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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
1
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 NigeriaAbuja, 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
2
USE OF TOBACCO - NCD EXPERT COMMITTEE LAGOS SURVEY
2003 SMOKING STATUS-- ONYEMELUKWE et al
Characteristic
Sex
Male
Female
Total
Residence
Urban
Rural
Age Group
15-24 yrs
Ever Smoked
Never Smoked Total
115 (26.4%)
8 (1.8%)
123 (14.1%)
320 (73.6%)
428 (98.2%)
748 (85.9%)
435 (100%)
436 (100%)
871 (100%)
68 (16.1%)
45 (10.9%)
355 (83.9%)
368 (89.1%)
423 (100%)
413 (100%)
12 (5.2%)
218 (94.8%)
230 (100%)
25-34
35-44
45-54
55-64
15 (6.9%)
20 (14.4%)
31 (25.2%)
24 (34.8%)
202 (93.1%)
119 (85.6%)
92 (74.8%)
45 (65.2%)
217 (100%)
139 (100%)
123 (100%)
69 (100%)
• 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 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
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
Pathophysiology of nicotine on CVS
6
Build-up of atherosclerotic
plaque in arterial wall
MRI of Brain
With an Acute Ischemic Stroke
Prefrontal
cortex
Nucleus
Accumbens
Ventral
tegmental
area
(reward centre)
nAChRs Stimulated by Nicotine &
Acetylcholine
α4
β2
α4
β2
β2
Simplified structure of α4 β2 nicotinic receptor
located on surface of a dopamine cell body
Hippocampus
Simplified diagram of the brain showing the
anatomic locations of the ventral tegmental
area and the nucleus accumbens
Surface of
dopamine
neuron
8
VARENICLINE BLOCKS NICOTINE RECEPTORS AND
PARTIALLY STIMULATES MODERATE DOPAMINE RELEASE
A
B
Nicotine
receptors
Nicotine
C
Varenicline ( )
blocks nicotine
receptors
Cell body of dopamine
neuron in ventral
tegmental area
Rapid/burst firing
Dopamine ( ) release
from dopamine terminal
in the nucleus accumbens
Partial agonist
effects stimulate
moderate
dopamine
release
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
9
PHARMACOTHERAPY
EXOGENOUS NICOTINE
BUPROPION
NICOTINE REPLACEMENT
NORTRYPTILINE*
NICOTINE PATCH
CLONIDINE*
NICOTINE GUM
CYSTISINE (Plant alkaloid)
VARENICLINE
NICOTINE INHALER
NICOTINE LOZENGES
NICOTINE NASAL SPRAY
*Rimonabant
(Endocannabinoid
Type I receptor inhibitor)
* Not Approved for
cessation treament
10
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
5 A’s-Model for tobacco Treatment in
Medical Care
1.
2.
3.
4.
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).
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
BEHAVIOR CHANGE MODEL- STAGES
1. PRE-CONTEMPLATION.
2. CONTEMPLATION.
3. PREPARATION
4. ACTION
5. MAINTENANCE
6. RELAPSE.
Requires devotion persistence and
understanding
13
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
•
•
•
•
•
•
•
•
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
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
3.5
3.06
2.49
2.5
2.0
1.5
1.0
Fibrinogen ASR mg/kg
Plasma Fibrinogen
Concentration (g/L)
3.0
25
16.1
15
10
5
0.0
0
Abstentiona
24.1
20
0.5
Smoking
P<.001
30
Smoking
Abstentiona
ASR=absolute rate of fibrinogen synthesis. aAbstention period of 2 weeks.
Hunter et al. Clin Sci (Lond). 2001;100(4):459-465.
Cardiovascular Benefits of Cessation:
White Blood Cells (After 17 weeks)
White Blood Cells (×109/l)
8
7.0
P<.026
7
6.1
6
5
4
3
2
1
0
Smoking
aAbstention
Abstentiona
period of 17 weeks.
Eliasson et al. Nicotine Tob Res. 2001;3(3):249255.
Cardiovascular Benefits of Cessation: Improved Lipid Profile
(After 17 weeks)
P<.001
2.0
1.32
1.16
1.0
LDL (mmol/L)
2.5
1.5
P<.015
5.0
3.78
4.0
3.52
3.0
2.0
1.0
0.5
0.0
0.0
Abstentiona
Smoking
Smoking
Abstentiona
1.0
HDL/LDL Ratio
HDL (mmol/L)
3.0
0.8
P<.001
0.6
0.42
0.4
0.33
0.2
0.0
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.
Cardiovascular Benefits of Cessation: Hemodynamic
Profile (After 6 Months)
120
100
120
P<.05
90
87
80
60
40
20
Heart Rate (Beats/min)
Mean Arterial Pressure (mm Hg)
• Smoking cessation is associated with an improvement in hemodynamic
parameters.
P<.05
100
76
80
72
60
40
20
0
0
Smoking
Abstentiona
a Abstention
Smoking
period of 6 months.
Oren et al. Angiology. 2006;57(5):564-568.
