Smokeless Tobacco- Fire without smoke: A Cardiologist’s perspective

Dr (Prof) Shekhar Kashyap MD (Med) DM (Cardiology) (AIIMS, New Delhi)

Grad en Intervent, Cardiologie (Univ of Rouen, Rouen, France)

Smokeless Tobacco (SLT) – a heterogenous product

• Includes Chewing tobacco and Snuff collectively referred to as spit tobacco • Now tobacco companies are manufacturing spitless ST products (pouched moist

snuff)/ compressed tobacco lozenges also Main constituents of SLT include • Nicotine- an alkaloid • Cancer-causing chemicals such as

• tobacco-specific nitrosamines, which form during the growing, curing, fermenting, and aging of tobacco.

• polycyclic aromatic hydrocarbons - Chemicals formed when tobacco is cured with heat

• Aldehydes • Harmful metals (arsenic, beryllium, cadmium, chromium, cobalt, lead, nickel,

mercury)

SLT products : Globally

America North America Chewing tobacco (spit tobacco): loose leaf, plug, twist (ie beechnut, levi) Iq’mik (tobacco and punk ash); Snuff (spit tobacco): Moist (Copenhagen, Bandit, Kodak), Dry (Al Capone, Wawith, Tube rose); Compresses tobacco lozenges : Ariva and stonewall; Snus : Exalt, Revel, Marlboro, Camel South America Chimo : tobacco with sodium bicarbonate, brown sugar and vanilla Europe Sweden Snus (finely ground moist tobacco) UK Gutkha, dry snuff

Asia Central Asia Gul, Nass, Niswar, pan masala or betel quid, Zarda East/Southeast Asia Gutkha, pan masala South Asia Snuff creamy, gul, gutkha, khaini, mawa, mishri, qiwam, red tooth powder, snus or snuff Middle East Iran, Saudi Arabia, Arab countries Nass, Niswar, shammah (tobacco & minerals), Zarda Africa Sudan Toombak (fermented ground powdered tobacco and sodium bicarbonate)

Circulation. 2010;122:1520-1544

Nicotine: Mechanism of action

• Is absorbed through oral mucosa, lungs, skin or gut, and metabolized by the liver in 2 phases

• In phase I: microsomal oxidation metabolites like cotinine etc. • In phase II: glucuronidation of the metabolites and excretion via urine, feces,

bile, saliva, sweat etc. There is evidence that nitrosation of nicotine in vivo could lead to formation of highly carcinogenic substances such as • N-nitrosonornicotine (NNN) • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

Inflammation in the oral cavity increases risk of nitrosation.

Mariann R. Piano. Circulation. Volume: 122, Issue: 15, Pages: 1520-1544

© 2010 American Heart Association, Inc.

Effect of tobacco products on Haemodynamics

Nicotine acts as a Sympathomimetic drug

• Heart rate effect of smoking and SLT use are similar

• SLT can precipitate hypertensive crisis including in patients of pheochromocytoma

• Additives in SLT products such as liquorice and sodium increase Blood pressure

Effect of Nicotine on the CVS

• Nicotine constricts coronary arteries

• Increased risk of heart failure – tissue remodeling,

fibrosis, hypertrophy, persistent increased sympathetic

activity

• Arrhythmogenicity – ventricular tachycardia/ fibrillation,

atrial fibrillation, sinus tachycardia

• Increased thromobogenesis – mediated through

platelets and epinephrine

Effect of Nicotine on the CVS

• Endothelial dysfunction – increased oxidative stress,

reduced bioavailability of Nitric oxide (NO)

• Pro-inflammatory effects due to chemotactic effects on

neutrophils, increased sympathetic activity

• Enhances angiogenesis – plaque formation

• Dyslipidemia

• Systemic Hypertension

Evidences from Systematic review and meta-analysis

Rostron BL et al 2018 – Circulatory risks associated with SLT use in

Europe and North America

Results indicate increased risk of heart disease (RR 1.17, 95% CI 1.09

to 1.27) and stroke (RR 1.28, 95%CI 1.01 to 1.62) among US SLT users

compared with non-users. However, this increased risk was not

observed among Swedish SLT users.

