-20 20 Ex-smokers (Years Since Cessation) aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for sex, region, diet, alcohol, physical activity, consumption of fruits, vegetables, and alcohol. Adapted from Teo. Lancet. 2006;368:647-658.

  28. Cardiovascular Benefits of Citywide Smoke-Free Ordinance: Reduced Incidence of Acute MI • 27% reduction in the incidence of acute myocardial infarction (MI) after implementation of a smoke-free ordinance in Pueblo City, Colorado P<.001 AMI Counts per 100,000Person-Years Bartecchi et al. Circulation. 2006;114:1490-1496.

  29. Cardiovascular Benefits of Cessation: Reduced Risk of Recurrent Cardiac Arrest (3yrs of cession ) • The risk for recurrent cardiac arrest is lower among those who quit smoking than among continuing smokers P=.038 Occurrence at 3 Years (%) Recurrent Cardiac Arrest aAbstention period of 3 years. Hallstrom et al. N Engl J Med. 1986;314:271-275.

  30. 0 2 3 4 5 6 7 8 9 10 11 12 Cardiovascular Benefits of Cessation: Reduced Mortality After Percutaneous Coronary Revascularization • Current smokers had a significantly greater risk of overall mortality after percutaneous coronary revascularization 100 80 60 Survival (%) 40 Quitters Persistent Smokers 20 0 Years After Index Procedure Hasdai. N Engl J Med. 1997;336(11):755-761.

  31. Cardiovascular Benefits of Cessation: Reduced Mortality After Coronary Artery Bypass Graft • Estimated survival benefit associated with smoking cessation increased from 3% at 5 years to 10% at 10 years and 15% at 15 years 100 80 P<.0001 (Ex-smokers vs Current Smokers) 60 Probability of Survival (%) Quitters 40 Nonsmokers Persistent Smokers 20 0 0 5 10 15 20 Years Adapted from van Domburg et al. J Am Coll Cardiol. 2000;36(3):878-883.

  32. 1 2 3 4 5 6 7 Cardiovascular Benefits of Cessation: Reduced Progression of Peripheral Vascular Disease (Over 7 yrs period) 30 Smoking Abstention P=.049 20 Rest Pain, Cumulative (%) 10 0 Years Jonason et al. Acta Med Scand. 1987;221:253-260.

  33. Cardiovascular Benefits of Cessation: Reduced Risk of Stroke P for trend <.0001 Relative Risk (95% CI)a Nonsmokers CurrentSmokers(<20 cig/d) CurrentSmokers(≥20 cig/d) Ex-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 treatment assignment.Robbins et al. Ann Intern Med. 1994;120(6):458-462.

  34. Cardiovascular Benefits of Smoking Cessation Short-term Benefits •  fibrinogen concentration •  rate of fibrinogen synthesis •  WBCs • Improved HDL/LDL ratio •  risk of stroke •  HDL; decreased LDL •  arterial pressure •  HR • Improved arterial compliance •  risk of arrhythmic death after MI •  platelet volume • Enhanced platelet cAMP response to stimulation of ADP with prostaglandin E1 •  smoking-induced platelet aggregability Long-term Benefits • Reduced risk of • Stroke • Repeat CABG • Recurrent coronary events after MI • Arrhythmic death after MI • Secondary CVD events • Revascularization procedure after CABG • Reduced • Mortality after CABG • Mortality after PTCA • Levels of inflammatory markers associated with progression of CVD (C-reactive protein, WBC, and fibrinogen) Twardella et al. Eur Heart J. 2004;25:2101-2108; Morita et al. J Am Coll Cardiol. 2005;45:589-594; Oren et al. Angiology. 2006;57:564-568; Terres et al. Am J Med. 1994; 97:242-249; Nilsson et al. J Int Med. 1996; 240:189-194; Peters et al. J Am Coll Cardiol. 1995;26:1287-1292; Rea et al. Ann Intern Med. 2002;137: 494-500; Hasdai et al. N Engl J Med. 1997;336:755-761; van Domburg et al. J Am Coll Cardiol. 2000; 36:878-883; Bakhru et al. PLoS Med. 2005;2:e160; Eliasson et al. Nicotine Tob Res. 2001;3 :249-255; Hunter et al . Clin Sci. 2001;100 :459-465; Wannamethee et al. JAMA. 1995;274:155-160.

  35. Cochrane Database of Systematic Reviews

  36. Varenicline vs Bupropion 1.Comparisons of varenicline and bupropion and placebo by Gonzales et al 2006, 2) Jorenby et al 2006. Result showed in 1 year (LONG TERM) varenicline with 22.5%, tobacco abstinence 15.7% bupropion, 9.4% placebo. • Vareniclineis superior to bupropion with lower urge to smoke and negative effect experience . 3. Stapleton et al 2006 Varenicline efficacious in patients with mental illness

  37. Varenicline vs. nicotine patchOpen label randomized controlled trial(5 countries, n= 746) 56 43 26 20 End of treatment OR 1.70 (1.26-2.28) Continuous abstinence OR 1.40 (0.99-1.99) Aubin HJ. Thorax 2008

  38. VARENICLINE SAFETY • Varenicline is one of the most effective drugs available to treat tobacco dependence. Continuing to smoke is clearly hazardous. • In most cases, the benefits of varenicline substantially outweigh the risk. • 1st line = varenicline alone or combination with NRT • Bupropion is used but 2nd line, with NRT • V-V = Varenicline – Victory over tobacco dependence

  39. Tobacco Dependence Thank you Victory Varenicline

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