In the 15 years since e-cigarettes became commercially available, there has been ongoing debate about the health risks of using these devices, as well as the potential utility of e-cigarettes in smoking cessation efforts.1 Among the various health effects of e-cigarette use (i.e., vaping), researchers continue to explore the cardiovascular (CV) impact of vaping, with somewhat mixed results.

Following 2 large cross-sectional studies showing no significant association between exclusive e-cigarette use and CV disease (CVD) risk, the authors of recent research aimed to further elucidate the potential effects of these products on heart health.2

In a 2022 study funded in part by the National Institutes of Health (NIH), Berlowitz et al conducted a longitudinal analysis based on self-reported data from roughly 24,000 adult participants (50% of whom were younger than 35 years) in the national PATH (Population Assessment of Tobacco and Health) Study to examine the link between e-cigarette use and incident CVD.2

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After adjusting for covariates including demographic factors, comorbidities, and smoking history, analyses showed no difference in CVD risk between exclusive e-cigarette users and nonusers of combustible cigarettes or e-cigarettes (hazard ratio [HR], 1.00; 95% CI, 0.69-1.45) in up to 4 years of follow-up.

In addition, the results revealed a 30% to 40% lower risk for the outcome of “any CVD” in association with e-cigarette users compared with combustible cigarette users.

Among individuals who identified as dual users of both e-cigarettes and combustible cigarettes, no difference in risk was observed for any CVD (HR, 1.01; 95% CI, 0.81–1.26) or for myocardial infarction (MI), heart failure (HF), or stroke (HR, 0.94; 95% CI, 0.65–1.36) compared with exclusive users of combustible cigarettes.

However, dual users demonstrated a significantly higher CVD risk compared with nonusers in any CVD outcome (HR, 1.54; 95% CI, 1.21-1.96) and in MI, HF, or stroke outcomes (HR, 2.08; 95% CI, 1.40-3.09).

The authors noted several limitations of their study, such as the use of self-reported data and the short follow-up period which may be inadequate to capture the development of CVD.2

Meanwhile, their results suggest that using e-cigarettes while attempting to taper the use of combustible cigarettes does not reduce CVD risk compared to the exclusive use of combustible cigarettes.3

On a related note, the authors of a study published in August 2022 in BMC Medicine conducted a single-center, 3-arm randomized controlled trial to investigate CV effects in 248 individuals attempting to quit smoking with the aid of e-cigarettes or prescription nicotine replacement therapy (NRT).4

Participants were assigned to 1 of 3 groups consisting of the following intervention along with behavioral support: e-cigarettes containing nicotine (18 mg/mL), e-cigarettes with no nicotine, or NRT.

Compared with baseline measures, all 3 groups demonstrated improvements in flow-mediated dilation at 3 months (β=3.33; 95% CI, 2.61-4.05; P <.0001) and 6 months (β=2.69; 95% CI, 2.02-3.35; P <.0001), with no significant difference between groups.

Improvements in the secondary outcomes of mean arterial pressure and peak cutaneous vascular conductance responses to acetylcholine and sodium nitroprusside were also noted after 3 and 6 months, with no significant between-group differences.

All approaches were associated with positive CV effects, and none of the interventions were associated with superior comparative CV outcomes.

Matthew L. Springer, PhD, professor of medicine in the division of cardiology at the University of California, San Francisco, School of Medicine and researcher in the UCSF Cardiovascular Research Institute and the UCSF Center for Tobacco Control Research and Education, has conducted numerous studies on the CV effects of e-cigarettes.

In a NIH-funded study published in October 2022, he and colleagues observed lower flow-mediated dilation as well as blood changes inhibiting endothelial nitric oxide (NO) release in both chronic smokers and chronic e-cigarette users compared to nonusers. The findings also revealed vaping-specific changes associated with increased microvascular endothelial permeability and greater intracellular oxidative stress.5

Other researchers have found increased acute or long-term arterial stiffness, blood pressure, heart rate, and sympathetic tone in e-cigarette users, with evidence indicating that some of these effects may result from nicotine exposure specifically.1

To clarify the evidence and clinical implications regarding the effects of e-cigarettes on cardiac health, we interviewed Dr Springer along with Sandhya Venugopal, MD, clinical professor of health sciences in the division of cardiovascular medicine, director of the ECG Lab, and associate dean of continuing medical education at the University of California Davis School of Medicine in Sacramento, and Kinjan Parikh, MD, cardiologist and clinical instructor in the Leon H. Charney Division of Cardiology at the New York University Grossman School of Medicine. 

