Tools in the Battle Against Smoking and

Tobacco

Tools in the Battle Against Smoking and

Tobacco

Heart Institute, Hadassah Hospital, Heart Institute, Hadassah Hospital, Jerusalem, ISRAELJerusalem, ISRAEL

Chaim Lotan, MDChaim Lotan, MD

3-C CON, AHMEDABAD, FEBRUARY 2011

Smoking and coronary artery disease

History

Epidemiology

CV Effects

Importance of Cessation

Cigarette Smoking as a Risk Factor for Cardiovascular Disease

was recognized in the results of the Framingham Heart Study

in 1960

Smoking kills more people each year than

alcohol

cocaine

crack

heroin

homicide

suicide

car accidents

fires

AIDS

C O M B I N ED!!!

Smoking and coronary artery disease

History

Epidemiology

CV Effects

Importance of Cessation

WHO World Health Report .Tobacco Atlas .2008.

Global Cigarette Consumption

Section 2: The Hazards of Smoking

1.25 billion smokers Worldwide

30 million smokers added every year

84% of smokers live in developing countries• Africa & Middle East (17% of World’s population)

accounts for 7% of World’s total cigarette consumption

8 smokers die every minute

Facts & Numbers

Voute J, World Heart Foundation

Gender-specific Smoking Prevalence Across the World

1. Mackay J, Eriksen M. The Tobacco Atlas. Second Ed. American Cancer Society, 2006.

1.25 billion smokers worldwide1

USUS24%24%19%19%

AustraliaAustralia19%19%16%16%

BelarusBelarus53%53%7%7%

BrazilBrazil22%22%14%14%

CanadaCanada22%22%17%17%

ChileChile48%48%37%37%

ChinaChina67%67%2%2%EgyptEgypt

45%45%

12%12%

FranceFrance30%30%21%21%

IcelandIceland25%25%20%20%

MexicoMexico13%13%5%5%

IranIran22% 22% 2%2%

KenyaKenya21%21%1%1%

SwedenSweden17%17%18%18%

PhilippinesPhilippines41%41%8%8%

PortugalPortugal33%33%10%10%

South AfricaSouth Africa23%23%8%8%

IndiaIndia47%47%17%17%

Russian FederationRussian Federation60%60%16%16%

ItalyItaly33%33%17%17%

SpainSpain39%39%25%25%

GermanyGermany37%37%28%28%

MenMenWomenWomen

4 year-old addict to smoking in Indonesia

Smoking and coronary artery disease

History

Epidemiology

CV Effects

Importance of Cessation

Smoking: Leading Preventable Cause of Disease and Death1

CancerLung (#1) Leukemia (AML, ALL, CLL)2-4

Oral cavity/pharynx LaryngealEsophageal StomachPancreatic KidneyBladder Cervical

CardiovascularIschemic heart disease (#2)Stroke – vascular dementia5 Peripheral vascular disease6

Abdominal aortic aneurysm

RespiratoryCOPD (#3)PneumoniaPoor asthma control

ReproductiveLow-birth weightPregnancy complicationsReduced fertilitySIDS

OtherAdverse surgical

outcomes/wound healingHip fracturesLow-bone densityCataractPeptic ulcer disease in

Helicobacter pylori-positive patients

AML = acute myeloid leukemia; ALL = acute lymphocytic leukemia; CLL = chronic lymphocytic leukemia; COPD = chronic obstructive pulmonary disease; SIDS = sudden infant death syndrome.

• Surgeon General’s Report. The Health Consequences of Smoking; 2004. • Sandler DP, et al. J Natl Cancer Inst. 1993;85:1994-2003. • Crane MM, et al. Cancer Epidemiol Biomarkers Prev. 1996;5:639-644. • Miligi L, et al. Am J Ind Med. 1999;36:60-69. • Roman GC. Cerebrovasc Dis. 2005;20:91-100. • Willigendael EM, et al. J Vasc Surg. 2004;40:1158-1165.

