Public Health Consequences of E-Cigarettes (2018) / Chapter Skim
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9 Cardiovascular Disease
9 Cardiovascular Disease
Pages 339-380
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From page 339... ...
. Data combined from multiple studies to estimate adjusted relative risks of cardiovascular mortality plotted against the estimated average daily dose of fine particulate matter from combustible tobacco cigarette smoke, secondhand tobacco smoke, and ambient air pollution showed that the exposure–response relationship between fine particulate matter and cardiovascular disease mortality is relatively steep at low levels of exposure and 339
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From page 340... ...
In addition to the particles, some toxicants in combustible tobacco cigarette smoke have been specifically related to cardiovascular disease risk, in particular metals, such as lead, nickel, and cadmium (Cosselman et al., 2015; Nigra et al., 2016)
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From page 341... ...
Clinical outcomes such as coronary heart disease (including myocardial infarction and sudden cardiac death) , stroke, and peripheral artery disease have been the cornerstone of prospective epidemiological studies evaluating the vascular effects of combustible tobacco cigarettes.
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From page 342... ...
. The evidence available on the possible cardiovascular effects of e-cigarettes can be classified as studies conducted in vitro, evaluating the cytotoxicity of e-cigarette aerosols and other alterations in myocardial cells and human vascular cells; studies conducted in vivo, evaluating relevant mechanistic pathways for cardiovascular toxicity in mice; and clinical experiments, generally crossover experiments that have assessed short-term cardiovascular effects, such as changes in heart rate, blood pressure, and arterial stiffness, of e-cigarettes as compared with combustible tobacco cigarettes and to not smoking.
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From page 343... ...
In the absence of clinical or subclinical studies on the long-term cardiovascular effects of e-cigarettes, evaluating the potential harm reduction of e-cigarettes is preliminary. EVIDENCE FROM HUMAN STUDIES OF CARDIOVASCULAR EFFECTS A total of 13 clinical intervention studies published between 2010 and 2017 have evaluated acute cardiovascular effects of e-cigarette use, such as changes in blood pressure levels, heart rate, arterial stiffness and endothelial function, cardiac geometry and function, and oxidative stress measured in minutes to hours following the intervention (see Table 9-1)
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trial with a (≤5 combustible NR minimum tobacco cigarettes 0% of 48-hour per day) from washout Richmond, VA, period using e-cigarettes for at least 3 months
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From page 345... ...
2.5 hours 74.4 (1.7) at 30, 60, and 90 Plasma nicotine comparing same minutes, respectively, after increased up to device and the onset of the ad lib but 4.6 ng/ml during e-liquid with compared with baseline of ad lib.
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From page 346... ...
346 PUBLIC HEALTH CONSEQUENCES OF E-CIGARETTES TABLE 9-1 Continued Mean Age % Men % C-Smoker % F-Smoker E-Cigarette Device % Naïve Characteristics and Reference Study Design Population E-Cigarette E-Liquid St.Helen et 1-arm trial Healthy sole and 38.4 years Usual brand of al., 2016 dual e-cigarette 54% device and e-liquid users (≤5 cigarettes 23% per day) NR 0% Carnevale et Single blinded Healthy smoking 28.0 years NR leading brand al., 2016 2-arm ordered and never smoking 47.5% charged; crossover trial participants 50% 16-mg nicotine with 1-week from Rome, Italy 0% cartridge (~250 puffs)
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, after combustible tobacco (equivalent to 0.6 - 1 combustible 8-iso-PGF2α cigarette/e-cigarette mg of nicotine)
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348 PUBLIC HEALTH CONSEQUENCES OF E-CIGARETTES TABLE 9-1 Continued Mean Age % Men % C-Smoker % F-Smoker E-Cigarette Device % Naïve Characteristics and Reference Study Design Population E-Cigarette E-Liquid Antoniewicz Single Healthy sporadic 28 years eGo XL (2ndet al., 2016 blinded 2-arm smokers from 64.3% generation) , 1,100 randomized Stockholm, Sweden, 100% mAh, 3.7-V, dual-coil crossover trial not smoking in 0% CE5 atomizer.
