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
Characteristic
Ever Smoked
Never Smoked
Total
Sex
Male
115 (26.4%)
320 (73.6%)
435 (100%)
Female
8 (1.8%)
428 (98.2%)
436 (100%)
123 (14.1%)
748 (85.9%)
871 (100%)
Residence
Urban
68 (16.1%)
355 (83.9%)
423 (100%)
Rural
45 (10.9%)
368 (89.1%)
413 (100%)
Age Group
15-24 yrs
12 (5.2%)
218 (94.8%)
230 (100%)
25-34
15 (6.9%)
202 (93.1%)
217 (100%)
35-44
20 (14.4%)
119 (85.6%)
139 (100%)
45-54
31 (25.2%)
92 (74.8%)
123 (100%)
55-64
24 (34.8%)
45 (65.2%)
69 (100%)
65 and above
20 (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)

5. Cigarette Smoking to Cardiovascular Disease and Its Risk Factors
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

6. Pathophysiology of nicotine on CVS

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

8. nAChRs Stimulated by Nicotine & Acetylcholine
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 α4 β2 nicotinic receptor
located on surface of a dopamine cell body

9. VARENICLINE BLOCKS NICOTINE RECEPTORS AND PARTIALLY STIMULATES MODERATE DOPAMINE RELEASE
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 EXOGENOUS NICOTINE BUPROPION VARENICLINE
NICOTINE REPLACEMENT
NORTRYPTILINE*
NICOTINE PATCH
CLONIDINE*
NICOTINE GUM
CYSTISINE (Plant alkaloid)
NICOTINE INHALER
NICOTINE LOZENGES
NICOTINE NASAL SPRAY
*Rimonabant
(Endocannabinoid
Type I receptor inhibitor)
* Not Approved for cessation treament

11. NICE: Smoking Cessation Guidelines. (U
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 cessation by 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 Fibrinogen Concentration (g/L)
Fibrinogen ASR mg/kg
Key Point
After 2 weeks of cessation by formerly chronic smokers, both fibrinogen concentration and the rate of fibrinogen synthesis are reduced.
Elevated plasma fibrinogen is an independent risk factor for cardiovascular disease. Hunt et al sought to elucidate the relationship between smoking and hyperfibrinoginemia. The authors performed 2 studies, reported in the cited article. Data in the above slide is derived from the second study in which 11 male chronic smokers were evaluated before and after a 2-week trial of smoking abstinence. Serum levels of fibrinogen, fibrinogen synthesis, albumin, albumin synthesis and C-reactive protein were evaluated before and after abstention. Compliance with the nonsmoking regimen was assessed by measuring urinary cotinine concentration on 2 separate occasions during the study period.
All subjects demonstrated a reduction in plasma fibrinogen concentration. Mean fibrinogen concentration while smoking was 3.060.11 g/L, which decreased approximately 19% to 2.490.14 g/L after abstention (P<.001).
Absolute rate of fibrinogen synthesis (ASR) was calculated as the product of the percentage of the intravascular fibrinogen pool synthesized per day and intravascular fibrinogen mass (fibrinogen concentration × plasma volume). Fibrinogen ASR decreased from a mean value of 24.11.7 mg/kg per day while smoking to 16.1± 1.0 mg/kg per day after abstention (P<.001). Fibrinogen ASR decreased approximately 33% after cessation.
Smoking
Abstentiona
Smoking
Abstentiona
ASR=absolute rate of fibrinogen synthesis. aAbstention period of 2 weeks.
Hunter et al. Clin Sci (Lond). 2001;100(4):
Reference
Hunter KA, Garlick PJ, Broom I, Anderson SE, McNurlan MA. Effects of smoking and abstention from smoking on fibrinogen synthesis in humans. Clin Sci (Lond). 2001;100(4):