INTERHEART: Smoking and MI

2

4

8

16

OR

(9

9%

CI)

0 1-5 6-10 11-15 16-20 21-25 26-30 31-40 >40 #cigarettes smoked per day

Odds of myocardial infarction

Causes Related to Smoking

WH

O t

op

ten

cau

ses

of

dea

th3

1 in 10 adult deaths are smoking-related2

500,000,000 people alive today will die from smoking-related causes2

1. Surgeon General’s Report, 2004. 2. World Bank, 1999. 3. World Health Organization, 2003.

Smoking Is Related To 5 of the Top 10 Leading Causes of Death Worldwide1

Plateletfunction

Coagulation(PAI-1)

Inflammation(hs-CRP, cytokine,chemokine)

Smoothmuscle cells

LDL-C

HDL-CTG

Viscosity

Endothelialfunction

Collagen

Macrophages

MMPs

How does smoking induce ACS ?

0.94-2.36

1.49

2.58-7.36

4.45

2.64-9.19

5.27

2.72-15.11

6.51

0

1

2

3

4

5

6

7

OD

DS

RA

TIO

<10/day 10-19/day 20-29/day >30/day

Number of Cigarettes / Beedies

Odds Ratio for AMI

Pais P, Fay MP, Yusuf S

Indian Heart J 2001; 53:731-5

N=300 AMI, 300 Controls

Role of AMI due to tobacco in India

Intl J Epidemiol 2005;43(6):1395-1402

Tobacco associated mortality in Mumbai (Bombay) India. Results of the Bombay Cohort StudyGupta PC, Pednekar MS, Parkin DM, Sankaranarayanan R

Background Little is known about the excess mortality from forms of tobacco use other than cigarette smoking that are widely prevalent in India, such as bidi smoking and the various forms of smokeless tobacco use. We report on absolute and relative risks of mortality among various kinds of ever tobacco users vs never-users in the city of Mumbai, India. (n=99570)

Results The adjusted relative risk was 1.37 (95% CI 1.23–1.53) for (men) cigarette smokers and 1.64 (95% CI 1.47–1.81) for bidi smokers, with a significant dose–response relationship for number of bidis or cigarettes smoked. Women were essentially smokeless tobacco users; the adjusted relative risk was 1.25 (95% CI 1.15–1.35).

Conclusions Bidi is no less hazardous than cigarette smoking, and smokeless tobacco use may also result in significantly increased mortality.

Tobacco consumption is a major source of mortality and morbidity in India.

Studies have shown contradictory results regarding smokeless tobacco use as a cardiovascular risk factor, but many show conclusive connection.

2003 Study of adults males in a rural village in Haryana, northern India (chosen randomly)

With smoke-free laws, smokeless tobacco (ST) products are being marketed as smoking substitutes: snuff, chewing tobacco, spitless pouched moist snuff, compressed tobacco lozenges.

A recent US study found no reduction in smoking rates among people using ST as replacement, although a previous (2006) Swedish study showed an overall country reduction in smoking with increased overall ST consumption.

smokeless tobacco smokeless tobacco

Chemical Composition of ST Products

Similar to cigarettes, nicotine is the principal alkaloid

Amount of total and free nicotine varies substantially - generally, concentration similar in oral snuff and cigarette tobacco, somewhat lower in chewing tobacco

Minor alkaloids: nornicotine, anatabine, anabasine

Carcinogens: Combustion-derived Benzo[a]pyrene and other polycyclics lower than in cigarette smoking

Carcinogens: Nitrosamines - highest known nonoccupational exposure

Nitrite, nitrate, formate, chloride, sulfate, phosphate

Impact of Smokeless Tobacco Products on Cardiovascular Disease: Implications for Policy, Prevention and Treatment: A Policy Statement

From The American Heart Association

Long-term use of smokeless tobacco products increases the odds of fatal heart attack or fatal stroke (according to analysis of several studies).

