Acute cardiovascular effects of 4th generation electronic cigarettes and combusted cigarettes: implications for harm reduction.

The health consequences associated with using electronic cigarettes (ECs) are of great public interest because of their potential role in smoking cessation. In 110 participants, including 41 nonusers, 34 people who exclusively use ECs (EC group), and 35 people who smoke tobacco cigarettes (TCs) including 12 dual users (collectively called the TC-D group), the heart rate (HR), blood pressure (BP), and heart rate variability (HRV) were compared at baseline. People in the EC or the TC-D groups were also compared after using a 4th generation EC with or without nicotine, a TC with or without nicotine (TC-D group only), and a straw-control. Baseline HR, BP, and HRV parameters were not different among the EC, the TC-D, and nonuser groups. In people who exclusively use ECs, acute nicotine-EC use increased HR and BP, and produced changes in HRV patterns suggestive of increased cardiac sympathetic influence. In people in the TC-D group, BP increased similarly after acutely smoking a nicotine-TC or a nicotine-EC. However, the increase in HR was significantly greater after smoking a TC compared with the nicotine-EC despite similar acute increases in plasma nicotine. Overall, all exposures containing nicotine significantly increased HR and BP in both cohorts when compared with non-nicotine exposures. Since acute EC use 1) produces an abnormal HRV pattern associated with increased cardiac sympathetic tone in people who chronically use ECs, and 2) similar hemodynamic increases compared with acute TC smoking in people who chronically smoke TCs including dual users, the role of ECs as part of a harm reduction strategy is questioned.NEW & NOTEWORTHY We found that nicotine, not the non-nicotine constituents in tobacco cigarette (TC) or electronic cigarette (EC) emissions, may be the instigator of the acute, potentially adverse, changes in hemodynamics and heart rate variability (HRV) that were recorded several minutes after tobacco product use. Furthermore, acute EC use produced an abnormal HRV pattern associated with increased cardiac risk in people who chronically smoke ECs and produced similar hemodynamic increases compared with acute TC use in people who chronically smoke TCs, including people who are dual users.

Chronic Electronic Cigarette Use and Atherosclerosis Risk in Young People: A Cross-Sectional Study-Brief Report.

BACKGROUND: Little is known whether electronic cigarettes (ECIG) increase vulnerability to future atherosclerotic cardiovascular disease. We determined, using an ex vivo mechanistic atherogenesis assay, whether proatherogenic changes including monocyte transendothelial migration and monocyte-derived foam cell formation are increased in people who use ECIGs. METHODS: In a cross-sectional single-center study using plasma and peripheral blood mononuclear cells from healthy participants who are nonsmokers or with exclusive use of ECIGs or tobacco cigarettes (TCIGs), autologous peripheral blood mononuclear cells with patient plasma and pooled peripheral blood mononuclear cells from healthy nonsmokers with patient plasma were utilized to dissect patient-specific ex vivo proatherogenic circulating factors present in plasma and cellular factors present in monocytes. Our main outcomes were monocyte transendothelial migration (% of blood monocyte cells that undergo transendothelial migration through a collagen gel) and monocyte-derived foam cell formation as determined by flow cytometry and the median fluorescence intensity of the lipid-staining fluorochrome BODIPY in monocytes of participants in the setting of an ex vivo model of atherogenesis. RESULTS: Study participants (N=60) had median age of 24.0 years (interquartile range [IQR], 22.0-25.0 years), and 31 were females. Monocyte transendothelial migration was increased in people who exclusively used TCIGs (n=18; median [IQR], 2.30 [ 1.29-2.82]; P<0.001) and in people who exclusively used ECIGs (n=21; median [IQR], 1.42 [ 0.96-1.91]; P<0.01) compared with nonsmoking controls (n=21; median [IQR], 1.05 [0.66-1.24]). Monocyte-derived foam cell formation was increased in people who exclusively used TCIGs (median [IQR], 2.01 [ 1.59-2.49]; P<0.001) and in people who exclusively used ECIGs (median [IQR], 1.54 [ 1.10-1.86]; P<0.001) compared with nonsmoker controls (median [IQR], 0.97 [0.86-1.22]). Both monocyte transendothelial migration and monocyte-derived foam cell formation were higher in TCIG smokers compared with ECIG users and in ECIG users who were former smokers versus ECIG users who were never smokers (P<0.05 for all comparisons). CONCLUSIONS: The finding of alterations in proatherogenic properties of blood monocytes and plasma in TCIG smokers compared with nonsmokers validates this assay as a strong ex vivo mechanistic tool with which to measure proatherogenic changes in people who use ECIGs. Similar yet significantly less severe alterations in proatherogenic properties of monocytes and plasma were detected in the blood from ECIG users. Future studies are necessary to determine whether these findings are attributable to a residual effect of prior smoking or are a direct effect of current ECIG use.

