Cardiovascular effects of nicotine vs. cigarette smoke · 2018-03-23 · Cardiovascular effects of nicotine vs. cigarette smoke Dr Konstantinos Farsalinos Researcher Onassis Cardiac

Cardiovascular effects of nicotine

vs. cigarette smoke

Dr Konstantinos Farsalinos Researcher Onassis Cardiac Surgery Center, Greece University of Patras, Greece National School of Public Health, Athens-Greece

1st (and last) slide

• Please look at last year’s presentation by Prof. Neil Benowitz

Cardiovascular effects of nicotine

vs. cigarette smoke


Emerging harm reduction (?) choices Tobacco heated products


Tobacco heated products An old story

1998, RJ Reynolds launched Premier

Tobacco heated products An old story

• Premier replaced by Eclipse

Tobacco heated products New developments

Tobacco heated products New developments

• Tobacco companies: JTI, PMI, BAT

• Two of them (PMI-IQOS, BAT-Glo) are heating tobacco through a resistance

(maximum 350oC and 240oC respectively)

• PMI: heats tobacco by penetrating the stick with a metal blade (heat source)

• BAT: heats the tobacco through resistors (heat source) surrounding the tobacco stick

• JTI product (Ploom TECH) is an e-cigarette with a tobacco cartridge at the mouth

piece (indirect heating of tobacco by the aerosol passing through the cartridge)

Tobacco heated products marketing

• PMI launched product in Japan in late 2014 ▫ Market share > 14% in Japan

▫ Available in about 30 countries

• JTI launched product in March 2016

▫ Also available in Switzerland

• BAT launched product in late 2016

▫ Market share 1.8% in Japan

▫ Now in Canada, S. Korea, Switzerland, Russia

A lot of research Almost all by the manufacturers

• Chemistry

• Toxicology

• Clinical

Chemistry

Forster et al., Regul Toxicol Pharmacol 2017

Glo

average > 95% reduction in toxic emissions

Chemistry

Schaller et al., Regulatory Toxicol Pharmacol 2016 (PMI - IQOS)

IQOS

average 90%

reduction in toxic

emissions

Chemistry

JTI poster, Global Forum on Nicotine 2017 (Ploom TECH)

Ploom-Tech

average > 95%

reduction in toxic

emissions

Clinical studies

BAT, poster presentation at Global Forum on Nicotine 2017 (Glo)

Clinical confinement for 5 days

Comparison between continuous smoking and switch to THP product

Clinical studies

Clinical confinement study

Comparison between continuous smoking, smoking cessation and

switch to THP product

Haziza et al., Regulatory Toxicol Pharmacol 2016 (PMI – IQOS)

Clinical studies

Haziza et al., Regulatory Toxicol Pharmacol 2016 (PMI - IQOS)

SA = smoking abstinence

THS = THP

Research replication

• Although science should not be discarded, a critical and very cautious approach is need due to the source of the information (manufacturers, tobacco industry)

• It is of outmost importance to replicate the studies, carefully reviewing the methodology, testing several puffing regimes, checking the accuracy of the reported values

Independent studies

• Mainly 3 independent studies have attempted to replicate manufacturer publications for 1 HnB product (IQOS)

Independent studies

0

4

8

12

16

20

HnB regular HnB methol

Nic

oti

ne

lev

els

(mg

/g t

ob

acc

o)

Nicotine concentration (mg/g) in unused tobacco sticks of

IQOS appear to be similar to tobacco cigarettes

Farsalinos et al. Nicotine Tob Res 2017

0.00

0.50

1.00

1.50

2.00

2.50

Regular

2 s

Menthol

2 s

Regular

4 s

Menthol

4 s

Vapour 2

2 s

Vapour 2

4 s

Epsilon

2 s

Epsilon

4 s

Nautilus

Mini

2 s

Nautilus

Mini

4 s

Regular

2 s

HnB HnB Ciga-like EC eGo style EC Variable wattage Tobacco

cigarette

Nic

oti

ne

lev

els

(mg

/12

pu

ffs)

Independent studies

Lower nicotine levels (-30%) to the aerosol compared to

tobacco cigarette smoke Farsalinos et al. Nicotine Tob Res 2017

Independent studies

Farsalinos, Leischow et al. (under preparation for submission)

0.0

0.4

0.8

1.2

1.6

2.0

55/2/30 80/3/30 90/3/25

mg

/sti

ck

Puffing regime (volume, duration, interval)

Nicotine delivery to the aerosol (IQOS)

Independent studies

Auer et al. JAMA Int Med 2017

Independent studies


Independent studies


0

50

100

150

200

250

Auer et al. PMI

Acetaldehyde

3.2

0.9 1.8

5.5

0.2

5.53

11.3

1.45

16.8

0.53

0

2

4

6

8

10

12

14

16

18

Auer et al.

PMI

Independent studies IQOS Tobacco cigarette % difference

• PMI responded that this is not a listed HPHC, but this is not good enough

justification

• Anything potentially toxic should be tested, irrespective of being listed in HPHC

lists

• Limited data on toxicity of acenaphthene, but it is a PAH produced during high

temperature carbonization – more studies are needed to verify the levels,

source and reasons it is formed

• Aldehyde levels were low in IQOS but were unusually low in tobacco cigarettes

Independent studies

Bekki et al. J UOEH 2017

Independent studies

Bekki et al. J UOEH 2017

19.2

34

4.5

12.3

0.44

6.7

20.5

3.15

6.7

0.53 0

5

10

15

20

25

30

35

40

NNN NAT NAB NNK CO

Bekki et al

PMI

Exhaled carbon monoxide

(Use by e-cigarette users) (Use by smokers)

Farsalinos et al. (unpublished data)

0

2

4

6

8

10

12

14

16

18

IQOS Tobacco cigarette

Before use

After use

Aldehydes in THP

Farsalinos, Leischow et al. under preparation for submission

0

1

2

3

4

5

6

7

IQOS REGULAR IQOS MENTHOL

Formaldehyde

PMI

Farsalinos et al.