17. Cardiovascular Benefits of Cessation: White Blood Cells (After 17 weeks)
P<.026
White Blood Cells (×109/l)
Key Point
Smoking cessation is associated with a significant reduction in white blood cells (WBC).
In an effort to evaluate the effect of smoking reduction and cessation on cardiovascular risk factors, Eliasson et al evaluated 58 current smokers (15 cigarettes/day for 3 years) in Göteborg, Sweden, and followed them up for a total of 12 months. The study consisted of 2 phases. During the initial phase (weeks 1-9), subjects reduced their daily cigarette smoking by a minimum of 50%. During the second phase (to week 17), subjects were required to completely abstain from smoking. All subjects were prescribed nicotine nasal spray, to be used as needed.
At 17 weeks, 33 subjects (57.8%) were abstinent. Smoking cessation was associated with significant reduction in WBC from 7.00.4(× 109) to 6.10.3 (× 109), P=.026.
Smoking
Abstentiona
aAbstention period of 17 weeks.
Eliasson et al. Nicotine Tob Res. 2001;3(3):
Reference
Eliasson B, Hjalmarson A, Kruse E, Landfeldt B, Westin A. Effect of smoking reduction and cessation on cardiovascular risk factors. Nicotine Tob Res. 2001;3(3):

18. Cardiovascular Benefits of Cessation: Improved Lipid Profile (After 17 weeks)
HDL (mmol/L)
LDL (mmol/L)
Smoking
Abstentiona
Smoking
Abstentiona
Key Point
Smoking cessation is associated with a significant increase in HDL, HDL/LDL ratio, and reduction in LDL.
In an effort to evaluate the effect of smoking reduction and cessation on cardiovascular risk factors, Eliasson et al evaluated 58 current smokers (15 cigarettes/day for 3 years) in Göteborg, Sweden, and followed up for a total of 12 months. The study consisted of 2 phases. During the initial phase (weeks 1-9), subjects reduced their daily cigarette smoking by a minimum of 50%. During the second phase (to week 17), subjects were required to completely abstain from smoking. All subjects were prescribed nicotine nasal spray, to be used as needed.
At 17 weeks, 33 subjects (57.8%) were abstinent. Smoking cessation was associated with significant increases in HDL concentration from 1.160.06 mmol/L to 1.320.06 mmol/L (P<.001), and in HDL/LDL ratio from 0.330.03 to 0.420.03 (P<.001) as well as a significant reduction in LDL concentration from 3.780.16 to 3.520.17 (P=.015).
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):
Reference
Eliasson B, Hjalmarson A, Kruse E, Landfeldt B, Westin A. Effect of smoking reduction and cessation on cardiovascular risk factors. Nicotine Tob Res. 2001;3(3):

19. Mean Arterial Pressure (mm Hg) Heart Rate (Beats/min)
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)
Key Point
Smoking cessation is associated with an improvement in hemodynamic parameters.
Oren et al performed an open-label study in which 60 chronic smokers (20 cigarettes a day for more than 10 years) were treated for 2 months with bupropion (300 mg/d) and participated in behavioral therapy. Complete physical exam was performed at baseline.
At the 6-month follow-up, 23 participants remained nonsmokers. Repeat physical exam demonstrated significant reductions in mean arterial pressure from 9010.7 to 8711.6 mm Hg (P<.05), and in heart rate from 7610 to 7210 (P<.05), as well as improvement in arterial compliance (as demonstrated in the next slide).
Smoking
Abstentiona
Smoking
Abstentiona
a Abstention period of 6 months.
Oren et al. Angiology. 2006;57(5):
Reference
Oren S, Isakov I, Golzman B, et al. The influence of smoking cessation on hemodynamics and arterial compliance. Angiology. 2006;57(5):

