tools in the battle against smoking and tobacco heart institute, hadassah hospital, jerusalem,...
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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
b er
o f b
a rm
e n w
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
nti
nu
ou
s A
bst
inen
ceR
ate
(%)
P = 0.001
Prevention of smoking
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