Review articleThe effect of emerging tobacco related products and their toxic constituents on thrombosis
Introduction
There is overwhelming evidence that conventional cigarette smoking (CS) is a major risk of cardiovascular disease (CVD), not only to active users, but also individuals within close vicinity [1], [2]. For instance, CS in both men and women increases the incidence of myocardial infarction (MI) and fatal coronary artery disease (CAD) [3]. Similarly, studies also demonstrated that even low-tar cigarettes increase the risk of acute cardiovascular events in comparison to nonsmokers [4]. Along the same lines, passive smoking or environmental tobacco exposure- with a smoke exposure that is only 0.01% that of active CS- was found to be associated with approximately a 30% increase in risk of CAD, compared with an 80% increase in active smokers [1]. It is worth mentioning that the risk of CVD due to CS is both dose and duration dependent [3], [5], [6]. In short, the available set of facts- that took decades to accumulate- document a clear link of CS to major negative health consequences, particularly in the case of CVD. This body of evidence, along with efforts from private and public entities mounted “push back” campaigns against CS use, which is considered a public health problem. Consequently, these efforts have resulted in noticeable decline in CS use in the United States (US) and Europe [7]. Nonetheless, although CS has experienced a declining trend on a global scale [8], emerging tobacco related products (ETRP) are gaining ground [9], especially among the youth [10], [11], and women of childbearing age [12], [13]. The observed increase in the use of ETRPs is multifactorial and complex but appears to be mainly driven by efforts from the major tobacco companies to reinvent themselves, and present more appealing and allegedly safe(r) tobacco products [14], [15], [16]. Fortunately, nonetheless, these ETRP are now the focus of rigorous research efforts-including from our team- to understand their safety profile and their effects on health outcomes, including in the context of thrombotic CVD. It is of utmost importance to note that thrombosis is a major mechanism of occlusive CVDs. To this end, thrombosis is defined as the pathological condition in which a blood clot is formed within blood vessels, lead to obstruction of blood flow, and that can manifest as an MI or stroke. Major players in thrombosis include hyperactive platelets, activated coagulation system, and vascular endothelium injury. Therefore, in this review we will discuss the potential impact of ETRPs on thrombotic based CVD. Furthermore, we will review how these products and the major chemicals they produce/emit can trigger inflammation, and oxidative stress, as well as how they impact platelets, coagulation, and the vascular endothelium- all of which are key players in the process of thrombosis- and the relationship between these effects.
Section snippets
Emerging tobacco related products
ETRPs are group of products that include electronic cigarettes, waterpipes/hookah, cigars/cigarillo, smokeless tobacco, and heat-not-burn (HNB) cigarettes (see Table 1). These products emerged on the premise of their safe profile – especially in current smokers trying to quit - in comparison to traditional cigarettes, and this assumption made them very appealing to many, including the youth (e.g., high and middle school students; Fig. 1A). In the next section, we will describe the different
Emerging tobacco related products and thrombosis
Thrombosis, which is the formation of blood clots inside blood vessels, can lead to a reduction in the blood supply to organs, and consequently hypoxia and/or tissue damage. Hemostasis on the other hand, is the physiologically balanced response to vascular/circulatory injury that results in the formation of a platelet-fibrin clot, which prevents further bleeding. The hemostatic machinery integrates many players, including the endothelium, the clotting factors (e.g., fibrinogen) and importantly
Emerging tobacco related products, inflammation, oxidative stress, and thrombosis
It is inferred from the evidence in the literature that inflammation, oxidative stress, and thrombosis are interconnected processes that can be very detrimental to our cardiovascular system health. Therefore, it is imperative to discuss this process in one framework to appreciate their role in this disease state. To this end, animal and human studies (including data from Population Assessment of Tobacco and Health Study (PATH)) indicate that the majority if not all of the tobacco products can
Toxic profile of emerging tobacco related products
Although the levels of toxic chemicals emitted by ETRPs vary, it is important to note that these tobacco products are not emission free, and the toxic chemicals they emit are hazardous (Table 1), and have the capacity to lead to serious health issues (including CVD), even at low levels [97]. According to accumulating data, tobacco's toxic chemicals that received the greatest scrutiny as possible contributors to CVD, include nicotine [98], particulate matter [99], polyaromatic hydrocarbons
Nicotine
Like conventional cigarettes, ETRPs contain considerable amounts of nicotine. For example, e-liquids, which are used in most ENDS such as e-cigarettes typically contain nicotine at concentrations ranging between 0 and 87.2 mg/mL [101], albeit some e-liquids are “nicotine free”. Furthermore, JUUL, which is one of the popular ENDS, contains e-liquid with nicotine concentrations that could reach as high as 59 mg/mL [102]. With regard to waterpipe, the average nicotine content ranges between 67 and
Conclusion
ETRPs were introduced into the market as safe/safer options, mainly for individuals who would like to transition and quit cigarette smoking. However, the safety of these products is questionable. In fact, in many instances, some of these products appear to exert greater negative health effects than cigarette smoking. This- at least in part- derives from the fact that ETRPs emit considerable and often comparable levels of toxic chemicals, in comparison with conventional cigarettes. A host of
CRediT authorship contribution statement
FA and FK: conceptualized the manuscript, and critically revised it; AA and PL: wrote the manuscript, and developed figures.
Sources of funding
Research reported in this publication was supported by the National Institute of Environmental Health Sciences and the National Heart, Lung, And Blood Institute of the National Institutes of Health under Awards Number R21ES029345, R03ES030486 and R01HL145053. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Declaration of competing interest
The authors declare that there are no conflicts of interest.
Abbreviations
- CS
- cigarette smoking
- CVD
- cardiovascular disease
- CAD
- coronary artery disease
- e-Cig
- electronic cigarettes
- ETRPs
- emerging tobacco related products
- ENDS
- electronic nicotine delivery system
- PAHs
- polyaromatic hydrocarbons
- ROS
- reactive oxygen species
- TSNAs
- tobacco-specific nitrosamines
- TXA2
- thromboxane A2
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These two authors contributed equally to this work.