Twenty-Four-Hour Cardiovascular Effects of Electronic Cigarettes Compared With Cigarette Smoking in Dual Users

Neal L Benowitz, Gideon St Helen, Natalie Nardone, Newton Addo, Junfeng Jim Zhang, Arit M Harvanko, Carolyn S Calfee, Peyton Jacob 3rd, Neal L Benowitz, Gideon St Helen, Natalie Nardone, Newton Addo, Junfeng Jim Zhang, Arit M Harvanko, Carolyn S Calfee, Peyton Jacob 3rd

Abstract

Background Cardiovascular safety is an important consideration regarding the benefits versus risks of electronic cigarette use (EC) for public health. The single-use cardiovascular effects of EC have been well studied but may not reflect effects of ad libitum use throughout the day. We aimed to compare the circadian hemodynamic effects as well as 24-hour biomarkers of oxidative stress, and platelet aggregation and inflammation, with ad libitum cigarette smoking (CS) versus EC versus no tobacco product use. Methods and Results Thirty-six healthy dual CS and EC users participated in a crossover study in a confined research setting. Circadian heart rate, blood pressure and plasma nicotine levels, 24-hour urinary catecholamines, 8-isoprostane and 11-dehydro-thromboxane B2, and plasma interleukin-6 and interleukin-8 were compared in CS, EC, and no nicotine conditions. Over 24 hours, and during daytime, heart rate and blood pressure were higher in CS and EC compared with no tobacco product conditions (P<0.01). Heart rate on average was higher with CS versus EC. Urinary catecholamines, 8-isoprostane, and 11-dehydro-thromboxane B2 were not significantly different, but plasma IL-6 and IL-8 were higher with both CS and EC compared with no tobacco product (P<0.01). Conclusions CS and EC had similar 24-hour patterns of hemodynamic effects compared with no tobacco product, with a higher average heart rate with CS versus EC, and similar effects on biomarkers of inflammation. EC may pose some cardiovascular risk, particularly to smokers with underlying cardiovascular disease, but may also provide a harm reduction opportunity for smokers willing to switch entirely to EC. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02470754.

Keywords: biomarkers; electronic cigarettes; nicotine; tobacco.

Conflict of interest statement

Dr. Benowitz is a consultant to Pfizer and Achieve Life Sciences, companies that market or are developing smoking‐cessation medications, and has served as a paid expert witness in litigation against tobacco companies. The remaining authors have no disclosures to report.

Figures

Figure 1. Plasma nicotine concentrations.
Figure 1. Plasma nicotine concentrations.
Twenty‐four‐hour plasma nicotine concentrations during ad libitum cigarette smoking or EC use, showing mean values and SE bars. EC indicates electronic cigarette.
Figure 2. Mean ambulatory heart rate and…
Figure 2. Mean ambulatory heart rate and blood pressure measurements.
Twenty‐four‐hour mean heart rate during ad libitum cigarette smoking or EC use compared with no nicotine product use. EC indicates electronic cigarette.
Figure 3. Within‐participant relative 24‐hour urine biomarkers…
Figure 3. Within‐participant relative 24‐hour urine biomarkers concentrations.
Estimated mean difference (%) in urinary biomarker concentrations from total 24‐h urine collection in 2 exposure periods (ad libitum cigarette smoking and EC use) relative to the nicotine abstinence period. Error bars indicate 95% CIs. 11‐dhTxB2 indicates 11‐dehydro‐thromboxane B2; and EC indicates electronic cigarette.
Figure 4. Within‐participant relative plasma biomarkers concentrations.
Figure 4. Within‐participant relative plasma biomarkers concentrations.
Estimated mean difference (%) in plasma biomarker concentrations in ad libitum exposure periods (cigarette smoking and EC use) relative to the nicotine abstinence period. Error bars indicate 95% CIs. and EC indicates electronic cigarette.