The AHA advises against smokeless tobacco products for smoking cessation - they are not a “safe” alternative to smoking, and carry the risk of addiction and return to smoking.

2010

The Effects of Second-Hand Smoke

 Short-term effects of second-hand smoke:Short-term effects of second-hand smoke: Coughing Headache Eye irritation Sore throat Sneezing and runny nose Feeling sick Breathing problems (and possibly an asthma attackasthma attack) Irregular heartbeat (a particular problem for people with heart diseaseIrregular heartbeat (a particular problem for people with heart disease))

Long-term effects of second-hand smoke:Long-term effects of second-hand smoke: Worsening of chest problems and allergies like asthma, hay fever, asthma, hay fever, bronchitis and emphysema bronchitis and emphysema Increased risk of heart diseaseIncreased risk of heart disease Increased risk of lung cancerlung cancer Pregnant women exposed to second hand smoke can pass on the harmful gases and

chemicals onto their babies.

The health consequences of smoking and second hand smoke evolve over a lifetime.

Pregnancy Infant health

AdolescenceAdulthood

Child Health and

Smoking

Fetal growthBirth weight

AbortionsPremature Birth

Fetal DeathSIDS

Physical GrowthBehavior and cognitive

developmentRespiratory infectionsMore hospitalization

Small airway dysfunction

CoughWheezing

Phlegm productionother respiratory

symptoms

Chronic bronchitisEmphysema

Lung cancer by 20%–30%Coronary heart disease

StrokeCOPD

1. News release, June 27, 2006; US Department of Health & Human Services. Available at: http://www.hhs.gov/news/press/2006pres/20060627.html.

2. Mackay J, et al. The Tobacco Atlas. World Health Organization, 2006. 3. Teo KK, et al. Lancet. 2006;368:647-658. 4. Fagerström K. Drugs. 2002;62:1-9. 5. Blizzard L, et al. Arch Pediatr Adolesc Med. 2004;158:687-693. 6. Leung GM, et al. Arch Pediatr Adolesc Med. 2004;158:687-693.

Passive Smoking and CV Disability

Have a clear relationship to CV disability & mortalityCV disability & mortality

~~ 37,000 to 40,000 people die from cardiovascular 37,000 to 40,000 people die from cardiovascular diseasedisease caused by other people’s smoke every caused by other people’s smoke every

yearyear. Of these, 35,000 non-smokers die from 35,000 non-smokers die from coronary heart disease.coronary heart disease.

American Heart Association 2007American Heart Association 2007

Smoking and coronary artery disease

History

Epidemiology

CV Effects

Importance of Cessation

Why Quit? Potential Health Benefits of Quitting Smoking

Ce

ss

ati

on

3 m

on

ths

Lung function may start to improve with decreased cough, sinus

congestion, fatigue, and shortness of breath

Cardiovascular Heart Disease (CHD): excess risk is reduced by 50% among ex-smokers

1 ye

ar

Stroke risk returns to the level of people who have never smoked at 5–15 years post-cessation

5 ye

ars

Lung cancer risk is 30%–50% that of continuing smokers

10 y

ears

CHD risk is similar to never smokers

15 y

ears

1. USDHHS. The Health Benefits of Smoking Cessation: A Report of the Surgeon General, 1990. Available at: http://profiles.nlm.nih.gov/NN/B/B/C/T/.

2. American Cancer Society. Guide to Quitting Smoking. Available at: http://www.cancer.org.

0

10

20

30

40

50

60

70

80

90

100

40 50 60 70 80 90 100

Quitting at Any Age May Increase Life Expectancy

Age Stopped Smoking: 45–54 Years Old

Age (Years)

Results From a Study of Male Physician Smokers in the UK

Age Stopped: 45–54

Nonsmokers

Cigarette Smokers

Per

cen

tag

e S

urv

ival

fr

om

Ag

e 5

0

Even quitting smoking later in life can lead to longer life expectancy

1. Doll R, et al. BMJ. 2004;328:1519-1527.

Smoking bans in public places and workplaces are significantly associated with a reduction in AMI incidence, particularly if enforced over several years.