0

50

100

150

200

250


Acetaldehyde

PMI

Farsalinos et al.

Aldehydes in THP


0

2

4

6

8

10

12


Acrolein

PMI

Farsalinos et al.

Aldehydes in THP


0

2

4

6

8

10

12

14

16


Propionaldehyde

PMI

Farsalinos et al.

Aldehydes in THP


0

1

2

3

4

5


Crotonaldehyde

PMI

Farsalinos et al.

Aldehydes in THP


0

5

10

15

20

25

30

35

40

IQOS REG IQOS MENTHOL

Formaldehyde

55/2/30

80/3/30

90/3/25

Aldehydes in THP different puffing regimes


0

50

100

150

200

250

300


Acetaldehyde

55/2/30

80/3/30

90/3/25




0

5

10

15

20


Acrolein

55/2/30

80/3/30

90/3/25



0

5

10

15

20

25

30


Propionaldehyde

55/2/30

80/3/30

90/3/25



0

2

4

6

8


Crotonaldehyde

55/2/30

80/3/30

90/3/25

Aldehydes in THP Comparing IQOS, tobacco cigarette and e-cigarette


0

10

20

30

40

50

60

70

IQOS Regular IQOS Menthol E-cigarette 10W E-cigarette 14W Tobaccocigarette

Formaldehyde (μg per 1 IQOS, 12 e-cigarette puffs, 1 cigarette)



0

200

400

600

800

1000

1200


Acetaldehyde (μg per 1 IQOS, 12 e-cigarette puffs, 1 cigarette)


0

20

40

60

80

100

120


Acrolein (μg per 1 IQOS, 12 e-cigarette puffs, 1 cigarette)



-100%

-90%

-80%

-70%

-60%

-50%

-40%

-30%

-20%

-10%

0%IQOS Regular IQOS Menthol E-cigarette 10W E-cigarette 14W

Formaldehyde % reduction compared to 20 cigarettes (for 20 IQOS and 5 gram e-liquid)

Aldehydes in THP difference from tobacco cigarettes



-100%

-90%

-80%

-70%

-60%

-50%

-40%

-30%

-20%

-10%


Acetaldehyde % reduction compared to 20 cigarettes (for 20 IQOS and 5 gram e-liquid)


-100%

-90%

-80%

-70%

-60%

-50%

-40%

-30%

-20%

-10%


Acrolein % reduction compared to 20 cigarettes (for 20 IQOS and 5 gram e-liquid)


Aldehydes in the environment

0

200

400

600

800

1000

1200

1400

1600

Common indoor levels(WHO)

HnB (20/day) Tobacco cigarette(20/day)

Daily formaldehyde exposure

20m3 ventilation

volume/day

THPs and heart disease risk?

• Exposed rats (n=8/group) via nose cone to 15 seconds of iQOS

aerosol, Marlboro cigarette mainstream smoke, or air 10 times

over 5 min

• FMD was quantitated pre- and post-exposure by measuring

femoral artery diameter with micro-ultrasound before and after 5

min of transient surgically induced ischemia

• Results: Acute exposure to iQOS aerosol can substantially

impair endothelial function in rats comparably to cigarette

smoke

THPs and heart disease risk?

4.5-fold

higher

levels

3 studies (2 independent) showed IQOS delivers 30% lower

nicotine levels to the aerosol than tobacco cigarettes

FMD and acute nicotine intake

… nicotine (NRT) alone causes acute

endothelial dysfunction, although

to a lesser extent than smoking a

cigarette of the same nicotine yield.

… coffee exerts an acute unfavourable effect

on the endothelial function in healthy

adults... This effect might be attributed to

caffeine, given that decaffeinated coffee was

not associated with any change in the

endothelial performance.

• HnB products are not absolutely safe

▫ The presence of tobacco and the temperatures of heating (at least for 2 of them) result in the unavoidable

emission of some potentially toxic compounds

• Manufacturers report exposure reductions from 85% to 99% (the latter for JTI product)

• Almost all scientific data is coming from the manufacturers

▫ This is currently the biggest problem, related to the justified mistrust for the industry

• Currently available evidence suggest substantial reduction in toxins and reduction in

biomarkers of exposure – but more evidence is needed, especially from independent

sources

Conclusions (1)

• Other factors besides the safety/risk profile should be considered in assessing the public health effects of these

products.

• Public health impactTHP = (hazardSM-THP x smoking cessation) – (hazardTHP x use among non-smokers)

– (hazardSM x smoking initiation)

• Other key issues:

▫ Do they lead to sustained smoking cessation?

▫ Are they promoted and used by never-smokers?

▫ Is there a “gateway to smoking” effect?

• Eventually, it depends on whether tobacco harm reduction is considered an acceptable and viable additional tool

to combat the smoking epidemic

Conclusions (2)

• Current evidence (verified in a small part by independent studies) support that

THPs can be considered harm reduction products

• There is a risk-continuum among harm reduction products, with e-cigarettes (new-

generation) emitting lower levels of toxins compared to THPs

▫ The absolute difference in toxic emissions from tobacco cigarettes is much higher than the absolute

difference between harm reduction products – smokers should make informed decisions

• THPs could be a viable option for smokers unable to quit by themselves or with

medications or with e-cigarettes or with snus (where available)

Conclusions (3)

Cardiovascular effects of nicotine vs. cigarette smoke · 2018-03-23 · Cardiovascular effects of nicotine vs. cigarette smoke Dr Konstantinos Farsalinos Researcher Onassis Cardiac

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