20. Oscillatory Compliance (mL/mm Hg × 100)a Augmentation Index (%)b
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
Key Point
Smoking cessation is associated with an improvement in hemodynamic parameters.
Oren et al performed an open-label study in which 60 chronic smokers (20 cigarettes a day for more than 10 years) were treated for 2 months with bupropion (300 mg/day) and participated in behavioral therapy. Complete physical exam was performed at baseline.
Arterial compliance was evaluated based upon noninvasive radial artery waveforms recorded from subjects while in the supine position. Computer analysis of waveforms and diastolic decay provided information regarding capacitive compliance and small artery reflective or oscillatory compliance. Augmentation index is the ratio of recorded augmentation pressure and pulse pressure. Augmentation index provides a measure of systolic arterial stiffness.
At the 6-month follow-up, 23 participants remained nonsmokers. Repeat physical exam demonstrated significant reduction in mean arterial pressure and heart rate, as well as improvement in oscillatory compliance from 5.12.3 to 6.33 (P<.01) and reduction in augmentation index from 63.122 to 50.617 (P<.05).
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):
Reference
Oren S, Isakov I, Golzman B, et al. The influence of smoking cessation on hemodynamics and arterial compliance. Angiology. 2006;57(5):

21. Cardiovascular Benefits of Cessation: Platelet Effects
Smoking cessation is associated with reduced platelet volume and enhanced platelet cAMPc response to stimulation of adenylate cyclase with prostaglandin E1
Smoking
Nicotine Chewing Gum
Nonsmoking/ Nonchewing
Smoking
Nicotine Chewing Gum
Nonsmoking/ Nonchewing
P=.02
P<.001 4 8 10 12 6
8.2
8.4
8.6
9.0
8.8
Key Point
Smoking cessation is associated with reduced platelet volume and enhanced platelet cyclic adenosine monophosphate (cAMP) response to stimulation of adenylate cyclase with prostaglandin E1.
Terres et al sought to evaluate serum lipids, blood pressure, adrenergic response and platelet function in newly abstinent smokers.
Subjects enrolled in the study were 121 current smokers who smoked a minimum of 20 cigarettes daily for 5 years or more. Participants were evaluated at baseline (while still smoking), and once abstinent from smoking (but using nicotine gum) after weeks 1, 4, 8, 9, and 12. Participants were advised to discontinue nicotine gum use after week 12. Study participants were examined again after weeks 1, 4, 8, 9, and 12 of complete nicotine abstention.
In addition to multiple parameters evaluated, platelet volume and platelet cAMP response to stimulation of platelet adenylate cyclase with prostaglandin E1 (measured after 30 seconds of incubation of platelet-rich plasma with prostaglandin E1) were determined at each visit.
Upon cessation of smoking, the mean number of platelets did not change; however, the mean platelet volume decreased significantly by 0.30 fL (95% CI, ), P<.001. The in vitro synthesis of cAMP after stimulation of platelet adenylate cyclase with prostaglandin E1 increased by 1.8 nmol/L (95% CI, ), P=.02. Elevation of cAMP levels is associated with inhibition of platelet reactivity.
cAMP After PGE (nmol/L) (95% CI)a
MPV (fL) (95% CI)b 1 2 4 8 9 12 1 2 4 8 9 12
Weeks
Weeks
aPGE=prostaglandin E1; bMPV=mean platelet volume; ccAMP= cyclic adenosine monophosphate. Terres et al. Am J Med. 1994;97:
Reference
Terres W, Becker P, Rosenberg A. Changes in cardiovascular risk profile during the cessation of smoking. Am J Med. 1994;97:

22. Cardiovascular Benefits of Cessation: Platelet Effects (cont’d)
Smoking abstinence is associated with reduced platelet aggregability 20 60
100 40 80
ADP=5.0 µmol/L
Group Aa
Group Bb NS
P<.01
P<.01 NS
Platelet Aggregation (%) NS
Key Point
Smoking abstinence is associated with reduced platelet aggregability.
In an attempt to evaluate the impact of smoking cessation on intracellular oxidative stress and platelet aggregability in long-term smokers, Morita et al evaluated 27 male smokers. Subjects smoked a minimum of 15 cigarettes per day for more than 5 years.
Participants were divided into 2 groups: group A abstained from smoking for 28 days, and group B abstained from smoking initially, but resumed smoking after 14 days. Bloodwork was assessed at baseline followed by days 7, 14, 21, and 28. Adenosine diphosphate (ADP) and collagen-induced platelet aggregation were assessed by adding ADP and collagen to washed platelet suspensions and light transmission was monitored using a platelet aggregometer.
Agonist (ADP or collagen)-induced platelet aggregations were similar between the 2 groups at baseline. In group A, agonist-induced platelet aggregations were significantly reduced throughout the period of abstinence. In group B, agonist-induced platelet aggregation significantly decreased through day 14; however, aggregability rapidly returned to baseline with reinitiation of smoking. 7 14 21 28
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:
Reference
Morita JH, Ikeda H, Haramaki N, Eguchi H, Imasizumi T. Only two-week smoking cessation improves platelet aggregability and intraplatelet redox imbalance of long-term smokers. J Am Coll Cardiol. 2005;45:

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, 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.

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. 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 20 40 60 80
100
P=.040
Survival (%)
Key Point
Cessation of cigarette smoking is associated with a reduction in arrhythmic death for patients with post-myocardial infarction (MI) left ventricular dysfunction.
Peters et al sought to evaluate the effect of smoking cessation on overall mortality and the incidence of arrhythmic death in participants of the Cardiac Arrhythmia Suppression Trial (CAST). There were 2 components to the CAST trial: CAST I and CAST II. Subjects in CAST I were treated with ecainide, flecainide, and moricizine between June 1987 and April Subjects in CAST II were treated with 3 doses of moricizine between April 1989 and August The CAST trials were multicenter, double-blind, placebo-controlled studies the objective of which was to determine whether suppression of ventricular ectopic activity, by means of antiarrhythmic therapy in patients with left ventricular dysfunction after acute MI, would reduce the incidence of arrhythmic death.
Ex-smokers were defined as patients who stopped smoking between the time of their index myocardial infarction and their 4-month follow-up visit. Current smokers were defined as those who continued to smoke until that time.
Of 2752 patients in the CAST trial, 1026 were smoking at the time of baseline examination and are the subjects of the Peters et al study. Of the 1026 current smokers, 517 stopped smoking between the time of the index MI and the 4-month follow-up. Ex-smokers had 17 arrhythmic deaths and 32 deaths overall, whereas current smokers had 30 arrhythmic deaths and 45 total deaths. The graph depicts the survival curves for smokers and ex-smokers and demonstrates that there was significantly reduced survival rates in smokers when compared with ex-smokers, P=.04.
Smokers
Ex-smokers 2 3 1
Survival in Years
Peters et al. J Am Coll Cardiol. 1995;26(5):
Reference
Peters RW, Brooks MM, Todd L, Liebson PR, Wilhelmsen L; the Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Smoking cessation and arrhythmic death: The CAST experience. J Am Coll Cardiol. 1995;26(5):

27. Cardiovascular Benefits of Cessation: Reduced Risk of Acute Myocardial Infarction (MI)4
P<.0001 2
Odds Ratio (95% CI)a
Key Point
Risk of acute MI associated with smoking is significantly reduced within a few years of quitting.
Teo et al evaluated 12,461 cases of first acute MI and 14,637 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.
Risk of acute MI associated with smoking was markedly reduced within a few years of quitting. Risk of acute MI decreased progressively with time since becoming abstinent; however, some increased risk persisted, even in those who had quit more than 20 years prior. 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:
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:

28. AMI Counts per 100,000 Person-Years
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 100,000 Person-Years
Key Point
Enactment of smoke-free ordinances results in significant reductions in hospital admission rates for acute MI.
Bartecchi et al completed an observational study to determine the effects of a citywide smoking ordinance in Pueblo, Colorado, 1.5 years after the enactment of the ordinance. The ordinance prohibited smoking inside the workplace and all buildings open to the public. The study compared acute MI rates in Pueblo City before and after ordinance enactment. The authors also compared acute MI in Pueblo City to rates in El Paso County, Colorado. El Paso County is a geographically isolated community similar to Pueblo that served as an external control because the smoking ordinance was not enacted there.
A 23% reduction in acute MI hospitalizations was observed (RR=0.73; 95% CI, ) in Pueblo City following the enactment of the ordinance, while there was no significant change in the external control, El Paso County (RR=0.97; 95% CI, ). There were 257 and 187 acute MI hospitalization counts per 100,000 person years in Pueblo City before and after enactment of the ordinance, respectively. The number of acute MI hospitalizations were significantly reduced after enactment of the ordinance; P<.001.
Bartecchi et al. Circulation. 2006;114:
Reference
Bartecchi C, Alsever RN, Nevin-Woods C, et al. Reduction in the incidence of acute myocardial infarction associated with a citywide smoking ordinance. Circulation. 2006;114;

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 (%)
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).
Recurrent Cardiac Arrest
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:

30. Years After Index Procedure
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 (%)
Key Point
Persistent smokers had a significantly greater risk of overall mortality after percutaneous coronary revascularization.
Patients (N=6600) who underwent percutaneous coronary revascularization at the Mayo Clinic from 1979 through 1995 were followed for up to 16 years by Hasdai et al. Patients were questioned about their smoking status at baseline and follow-up. Study population was divided into 4 groups on the basis of smoking status at baseline: nonsmokers, defined as patients who had never smoked cigarettes regularly; ex-smokers, who had quit smoking a minimum of 6 months before the procedure; quitters, those who had permanently quit smoking immediately after the procedure; and persistent smokers, who smoked before and after the procedure.
The study end points were death from any cause, Q-wave acute myocardial infarction or severe angina, and the need for coronary artery bypass grafting or repeated percutaneous coronary revascularization.
After adjusting for significant differences in baseline variables, risk of death from all causes among persistent smokers was compared with risk among quitters. Persistent smokers had significantly greater risk of overall mortality (RR, 1.44; 95% CI, ). The estimated survival curves diverged soon after the initial revascularization procedure. The difference between the curves continued to increase throughout the follow-up period. 40
Quitters
Persistent Smokers 20 2 3 4 5 6 7 8 9 10 11 12
Years After Index Procedure
Hasdai. N Engl J Med. 1997;336(11):
Reference
Hasdai D, Garratt KN, Grill DE, Lerman A, Holmes DR Jr. Effect of smoking status on the long-term outcome after successful percutaneous coronary revascularization. N Engl J Med. 1997;336(11):

31. Probability of Survival (%)
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 60
P<.0001 (Ex-smokers vs
Current Smokers)
Probability of Survival (%)
Quitters
Key Point
Patients who continue to smoke after Coronary Artery Bypass Graft (CABG) surgery have a greater risk of death than those who stop smoking.
van Domburg et al sought to evaluate the influence of smoking cessation on mortality in patients undergoing CABG surgery. The authors identified 1041 patients undergoing their first CABG procedure between February 1971 and June Baseline smoking history was obtained at the time of surgery. Patients were followed up for a median of 20 years (range: years). Postoperative smoking status was obtained in 985 patients.
Mortality was divided into perioperative mortality (death occurring within 28 days after surgery) and late mortality. Late mortality was subdivided into death at re-CABG or PTCA, acute cardiac death, death caused by MI, death due to chronic heart failure, death due to noncardiac cause, and unknown causes of death.
The study population was divided into smokers and nonsmokers. Nonsmokers included ex- and never smokers. Smokers before surgery were further subdivided as quitters (those who stopped smoking in the first year after their CABG) and persistent smokers (those who had smoked before CABG and continued to smoke for at least one year after CABG).
Persistent smokers had a significantly greater risk of death from all causes, (RR, 1.68; 95% CI, ) and of cardiac death, (RR, 1.75; 95% CI, ) compared with patients who abstained from smoking after bypass surgery.
The above graph depicts the survival curves for ex-smokers, current smokers, and nonsmokers. Benefits of smoking abstinence were demonstrated as early as 4 years after the initial CABG, at which point the curves diverged. The estimated benefit in survival associated with smoking abstinence increased from 3% at 5 years (98% vs 95%), to 10% at 10 years (88% vs 78%), and 15% at 15 years (70% vs 55%). 40
Nonsmokers
Persistent Smokers 20 5 10 15 20
Years
Adapted from van Domburg et al. J Am Coll Cardiol. 2000;36(3):
Reference
van Domburg RT, Meeter K, van Berkel DFM, Veldkanys RF, van Herwerden LA, Bogers AJJC. Smoking cessation reduces mortality after coronary artery bypass surgery: a 20-year follow-up study. J Am Coll Cardiol. 2000;36(3):

