LAUSR

Electronic cigarettes (e-cigarettes) first became widely available in 2003. E-cigarettes are particularly popular among current and former smokers and youth.1 Among smokers, many express interest in utilizing e-cigarettes as a smoking cessation device, but the current literature creates an unclear picture as to whether e-cigarettes support complete cessation from tobacco products.2 The majority of adult e-cigarette users continue to smoke combustible cigarettes, with reports suggesting close to a quarter are dual users of both electronic and combustible cigarettes.1 A recent study showed that regular but not occasional e-cigarette use was associated with cessation of combustible cigarette use.2 Regular e-cigarette use may help reduce daily consumption of combustible cigarettes, but there are cardiovascular risks associated with even low-intensity combustible cigarette smoking. Thus, the health impact of dual-use smoking patterns is not clear. Additional evidence about the health effects of e-cigarettes is required to ascertain their relative safety to combustible cigarettes and to advise policy makers regarding the risk of youth uptake. E-cigarettes are electronic nicotine devices that encompass a wide array of products with varying battery sizes, voltage options, designs, nicotine concentrations, solvents, and flavored e-liquids. With thousands of e-cigarette products currently on the market, this diversity creates challenges in evaluating the health effects.3 Because most of the diseases associated with smoking are chronic, requiring years and even decades to develop, the chronic effects of e-cigarettes on human health will likely not be fully appreciated for many years to come. Consequently, intermediate biomarkers of cardiovascular injury must be utilized to begin to understand the potential health consequences of e-cigarette use. The cardiovascular impact of combustible cigarette smoking is well described and is a major contributor to morbidity and mortality. Measures of arterial stiffness and endothelial function serve as intermediate dynamic biomarkers of cardiovascular injury that are associated with the risk of cardiovascular events.4 Prior studies have shown that combustible cigarette smokers have lower flow-mediated dilation (indicative of endothelial dysfunction), and nicotine itself has been shown to reduce flow-mediated vasodilation, albeit to a lesser degree than combustible cigarette smoking.5 Antioxidant treatment in smokers improves flow-mediated vasodilation, suggesting that smoking-induced endothelial dysfunction may be the result of increased oxidative stress.6 Only a few studies have evaluated the acute impact of e-cigarette use on intermediate cardiovascular biomarkers of injury in people. In a study of young, healthy non-smokers and smokers, a single use of an e-cigarette containing nicotine lowered flow-mediated dilation.7 Further, measures of oxidative stress, serum 8-isoprostanes, and soluble NOX2 were shown to increase with acute use of e-cigarettes, suggesting that oxidant scavenging of nitric oxide may be a mechanism for e-cigarette-induced endothelial dysfunction.7 Consistent with this, in a study of combustible cigarette smokers, acute use of an e-cigarette containing nicotine increased malondialdehyde (MDA) levels, suggestive of oxidative stress.8 This same study found that 30 days of e-cigarette use in smokers was associated with an intermediate level of MDA compared to those who continued to smoke only combustible cigarettes and those who quit smoking completely. Further, smokers who used an e-cigarette device for 30 days had improved augmentation index (corrected for heart rate), suggestive of an improvement in arterial stiffness compared to those who continued to smoke only combustible cigarettes. Collectively, these studies to date have shown that transition to e-cigarettes may improve cardiovascular function among smokers, resulting in an intermediate level of injury compared to complete cessation and ongoing combustible cigarette smoking. In this issue of Vascular Medicine, Franzen and colleagues describe the hemodynamic impact of acute e-cigarette use compared to combustible cigarettes in young healthy smokers.9 Smokers were studied three times in random order: following the use of a combustible cigarette, a third-generation e-cigarette with nicotine, and an ecigarette without nicotine. The primary endpoints were peripheral and central blood pressures and measures of arterial stiffness. Although the number of study participants was small (n=15 participants), the e-cigarette exposure used the same device, e-liquid, and settings. Further, the participants received instructions to minimize A cautionary note on electronic cigarettes and vascular health