What does the latest evidence suggest about the CV effects of e-cigarette use in general and as compared to combustible cigarettes?

Dr Venugopal: Even though the use of cigarettes may have decreased in the last few years, nicotine addiction has continued secondary to e-cigarettes in the market. Because nicotine in any form is highly addictive, vaping with nicotine-containing substances can become habitual. Michael Blaha, MD, at the Johns Hopkins University School of Medicine, points to evidence suggesting that vaping by young people increases the probability of subsequent use of illicit drugs and tobacco products.6 E-cigarettes were the most commonly used smoking products among youth in 2015, with a more than 9‐fold increase in usage from 2011 to 2015.7

Although e-cigarettes have the potential to be less harmful than conventional cigarettes due to their reduced number of harmful chemicals, the effects of e-cigarettes on the CV system are not well-known. One of the complexities of studying the CV effects of e-cigarettes is the large variety of devices and chemical compositions of e-liquids.

Many constituents of e-cigarette aerosols, including nicotine, carbonyl compounds, delicate particulate matter, and metals are associated with substantial toxicity. Inhalation of e-cigarette aerosols among young, healthy adults induces inflammation and oxidative stress. Cross-sectional analysis of CV symptoms showed that e-cigarette users have a higher risk of coronary heart disease, arrhythmia, chest pain, and palpitations.8

The literature on the consequences of second-hand e-cigarette vaping is limited.

Dr Parikh: Recent research funded by the NIH shows likely similar long-term CV risk from e-cigarettes as from traditional combustible cigarettes.2 The constituents of e-cigarette – which include many of the same components from classic cigarettes – increase inflammation in the body and oxidative stress directly to the blood vessels, including the coronary arteries supplying the heart.

Through intermediaries such as a decrease in NO and an increase in hydrogen peroxide and permeability, direct damage is caused to the blood vessels, creating the substrate for long term CVD. Notably, e-cigarettes are relatively new, thus more data is needed to fully understand their long-term health effects.  

Dr Springer: It’s pretty clear from our work and that of several other research groups that e-cigarette use involves some of the same risks as combustible cigarette smoking. Adverse effects of acute exposure to e-cigarette aerosol on vascular endothelial function have been demonstrated in humans and rats, using standard freebase nicotine e-cigarettes, nicotine salt e-cigarettes like JUUL, and e-cigarettes using only the proplyene glycol and vegetable glycerin (PG/VG) vehicle with no nicotine.

We’ve shown that chronic e-cigarette users also have impaired endothelial function relative to nonusers and comparable to that of chronic smokers, and that both the chronic e-cigarette users and chronic smokers have serum that blunts the production of NO by cultured endothelial cells relative to non-user serum.5

Recent work out of the University of West Virginia shows that rats exposed to e-cigarette aerosol only while in utero have persistent vascular problems into adulthood, such as vascular stiffness and impaired aortic relaxation.9

In rat experiments that we recently published, we saw that a daily realistic vaping session for 8 weeks caused a decrease in cardiac function and adverse effects on heart rate variability, susceptibility to arrhythmias, cardiac fibrosis, cardiac microvessel density, and remodeling of cardiac nerves to a more sympathetic balance.10

Since e-cigarette aerosol contains far fewer chemicals than combustion smoke, it’s presumably less harmful than cigarette smoke overall. However, the aerosol contains not just the components initially present in the e-liquid, but also toxic chemical reaction products that occur in the liquid upon storage for many months, reaction products that occur during heating at the heating coil, and metals and particles that come off the coil and wick.