32. Rest Pain, Cumulative (%)
Cardiovascular Benefits of Cessation: Reduced Progression of Peripheral Vascular Disease (Over 7 yrs period) 30
Smoking
Abstention 20
P=.049
Rest Pain, Cumulative (%)
Key Point
Smokers with intermittent claudication (IC), who discontinue smoking demonstrate reductions in progression of peripheral vascular disease (PVD).
Three hundred forty-three Swedish patients with IC were evaluated at baseline, at follow-up 12 months later, and 7 years after the follow-up exam. Subjects were designated ex-smokers if they had stopped smoking within 6 months before or 12 months after the initial examination. Patients who continued to smoke or stopped more than 12 months after the initial examination were designated as current smokers.
At baseline, evidence of PVD was determined based upon the results of a combination of segmental blood pressure measurements as well as Doppler assessment of the velocity and direction of the blood flow in the popliteal and common femoral arteries. Walking tolerance was also estimated by a symptom-limited treadmill test.
Rest pain was defined as pain in the leg or foot when the patient was recumbent that was relieved when the leg was lowered.
Patients who had stopped smoking within 6 months before or within 12 months after the initial examination were designated nonsmokers. Patients who continued to smoke or stopped smoking more
During the 7-year follow-up period, rest pain developed in 26 patients, all of whom were current smokers. None of the ex-smokers developed rest pain. After 7 years, the cumulative proportion of patients with rest pain was 16% among the current smokers (P=.049). 10 2 7 1 6 5 4 3
Years
Jonason et al. Acta Med Scand. 1987;221:
Reference
Jonason T, Bergstrom R. Cessation of smoking in patients with intermittent claudication: effects on the risk of peripheral vascular complications, myocardial infarction and mortality. Acta med Scand. 1987;221:

33. Cardiovascular Benefits of Cessation: Reduced Risk of Stroke
P for trend <.0001
Relative Risk (95% CI)a
Key Point
Compared with current smokers, male ex-smokers have a reduced risk of nonfatal stroke.
Robbins et al prospectively evaluated 22,071 male physicians in the Physicians’ Health Study, a randomized, double-blind, placebo-controlled study evaluating the effect of low-dose aspirin on cardiovascular disease, as well as the effect of beta-carotene on cancer and cardiovascular disease.
Subjects were men aged 40 to 84 years, without history of myocardial infarction (MI), stroke, or transient ischemic attacks. Data regarding smoking habits was derived from a self-completed questionnaire. Smokers were defined as nonsmokers, ex-smokers, current smokers smoking less than 20 cigarettes per day, or current smokers smoking more than 20 cigarettes per day. Every 6 months during the first year, then annually thereafter, subjects completed a questionnaire regarding compliance with the prescribed regimen and incidence of cardiac events (stroke, MI, etc). Follow-up continued either until participants experienced nonfatal or fatal stroke, or any other fatal event.
Participants were followed up for an average of 9.7 years. After adjusting for age and treatment assignment, ex-smokers had lower relative risk of total nonfatal stroke (1.2; 95% CI, ) than physicians currently smoking less than 20 and more than 20 cigarettes daily, (2.0, 95% CI, ) and (2.5, 95% CI, ), respectively.
Nonsmokers
Ex-smokers
Current Smokers (<20 cig/d)
Current Smokers (≥20 cig/d)
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):
Reference
Robbins AS, Manson JE, Lee I-M, Satterfield S, Hennekens CH. Cigarette smoking and stroke in a cohort of US male physicians. Ann Intern Med. 1994;120(6):

