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BENEFITS OF TOBACCO CESSATION ON CARDIOVASCULAR HEALTH PROF. G.C. ONYEMELUKWE PROF. G.C. ONYEMELUKWE MON MEMBER, SMOKING CESSATION ADVISORY BOARD 1 DEPARTMENT.

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Presentation on theme: "BENEFITS OF TOBACCO CESSATION ON CARDIOVASCULAR HEALTH PROF. G.C. ONYEMELUKWE PROF. G.C. ONYEMELUKWE MON MEMBER, SMOKING CESSATION ADVISORY BOARD 1 DEPARTMENT."— Presentation transcript:

1 BENEFITS OF TOBACCO CESSATION ON CARDIOVASCULAR HEALTH PROF. G.C. ONYEMELUKWE PROF. G.C. ONYEMELUKWE MON MEMBER, SMOKING CESSATION ADVISORY BOARD 1 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

3 USE OF TOBACCO - NCD EXPERT COMMITTEE LAGOS SURVEY 2003 SMOKING STATUS-- ONYEMELUKWE et al CharacteristicEver SmokedNever SmokedTotal Sex Male115 (26.4%)320 (73.6%)435 (100%) Female 8 (1.8%)428 (98.2%)436 (100%) Total123 (14.1%)748 (85.9%)871 (100%) Residence Urban68 (16.1%)355 (83.9%)423 (100%) Rural45 (10.9%)368 (89.1%)413 (100%) Age Group yrs12 (5.2%)218 (94.8%)230 (100%) (6.9%)202 (93.1%)217 (100%) (14.4%)119 (85.6%)139 (100%) (25.2%) 92 (74.8%)123 (100%) (34.8%) 45 (65.2%) 69 (100%) 65 and above20 (24.4%) 62 (75.6%) 82 (100%)

4 Metabolic Syndrome in adolescents associated with cotinine from tobacco smoke exposure Weiztman M at al Circulation 2005: 112: Maternal smoking associated with low birth weight syndrome leading 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) 4

5 Cigarette Smoking to Cardiovascular Disease and Its Risk Factors Cardiovascular Disease Angina + Myocardial Infarction + Ischemic Stroke + Hemorrhagic Stroke + Congestive Heart Failure + Erectile impotence + Aortic aneurysm + Limb vessel atherosclerosis + Cardiovascular Risk Factors HDL-C - Triglycerides + Blood Pressure + CRP + Platelet Function + Homocysteine + Insulin resistance + Fibrogen and clotting factors + 5

6 6 Pathophysiology of nicotine on CVS

7 MRI of Brain With an Acute Ischemic Stroke Build-up of atherosclerotic plaque in arterial wall

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

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

10 PHARMACOTHERAPY EXOGENOUS NICOTINEBUPROPIONVARENICLINE NICOTINE REPLACEMENTNORTRYPTILINE* NICOTINE PATCHCLONIDINE* NICOTINE GUMCYSTISINE (Plant alkaloid) NICOTINE INHALER NICOTINE LOZENGES NICOTINE NASAL SPRAY*Rimonabant (Endocannabinoid Type I receptor inhibitor) * Not Approved for cessation treament 10

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 11

12 5 As-Model for tobacco Treatment in Medical Care 1.ASK patients about smoking at every visit. 2.ADVISE all tobacco users to quit. 3.ASSESS patients willingness to try to quit. 4.ASSIST patients quitting effort (Provide smoking cessation treatment or referral). 5.ARRANGE follow up (Supportive Contacts). * Note Fagerstrom Screening of Smokers. * Note that CS consist of 1.Psychological (Behavioral Support). 2.Pharmacological Support for Nicotine Dependence. 12

13 BEHAVIOR CHANGE MODEL- STAGES 1.PRE-CONTEMPLATION. 2.CONTEMPLATION. 3.PREPARATION 4.ACTION 5.MAINTENANCE 6.RELAPSE. Requires devotion persistence and understanding 13

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 14

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 15

16 Cardiovascular Benefits of Cessation: Fibrinogen After 2 weeks of cessation by formerly chronic smokers, both fibrinogen concentration and the rate of fibrinogen synthesis are reduced ASR=absolute rate of fibrinogen synthesis. a Abstention period of 2 weeks. Hunter et al. Clin Sci (Lond). 2001;100(4): Fibrinogen ASR mg/kg Plasma Fibrinogen Concentration (g/L) P<.001 Smoking Abstention a Smoking

17 Cardiovascular Benefits of Cessation: White Blood Cells (After 17 weeks) a Abstention period of 17 weeks. Eliasson et al. Nicotine Tob Res. 2001;3(3): Abstention a Smoking White Blood Cells (×10 9 /l) P<.026

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

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

20 Augmentation Index (%) b Cardiovascular Benefits of Cessation: Hemodynamic Profile (contd) (After 6 Months) Smoking cessation is associated with an improvement in arterial compliance a Provides an assessment of small arteriolar compliance. b The 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. c Abstention period of 6 months. Oren et al. Angiology. 2006;57(5): Oscillatory Compliance (mL/mm Hg × 100) a P<.01 P<.05 SmokingAbstention c SmokingAbstention c