Conclusion: US SLT users were found to have increased risk of heart

disease and stroke

The increased risk among US users was attributed to product

characteristics and behavioural use.

[Swedish products are pasteurized, have lower concentration of harmful

substances as they are subject to quality control standards etc.]

Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction

Circulation. Volume: 130, Issue: 4, Pages: 325-332,

Gabriel Arefalk et al 2014 – hypothesized

that discontinuation of snus use after MI

would reduce mortality risk.

They followed up MI patients (<75 years of

age, enrolled from 2 months after MI) for

two years between 2005-2009. There were

675 post MI quitters and 1799 post MI

continuing users of SLT. 83 participants

died during follow up.

Conclusion: Discontinuation of snus use

after MI was associated with nearly halved

mortality risk similar to the benefit

associated with smoking cessation.

Mechanism involved

Vulnerability to arrhythmic complications among SLT users

Experiments on dogs using nicotine infusion indicate dose-

dependent arrhythmias

In post MI studies nicotine infusion promotes ventricular

fibrillation

In a post infarction study, nicotine exposed rats had impaired

myocardial healing and altered ventricular remodelling as

compared to controls

Continued use of SLT induces acute hemodynamic changes like

increased heart rate, increased BP, endothelial dysfunction and

increased levels of adrenaline

Acute effects of chewing tobacco on coronary microcirculation and hemodynamcis

Habitual tobacco chewers (n=7) with stable coronary artery disease undergoing elective

percutaneous coronary intervention (PCI) kept 1 g of crushed dried tobacco leaves in the mouth

after a successful PCI. Lesion in last stented vessels was evaluated for fractional flow reserve

(FFR), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) post-PCI, after

15 min and 30 min of tobacco chewing along with the measurement of serum cotinine levels.

Results:

• Oral tobacco led to high levels of cotinine in the majority of patients.

• Insignificant rise in heart rate, systolic & diastolic BP following tobacco consumption.

• Baseline CFR (median 1.6, range 1.1–5.5) was low in tobacco chewers after PCI even after

optimum FFR (0.9 ± 0.05) in the majority of patients suggesting abnormal microvascular

hemodynamics (high IMR in 3 patients, overall median 14.2, range 7–36.2).

Conclusion: Tobacco chewers have abnormal coronary microcirculation hemodynamics even

following a successful PCI. J Pract Cardiovasc Sci 2015;1:138-42.

Switch from cigarettes to spit tobacco – Does it affect mortality from tobacco-related diseases?

A cohort of 116,395 smokers (men) enrolled in the ongoing US American Cancer

Society Cancer Prevention Study II were followed up from 1982 to 2002.

Of these 111,952 men quit using tobacco entirely, and 4443 switched to spit tobacco.

During follow up, 44 374 men died.

Results: After 20 years of follow-up, switchers had a higher rate of death from any

cause (HR 1.08, 95% confidence interval (CI) 1.01 to 1.15), lung cancer (HR 1.46, 95%

CI 1.24 to 1.73), coronary heart disease (HR 1.13, 95% CI 1.00 to 1.29) and stroke (HR 1.24, 95% CI 1.01 to 1.53) than those who quit using tobacco entirely.

Conclusion: The risks of dying from major tobacco-related diseases were higher

among former cigarette smokers who switched to spit tobacco after they stopped

smoking than among those who quit using tobacco entirely.

Tob Control . 2007 Feb;16(1):22-8.

Absence of evidence is not evidence of absence.

Martin Reeves

Were One-Third of Quake Victims Scared to Death? : Health: A high percentage of earthquake-related cardiac deaths does not surprise medical experts who have new respect for the power of human emotions.

Jump in Fatal Heart Attacks Is Tied to Quake By Warren E. Leary •Feb. 15, 1996

Nishimoto Y, Firth BR, Kloner RA, et al. The 1994 Northridge

earthquake triggered shocks from implantable cardioverter

defibrillators.

Circulation 1995;92:Suppl I:I-606

THANK YOU