Electronic cigarettes prolong ventricular repolarization in people who smoke tobacco cigarettes: implications for harm reduction.

Electronic cigarettes are often used for smoking cessation as a harm reduction strategy, but studies comparing risks of electronic cigarettes (ECs) and tobacco cigarettes (TCs) are scarce. Ventricular repolarization in people who smoke TCs is abnormal. Baseline repolarization was compared among nonusers (people who do not use TCs or ECs) and people who use ECs or TCs. The acute effects of ECs and TCs on metrics of ventricular repolarization were then compared in people who chronically smoke. A total of 110 participants (59 female), including 35 people (21 females) in the TC cohort, 34 people (17 females) in the EC cohort, and 41 people (21 females) in the nonuser cohort, were included. None of the primary outcomes, Tpeak-end (Tp-e), Tp-e/QT, and Tp-e/QTc, were different among the three cohorts at supine baseline, even when adjusted for sex. When compared with the control exposure standing after acutely using the EC but not the TC, significantly prolonged all three primary indices of ventricular repolarization in people who smoke TCs. The major new finding in this study is that in people who smoke TCs, using an EC compared with a TC significantly prolongs ventricular repolarization. Furthermore, in our subgroup analysis by sex, this adverse effect on repolarization is found only in male, not female, smokers. In summary, chronic TC smoking is the most prevalent, modifiable risk factor for cardiovascular death, including sudden cardiac death. If used for smoking cessation, ECs should only be used in the short term since they too carry their own risks; this risk appears to be greatest in males compared with females who smoke.NEW & NOTEWORTHY The major new finding in this study is that in people who smoke tobacco cigarettes, using an electronic cigarette but not a tobacco cigarette acutely and significantly prolongs several metrics of ventricular repolarization, including Tpeak-Tend, Tpeak-Tend/QT, and Tpeak-Tend/QTc. Furthermore, in our subgroup analysis by sex, this adverse effect on repolarization is found only in male, not female, smokers.

Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders.

The remarkable decline in cigarette smoking since 1964 has plateaued; approximately 12.5% of Americans still smoke. People who continue to smoke are largely members of marginalized groups, such as people with behavioral health conditions (BHC), encompassing both mental health and substance use disorders. Certified smoking cessation interventions can increase smoking abstinence in trials in people with BHC, yet smoking rates remain markedly increased, leading to increased mortality from smoking-related diseases, and worsening health disparities. A novel approach tailored to the unique needs, characteristics, and circumstances of people with BHC is mandated. One promising approach, the electronic cigarette, has not been embraced in the USA, likely due to an understandable concern for non-smoking young people among whom electronic cigarettes have been popular. Recent data confirm that electronic cigarette use is declining among young people, yet cigarette smoking is not declining among people with BHC. We propose smoking cessation trials utilizing electronic cigarettes in people with BHC. To this goal, the UK has already begun allowing companies to submit their products for approval as medically licensed electronic cigarettes that can be prescribed as smoking cessation aids. Our proposal is timely, backed by evidence, and aims to save hundreds of thousands of American lives.