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CARDIOVASCULAR DISEASE 349 Intervention Pattern and Comparison Cotinine Levels Groups na Study Endpoints Results 10 puffs in Before and 1, 16 EPC (leukocytes, EPCs increased after 10 minutes in 4, and 24 hours events) e-cigarette use at 1 hour semisupine after: Microvesicles (p = 0.003)
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350 PUBLIC HEALTH CONSEQUENCES OF E-CIGARETTES TABLE 9-1 Continued Mean Age % Men % C-Smoker % F-Smoker E-Cigarette Device % Naïve Characteristics and Reference Study Design Population E-Cigarette E-Liquid Fogt et al., Double Healthy 23.1 (±2.5) GreenSmartLiving 2016 blinded, participants from years e-cigarette (details 2-arm ordered San Antonio, TX 50% not described)
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CARDIOVASCULAR DISEASE 351 Intervention Pattern and Comparison Cotinine Levels Groups na Study Endpoints Results 20 puffs in 10 40 minutes 20 Resting: Mean (SD) 0/18 mg/ml minutes inhaling post-exposure: SBP (mmHg)
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352 PUBLIC HEALTH CONSEQUENCES OF E-CIGARETTES TABLE 9-1 Continued Mean Age % Men % C-Smoker % F-Smoker E-Cigarette Device % Naïve Characteristics and Reference Study Design Population E-Cigarette E-Liquid Yan and Single Healthy 38.7 years blu e-cigarettes with D'Ruiz, 2015 blinded, participants 48% the following e-liquid randomized smoking in past 100% formulations: 6-arm 12 months from 0% A: classic e-cigarette crossover trial Lincoln, NE, and 0% 2.4% nicotine 75% with 36-hour after a lead-in glycerol washout period for 7 days B: classic e-cigarette period to get accustomed 2.4% nicotine 50/20% to using e-cigarette glycerol/PG products and C: menthol abstaining from e-cigarette, 2.4% nicotine for 36 nicotine 75% glycerol hours D: classic e-cigarette 1.6% nicotine 75% glycerol E: classic e-cigarette 1.6% nicotine 50/20% glycerol/PG Szołtysek- Single Healthy students 23 (±2) years Ego-3 (clearomizer Bołdys et al., blinded, 2-arm of University of 0% Crystal 2 with coil, 2014 ordered cross- Silesia, Poland, 100% 2.4-Ω voltage battery over trial with smoking >5 0% 900-mAh, 3.4-V)
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. 1-hour sessions: 10 minutes 15 Arterial stiffness: Mean (95% CI)
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and e-cigarette users similar at baseline except e-cigarette users formerly smoked 10 combustible tobacco cigarettes per day more when they smoked than current smokers
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p = 0.57/1.2 (5.0) tobacco cigarettes IVRTc (ms)
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356 PUBLIC HEALTH CONSEQUENCES OF E-CIGARETTES TABLE 9-1 Continued Mean Age % Men % C-Smoker % F-Smoker E-Cigarette Device % Naïve Characteristics and Reference Study Design Population E-Cigarette E-Liquid Czogała et Not blinded, Healthy daily 34.9 (15.3) MILD M2001 (1st al., 2012 2-arm ordered cigarette smokers years generation)
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From page 357... ...
355) Also run analysis for the effect of combustible tobacco cigarette versus e-cigarette on changes of echocardiographic measures after adjustment for changes in SPB and HR (IVRT, IVRTc, MPI, Em, MPIt, SRe remained significantly associated)
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From page 358... ...
b Numbers approximated because abstracted from a figure. NOTES: 8-iso-PGF2α = 8-iso-prostaglandin F2α; EPC = endothelial progenitor cells; FMD = flow-mediated dilation; HR = heart rate; LA = left atrial; LV = left ventricle; MSNA = efferent received 2 or more interventions (in 6 of them the order of the intervention was randomized)
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From page 359... ...
The literature search also identified 3 studies evaluating cardiovascularrelated outcomes over a longer period than the 13 acute clinical studies (see Table 9-2) , including a cross-sectional study of e-cigarette users compared with non-users conducted in Los Angeles, California (n = 34)
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From page 360... ...
