Electronic cigarettes and cardiovascular health: what do we know so far?

Vascular Health and Risk Management Dovepress open access to scientific and medical research Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 78.235.144.116 on 02-Jul-2020 For personal use only. Open Access Full Text Article Electronic cigarettes and cardiovascular health: what do we know so far? This article was published in the following Dove Press journal: Vascular Health and Risk Management Andrea MacDonald 1 Holly R Middlekauff 2 1 Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2Department of Medicine, Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Abstract: While tobacco cigarette (TC) smoking has continued to drop to all-time lows, the use of electronic cigarettes (ECs), introduced in the US in 2007, has been rising dramatically, especially among youth. In EC emissions, nicotine is the major biologically active element, while levels of carcinogens and harmful combustion products that typify TC smoke are very low or even undetectable. TCs cause cardiovascular harm by activation of inflammatory pathways and oxidative damage, leading to atherogenesis and thrombosis, as well as through sympathetic activation triggering ischemia and arrhythmia. While ECs are generally believed to be safer than TCs, there remain many uncertainties regarding the overall cardiovascular health effects of EC usage. In this review, we discuss the various components of EC smoke and review the potential mechanisms of cardiovascular injury caused by EC use. We also discuss the controversy regarding the increasing epidemic of youth EC use weighed against the use of ECs as a smoking-cessation aid. Keywords: electronic cigarettes, cigarette smoking, cardiovascular disease, nicotine Introduction Correspondence: Holly R Middlekauff Department of Medicine, Division of Cardiology, David Geffen School of Medicine at UCLA, A2-237 CHS, 650 Charles Young Drive South, Los Angeles, CA 90025, USA Tel +1 310 206 6672 Fax +1 310 206 9133 Email Tobacco cigarette (TC) smoking is the primary cause of preventable cardiovascular death in the US, and tobacco-use cessation has long been the focus of significant public health efforts. According to a Surgeon General report from 2014, rates of smoking in the US have reached historic lows.1 Concomitant with this decline in TC smoking, the use of electronic cigarettes (ECs), introduced in the US in 2007, has markedly increased, especially among young people.2 ECs are comprised of a battery that heats but does not burn a flavored liquid typically containing nicotine to form an aerosol that the user inhales by puffing on the device. As such, ECs are free of the typical combustion products of TCs, including harmful carbon monoxide and almost all carcinogens, and have been promoted as a safer alternative to TCs. A mixed body of evidence suggests that ECs may promote quitting attempts, and recent evidence supports the notion that they may aid in TC-smoking cessation as well. Although analysis of the constituents in EC emissions compared to TC emissions supports the concept that ECs would be expected to be less harmful to cardiovascular health, long-term outcome studies are lacking. Additionally, the possible benefit of ECs as a smoking-cessation aid must be balanced with their increased popularity among never-smokers, especially teens. In this review, we summarize what is known and what areas remain open for more research regarding the effects of ECs on cardiovascular health, and touch upon the debate about the public health implications of ECs. 159 submit your manuscript | www.dovepress.com Vascular Health and Risk Management 2019:15 159–174 DovePress © 2019 MacDonald and Middlekauff. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www. dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://doi.org/10.2147/VHRM.S175970 Powered by TCPDF (www.tcpdf.org) REVIEW Dovepress MacDonald and Middlekauff Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 78.235.144.116 on 02-Jul-2020 For personal use only. TC effects on cardiovascular disease Before discussing the current data reflecting the cardiovascular effects of ECs, it is important to review the known adverse effects of TC smoke and the similarities and differences in TC and EC emissions. The cardiovascular effects of TCs have been extensively studied and reviewed previously1,3,4 (Figure 1). TCs produce accelerated atherosclerosis and cardiovascular disease through a number of mechanisms, including increased oxidative stress and promotion of a proinflammatory state, leading to both lipid oxidation and thrombogenesis.5,6 TCs also increase catecholamine release and activation of the sympathetic nervous system, contributing to ischemia and arrhythmia risk.7 Through these mechanisms, TC smoking is associated with acute myocardial infarction (MI) and stent rethrombosis, both atrial and ventricular arrhythmias, and sudden death.5–7 Nicotine vs other components of TCs and ECs Regarding the aforementioned adverse cardiovascular effects of TCs, the relative contributions of nicotine versus nonnicotine components of TC smoke are unknown. This is an important distinction, since nicotine is the most biologically active agent dispensed by ECs, and nonnicotine toxicants in EC emissions are present in much lower concentrations, if present at all, than TCs. One approach to answer this question comes from studies of nicotine-replacement therapy (NRT) and smokeless tobacco (ST) products, in which the nonnicotine combustion components are absent. Nicotine-replacement therapy Several short-term studies on the safety of NRT have been published. An early trial published in 1996 evaluated 584 patients with known cardiovascular disease who were randomized to a 10-week course of transdermal nicotine versus placebo. Cardiac end points in this study were cardiac arrest, MI, or admission to hospital for symptomatic angina, arrhythmia, or heart failure. NRT was not associated with an increase in any of these outcomes compared to placebo, a finding corroborated by other early studies.8,9 More recent meta-analyses showed elevated risk of cardiovascular events with NRT compared to placebo, though this difference was largely due to less serious events. NRTs did not increase risk of serious cardiovascular events, such as MI or sudden death.10 A 160 Powered by TCPDF (www.tcpdf.org) submi (...truncated)