Neural-hematopoietic-inflammatory axis in nonsmokers, electronic cigarette users, and tobacco smokers.

Amygdala activity in context of the splenocardiac model has not been investigated in healthy, young adults and has not been compared between nonsmokers, electronic cigarette users, and smokers. The purpose of the current study was to determine whether fluorodeoxyglucose positron emission tomography/computer tomography (FDG PET/CT) scans would demonstrate positively correlated metabolic activity in the amygdala, bone marrow, spleen, and aorta, elucidating activation of the splenocardiac axis in otherwise healthy young people who use tobacco products compared to nonusers. Moreover, the study was conducted to evaluate whether electronic cigarette users and tobacco smokers have similar levels of inflammation compared to nonusers. In 45 healthy adults (mean age = 25 years), including nonsmoker (n = 15), electronic cigarette user (n = 16), and smoker (n = 14) groups, metabolic activity in the amygdala, spleen, aorta, bone marrow of thoracic vertebrae, and adjacent erector spinae skeletal muscle was quantified through visualization of radioactive glucose (18 FDG) uptake by FDG-PET/CT. The maximum standardized uptake value for each region was calculated for correlation analyses and comparisons between groups. In correlation analyses, metabolic activity of the amygdala correlated with metabolic activity in the aorta (r = 0.757), bone marrow (r = 0.750), and spleen (r = 0.665), respectively. Metabolic activity in the aorta correlated with 18 FDG uptake in the thoracic vertebrae (r = 0.703) and spleen (r = 0.594), respectively. Metabolic activity in the spleen also correlated with 18 FDG uptake in the bone marrow (r = 0.620). Metabolic activity in the adjacent erector spinae skeletal muscle (our control tissue) was not positively correlated with any other region of interest. Finally, there were no statistically significant mean differences in metabolic activity between the three groups: nonsmokers, electronic cigarette users, and smokers in any target tissue. Amygdala metabolic activity, as measured by 18 FDG uptake in FDG-PET/CT scans, positively correlated with inflammation in the splenocardiac tissues, including: the aorta, bone marrow, and spleen, underscoring the existence of a neural-hematopoietic-inflammatory axis in healthy, young adults.

Optimizing ECG lead selection for detection of prolongation of ventricular repolarization as measured by the Tpeak-end interval.

BACKGROUND: The Tpeak-end(Tp-e) has not been compared in all 12 ECG leads in healthy adults to determine if the Tp-e varies across leads. If there is variation, it remains uncertain, which lead(s) are preferred for recording in order to capture the maximal Tp-e value. OBJECTIVE: The purpose of the current study was to determine the optimal leads, if any, to capture the maximal Tp-e interval in healthy young adults. METHODS: In 88 healthy adults (ages 21-38 years), including derivation (n = 21), validation (n = 20), and smoker/vaper (n = 47) cohorts, the Tp-e was measured using commercial computer software (LabChart Pro 8 with ECG module, ADInstruments) in all 12 leads at rest and following a provocative maneuver, abrupt standing. Tp-e was compared to determine which lead(s) most frequently captured the maximal Tp-e interval. RESULTS: In the rest and abrupt standing positions, the Tp-e was not uniform among the 12 leads; the maximal Tp-e was most frequently captured in the precordial leads. At rest, grouping leads V2-V4 resulted in detection of the maximum Tp-e in 85.7% of participants (CI 70.7, 99.9%) versus all other leads (p < .001). Upon abrupt standing, grouping leads V2-V6 together, resulted in detection of the maximum Tp-e 85.0% of participants (CI 69.4, 99.9% versus all other leads; p < .001). These findings were confirmed in the validation cohort, and extended to the smoking/vaping cohort. CONCLUSION: If only a subset of ECG leads will be recorded or analyzed for the Tp-e interval, selection of the precordial leads is preferred since these leads are most likely to capture the maximal Tp-e value.