according to their continuation of combustible tobacco smoking (n = 145 for participants with continuous e-cigarette/smoking status over time) (Farsalinos et al., 2016)
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Seven studies compared the short-term effects of one or more e-cigarettes versus combustible tobacco cigarettes (Carnevale et al., 2016; Czogała et al., 2012; Eissenberg, 2010; Farsalinos et al., 2014; Szołtysek-Bołdys et al., 2014; Vansickel et al., 2010; Yan and D'Ruiz, 2015) (one of those also included one arm with sham puffing [Eissenberg et al., 2010]
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362 PUBLIC HEALTH CONSEQUENCES OF E-CIGARETTES TABLE 9-2 Epidemiological Studies on Chronic E-Cigarette Use and Cardiovascular Endpoints Age Range E-Cigarette % Men E-Cigarette Pattern of Use Study % C-Smoker Device and Cotinine Reference Design Population % F-Smoker Characteristics Levels Moheimani et XS Los Angeles, 21–45 years NR Mean = 241 al., 2017 CA, recruited 59% minutes per day in 2015–2016 0% Mean = 1.6 (source or 35% years recruitment Plasma cotinine methods NR) range = 2.6–27.3 mg/L
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CARDIOVASCULAR DISEASE 363 Comparison Study Groups na Endpoints Results Adjustmentb - E-cigarette 16/18 SBP (mmHg) Mean user/non-user 115.8/109.0 None users 12/18 DBP (mmHg)
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10 to 14 months treatment for 56% (83.7% more hypertension 48% (some than 12 months) at an dual users)
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with no difference by weight change CO groups: 34/ and at 8 treatment group. - Smokers 18 follow-up CO: adjusted mean change (95% - Dual users visits over 52 CI)
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; • blood pressure in 9 studies (Cooke et al., 2015; Czogała et al., 2012; Farsalinos et al., 2014, 2016; Fogt et al., 2016; Moheimani et al., 2017; Polosa et al., 2016; Szołtysek-Bołdys et al., 2014; Yan and D'Ruiz, 2015) ; • hypertension control in 1 study (Polosa et al., 2016)
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From page 367... ...
Studies that compared changes in heart rate levels before and after smoking a combustible tobacco cigarette found marked increases in heart rate, generally larger than those found with e-cigarettes. However, most of the studies comparing e-cigarettes with combustible tobacco cigarettes have been done using first- and secondgeneration devices that did not markedly increase nicotine or cotinine levels in plasma.
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From page 368... ...
These results indicate that in some instances the changes in heart rate induced by e-cigarettes are similar to those induced by combustible tobacco cigarettes. Short-term effects of e-cigarette use on heart rate do not necessarily mean that chronic e-cigarette use increases resting heart rate, which is an established predictor of poor clinical cardiovascular health.
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From page 369... ...
. In the study that compared blood pressure levels before and 10 minutes after a personal cigarette or an e-cigarette (Ego-3)
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From page 370... ...
, although the study did not adjust for sociodemographic characteristics and cardiovascular disease risk factors between e-cigarette users and non-users. In the studies from Catania, Italy, SBP and DBP decreased over time in participants who switched from tobacco cigarettes to e-cigarettes, especially those who achieved sole use (Farsalinos et al., 2016; Polosa et al., 2016)
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From page 371... ...
Regarding chronic health effects on blood pressure levels, the evidence is very limited as there is only one study comparing e-cigarette use to non-use, and two studies comparing e-cigarette use to smoking, one including patients with hypertension. Oxidative Stress, Inflammation, Endothelial Function, and Arterial Stiffness (Arteriosclerosis)
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From page 372... ...
Although the magnitude of the effect was weaker compared with the changes induced by a combustible tobacco cigarette, these experiments suggest that e-cigarettes can also increase levels of oxidative stress and reduce the levels of antioxidants. A major limitation of this study is the lack of information on the type of e-cigarette device and e-liquid used.
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From page 373... ...
The use of novel, relatively easy-to-obtain biomarkers such as EPCs and MVs could be useful to assess both the short-term and the long-term effects of e-cigarettes on cardiovascular disease. Arterial elasticity is essential for blood flow.
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The findings of this experiment would indicate that e-cigarettes would not induce short-term changes in arterial stiffness, contrary to combustible tobacco cigarettes. Given the findings FIGURE 9-2 Endothelial progenitor cells (EPCs)
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From page 375... ...
Cardiac Geometry and Function The two-arm intervention study comparing the short-term effects of combustible tobacco cigarettes in smokers and e-cigarettes in e-cigarette users conducted measures of echocardiography before and 5 minutes after smoking a cigarette or using an e-cigarette (Farsalinos et al., 2014)
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From page 376... ...
Study limitations include the small sample size, unclear description of the sources and forms of recruitment and response rate, the lack of adjustment or matching for sociodemographic and lifestyle risk factors (in particular given the imbalance by sex, former smoking status, and pack-years) , and the lack of details on the e-cigarette devices and the e-liquid used by the participant.
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Conclusion 9-4. There is limited evidence that e-cigarette use is asso ciated with a short-term increase in systolic blood pressure, changes in biomarkers of oxidative stress, increased endothelial dysfunction and arterial stiffness, and autonomic control.
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From page 378... ...
2016. Effect of continuous smoking reduction and abstinence on blood pressure and heart rate in smokers switching to electronic cigarettes.
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From page 379... ...
2016. En vironmental metals and cardiovascular disease in adults: A systematic review beyond lead and cadmium.
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