Countries Banning Smoking in Public Places

Albania 2007

Andorra (partial)

Argentina-Buenos Aires 2006

Armenia (partial)

Australia 2007-10

Austria (partial)

Bahrain 2008

Bosnia-Herzegv.2007

Brazil 2009

Bulgaria (partial)

Canada

Chile (partial)

China (partial)

Colombia 2009

Croatia 2008-9

Cyprus 2009

Czech Rep.(partial)

Denmark 2007

Estonia (partial)

Finland 2007

France 2008

Germany (contested)

Greece 1010

Guatemala

Hong Kong 2007

Hungary (partial)

Iceland

India (partial)

Indonesia (partial)

Ireland 2004

Israel

Kazakhstan 2003-9

Kenya 2007

Latvia 2010

Lithuania (partial)

Luxemburg (partial)

Macedonia 2010

Malta

Malaysia

Mexico 2008

Monaco (partial)

Montenegro

Morocco

Mozambique 2007

Namibia 2010

Netherlands

New Zealand 2004

Nigeria

Norway 2004

Paraguay

Peru

Philippines (partial)

Poland (partial)

Portugal 2007

Puerto Rico

Singapore

Serbia

Slovenia

South Africa 2001

Spain 2006-10

Sweden (partial)

Syria 2009

Thailand 2008 and more!Source: Wikipedia

Beneficial Effects of Smoking Ban for Employees

Eisner M et coll., JAMA 1998, 280, 1909-1914Eisner M et coll., JAMA 1998, 280, 1909-1914

Num

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i th s

y mpt

oms

Source:Source:

10

20

30

40

Before ban After Ban0

Symptoms among 67 barmen beforeand after ban

dyspneamorning coughcough sputumeye irritationnose irritationthroat irritation

Smoking and coronary artery disease

History

Epidemiology

CV Effects

Importance of Cessation

Nicotine addiction

Nicotine Addictive or Just a Bad Habit??????

Mechanism of Action of Nicotine in the Central Nervous System

Nicotine binds preferentially to nAChRs in the central nervous system; one key area is the α4β2 nicotinic receptor in the VTA

After nicotine binds to the α4β2 nAChR in the VTA, dopamine is released in the nAcc which is believed to be linked to reward

4 2224

42nicotinic

acetylcholine receptor (nAChR)

The Cycle of Nicotine Addiction

Nicotine binding causes an increase in release of dopamine1,2

Dopamine gives feelings of pleasure and calmness1

competitive binding of nicotine to nicotinic acetylcholine receptors

causes prolonged activation, desensitization, and upregulation2

1. Jarvis MJ. BMJ. 2004; 328:277-279.2. Picciotto MR, et al. Nicotine and Tob Res. 1999:Suppl 2:S121-S125.

DopamineDopamine

NicotineNicotine

Withdrawal Syndrome: A Combination of Physical and Psychological Conditions,

Making Smoking Hard to Treat

Restlessness or impatience

Increased appetite or weight gain

Anxiety(may increase or

decrease with quitting)

Dysphoric or depressed mood

Irritability, frustration,

or anger

Difficulty concentrating

Insomnia/sleep disturbance

1. DSM-IV-TR. APA; 2006: Available at: http://psychiatryonline.com

Decreased heart rate

The greatest risk of relapse is during the first three months after quitting.

