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BENEFITS OF TOBACCO CESSATION ON CARDIOVASCULAR HEALTH
PROF. G.C. ONYEMELUKWE PROF. G.C. ONYEMELUKWE MONMEMBER, SMOKING CESSATION ADVISORY BOARD MEMBER, SMOKING CESSATION ADVISORY BOARD
1
DEPARTMENT OF MEDICINE,AHMADU BELLO UNIVERSITY TEACHING
HOSPITAL, ZARIA
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 2
USE OF TOBACCO - NCD EXPERT COMMITTEE LAGOS SURVEY 2003 SMOKING STATUS-- ONYEMELUKWE et al
Characteristic Ever Smoked Never Smoked TotalSex Male 115 (26.4%) 320 (73.6%) 435 (100%)Female 8 (1.8%) 428 (98.2%) 436 (100%) Total 123 (14.1%) 748 (85.9%) 871 (100%)ResidenceUrban 68 (16.1%) 355 (83.9%) 423 (100%)Rural 45 (10.9%) 368 (89.1%) 413 (100%)Age Group15-24 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%)
• 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
6
Pathophysiology of nicotine on CVSPathophysiology of nicotine on CVS
MRI of BrainWith an Acute Ischemic Stroke
Build-up of atherosclerotic plaque in arterial wall
8
Prefrontalcortex
VentraltegmentalareaNucleus
Accumbens
Hippocampus
Simplified diagram of the brain showing theanatomic locations of the ventral tegmental area and the nucleus accumbens
Surface ofdopamineneuron
β2
β2
α4β2
α4
Simplified structure of α4 β2 nicotinic receptorlocated on surface of a dopamine cell body
nAChRs Stimulated by Nicotine & Acetylcholine
(reward centre)
VARENICLINE BLOCKS NICOTINE RECEPTORS AND PARTIALLY STIMULATES MODERATE DOPAMINE RELEASE
9
Varenicline ( )blocks nicotinereceptors
Partial agonisteffects stimulatemoderate dopaminerelease
Cell body of dopamineneuron in ventraltegmental area
Nicotinereceptors
A C B
Nicotine
Rapid/burst firing
Dopamine ( ) releasefrom dopamine terminalin 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
PHARMACOTHERAPYEXOGENOUS NICOTINE BUPROPION VARENICLINE
NICOTINE REPLACEMENT NORTRYPTILINE*
NICOTINE PATCH CLONIDINE*
NICOTINE GUM CYSTISINE (Plant alkaloid)
NICOTINE INHALER
NICOTINE LOZENGES
NICOTINE NASAL SPRAY *Rimonabant(EndocannabinoidType 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. ASK patients about smoking at every visit.2. ADVISE all tobacco users to quit.3. ASSESS patients willingness to try to quit.4. 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. PREPARATION4. ACTION5. MAINTENANCE6. 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
ASR=absolute rate of fibrinogen synthesis. aAbstention period of 2 weeks. Hunter et al. Clin Sci (Lond). 2001;100(4):459-465.
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
0
5
10
15
20
25
30
Fibr
inog
en A
SR m
g/kg
Fibr
inog
en A
SR m
g/kg
Plas
ma
Fibr
inog
enPl
asm
a Fi
brin
ogen
Conc
entr
ation
(g/L
)Co
ncen
trati
on (g
/L)
P<.001 P<.001
SmokingSmoking AbstentionAbstentionaa SmokingSmoking AbstentionAbstentionaa
16.1
24.12.49
3.06
6.1
7.0
0
1
2
3
4
5
6
7
8
Cardiovascular Benefits of Cessation: White Blood Cells (After 17 weeks)
aAbstention period of 17 weeks.Eliasson et al. Nicotine Tob Res. 2001;3(3):249-
255.
AbstentionaSmoking
Whi
te B
lood
Cel
ls (×
109 /
l)
P<.026
0.420.33
0.0
0.2
0.4
0.6
0.8
1.0
1.321.16
0.0
0.5
1.0
1.5
2.0
2.5
3.0
Cardiovascular Benefits of Cessation: Improved Lipid Profile(After 17 weeks)
HDL=high-density lipoprotein; LDL=low-density lipoprotein. aAbstention period of 17 weeks. Eliasson et al. Nicotine Tob Res. 2001;3(3):249-255.
P<.001
HD
L (m
mol
/L) 3.52
3.78
0.0
1.0
2.0
3.0
4.0
5.0
LD
L (m
mol
/L)
Smoking Abstentiona
Smoking Abstentiona
HD
L/LD
L Ra
tio
P<.015
P<.001
Smoking Abstentiona
7276
0
20
40
60
80
100
120
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):564-568.
8790
0
20
40
60
80
100
120
Hea
rt R
ate
(Bea
ts/m
in)
P<.05
Mea
n Ar
teria
l Pre
ssur
e (m
m H
g)
Smoking
P<.05
SmokingAbstentiona Abstentiona
0
10
20
30
40
50
60
70
80
90
Augm
enta
tion
Inde
x (%
)b
Cardiovascular Benefits of Cessation: Hemodynamic Profile (cont’d) (After 6 Months)
• Smoking cessation is associated with an improvement in arterial compliance
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.