In fact, some of the adverse effects of smoking and vaping on endothelial function appear to be not specific to individual chemicals and instead to derive from airway irritation, as we have recently found that severing the vagus nerve in anesthetized rats completely protects them from tobacco smoke-induced vascular dysfunction.11

So, there are a number of reasons to expect that vaping involves some of the same adverse effects as smoking and presumably lacks other adverse effects of smoking. However, vaping also caused adverse effects that smoking does not cause. For example, in our recent study of chronic e-cigarette users and smokers, serum from the chronic e-cigarette users caused an increase in microvascular endothelial cell permeability in culture that was not caused by serum from chronic smokers or from non-users.5 

Furthermore, serum samples from smokers and from vapers contain elevated levels of circulating inflammatory biomarkers, but the 2 groups have elevated levels of different subsets of these markers.5

The takeaway from all of this is that vaping causes some harmful effects of smoking, vaping lacks other harmful effects of smoking, and vaping causes harmful effects that smoking does not cause. Therefore, while it’s likely that someone who completely switches from smoking cigarettes to vaping will experience a reduction in overall risk, the vaping is not harmless. What’s more, incompletely switching so that someone who used to exclusively smoke now vapes but still smokes a little, may result in experiencing the adverse effects of both behaviors.

How should physicians advise patients on the risks of e-cigarettes?

Dr Venugopal: Doctors should convey the information about e-cigarettes in a nonjudgmental way and let patients know that further data is still needed to clarify their effects.

Dr Parikh: I counsel my patients to refrain from e-cigarettes the same as I would for combustible cigarettes. While we are continuing to collect data supporting the potential health risks and damage these agents can cause, we have little to no data showing any benefit with their use.  

Dr Springer: If you don’t smoke or vape, don’t start vaping. If you smoke, it’s best to completely quit. If a quitting smoker feels the need to vape and can’t be convinced not to, then they should be strongly encouraged to switch completely and not still smoke.

Is there a role for e-cigarettes in smoking cessation? If so, which patients seem to be good candidates?

Dr Venugopal: There are no current evidence-based guidelines for physicians to follow on the use of e-cigarettes. The US Preventive Services Task Force and American College of Physicians recommended against the use of them as a smoking cessation tool given the conflicting and limited evidence.12

In previously published studies, the percentage of healthcare providers who prescribed e-cigarettes to help quit smoking ranged from 4% to 35%, implying a significant variation in clinical practice.13,14

A meta-analysis of CV outcomes of smokers switching from traditional cigarettes to e-cigarettes did not show any improvement in stroke, MI, or coronary heart disease outcomes. However, this work showed reduced adverse respiratory effects in smokers who switched to e-cigarettes.15 Additionally, more extensive studies have shown that smokers who do not stop smoking often use both conventional cigarettes and e-cigarettes, and these dual users have a higher CV risk compared to those who only smoke conventional cigarettes.15

Dr Parikh: No. E-cigarettes are just as addictive as traditional cigarettes, and there is also the recent data supporting a likely additive harm to using both types of cigarettes. The proposed mechanism is that they may activate different pathways that compound one another’s harmful effects.  

Dr Springer: Possibly. Studies have shown that e-cigarettes can be part of an effective smoking cessation program when the program includes other aspects like counseling. Other studies indicate that vaping without the other aspects of the program isn’t a clearly effective cessation tool, although I’m sure for some individuals, it has worked.

What are the top priorities in terms of research and education regarding e-cigarette use? 

Dr Venugopal: One of the complexities of studying the CV effects of e-cigarettes is the large variety of devices and chemical compositions of e-liquids. There is a need for continued FDA regulation and safety testing of new flavors and devices. In addition, more data is still needed regarding the long-term effects of e-cigarettes, especially their impact on CVD in susceptible populations. 

Dr Parikh: Studies to improve our understanding of the long-term effects of e-cigarettes are needed. There is also an ongoing need for education, particularly to the younger population, that e-cigarettes are not a safer alternative to combustible smoking but rather have similar dangerous effects.

Dr Springer: I’m very concerned about the “anything goes” nature of e-cigarettes. Some of the ingredients can be regulated to minimize those that have specific harmful effects, but people can and do put anything in an e-cigarette that they want to. Many ingredients in your kitchen are fine to eat but may be harmful if inhaled; the buttery popcorn flavoring agent is one of the earliest examples of this, tasted great but causes permanent lung disease.17 

I think people need to be very careful of what they put into their lungs. We should do our best to prevent kids from starting to vape, and if adults want to vape, it should be an informed decision with the knowledge that this is not a harmless activity – that is, it’s not “harmless water vapor.”

