Disclosures Dr. Benowitz has been a consultant to pharmaceutical - - PDF document
12/7/19 Cardiovascular Effects of Vaping Neal L Benowitz MD Professor of Medicine University of California San Francisco UCSF Heart Disease Dec 7, 2019 1 Disclosures Dr. Benowitz has been a consultant to pharmaceutical companies that
12/7/19 1
Neal L Benowitz MD Professor of Medicine University of California San Francisco UCSF Heart Disease Dec 7, 2019
1
2
12/7/19 2
3
Nickels, AnnalsATS 2017
4
12/7/19 3
smoking are caused by tobacco combustion products.
deliver nicotine without combustion products, are an essential consideration in assessing the public health impact of nicotine-based harm reduction.
electronic cigarettes?
5
6
12/7/19 4
less harmful than cigarette smoking
and their health effects are likely to be quite different
have not been determined and need to be studied
7
8
12/7/19 5
9
Cumulative Deaths (millions) Year
Henningfield and Slade, FDLI, 1998
10
12/7/19 6
Hajek et al, NEJM, 2019
11
Hajek et al, NEJM, 2019
18.0 % 9.9% 5 10 15 20
CO-verified smoking abstinence at one year
E-Cigarettes NRT
12
12/7/19 7
Gottlieb and Zeller, NEJM, 2016 Despite extraordinary progress in tobacco control and prevention, tobacco use remains the leading cause
majority of tobacco-related disease and are responsible for more than 480,000 U.S. deaths each year. Indeed, when used as intended, combustible cigarettes kill half of all long-term users.1 With the tools provided to the Food and Drug Administration (FDA) under the Family Smoking Prevention and Tobacco Control Act of 2009, the agency has taken consequential steps to prevent sales of tobacco products to children, expand the science base for understanding traditional and newer tobacco products, and conduct public education campaigns. But the agency needs to do more to protect Americans;
13
Addictiveness/Appeal Toxicity
14
12/7/19 8
As for smoking, teenagers now won’t go near a cigarette, but they do vape.
15
5 10 15 20 25 30 2011 2012 2013 2014 2015 2016 2017 2018 2019 Prevalence (%)
Past 30-Day Product Use by High School Students (9th - 12th Grade) Cigarettes E-Cigarettes
16
12/7/19 9
17
Clearomizer Battery
18
12/7/19 10
coil wick
battery end
air
aerosol
mouth end
liquid
19
20
12/7/19 11
21
22
12/7/19 12
(Sleiman et al. Envir Sci Tech 2016)
23
24
12/7/19 13
Tobacco Smoke Chemicals That May Contribute to Cardiovascular Disease
chemicals
25
Mechanisms of Smoking-Induced Cardiovascular Disease
* Nicotine may contribute
26
12/7/19 14
27 28
12/7/19 15
29
Oxidant chemicals Particulates Other combustion products Inflammation Platelet activation/ thrombosis Endothelial dysfunction Carbon monoxide Reduced myocardial blood, oxygen, and nutrient supply Coronary occlusion Coronary Vasoconstrictio n Myocardial ischemia Myocardial infarction
Sudden death Increased Myocardial demand for oxygen and nutrients Increased heart rate Increased blood pressure Increased myocardial contractility
Sympathetic nervous system activation Nicotine Reduced
availability
Mechanisms of Smoking Induced Acute CV Events
30
12/7/19 16
31
32
12/7/19 17
thermal degradation products. Some products probably more harmful than others
dosing or duration
useful predictors of future events
because most EC users current or former smokers, most EC users are young so there are small numbers of events, unclear timing between EC use and CV events, high prevalence of dual use, diagnosis of MI by self-report and
33
Constituents of Tobacco Smoke and EC aerosol that could contribute to CVD
* Not present in EC aerosol # Present at much lower levels - levels depend on coil heating temperature
34
12/7/19 18
Goniewicz et al. NTR 2016
Reduced toxicant exposure after switching from tobacco to electronic cigarettes
Carbon Monoxide
20 40
Baseline Week 1 Week 2
ppm (exhaled) Acrylonitrile 200 400 600
Baseline Week 1 Week 2
CNEMA (µg/g) Acrolein 500 1000 1500 2000
Baseline Week 1 Week 2
3 HPMA (µg/g) Benzene 500 1000 1500 2000
Baseline Week 1 Week 2
SPMA (ng/g)
35
36
12/7/19 19
4.1 mg/ml 430 ng/ml 22.5 mg/ml 316 ng/ml 59 mg/ml 172 ng/ml (50 – 313)
Nicotine Concentration Blood/saliva Cotinine 37
38
12/7/19 20
39
40
12/7/19 21
41
(e.g. dopamine)
42
12/7/19 22
Action
Probable Contribution
43
contractility and myocardial work
Reduced coronary flow reserve
44
12/7/19 23
Tobacco E-Cigarette Abstinence
HR
Heart rate acceleration indicates persistent sympathetic neural activation
45
46
12/7/19 24
47
www.trinketsandtrash.org
Swedish snus American snus
48
12/7/19 25
slower absorption
intimal thickness
increase in case fatality
after MI
atrial fibrillation
9.7 18.7 13.7 28.4
10 20 30
Q U Q U
Snus Cigarettes
Mortality (per 1000 pyr)
Arefalk, 2014
%
49
E-cigarette Aerosol
Oxidizing Chemicals Particulates Acrolein Nicotine
Inflammation Sympathetic Nervous System Activation Catecholamine Release Platelet Activation Thrombosis Endothelial Dysfunctio n Myocardial Blood Flow Coronary Occlusion Coronary Vasoconstriction Heart Rate Blood Pressure Myocardial Contractility Ventricular Arrhythmogenesis Sudden Death Myocardial Ischemia Myocardial Infarction Myocardial Demand for oxygen and nutrients
Mechanisms by which E-cigarettes could cause Acute CV Events
50
12/7/19 26
effects)
circulating EPCs)
infarction
51
George et al. JACC 2019
Improved Endothelial Function after Switching from Tobacco Cigarettes to E-cigarettes
52
12/7/19 27
J Am Heart Assoc. 2019;8:e012317. DOI: 10.1161/JAHA.119.012317.) Am J Prev Med 2018; 55(4)455-461 DOI: 10.1016/j.amepre.2018.05.004
Reports of Association Between E-Cigarettes and Myocardial Infarction
53
based on qualitative and quantitative comparisons of emission constituents, the CV risk of E-cigarettes is most likely considerably less than that of conventional cigarette smoking
conventional cigarettes, the result could be a substantial benefit for public health
product regulation could minimize risk. Benowitz and Fraiman, Nat Rev Cardiol 2017
54
12/7/19 28
AHA Policy Statement on Electronic Cigarettes, Circulation 2014
55
smoking, but …
chemicals
prevent relapse to smoking)
56