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

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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.

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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.

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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