Cardiovascular morbidity and mortality as a result of tobacco products continues to be a global healthcare crisis, particularly in low- and middle-income nations. tobacco products continue to evolve faster than the scientific understanding of their biological effects posing fresh challenges. When tobacco is burned, a complex chemical mixture of more than 7,000 compounds is produced, many of which are causally associated with premature deaths and diseases affecting nearly every organ system in the body. Even brief exposure to parental and peers smoke sets in permanent adverse biological changes in children. None of the tobacco products is safe and there is no minimum threshold below which tobacco is safe.

1. Smoker’s Heart
Dr. S K Agarwal
MBBS, MD, DM, FACC, CBCCT
Consultant Interventional Cardiologist
@skacardio

2. Statistics
• 6.3 million deaths annually from cigarette
smoke exposure and SHS
• One-third of deaths are secondary to CVD and
11.1% of these deaths occur in people
exposed to SHS.
• Nearly one-third of nonsmokers in the US are
passively exposed to cigarette smoke
• SHS has a strong causal relationship with a
25% to 30% increase in CHD

3. “There is no safe level of exposure to
tobacco smoke”

4. CHD Risk by Cigarette Smoking. Filter Vs. Non-filter.
Framingham Study. Men <55 Yrs.
0
50
100
150
200
250
Total CHD Myocardial
Infarction
Non-Smoker
Reg. Cig. Smoker
Filter Cig. Smoker
14-yr. Rate/1000
119
206 210
59
112
210

5. Pathogenic Effects of Tobacco: Setting the Stage for
Atherosclerotic Plaque Formation
Morris, P.B. et al. J Am Coll Cardiol. 2015

6. Clinical effects of CSE & SHS
• Several-fold higher risk of developing CHD and MI
• Major risk factor for acute coronary thrombosis.
• Risk of re-infarction
• Risk of developing heart failure by as much as
33% to 93% 1-2and risk of multiple hospital
admissions3
• Risk of stent thrombosis/graft occlusion
• Increased length of hospital stay after CABG
• Risk of PAD, AAA
• Risk of stroke
1-Am H J 2012, 164,236
2-Arch Intern Med 2001, 161,996
3-Am J Cardiol 2000,86,1339
CSE-cig smoke exposure, SHS-second hand smoke

7. Tobacco use and risk of MI in 52 countries in
INTERHEART study
Risk of AMI associated with numbers smoked, by age group Lancet 2006; 368: 647–58

8. INTERHEART study
Risk of AMI associated with type of tobacco used
Koon K Teo Lancet 2006; 368

9. Risk of AMI with increasing numbers of
cigarettes smoked
Koon K Teo Lancet 2006; 368

10. Diminishing risk of AMI associated
with quitting
Koon K Teo Lancet 2006; 368

11. Mechanistic role
• lipid oxidation
• Inflammation
• thrombosis, with
• Oxidative stress
gains in life expectancy by age of quitting
• quit by age 30 years avoided most of the added risk,
• Quit at age 50 years halved the additional hazard
• quitting at age 60 years conferred significant survival
advantage.

12. Associations between baseline Smoking status at
visit 1 and incident Diabetes Mellitus at visit 3
15%
19.70%
16.60%
14.10%
21.90%
0%
5%
10%
15%
20%
25%
Never Smokers Past Smokers Current
Smokers
1-19 cig/day ≥20 cig/day
HOMA-B was lower in current smokers compared with never smokers and with increasing
smoking dose (pack-years), suggesting reduced beta cell function is the likely factor.
The Jackson Heart Study
Incident rate ratios of DM
Vs. Never smokers 1.08 1.28 1.04 1.79
J Am Heart Assoc. 2018

13. Smoking status and long-term survival
after first Acute MI
Among persistent smokers, upon multivariable adjustment including pre-
AMI intensity, each reduction of 5 cigarettes smoked daily after AMI was
associated with an 18% decline in mortality risk (p < 0.001)
J Am Coll Cardiol 2009
Lifetime nonsmoking and quitting before or after initial AMI confer survival benefits

14. Smoking: strongest independent long-
term predictor for recurrent MACE
Am Heart J 2015;169

15. Effect of smoking on CHD in women
compared with men
After allowing for classic cardiovascular risk
factors, women had a significant 25% increased
risk for coronary heart disease conferred by
cigarette smoking compared with men.
The RRR increased by 2% for every additional year of study
follow-up (p=0·03).
women might extract a greater quantity of
carcinogens and other toxic agents from the same
number of cigarettes than men
Lancet 2011; 378

