Introduction
Over the past 2 decades, electronic cigarettes (e-cigarettes) have soared in popularity for multitude of reasons, including claims of being a safer alternative to traditional tobacco and pop culture-bolstered influence.1,2 Since its introduction to the US market in 2003,2 questions have risen as to the safety, long-term consequences, and risk of cardiovascular detriments that e-cigarettes pose to users.

As research has ensued, more harmful compounds have been found present in e-cigarette aerosol, similar to the well-established negative health outcomes associated with traditional tobacco cigarettes.2,3 Although it has been established that e-cigarette vapors, by and large, contain fewer total compounds than traditional tobacco cigarettes, they often still contain numerous toxic substances, albeit at lower concentrations.4

Atherosclerosis and Nicotine
Nicotine, the primary shared compound between e-cigarette and traditional tobacco, has been a well-established catalyst for the development of atherosclerotic cardiovascular disease. Nicotine has been shown to induce the release of catecholamines and cortisol, cause hemodynamic changes (increased blood pressure, heart rate, and vasoconstriction), and cause adverse changes in lipid profiles (increased saturated fat content, decreased unsaturated fat content, and increased total cholesterol).5

Additionally, e-cigarette users have been found to have significantly decreased vascular elasticity, which may lead to heart disease and stroke, along with similar inflammatory infiltrate of the vasculature seen in cigarette smokers that lead to atherosclerosis over time.5 Other findings that correlate to nicotine exposure, either first- or second-hand, include aortic stiffness, insulin resistance, inhibition of apoptosis, and promotion of angiogenesis—all of which may accelerate atherosclerotic (and malignancy) progression.

Epidemiological Findings with E-Cigarette Use and Cardiovascular Events
Recent findings presented at the American College of Cardiology 68th Annual Scientific Session link e-cigarette use to cardiovascular events such as myocardial infarction, coronary artery disease, and, interestingly, depression (believed to have an inflammatory contributing cause).6 The study was a cross-sectional analysis of pooled data from 96,467 respondents to the CDC National Health Interview Survey conducted in the years 2014, 2016, and 2017.

Compared with non-users, adults who reported use of e-cigarettes had significantly greater likelihood of having myocardial infarction (OR 1.558, 95% CI, 1.447-1.678), stroke (OR 1.297, 95% CI, 1.201-1.400), depression/anxiety/emotional problems (OR 2.200, 95% CI, 2.06-2.347), and circulatory issues (OR 1.436, 95% CI (1.251-1.648).6,7

It is important to note, however, that epidemiological data from a survey such as this does have its limitations, including the potential for recall bias and a lack of ability to establish temporal causation. Although there are more longitudinal data needed to more concretely establish whether there are cardiovascular risks associated with e-cigarette use, the fact that many of the same common toxins found in traditional tobacco products are also found in e-cigarettes should be a cause for concern and an initial starting point when discussing e-cigarette use with patients.

Contemporary epidemiological data suggest, but do not prove, that there is an increased risk of cardiovascular events with the use of e-cigarettes when compared with non-users. Regardless, the cardiovascular detriments caused by nicotine, as noted by previous scientific research, should be considered in all clinician-patient conversations about cigarette use, whether electronic or traditional. Many patients may not be aware of the risks posed by nicotine alone.

The lack of FDA regulation of nicotine content and e-liquid preservative content, along with the lack of FDA-approval for e-cigarettes as a smoking cessation aid, make for a difficult argument to be made in favor of their use as such. Behavioral therapy combined with existing FDA-approved therapies for smoking cessation (ie, nicotine replacement therapies, varenicline, bupropion) have been well-established with evidence backing their safety and efficacy for this use. As such, this should continue to remain the first-line consideration for smoking cessation.

It is our opinion that the use of e-cigarettes, whether for leisure or as a smoking cessation aid, should not be recommended to any patient. The presence of toxic compounds with known cardiovascular detriments and the absence of clear smoking cessation benefit within the current literature should lead us as clinicians to err on the side of caution, avoiding e-cigarettes altogether.

Patients may believe that there are no harmful chemicals within e-cigarette aerosol, which can and should be, refuted if brought up during clinician-patient discussions. Patients should be educated on the cardiovascular risks of nicotine consumption alone, as well as those risks posed by the other common additives found in e-cigarettes. Emphasis should be placed on the preliminary findings suggestive of positive correlations between the use of e-cigarettes and cardiovascular disease occurrence.