Reference

  1. Wold LE, Tarran R, Crotty Alexander LE, et al; on behalf of the American Heart Association Council on Basic Cardiovascular Sciences; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Hypertension; and Stroke Council. Cardiopulmonary consequences of vaping in adolescents: a scientific statement from the American Heart Association. Circ Res. Published online June 21, 2022. doi:10.1161/RES.0000000000000544
  2. Berlowitz JB, Xie W, Harlow AF, et al. E-Cigarette use and risk of cardiovascular disease: a longitudinal analysis of the PATH Study (2013-2019). Circulation. Published online May 6, 2022. doi:10.1161/CIRCULATIONAHA.121.057369
  3. American Heart Association. Smoking both traditional and e-cigarettes may carry same heart risks as cigarettes alone. Published online May 6, 2022. Accessed December 11, 2022.
  4. Klonizakis M, Gumber A, McIntosh E, Brose LS. Medium- and longer-term cardiovascular effects of e-cigarettes in adults making a stop-smoking attempt: a randomized controlled trial. BMC Med. Published online August 16, 2022. doi:10.1186/s12916-022-02451-9
  5. Mohammadi L, Han DD, Xu F, et al. Chronic e-cigarette use impairs endothelial function on the physiological and cellular levels. Arterioscler Thromb Vasc Biol. Published online October 26, 2022. doi:10.1161/ATVBAHA.121.317749
  6. Wood S. Cardiologists take note: troubling e-cigarette trends warrant new tack. TCTMD. Published online July 26, 2022. Accessed December 11, 2022.
  7. Singh T, Arrazola RA, Corey CG, et al. Tobacco use among middle and high school students — United States, 2011–2015. MMWR Morb Mortal Wkly Rep. Published online April 15, 2016. doi:10.15585/mmwr.mm6514a1
  8. Wang JB, Olgin JE, Nah G, et al. Cigarette and e-cigarette dual use and risk of cardiopulmonary symptoms in the Health eHeart Study. PLoS One. Published online July 25, 2018. doi:10.1371/journal.pone.0198681
  9. Burrage EN, Aboaziza E, Hare L, et al. Long-term cerebrovascular dysfunction in the offspring from maternal electronic cigarette use during pregnancy. Am J Physiol Heart Circ Physiol. Published online July 27, 2021. doi:10.1152/ajpheart.00206.2021
  10. Qiu H, Zhang H, Derakhshandeh R, et al. Abstract 9922: Increased susceptibility to arrhythmias, hypertension, and hypertrophy in a rat model of exposure to electronic, heat-not-burn, or conventional cigarettes, or marijuana. Circulation. Published online November 8, 2021
  11. Nabavizadeh P, Liu J, Rao P, et al. Impairment of endothelial function by cigarette smoke is not caused by a specific smoke constituent, but by vagal input from the airway. Arterioscler Thromb Vasc Biol. Published online October 26, 2022. doi:10.1161/ATVBAHA.122.318051
  12. US Preventive Services Task Force, Krist AH, Davidson KW, Mangione CM, et al. Interventions for tobacco smoking cessation in adults, including pregnant persons: US Preventive Services Task Force recommendation statement. JAMA. Published online January 19, 2021. doi:10.1001/jama.2020.25019
  13. Cummins S, Leischow S, Bailey L, et al. Knowledge and beliefs about electronic cigarettes among quitline cessation staff. Addict Behav. Published online April 6, 2016. doi:10.1016/j.addbeh.2016.03.031
  14. Kandra KL, Ranney LM, Lee JG, Goldstein AO. Physicians’ attitudes and use of e-cigarettes as cessation devices, North Carolina, 2013. PLoS One. Published online July 29, 2014. doi:10.1371/journal.pone.0103462
  15. Goniewicz ML, Miller CR, Sutanto E, Li D. How effective are electronic cigarettes for reducing respiratory and cardiovascular risk in smokers? A systematic review. Harm Reduct J. Published online November 23, 2020. doi:10.1186/s12954-020-00440-w
  16. Kim CY, Paek YJ, Seo HG, et al. Dual use of electronic and conventional cigarettes is associated with higher cardiovascular risk factors in Korean men. Sci Rep. Published online March 27, 2020. doi:10.1038/s41598-020-62545-3
  17. Egilman DS, Schilling JH. Bronchiolitis obliterans and consumer exposure to butter-flavored microwave popcorn: a case series. Int J Occup Environ Health. Published online November 12, 2013. doi:10.1179/1077352512Z.0000000005

This article originally appeared on The Cardiology Advisor

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Cardiovascular Disease Smoking