16. smoking increases cardiac overload
Am J Cardiol 2010;106

17. Cumulative HF incidence by smoking status at
inception in Health ABC Study
--- Current smokers
…. Former smokers
- - - Nonsmokers
0 2 4 6 8
Follow up (years)
CumulativeHFincidence
0.25
0.20
0.15
0.10
0.05
0.00
Am Heart J 2012;164
[HR] vs. nonsmokers 1.33
[HR] vs. nonsmokers 1.93

18. Cumulative HF incidence over time according to pack
years of smoking exposure among past smokers
HR 1.05
HR 1.23
HR 1.64

19. SMOKING AND OUTCOMES IN OLDER
PATIENTS WITH HFPEF
All-cause mortality occurred in 69% and 60% of smokers and non-
smokers, respectively during 6 (median 3) years of follow-up (HR, 1.21)
JACC March 20, 2018

20. Clinical outcomes according to smoking status in the overall
SYNTAX trial population
Smokers had worse clinical outcomes due to a higher
incidence of recurrent MI in both revascularization arms
(J Am Coll Cardiol 2015;65:1107–15)

21. Clinical outcomes according to smoking status in the
overall SYNTAX trial population and PCI or CABG

22. Smoking and Arrhythmias
Smoking
(Nicotine)
↑epinephrine and
norepinephrine release
↑sympathetic tone
Proarrhythmic effect
Atrial and Ventricular
arrhythmias
↓Parasympathetic tone
↓
↓Heart Rate Variability

23. Smoking and atrial Arrhythmias
• Inflammation, endothelial dysfunction, atrial
fibrosis
• Risk is proportional to the quantity and
duration of smoking
• Rotterdam study1: incidence of AF in current
and previous smokers was 51% and 49%
higher than in nonsmokers
• Atherosclerosis Risk in Communities study2:
smoking doubled the incidence of AF
1-Am Heart J 2008;156
2-Heart Rhythm 2011;8

24. Smoking and ventricular Arrhythmias
MADIT-II (Multicenter Automatic Defibrillator Implantation Trial II)1
• 2-fold increased risk of appropriate ICD shocks caused by fast VT(rate >180
beats/min) and VF
• Incidence of inappropriate shocks was 20% in current smokers, 14% in ex-
smokers, and 11% for never-smoker
Bezafibrate Infarction Prevention trial2 and Nurses’ Health Study3
• Increased risk of sudden cardiac death. Hazard ratio: 2.47in smokers in BIP
• Risk increased linearly with the quantity and the duration of smoking
• SC reduced this risk over time in a linear fashion.
1-J am coll cardiol 2008;51
2-Arch Intern Med 2003;163
3-Circ arrhythm electro 2012;5

25. Smokeless tobacco products
• Snuff: moist snuff, dry snuff or snus (Sweden)
• Chewing tobacco: loose leaf, plug, and twist formulations
• Toothpaste
• Iq’mik: fire-cured tobacco leaves mixed with punk ash (ash generated
by burning woody fungus off of the bark of birch trees).
“pleasure for whenever”
Spit tobacco products
Spitless ST products: pouched moist snuff, compressed tobacco lozenges
(Ariva and Stonewall), tobacco pellets (Camel Orbs like candy Tic-Tac),
Camel Sticks (resembling a toothpick) and Camel Strips

26. Global ST Products
• Americas
North America Chewing tobacco (spit tobacco): Loose leaf, Plug, Twist (ie, Red Man, Beechnut, Levi Garrett); Iq’mik (predominantly in
Alaska; tobacco and punk ash)
1. Snuff (spit tobacco): Moist (ie, Copenhagen, Bandit, Kodak; loose particles or sachets); Dry (ie, Al Capone, Wawith, Tube Rose)
2. Oral Compressed: Ariva and Stonewall (compressed tobacco lozenges)
3. Snus (ie, Exalt, Revel, Marlboro, Camel)
South America Chimo (predominantly in Venezuela; tobacco with sodium bicarbonate, brown sugar, and vanilla)
• Europe
Sweden Snus (finely ground moist tobacco)
United Kingdom Gutkha (betal quid with tobacco, betel nut, and slaked lime); Snuff (dry)
• Asia
Central Asia Gul (tobacco powder and molasses); Nass or Naswar, Niswar (tobacco, ash, lime and cotton or sesame oil); Pan Masala or
Betel quid (betel leaf with or without tobacco, areca nuts, and slaked lime); Zarda (tobacco, slaked lime, spices, and areca nut)
East/Southeast Asia Gutkha (betal quid with tobacco, betel nut, and lime); Pan Masala or Betel quid (betal leaf with or without tobacco,
areca nuts, and slaked lime)
South Asia: Snuff (creamy); Gul (tobacco powder and molasses); Gutkha (betal quid with tobacco, betel nut, and lime); Khaini
(tobacco, slaked lime, and areca nut); Mawa (tobacco, slaked lime, and areca nut); Mishri or Masheri, Misheri (partially burnt
tobacco used on gums and teeth as a powder); Qiwam or Kima (tobacco and spices); Red Tooth Powder; Snus or snuff
• Middle East
Iran, Saudi Arabia, Arab countries: Nass or Naswar, Niswar (tobacco, ash, slaked lime, and cotton or sesame oil); Shammah (tobacco and
minerals); Zarda (tobacco, slaked lime, spices, and areca nut)
• Africa
Sudan Toombak (fermented ground powdered tobacco and sodium bicarbonate)

