Is it time to be concerned about the effects of e-cigarettes on cardiovascular health?

KEYWORDS:

• E-cigarette
• electronic nicotine delivery system
• health
• cardiovascular disease
• myocardial infarction

According to the World Health Organization (WHO), an e-cigarette (also called electronic nicotine delivery system; ENDS) is defined as a device which does not directly burn tobacco, but vaporizes a solution which can then be inhaled by the user [1]. The leading components of this solution usually include nicotine, propylene glycol, vegetable glycerin, and flavoring agents. Recent statistics attests that the global worldwide market of ENDSs amounted to approximately 11.5 billion US$ in 2016, but is predicted to undergo a double-digit growth up to 2025, with up to 30% of current cigarette smokers predicted to shift to using e-cigarettes [2]. These notable figures prompt many international, national healthcare and consumer organizations to raise safety issues about the possible harm caused by ENDSs use. Among these, the WHO has recently endorsed a number of official warnings aimed to: (i) prevent initiation of ENDS and/or electronic non-nicotine delivery systems use among nonsmokers, young people, and vulnerable groups; (ii) minimize health risks associated with the use of ENDS; (iii) prevent unconfirmed health claims made about ENDS; and (iv) protect people from particular interests connected with ENDS industry [1]. Regardless of these straightforward advices, it may be useful to briefly summarize here the recent scientific evidence on the potential impact of ENDSs on cardiovascular health. Although the research is still rudimentary due to the relatively recent commercialization of ENDSs, some preliminary findings have been published.

Polosa et al. recently published the results of a small, 3.5-year prospective observational study consisting of 9 daily ENDSs users (mean age 30 ± 6 years) and 12 matched controls who had never smoked [3]. At the end of the follow-up period, pathological findings in the lung and heart rate, blood pressure, and respiratory symptoms were found to be similar between the two cohorts. Hua and Talbot carried out an Internet search for identifying case reports describing health problems associated with ENDSs use [4]. Overall, 27 cases could be detected with this search, which could be classified in 3 categories of unfavorable health effects (i.e., systemic effects, mechanical injury, and nicotine poisoning). More specifically, respiratory symptoms were the most frequent and could be identified in six subjects, followed by gastrointestinal (n = 3), cardiovascular (n = 2), neurological (n = 1), and immune (n = 1) complications. Importantly, as many as 12 cases of nicotine poisoning could be identified, resulting from accidental, misuse/abuse, or suicidal/intentional ingestion. Finally, two cases could be found of people injured by ENDSs battery explosion.

A preliminary report of a large cross-sectional study based on the 2014 US National Health Interview Survey database, totaling over 35,000 subjects, has been recently published by Temesgen et al. [5]. Predictably, the risk of acute myocardial infarction (AMI) compared to subjects who had never smoked was found to be 2.7-fold higher in every day combustible cigarettes smokers and 1.8-fold higher in former combustible cigarettes smokers, respectively. Although the risk of AMI in ENDSs users was lower than in combustible cigarettes smokers, it was still 42% higher than in subjects who had never used these devices.

Although no epidemiological studies, either cross-sectional or perspective, have been published on the potential association between ENDSs and cancer up until now, Lee et al. recently carried out an experimental study aimed at assessing the DNA damage triggered in mice exposed to ENDS smoke [6]. Notably, not only could a number of mutagenic compounds be detected in lung, heart, and bladder tissues, but DNA-repair activity was also found to be significantly decreased in the lung tissue. A similar mutational vulnerability and carcinogenic transformation could be observed in cultured human urothelial and bronchial epithelial cells exposed to ENDS vapor. These finding persuaded the authors to conclude that ENDS vapor exposure may predispose users to bladder and lung cancers, and may also enhance the risk of cardiac diseases and dysfunction.

Some reasonable biological explanations were found in experimental and clinical studies to justify the cardiovascular and respiratory harms possibly caused by ENDS vapor. These mostly include upper and lower respiratory tract inflammation, increased airway resistance, lower efficiency of immune system, increase of heart rate and blood pressure, endothelial cell dysfunction, blood platelets activation, oxidative stress, along with direct vascular injury, which would ultimately predispose subjects to an enhanced risk of both atherosclerosis and thrombosis [7]. A very recent study published by Olfert et al. [8] investigated the effect of ENDS vapor on vascular function in mice. Notably, intermittent daily exposure to ENDS vapor for 8 months was associated with a 2.5-fold increase of arterial stiffness, 24% decrease of maximal aortic relaxation in response to methacholine, with a trend toward reduced fractional shortening and ejection fraction. Most of the unfavorable cardiovascular effects were similar to those observed in mice exposed to combustible cigarette smoke over the same period of time, except for emphysema-associated changes which were absent in ENDS vapor-exposed mice. Impaired pulmonary antimicrobial defenses have also been observed in mice exposed to ENDS vapors for 2 weeks [9], thus enhancing vulnerability to both bacterial and viral infections. Moheimani et al. evaluated the effects of ENDS on cardiac autonomic tone, systemic oxidative stress and inflammation in 23 habitual e-cigarette users and 19 nontobacco cigarette, non–e-cigarette users [10]. These authors finally reported that habitual ENDS use increases sympathetic activity and oxidative stress, thus contributing to enhance the cardiovascular risk.

It is now unquestionable that combustible cigarette smoke is directly associated with a vast array of biological damages, especially with a remarkably enhanced risk of cancer, cardiovascular, and pulmonary diseases. The use of ENDSs has hence been advocated as a surrogate or replacement of combustible cigarette smoke based on claims that these devices may be safer and would trigger lower health threats. Nonetheless, the findings of recent studies seem at odds with this assumption. Kalkhoran and Glantz carried out a systematic review and meta-analysis based on 38 studies (20 studies including a control group) on the impact of ENDS on smoking cessation [11] and concluded that the probability of quitting combustible cigarette smoke was 28% lower in subjects using ENDSs compared to those who did not use these devices. Even more importantly, Soneji et al. carried out another more recent systematic review and meta-analysis based on 9 studies and totaling 17,389 adolescents or young adults aged between 14 and 30 years [12], concluding that the risk of subsequent combustible cigarette smoke initiation was over 3.6-fold higher in young people using ENDSs compared to those who did not use these devices. Taken together, the results of these two meta-analyses are concordant to conclude that ENDSs are not efficient for quitting current tobacco smoke, long-term substitutes for smoking or as deterrents for future combustible cigarette smoke initiation. Interestingly, Benowitz and Fraiman recently concluded that the impact of ENDSs on cardiovascular system partially mirrors that of nicotine [13], thus possibly contributing to accelerate atherosclerosis and predisposing the smokers to an enhanced risk of acute cardiovascular diseases, especially in patients with underlying coronary artery disease.

While theoretically straightforward, the long-term adverse biological effects of ENDSs on cardiovascular function are still poorly defined. Further studies, in which appropriate parameters are specifically evaluated and confounding variables are strictly considered, will hence be needed to definitely establish the possible cardiovascular harms of ENDSs [14]. Nonetheless, the currently available evidence does not convincingly reassure that these devices are as safe as often claimed. In fact, although it seems reasonable to infer that the ENDS vapors may contain less toxic compounds than combustible cigarette smoke and may hence be safer [15–17], the vapor generated by these devices still contains a large number of potentially unhealthy substances. Therefore, although replacing conventional cigarettes with ENDSs may generate possible benefits for public health, their usage should be firmly discouraged in people who had never used combustible cigarettes and in vulnerable individuals subjected to secondhand exposure.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

This paper was not funded.