37% have their first lapse between 8:00pm and midnight

50% are likely to relapse in the first month

67% are likely to relapse in the first three months

DSM-IV-TR. APA; 2006: Available at: http://psychiatryonline.com

“Nine out of ten ex-smokers who have a cigarette after quitting later return to smoking”

(Brandon, 1990)

Many Health Organizations Emphasise the Important Role Physicians Can Play in Helping Their Patients Quit Smoking

1. World Health Organization. Mayo report on addressing the worldwide tobacco epidemic through effective, evidence-based treatment. Report of an expert meeting, March 1999, Rochester (Minnesota) USA. Available at: http://www.who.int/tobacco/resources/publications/mayo/en/print.html. Accessed July 2006.

2. American Cancer Society. Tobacco control strategy planning, companion guide #2: Engaging doctors in tobacco control. Available at: http://strategyguides.globalink.org/doctors.htm.

3. The American Academy of Family Physicians. Tobacco use, prevention and cessation. Available at: http://www.aafp.org/online/en/home/policy/policies/t/tobacco.printerview.html.

4. National Institute for Health and Clinical Excellence. Brief interventions and referral for smoking cessation in primary care and other settings. Available at: www.nice.org.uk/page.aspx?o=299611.

World Health Organization1

Health Professionals Against Smoking2

The American Academy of Family Physicians3

American Medical Association2

National Institute for Health and Clinical Excellence4

ASK about tobacco USE

ADVISE tobacco users to QUIT

ASSESS READINESS to make a quit attempt

ASSIST with the QUIT ATTEMPT

ARRANGE FOLLOW-UP care

US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update

Tobacco Dependence Support – The “5 A’s”

US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update

First-line Pharmacotherapies for Tobacco Dependence1

Nicotine replacement therapy (NRT)Patch Gum Inhaler Nasal spray Sublingual tablets/lozenges

Bupropion SR

Champix (Varenicline)

1. Fiore MC, et al. Clinical Practice Guideline. Treating Tobacco Use and Dependence: 2008 Update. USDHHS. PHS. Rockville, MD. 2008.

All decrease cravings, withdrawal

20-25% quit rates at 1 year

21

(varenicline) A Selective 42 Nicotinic

Acetylcholine Receptor Partial Agonist

Binding of nicotine at the 42 nicotinic

receptor in the Ventral Tegmental Area

(VTA) is believed to cause large amounts of

dopamine to be released at the Nucleus

Accumbens (nAcc)

Champix (varenicline): A Highly Selective 42 Receptor Partial Agonist

Nicotine

1. Coe JW et al. Presented at the 11th Annual Meeting and 7th European Conference of the Society for Research on Nicotine and Tobacco. 2005. Prague, Czech Republic. 2. Picciotto MR et al. Nicotine Tob Res. 1999; Suppl 2:S121-125.

Varenicline

Binding of nicotine at the 42 nicotinic receptor in the Ventral Tegmental Area (VTA) is believed to cause release of dopamine at the Nucleus Accumbens (nAcc)

Varenicline is an 42 nicotinic receptor partial agonist, a compound with dual agonist and antagonist activities. This is believed to result in both a lesser amount of dopamine release from the VTA at the nAcc as well as the prevention of nicotine binding at the 42 receptors

Champix (varenicline) Efficacy Measurements:

CO-Confirmed 4-Wk Continuous Abstinence Rates Wks 9–12

Gonzales et al. Jorenby et al.

Varenicline Bupropion SR Placebo

100

44.0 43.9

29.829.5

17.617.7

0

20

40

60

n=352 n=329 n=344 n=344 n=342 n=341

1. Gonzalez D et al. JAMA. 2006;296:47-55. 2. Jorenby DE et al. JAMA. 2006;296:56-63.

The 9-12 week Continuous Abstinence Rate is defined as the percentage of subjects who abstained from smoking (not even a puff) from Week 9 through 12 of the study as confirmed by both subject self-report and by end-expiratory carbon monoxide (CO) measurement

P < 0.001

P < 0.001

P < 0.001

P < 0.001

P < 0.001

Co

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ou

s A

bst

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(%)

P = 0.001

Prevention of smoking

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