27. Manufacturing ST products
• Finely ground/shredded or powdered tobacco
• Additives
Flavor: (sugar, nuts, spices, and oils)
Alkaline buffers: ammonium carbonate and sodium
carbonate → increase pH → increase
Unprotonated or free base nicotine → quick
absorption
chemicals, including nicotine, nitrosamines,
nitrosamine acids, polycyclic aromatic
hydrocarbons (PAHs), aldehydes, and metals

28. Nicotine Concentrations in ST Products
and Cigarettes in USA
Chewing
Tobacco*
(Mean
Range)
Dry Snuff*
(Mean
Range)
Moist
Snuff*
(Mean
Range)
Cigarettes Sold in USA
High Moderate Low
Nicotine 9.9 (3.41–
39.7)
16.8(10.48
–24.84)
12.6 (4.7–
24.29)
9.5–13.4 8.9 –11.4 7.2–11.5
*(milligrams per gram of tobacco)

29. ST products and CV risk
• Aggravation of hypertension and heart failure because
of sodium load of some ST products
• Hypertension and produce potassium wasting due to
licorice flavorant of some ST products
• “one-time” use of snuff or chewing tobacco results in
acute, transient (30 to 60 minutes) increases in BP and
HR
• Modest increased risk of fatal MI among ST users and
ever (past + current users) Swedish snuff users
• INTERHEART study: ST product use is associated with
an increased risk of acute MI

30. ST consumption & MetSy
• Multivariate analyses revealed an increased
OR of developing MetSy (OR=1.5, 95% CI: 1.13
to 2.10) for those using 5 to 6 cans per week
of moist snuff and a greater risk for those
using 7 cans per week (OR 2.0, 95% CI: 1.20 to
1.39). Those consuming <2 cans of snus per
week or 2 to 4 cans per week did not have an
elevated OR for developing MetSy
Scand J Public Health. 2006;34:576 –583.

31. Is There a Role for ST Use in Reducing
Smoking-Associated CV Risk?
• Compared with cigarette smoking, the CV risk associated with ST
use is markedly lower. Data, however, are lacking to support ST use
as a safe and long-term strategy for smoking cessation.
• ST users were more likely to switch to cigarettes.
• Unsuccessful past-year attempts by daily cigarette smokers were
more prevalent among daily snuff users (41.5%) compared with
never snuff users (29.6%)
whether individuals who switch from cigarettes to ST products reduce their
disease risk?
people who switched from CS to ST (“switchers”) had a higher rate of death
from any cause, including CAD, than those who quit tobacco use altogether
Tob Control. 2007;16:22–28
AHA policy statement 2010

32. Electronic Cigarettes
• Battery-powered heating element
• High-frequency, ultrasonic technology-atomiser
Inhalation or button activated
>500 brands and 7764 unique flavors of e-cigarette products
Cartridges or refillable tanks with a liquid mixture of propylene glycol and/or glycerol and
Nicotine + flavorings and other chemicals
No smoke, tar, or carbon monoxide-very low levels of air toxins
Materials in e-cig: tin, iron, nickel, and chromium. ceramics, plastics, rubber, filament fibers,
and foams
Individual puffs contained from 0 to 35 μg nicotine per puff. Assuming a high nicotine delivery
of 30 μg per puff, it would take ≈30 puffs to deliver the 1 mg nicotine typically delivered by
smoking a conventional cigarette.
2014 American Heart Association
Electronic nicotine delivery systems (ENDS)