6.3
5.1
0
2
4
6
8
10
Osc
illat
ory
Com
plia
nce
(mL/
mm
Hg
× 10
0)a
P<.01
P<.05
Smoking Abstentionc Smoking Abstentionc
63.1
50.6
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
aPGE=prostaglandin E1; bMPV=mean platelet volume; ccAMP= cyclic adenosine monophosphate. Terres et al. Am J Med. 1994;97:242-249.
0 1 2 1 4 8 9 1 4 8 9 12Weeks
4
8
10
12
6
cAM
P A
fter P
GE
(nm
ol/L
) (95
% C
I)a
P=.02
MPV
(fL)
(95%
CI)b
Weeks
P<.001
8.2
8.4
8.6
9.0
8.8
0 1 2 1 4 8 9 1 4 8 9 12
NicotineChewing
Gum
Smoking Nonsmoking/Nonchewing
Smoking NicotineChewing
Gum
Nonsmoking/Nonchewing
Cardiovascular Benefits of Cessation: Platelet Effects (cont’d)
• Smoking abstinence is associated with reduced platelet aggregability
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.
ADP=5.0 µmol/L
Group Aa Group Bb
Plat
elet
Agg
rega
tion
(%)
0
20
60
100
40
80
Time (Days)0 7 14 21 28
NS
P<.01
NS
NS
P<.01
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
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 theMONICA 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
Peters et al. J Am Coll Cardiol. 1995;26(5):1287-1292.
P=.040
Survival in Years
Surv
ival
(%)
0
20
40
60
80
100
0 2 31
Ex-smokers
Smokers
Cardiovascular Benefits of Cessation: Reduced Risk of Acute Myocardial Infarction (MI)
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.
PP<.0001<.0001
CurrentCurrent >1-3>1-3 >5-10>5-10 >10-15>10-15 2020
Ex-smokers (Years Since Cessation)Ex-smokers (Years Since Cessation)
>3-5>3-5 >15-20>15-20
Odd
s Ra
tio (9
5% C
I)O
dds
Ratio
(95%
CI)aa
44
22
11
Cardiovascular Benefits of Citywide Smoke-Free Ordinance: Reduced Incidence of Acute MI
Bartecchi et al. Circulation. 2006;114:1490-1496.
27% reduction in the incidence of acute myocardial infarction (MI) after 27% reduction in the incidence of acute myocardial infarction (MI) after implementation of a smoke-free ordinance in Pueblo City, Coloradoimplementation of a smoke-free ordinance in Pueblo City, Colorado
AMI C
ount
s pe
r 100
,000
Pers
on-Y
ears
257
119
187
116
0
50
100
150
200
250
300
Pueblo City El Paso County
Preordinance Postordinance
P<.001
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
aAbstention period of 3 years. Hallstrom et al. N Engl J Med. 1986;314:271-275.
27
19
0
5
10
15
20
25
30
Current Smokers Ex-smokersa
Occ
urre
nce
at 3
Yea
rs (%
)
P=.038
Recurrent Cardiac Arrest
Cardiovascular Benefits of Cessation: Reduced Mortality After Percutaneous Coronary Revascularization
• Current smokers had a significantly greater risk of overall mortality after percutaneous coronary revascularization
Surv
ival
(%)
100
80
60
40
20
00 2 3 4 5 6 7 8 9 10 11 12
Years After Index Procedure
Hasdai. N Engl J Med. 1997;336(11):755-761.
Quitters
Persistent Smokers
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):878-883.
Prob
abili
ty o
f Sur
viva
l (%
)
0 5 10 15 20Years
PP<.0001 (Ex-smokers vs <.0001 (Ex-smokers vs Current Smokers)Current Smokers)
NonsmokersPersistent Smokers
100
80
60
40
20
0
Quitters
Cardiovascular Benefits of Cessation: Reduced Progression of Peripheral Vascular Disease (Over 7 yrs
period)
Jonason et al. Acta Med Scand. 1987;221:253-260.
Years
Rest
Pai
n, C
umul
ative
(%)
30
20
10
0
P=.049
2 71 6543
Abstention
Smoking
Cardiovascular Benefits of Cessation: Reduced Risk of Stroke
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.
1.0
2.5
2.0
1.2
0
1
2
3
4
Nonsmokers Ex-smokers CurrentSmokers
(<20 cig/d)
CurrentSmokers
(≥20 cig/d)
Rela
tive
Risk
(95%
CI)a
P for trend <.0001
Cardiovascular Benefits of Smoking CessationShort-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.
Cochrane Database of Systematic ReviewsDrug Update
Number of comparisons
Number of abstinent active arm (%)
Number of abstinent control arm (%)
Nortriptyline 7 20.2 8.9Bupropion 21 20.1 10.7Clonidine 6 24.9 14.4Nicotine gum 52 19.5 11.5Nicotine patch 42 14.6 8.6Nicotine inhaler 4 17.1 9.1Nicotine nasal spray
4 23.9 11.1
Nicotine lozenge/tablet
5 16.4 8.8
35
Varenicline vs Bupropion1.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 patchOpen label randomized controlled trial
(5 countries, n= 746)
0
10
20
30
40
50
60
Weeks 9-12 Weeks 9-52
Varenicline NRT
37Aubin HJ. Thorax 2008
End of treatmentOR 1.70 (1.26-2.28)
Continuous abstinenceOR 1.40 (0.99-1.99)
2620
56
43
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
04/10/23 39
Thank you
Tobacco Dependence
Varenicline
Victory