Are e-cigarettes, or electronic nicotine delivery devices (ENDS), sufficiently less harmful than combustible cigarettes? Can they help people quit smoking combustible cigarettes? Will they save lives? While we do not know the ultimate answers to these questions, a clearer picture is emerging. Notably, the tobacco industry touts smokeless tobacco as a "less harmful" alternative to smoking, yet the American Heart Association (AHA) published a review and policy statement in 2010 finding evidence of sufficient risk to the cardiovascular system from the use of smokeless tobacco.¹ Today we are seeing the same harm reduction assertions regarding e-cigarettes.

The lack of regulation of these products in the US makes it difficult to determine if e-cigarettes are actually less harmful than combustible cigarettes. There are over 400 different e-cigarettes that contain a mix of about 40-60 chemicals from over 7,000 identified chemicals and flavorings.² Without regulated labeling or uniform testing, there is no current standard for e-cigarette design or its components, including the aerosolized particulates formed by the heating of chemicals in e-liquids. Concerns have been raised regarding the cytotoxic effects of chemicals, particularly certain flavorings commonly found in e-liquids.^3,4 The National Academies of Science, Engineering, and Medicine (NASEM) released a report in 2018 noting that e-cigarettes contain fewer and less concentrated toxicant levels than combustible cigarettes; however exposure to these chemicals, including nicotine, is highly variable and device dependent.⁵ The NASEM report concludes that while these products have known biological effects, most are largely unknown.⁵

Harm reduction on a population level rests on two key questions: 1) Will e-cigarettes help people quit and maintain long-term abstinence from nicotine and tobacco product use? and 2) Will e-cigarettes deter nicotine addiction in youth and reduce long-term exposure to tobacco products? First, a 2016 review found less success quitting among persons using e-cigarettes.⁶ Yet, in the largest randomized control trial (N = 886) to date comparing quitting from e-cigarettes versus nicotine replacement therapy (NRT), 18% of the e-cigarette only group remained abstinent from smoking at one year, compared to 9.9% of the NRT group.⁷ However, 80% were still using e-cigarettes at one-year follow up, compared to only 9% who were still using NRT. One participant in the e-cigarette group died of ischemic heart disease.

Second, youth use of e-cigarettes is particularly troubling, with recent escalating use of pod-based e-cigarette devices that expose users to high levels of nicotine.⁸ E-cigarette use among youth has been associated with later use of combustible cigarettes.⁹ Despite this association, some researchers contend that the benefits of reducing adult combustible use will outweigh the increased risk to youth.¹⁰ However, the NASEM report notes that the long-term benefits are likely to be substantially less than those presumed in the short term, with some predictive models finding net harm.⁵

An important and related population health concern is dual use (e-cigarette plus combustible cigarette use) which is common among adults in the US.^11,12 This raises concerns that dual use may actually increase, rather than decrease toxin and particulate exposure. Most experts agree that complete abstinence from all tobacco products, including e-cigarettes, is the only way to sufficiently reduce cardiovascular risk.^13,14

How do e-cigarettes affect the cardiovascular system? We know that e-cigarettes contain oxidizing chemicals, polycyclic aromatic hydrocarbons, and particulates, which have been associated with endothelial dysfunction and platelet activation, mechanisms long associated with increased cardiovascular risk.^15-17 The impacts of e-cigarettes on the cardiovascular system are also informed by the immediate and well-known effects of nicotine on the cardiovascular system, which are generally dose-dependent.¹⁸ For example, the slower delivery of lower doses in nicotine replacement medications (e.g., nicotine gum) do not expose the user to the same cardiovascular risks as smoking combustible cigarettes, which deliver a near-immediate, high level exposure from the initial "hit".¹³ The newer pod-based e-cigarette devices most closely mimic the "hit" levels of combustibles with a more rapid delivery of higher levels of nicotine. This "hit" effect of the newer pod-based devices may change e-cigarette nicotine delivery, having the potential to improve product acceptability and help combustible users quit.¹⁹ However, the cardiovascular effects of the new nicotine salt formulation in the pod-based devices, allowing for the increased bioavailability of nicotine, are largely unknown.

In addition to the cardiovascular harms to the user, e-cigarettes pollute the air by emitting harmful aerosol. Bystanders and users are exposed to toxic chemicals, nicotine, and fine and ultrafine particulates that negatively affect the heart, lungs, and circulation.^14,20 According to the new Prevention Guideline, clinicians are urged to advise patients to avoid exposure to secondhand aerosol from all tobacco products by adopting smoking restrictions that prohibit e-smoking inside all homes, vehicles and within 25 feet from all entryways, windows, and building vents.²¹

In summary, it is clear that e-cigarettes are not a panacea to eliminate the deadly effects of tobacco use. Just as clearly, while research continues, it is critical that clinical practice related to the use of these products, specifically in the context of cardiovascular disease, be cautious and evidence-based. Considering the new Primary Prevention of Cardiovascular Disease Guideline, we recommend:

1. Use a cautious approach to e-cigarettes. Less harm does not equal no harm. Much of the nascent evidence on e-cigarettes points to unknown harms, particularly from long-term use. Evidence regarding the acute effects of e-cigarette use on endothelial dysfunction and platelet activation is clearly notable and warrants additional research.
2. Do not advise patients to use e-cigarettes as a tobacco treatment method. The evidence is unclear whether e-cigarettes are useful or effective for tobacco cessation, and they may be potentially harmful. The evidence on the use of e-cigarettes as a smoking cessation strategy in adults and adolescents is insufficient or limited.²¹
3. Do not advise adult patients to switch to e-cigarettes. The tobacco industry has a long history of promoting "switch to quit" strategies with adults, while concurrently promoting youth initiation of tobacco products.
4. Advise all adults and adolescents to avoid exposure to secondhand smoke and aerosol. E-cigarettes pollute the air.
5. Direct patients who use tobacco to other cessation interventions with established effectiveness and safety.²¹ Established tobacco treatments can promote quitting and make an impact on cardiovascular health if they follow evidence-based guidelines. See the 2018 ACC Expert Consensus Decision Pathway on Tobacco Cessation Treatment for a full discussion.¹³

References

1. Piano MR, Benowitz NL, Fitzgerald GA, et al. Impact of smokeless tobacco products on cardiovascular disease: implications for policy, prevention, and treatment: a policy statement from the American Heart Association. Circulation 2010;122:1520-44.
2. Zhu SH, Sun JY, Bonnevie E, et al. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control 2014;23:iii3-9.
3. Hua M, Omaiye EE, Luo W, McWhirter KJ, Pankow JF, Talbot P. Identification of cytotoxic flavor chemicals in top-selling electronic cigarette refill fluids. Sci Rep 2019;9:2782.
4. Omaiye EE, McWhirter KJ, Luo W, Pankow JF, Talbot P. High-nicotine electronic cigarette products: toxicity of JUUL fluids and aerosols correlates strongly with nicotine and some flavor chemical concentrations. Chem Res Toxicol 2019;32:1058-69.
5. National Academy of Sciences, Engineering, and Medicine. Public health consequences of e-cigarettes. Washington, D.C.; 2018.
6. Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med 2016;4:116-28.
7. Hajek P, Phillips-Waller A, Przulj D, et al. A randomized trial of e-Cigarettes versus nicotine-replacement therapy. N Engl J Med 2019;380:629-37.
8. King BA, Gammon DG, Marynak KL, Rogers T. Electronic cigarette sales in the United States, 2013-2017. JAMA 2018;320:1379-80.
9. Soneji S, Barrington-Trimis JL, Wills TA, et al. Association between initial use of e-cigarettes and subsequent cigarette smoking among adolescents and young adults: a systematic review and meta-analysis. JAMA Pediatr 2017;171:788-97.
10. Warner KE, Mendez D. E-cigarettes: comparing the possible risks of increasing smoking initiation with the potential benefits of increasing smoking cessation. Nicotine Tob Res 2019;21:41-47.
11. Bao W, Xu G, Lu J, Snetselaar LG, Wallace RB. Changes in electronic cigarette use among adults in the United States, 2014-2016. JAMA 2018;319:2039-41.
12. Jaber RM, Mirbolouk M, DeFilippis AP, et al. Electronic cigarette use prevalence, associated factors, and pattern by cigarette smoking status in the United States from NHANES (National Health and Nutrition Examination Survey) 2013-2014. J Am Heart Assoc 2018;7:pii:e008178.
13. Barua RS, Rigotti NA, Benowitz NL, et al. 2018 ACC expert consensus decision pathway on tobacco cessation treatment: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2018;72:3332-65.
14. Bhatnagar A. Cardiovascular perspective of the promises and perils of e-cigarettes. circulation research. Circ Res 2016;118:1872-5.
15. Chaumont M, de Becker B, Zaher W, et al. Differential effects of e-cigarette on microvascular endothelial function, arterial stiffness and oxidative stress: a randomized crossover trial. Sci Rep 2018;8:10378.
16. Ikonomidis I, Vlastos D, Kourea K, et al. Electronic cigarette smoking increases arterial stiffness and oxidative stress to a lesser extent than a single conventional cigarette: an acute and chronic study. Circulation 2018;137:303-6.
17. Nocella C, Biondi-Zoccai G, Sciarretta S, et al. Impact of tobacco versus electronic cigarette smoking on platelet function. Am J Cardiol 2018;122:1477-81.
18. Benowitz NL, Burbank AD. Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. Trends Cardiovasc Med 2016;26:515-23.
19. Chen C, Zhuang YL, Zhu SH. E-cigarette design preference and smoking cessation: a U.S. population study. Am J Prev Med 2016;51:356-63.
20. DeJarnett N, Conklin DJ, Riggs DW, et al. Acrolein exposure is associated with increased cardiovascular disease risk. J Am Heart Assoc 2014;3:pii:e000934
21. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation 2019;140:e596-e646.

Keywords: Electronic Nicotine Delivery Systems, Nicotine, Tobacco, Tobacco Industry, Tobacco Use Cessation, Tobacco, Smokeless, Tobacco Smoke Pollution, Tobacco Products, Harm Reduction, American Heart Association, Biological Availability, Polycyclic Aromatic Hydrocarbons, Cardiovascular Diseases, Follow-Up Studies, Risk Factors, Smoking, Smoking Cessation, Myocardial Ischemia, Cardiovascular System, Primary Prevention, Platelet Activation

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