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)
Smoking cessation is associated with multiple short- and long-term cardiovascular benefits.
Twardella D, Kupper-Nybelen J, Rothenbacher D, Hahmann H, Wusten B, Brenner H. Short-term benefit of smoking cessation in patients with coronary heart disease: estimates based on self-reported smoking data and serum cotinine measurements. Eur Heart J. 2004;25(23):
Morita J, Ikeda H, Haramaki N, Eguchi H, Imasizumi T. Only two-week smoking cessation improves platelet aggregability and intraplatelet redox imbalance of long-term smokers. J Am Coll Cardiol. 2005;45(4):
Oren S, Isakov I, Golzman B, et al. The influence of smoking cessation on hemodynamics and arterial compliance. Angiology. 2006;57(5):
Terres W, Becker P, Rosenberg A. Changed in cardiovascular risk profile during the cessation of smoking. Am J Med. 1994;97:
Nilsson P, Lundgren H, Söderström M, Fagerström K-O, Nilsson-Ehle P. Effects of smoking cessation on insulin and cardiovascular risk factors—a controlled study of 4 months' duration. J Intern Med. 1996;240(4):
Peters R, Brooks M, Todd L, Liebson P, Wilhelmsen L; The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Smoking cessation and arrhythmic death: the CAST experience. J Am Coll Cardiol. 1995;26:
Rea TD, Heckbert SP, Kaplan RC, Smith NL, Lemaitre RN, Psaty BM. Smoking status and risk for recurrent events after myocardial infarction. Ann Intern Med. 2002;137:
Hasdai D, Garratt K, Grill D, Lerman A, Holmes D. Effect of smoking status on the long-term outcome after successful percutaneous coronary revascularization. N Engl J Med. 1997;336:
van Domburg RT, Meeter K, van Berkel DFM, Veldkamp RF, van Herwerden LA, Bogers JAJC. Smoking cessation reduces mortality after coronary artery bypass surgery: a 20-year follow-up study. J Am Coll Cardiol. 2000;36:
Bakhru A, Erlinger TP. Smoking cessation and cardiovascular disease risk factors: results from the Third National Health and Nutrition Examination Survey. PLos Med. 2005;2(6, e160):
Eliasson B, Hjalmarson A, Kruse E, Landfeldt B, Westin A. Effect of smoking reduction and cessation on cardiovascular risk factors. Nicotine Tob Res. 2001;3(3):
Hunter KA, Garlick PJ, Broom I, Anderson SE, McNurlan MA. Effects of smoking and abstention from smoking on fibrinogen synthesis in humans. Clin Sci (Lond). 2001;100(4):
Wannamethee G, Shaper AG, Whincup PW, Walker M. Smoking cessation and the risk of stroke in middle-aged men. JAMA. 1995;274:
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 7
20.2
8.9
Bupropion 21
20.1
10.7
Clonidine 6
24.9
14.4
Nicotine gum 52
19.5
11.5
Nicotine patch 42
14.6
8.6
Nicotine inhaler 4
17.1
9.1
Nicotine nasal spray
23.9
11.1
Nicotine lozenge/tablet 5
16.4
8.8

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. Continuous abstinence
Varenicline vs. nicotine patch Open label randomized controlled trial (5 countries, n= 746) 56 43 26 20
End of treatment
OR ( )
Continuous abstinence
OR 1.40 ( )
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
3/25/2017