21 Cardiovascular Benefits of Cessation: Platelet Effects Smoking cessation is associated with reduced platelet volume and enhanced platelet cAMP c response to stimulation of adenylate cyclase with prostaglandin E 1 a PGE=prostaglandin E 1 ; b MPV=mean platelet volume; c cAMP= cyclic adenosine monophosphate. Terres et al. Am J Med. 1994;97: Weeks cAMP After PGE (nmol/L) (95% CI) a P =.02 MPV (fL) (95% CI) b Weeks P< Nicotine Chewing Gum SmokingNonsmoking/ Nonchewing SmokingNicotine Chewing Gum Nonsmoking/ Nonchewing

22 Cardiovascular Benefits of Cessation: Platelet Effects (contd) Smoking abstinence is associated with reduced platelet aggregability a Quit smoking for 28 days. b Resumed smoking after quitting for 14 days. ADP=adenosine diphosphate. ADP is a platelet aggregation agonist. Morita et al. J Am Coll Cardiol. 2005;45: ADP=5.0 µmol/L Group A a Group B b Platelet Aggregation (%) Time (Days) NS P<.01 NS P<.01

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: 1.Markers of inflammation which include C- reactive protein, plasma fibrinogen and white blood Cell Count with cessation of smoking. 2.Smoking Associated Inflammatory response subsides within 5 years. 23

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

25 LONG TERM BENEFITS OF SMOKING CESSATION (CS) 1.Risk of Coronary Heart Disease by 50% after one year. 2.Risk of Stroke similar to that of Non Smoker within 5-15 years. 3.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 25

26 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 Peters et al. J Am Coll Cardiol. 1995;26(5): P=.040 Survival in Years Survival (%) Ex-smokers Smokers

27 Cardiovascular Benefits of Cessation: Reduced Risk of Acute Myocardial Infarction (MI) a The 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: P<.0001 Current>1-3>5-10> Ex-smokers (Years Since Cessation) >3-5>15-20 Odds Ratio (95% CI) a 4 2 1

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

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 a Abstention period of 3 years. Hallstrom et al. N Engl J Med. 1986;314: Occurrence at 3 Years (%) P=.038 Recurrent Cardiac Arrest

30 Cardiovascular Benefits of Cessation: Reduced Mortality After Percutaneous Coronary Revascularization Current smokers had a significantly greater risk of overall mortality after percutaneous coronary revascularization Survival (%) Years After Index Procedure Hasdai. N Engl J Med. 1997;336(11): Quitters Persistent Smokers

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 Adapted from van Domburg et al. J Am Coll Cardiol. 2000;36(3): Probability of Survival (%) Years P<.0001 (Ex-smokers vs Current Smokers) Nonsmokers Persistent Smokers Quitters

32 Cardiovascular Benefits of Cessation: Reduced Progression of Peripheral Vascular Disease (Over 7 yrs period) Jonason et al. Acta Med Scand. 1987;221: Years Rest Pain, Cumulative (%) P= Abstention Smoking

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

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: ; Morita et al. J Am Coll Cardiol. 2005;45: ; Oren et al. Angiology. 2006;57: ; Terres et al. Am J Med. 1994; 97: ; Nilsson et al. J Int Med. 1996; 240: ; Peters et al. J Am Coll Cardiol. 1995;26: ; Rea et al. Ann Intern Med. 2002;137: ; Hasdai et al. N Engl J Med. 1997;336: ; van Domburg et al. J Am Coll Cardiol. 2000; 36: ; Bakhru et al. PLoS Med. 2005;2:e160; Eliasson et al. Nicotine Tob Res. 2001;3 : ; Hunter et al. Clin Sci. 2001;100 : ; Wannamethee et al. JAMA. 1995;274:

35 Cochrane Database of Systematic Reviews Drug Update Number of comparisons Number of abstinent active arm (%) Number of abstinent control arm (%) Nortriptyline Bupropion Clonidine Nicotine gum Nicotine patch Nicotine inhaler Nicotine nasal spray Nicotine lozenge/tablet

36 Varenicline vs Bupropion 1.Comparisons of varenicline and bupropion and placebo by Gonzales et al 2006, 2) Jorenby et al Result showed in 1 year (LONG TERM) varenicline with 22.5%, tobacco abstinence 15.7% bupropion, 9.4% placebo. Varenicline is 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 patch Open label randomized controlled trial (5 countries, n= 746) 37 Aubin HJ. Thorax 2008 End of treatment OR 1.70 ( ) Continuous abstinence OR 1.40 ( )

38 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. 1 st line = varenicline alone or combination with NRT Bupropion is used but 2 nd line, with NRT V-V = Varenicline – Victory over tobacco dependence

39 12/25/ Thank you Tobacco Dependence Varenicline Victory


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