The Role of Pharmacists
Although trends in the use of e-cigarette and vaping products may be cause for concern, they present yet another opportunity for pharmacists—regardless of practice setting—to make a positive impact on the lives of patients. For nearly 2 decades, pharmacists have been rated by Gallup’s Honesty and Ethics survey as 1 of the top 3 most trusted professionals as perceived by the public.8

This trust has been hard-earned, and pharmacists can harness this relationship with the public to improve public health by having conversations with their patients about the potential harm of e-cigarettes or vapes. Pharmacists continue to play an important role in aiding traditional smoking cessation using nicotine replacement therapies, varenicline, and bupropion, along with referrals to counseling services, particularly referral to the national Quitline (800-QUIT-NOW), when needed.

Regarding e-cigarette and vaping products, pharmacists have a role in furthering patients’ ability to successfully stop smoking by educating patients about the myths surrounding e-cigarette use as a smoking cessation aid and exposing other risks such as accidental e-liquid ingestion and potentially dangerous e-cigarette malfunctions (eg, combustion).

Table 1: Data from the American College of Cardiology on adverse events associated with e-cigarette and traditional tobacco, as compared to non-users.6,7
Cardiovascular Event or Disease State Percent Increase in Probability of an Event in E-Cigarette Users
Compared to Non-Users (before controlling confounding variables*)
Percent Increase in Probability of an Event in E-Cigarette Users
Compared to Non-Users (after controlling confounding variables*)
Percent Increase in Probability of an Event in Traditional Tobacco Smokers Compared to Non-Smokers
Myocardial Infarction 56% (95% CI 45%-68%),
p<0.0001
34% 165% (95% CI 151%-180%), p<0.0001
Cerebrovascular Accident (Stroke) 30% (95% CI 20%-40%), p<0.0001 No statistically significant difference 78% (95% CI (69%-88%), p<0.0001
Circulatory insufficiency; Thromboembolic events 44% (95% CI 25%-65%), p=0.0001 No statistically significant difference Percent increase not given however, 95% CI 34%-66%, p<0.0001
Coronary Artery Disease 10% 25% +94%,
*Confounding variables included age, sex, body mass index, past diagnosis of hyperlipidemia, past diagnosis of hypertension, and concomitant tobacco cigarette use.

References
  1. Perikleous EP, Steiropoulos P, Paraskakis E, Constantinidis TC, Nena E. E-Cigarette use among adolescents: an overview of the literature and future perspectives. Front Public Health. 2018;6:86. doi:10.3389/fpubh.2018.00086
  2. US Department of Health and Human Services. E-cigarette use among youth and young adults: A report of the surgeon general. Atlanta, GA: US Department of Health and Human Services, CDC; 2016. https://e-cigarettes.surgeongeneral.gov/documents/2016_SGR_Full_Report_non-508.pdf
  3. Darville A, Hahn EJ. E-cigarettes and atherosclerotic cardiovascular disease: what clinicians and researchers need to know. Curr Atheroscler Rep. 2019;21(5):15. doi:10.1007/s11883-019-0777-7
  4. Rehan HS, Maini J, Hungin APS. Vaping versus smoking: a quest for efficacy and safety of e-cigarette. Curr Drug Saf. 2018;13(2):92-101. doi:10.2174/1574886313666180227110556
  5. Zhang G, Wang Z, Zhang K, et al. Safety assessment of electronic cigarettes and their relationship with cardiovascular disease. Int J Environ Res Public Health. 2018;15(1):75. doi:10.3390/ijerph15010075
  6. American College of Cardiology. E-cigarettes linked to heart attacks, coronary artery disease and depression. American College of Cardiology. 2020. [online] Available at: <https://www.acc.org/about-acc/press-releases/2019/03/07/10/03/ecigarettes-linked-to-heart-attacks-coronary-artery-disease-and-depression#:~:text=New%20research%20shows%20that%20adults,them%20or%20any%20tobacco%20products.> [Accessed 30 July 2020].
  7. Vindhyal Mohinder R, Paul N, Cyrus M, Shravani V, Hayrettin O. Impact on cardiovascular outcomes among e-cigarette users: A review from national health interview surveys. J Am Coll Cardiol. 2019;73(9):11. https://doi.org/10.1016/S0735-1097(19)33773-8. doi: 10.1016/S0735-1097(19)33773-8.
  8. National Association of Chain Drug Stores. Pharmacists rank second again among Gallup’s most trusted professionals. NACDS.org. 2016. https://www.nacds.org/news/pharmacists-rank-second-again-among-gallups-most-trusted-professionals/. Published December 21, 2016. [Accessed January 6, 2021].