33. Particle number distribution from mainstream aerosol
and from conventional cigarette.

34. Adverse effects of e-cig (Vaping)
• Adverse health effects tobacco combustion products
• Health concerns that are related to nicotine: release of
catecholamines, including hemodynamic effects (increase in HR, a
transient increase in BP, vasoconstriction of coronary and other
vascular beds), adverse effects on lipids, and induction of insulin
resistance. Endothelial dysfunction
• Heating of glycerol can form acrolein, which is an irritant and
oxidizing agent leading to adverse pulmonary and cardiovascular
effects of cigarette smoking
• few data on the health effects of prolonged exposure to pure
nicotine
• Adverse health effects are likely to be much less than those of
cigarette smoking, but could be significant in individuals with heart
disease.
• Acute nicotine toxicity: ingestion or skin exposure to e-liquid
AHA policy statement 2014
Toxicity thresholds for the potentially toxic substances found in e- cigarettes are unknown
Poor quality control, potential to deliver drugs like marijuana

35. Parental smoking leads to irreversible
impairment of endothelial function of children
Arterioscler Thromb Vasc Biol. 2012

36. FMD in adulthood according to parental smoking in
childhood and own life-time smoking
Arterioscler Thromb Vasc Biol. 2012

37. Mechanism & message
• Cigarette smoke induces the surface expression of adhesion
molecules and promotes trans-endothelial migration of
monocyte-like cells
• It turns the acetylcholine-induced artery relaxation to
vasoconstriction
• Passive smoking reduces the activity of endothelial nitric
oxide synthase
• Impairs endothelial regeneration, maintenance and viability
• ↓ HDL2, ↑oxLDL similar to active smokers
• ↑ in carotid IMT
• Active smoking was not associated with adaptation of
brachial artery size.
Independent and persistent effect of passive smoke exposure in childhood
Adults who were exposed to passive smoking as a child are at risk for
cardiovascular disease

38. Brief Secondhand Smoke Exposure Depresses
Endothelial Progenitor Cells Activity and
Endothelial Function
Secondhand smoke exposure increased EPCs and plasma vascular endothelial
growth factor and completely abolished EPC chemotaxis during 24 h after
exposure. Secondhand smoke increased EMPs and decreased FMD.
J Am Coll Cardiol 2008;51

39. CV Effects of Secondhand Smoke
Nearly as Large as Smoking
Exposure to 60 minutes of SHS increased measures of platelet activation; repeated
exposures over several days led to levels in nonsmokers comparable to smokers.

40. REVERSAL
Although smoking cessation leads to a
decreased risk of cardiovascular events and
mortality, there is evidence that inflammatory,
hemostatic, and atherosclerotic changes can
take up to 20 years to revert back to nonsmoker
levels, underscoring the importance of avoiding
smoking.
JAMA 2003;290:86-97.
Int J Epidemiol 2005;34:1036-45

41. FDA Rules, 2010
The rules prohibit:
1. Sales of cigarettes or smokeless tobacco to individuals 18 years of
age; sales of cigarette packages with <20 cigarettes
2. Sales of cigarettes and smokeless tobacco in vending machines, self-service
displays, or other impersonal modes of sale, except in very limited
situations;
3. Free samples of cigarettes; tobacco brand name sponsorship of any
athletic, musical, or other social or cultural event, or any team or entry in
those events;
4. Gifts or other items in exchange for buying cigarettes or smokeless tobacco
products; and sale or distribution of items, such as hats and tee shirts,
with tobacco brands or logos;
5. The new regulations also limit distribution of smokeless tobacco products
and require that audio advertisements use only words with no music or
sound effects.

42. • Combustion-derived benzo[a]pyrene and other polycyclic
• aromatic carcinogens are present in lower concentration in ST
• compared with cigarette smoke (CS). In contrast, nitrosamines,
• such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-
• butane (NNK) and N-nitrosonornicotine (NNN) are present
• in relatively high concentrations in ST products.15 In fact, the
• highest known nonoccupational exposure to nitrosamines
• occurs with ST use. Every gram of ST contains approximately
• 1 to 5 g of tobacco-specific nitrosamines such as
• NNN and NNK, two established carcinogens.15 Other
• tobacco-specific carcinogens in ST products include N-
• nitrosoanabasine (NAB), N-nitrosoanatabine (NAT), and
• nitrosamine acids (eg, 3-[methylnitrosamino] propionic acid)