Abstentiona
Cardiovascular Benefits of Cessation: Hemodynamic
Profile (cont’d) (After 6 Months)
10
90
P<.01
80
8
6.3
6
5.1
4
2
Augmentation Index (%)b
Oscillatory Compliance (mL/mm Hg
× 100)a
• Smoking cessation is associated with an improvement in arterial
compliance
70
P<.05
63.1
60
50.6
50
40
30
20
10
0
aProvides
Smoking
Abstentionc
0
Smoking
Abstentionc
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.
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
Nonsmoking/
Nonchewing
Smoking Nicotine
Chewing
Gum
P=.02
Nonsmoking/
Nonchewing
P<.001
12
9.0
MPV (fL) (95% CI)b
cAMP After PGE (nmol/L) (95% CI)a
Smoking Nicotine
Chewing
Gum
10
8
6
4
0 1 2 1 4 8 9
1 4 8 9 12
Weeks
aPGE=prostaglandin
8.8
8.6
8.4
8.2
0 1 2 1 4 8 9
1 4 8 9 12
Weeks
E1; bMPV=mean platelet volume; ccAMP= cyclic adenosine
monophosphate. Terres et al. Am J Med. 1994;97:242-249.
Cardiovascular Benefits of Cessation: Platelet Effects (cont’d)
• Smoking abstinence is associated with reduced platelet
aggregability
ADP=5.0 µmol/L
Platelet Aggregation (%)
100
80
Group Aa
NS
P<.01
NS
60
Group Bb
P<.01
NS
40
20
0
0
aQuit
7
14
Time (Days)
21
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.
28
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 Creactive protein, plasma fibrinogen and white
blood Cell Count ↓↓ with cessation of
smoking .
2. Smoking Associated Inflammatory response
subsides within 5 years.
23
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.
24
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
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
100
P=.040
Survival (%)
80
60
40
Smokers
Ex-smokers
20
0
0
1
2
Survival in Years
Peters et al. J Am Coll Cardiol. 1995;26(5):1287-1292.
3
Cardiovascular Benefits of Cessation: Reduced
Risk of Acute Myocardial Infarction (MI)
P<.0001
Odds Ratio (95% CI)a
4
2
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.
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
300
AMI Counts per 100,000
Person-Years
257
P<.001
Preordinance
250
200
Postordinance
187
150
119
116
100
50
0
Pueblo City
El Paso County
Bartecchi et al. Circulation. 2006;114:1490-1496.
Cardiovascular Benefits of Cessation: Reduced Risk of
Recurrent Cardiac Arrest (3yrs of cession )
Occurrence at 3 Years (%)
•
The risk for recurrent cardiac arrest is lower among those who quit smoking than
among continuing smokers
P=.038
30
27
25
19
20
15
10
5
0
Current Smokers
Ex-smokersa
Recurrent Cardiac Arrest
aAbstention
period of 3 years.
Hallstrom et al. N Engl J Med. 1986;314:271-275.
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
Survival (%)
80
60
40
Quitters
Persistent Smokers
20
0
0
2
3
4
5
6
7
8
9
Years After Index Procedure
Hasdai. N Engl J Med. 1997;336(11):755-761.
10
11
12
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
Probability of Survival (%)
100
80
60
P<.0001 (Ex-smokers vs
Current Smokers)
Quitters
40
Nonsmokers
Persistent Smokers
20
0
0
5
10
Years
15
Adapted from van Domburg et al. J Am Coll Cardiol.
2000;36(3):878-883.
20
Cardiovascular Benefits of Cessation: Reduced
Progression of Peripheral Vascular Disease (Over 7 yrs
period)
Rest Pain, Cumulative (%)
30
Smoking
Abstention
20
P=.049
10
0
1
2
3
4
5
Years
Jonason et al. Acta Med Scand. 1987;221:253-260.
6
7
Cardiovascular Benefits of Cessation:
Reduced Risk of Stroke
Relative Risk (95% CI)a
4
P for trend <.0001
3
2.5
2.0
2
1.0
1.2
1
0
Nonsmokers
aThe
Ex-smokers
Current
Smokers
(<20 cig/d)
Current
Smokers
(≥20 cig/d)
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.
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; 240:189194; 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.
Cochrane Database of Systematic Reviews
Drug
Nortriptyline
Bupropion
Clonidine
Nicotine gum
Nicotine patch
Nicotine inhaler
Nicotine nasal spray
Nicotine
lozenge/tablet
Update
Number of
comparisons
7
21
6
52
42
4
4
5
Number of
abstinent
active arm
(%)
20.2
20.1
24.9
19.5
14.6
17.1
23.9
16.4
Number of
abstinent
control arm (%)
8.9
10.7
14.4
11.5
8.6
9.1
11.1
8.8
35
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.
• 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
Varenicline vs. nicotine patch
Open label randomized controlled trial
(5 countries, n= 746)
Varenicline
NRT
60
50
40
56
43
30
20
26
20
10
0
Weeks 9-12
Weeks 9-52
End of treatment
Continuous abstinence
OR 1.70 (1.26-2.28)
OR 1.40 (0.99-1.99)
37
Aubin HJ. Thorax 2008
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
38
Tobacco
Dependence
Thank you
Victory
5/8/2017
Varenicline
39