References

    1. Barua RS, Rigotti NA, Benowitz NL, Cummings KM, Jazayeri M‐A, Morris PB, Ratchford EV, Sarna L, Stecker EC, Wiggins BS. 2018 ACC expert consensus decision pathway on tobacco cessation treatment: a report of the American college of cardiology task force on clinical expert consensus documents. J Am Coll Cardiol. 2018;72:3332–3365.
    1. Morris PB, Ference BA, Jahangir E, Feldman DN, Ryan JJ, Bahrami H, El‐Chami MF, Bhakta S, Winchester DE, Al‐Mallah MH, et al. Cardiovascular effects of exposure to cigarette smoke and electronic cigarettes: clinical perspectives from the prevention of cardiovascular disease section leadership council and early career councils of the American College of Cardiology. J Am Coll Cardiol. 2015;66:1378–1391.
    1. Hajek P, Phillips‐Waller A, Przulj D, Pesola F, Myers Smith K, Bisal N, Li J, Parrott S, Sasieni P, Dawkins L, et al. A randomized trial of e‐cigarettes versus nicotine‐replacement therapy. N Engl J Med. 2019;380:629–637.
    1. Zhu S‐H, Zhuang Y‐L, Wong S, Cummins SE, Tedeschi GJ. E‐cigarette use and associated changes in population smoking cessation: evidence from US current population surveys. BMJ. 2017;358:j3262.
    1. U.S. Department of Health and Human Services . How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking‐Attributable Disease: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2010.
    1. Belushkin M, Tafin Djoko D, Esposito M, Korneliou A, Jeannet C, Lazzerini M, Jaccard G. Selected harmful and potentially harmful constituents levels in commercial e‐cigarettes. Chem Res Toxicol. 2020;33:657–668.
    1. Bitzer ZT, Goel R, Reilly SM, Bhangu G, Trushin N, Foulds J, Muscat J, Richie JP. Emissions of free radicals, carbonyls, and nicotine from the NIDA standardized research electronic cigarette and comparison to similar commercial devices. Chem Res Toxicol. 2019;32:130–138.
    1. Gray N, Halstead M, Gonzalez‐Jimenez N, Valentin‐Blasini L, Watson C, Pappas RS. Analysis of toxic metals in liquid from electronic cigarettes. Int J Environ Res Public Health. 2019;16:4550.
    1. Mulder HA, Patterson JL, Halquist MS, Kosmider L, Turner JBM, Poklis JL, Poklis A, Peace MR. The effect of electronic cigarette user modifications and e‐liquid adulteration on the particle size profile of an aerosolized product. Sci Rep. 2019;9:10221.
    1. Benowitz NL, Burbank AD. Cardiovascular toxicity of nicotine: implications for electronic cigarette use. Trends Cardiovasc Med. 2016;26:515–523.
    1. Benowitz NL, Fraiman JB. Cardiovascular effects of electronic cigarettes. Nat Rev Cardiol. 2017;14:447–456.
    1. Boas Z, Gupta P, Moheimani RS, Bhetraratana M, Yin F, Peters KM, Gornbein J, Araujo JA, Czernin J, Middlekauff HR. Activation of the "splenocardiac axis" by electronic and tobacco cigarettes in otherwise healthy young adults. Physiol Rep. 2017;5:e13393.
    1. Moheimani RS, Bhetraratana M, Yin F, Peters KM, Gornbein J, Araujo JA, Middlekauff HR. Increased cardiac sympathetic activity and oxidative stress in habitual electronic cigarette users: implications for cardiovascular risk. JAMA Cardiol. 2017;2:278–284.
    1. Nocella C, Biondi‐Zoccai G, Sciarretta S, Peruzzi M, Pagano F, Loffredo L, Pignatelli P, Bullen C, Frati G, Carnevale R. Impact of tobacco versus electronic cigarette smoking on platelet function. Am J Cardiol. 2018;122:1477–1481.
    1. St Helen G, Ross KC, Dempsey DA, Havel CM, Jacob P, Benowitz NL. Nicotine delivery and vaping behavior during ad libitum e‐cigarette access. Tob Regul Sci. 2016;2:363–376.
    1. George J, Hussain M, Vadiveloo T, Ireland S, Hopkinson P, Struthers AD, Donnan PT, Khan F, Lang CC. Cardiovascular effects of switching from tobacco cigarettes to electronic cigarettes. J Am Coll Cardiol. 2019;74:3112–3120.
    1. Fattinger K, Verotta D, Benowitz NL. Pharmacodynamics of acute tolerance to multiple nicotinic effects in humans. J Pharmacol Exp Ther. 1997;281:1238–1246.
    1. Porchet HC, Benowitz NL, Sheiner LB. Pharmacodynamic model of tolerance: application to nicotine. J Pharmacol Exp Ther. 1988;244:231–236.
    1. Caetano J, Delgado AJ. Heart rate and cardiovascular protection. Eur J Intern Med. 2015;26:217–222.
    1. Stone PH. Triggers of transient myocardial ischemia: circadian variation and relation to plaque rupture and coronary thrombosis in stable coronary artery disease. Am J Cardiol. 1990;66:32G–36G.
    1. Harvanko AM, St Helen G, Nardone N, Addo N, Benowitz NL. Twenty‐four‐hour subjective and pharmacological effects of ad‐libitum electronic and combustible cigarette use among dual users. Addiction. 2020;115:1149–1159.
    1. St Helen G, Liakoni E, Nardone N, Addo N, Jacob P III, Benowitz NL. Comparison of systemic exposure to toxic and/or carcinogenic volatile organic compounds (VOC) during vaping, smoking, and abstention. Cancer Prev Res. 2020;13:153–162.
    1. St Helen G, Nardone N, Addo N, Dempsey D, Havel C, Jacob P III, Benowitz NL. Differences in nicotine intake and effects from electronic and combustible cigarettes among dual users. Addiction. 2020;115:757–767.
    1. Jacob P III, Wilson M, Benowitz NL. Improved gas chromatographic method for the determination of nicotine and cotinine in biologic fluids. J Chromatogr. 1981;222:61–70.
    1. Jacob P III, Yu L, Wilson M, Benowitz NL. Selected ion monitoring method for determination of nicotine, cotinine and deuterium‐labeled analogs: absence of an isotope effect in the clearance of (s)‐nicotine‐3',3'‐d2 in humans. Biol Mass Spectrom. 1991;20:247–252.
    1. Scherer G. Suitability of biomarkers of biological effects (BOBEs) for assessing the likelihood of reducing the tobacco related disease risk by new and innovative tobacco products: a literature review. Regul Toxicol Pharmacol. 2018;94:203–233.
    1. Zevin S, Jacob P III, Benowitz NL. Dose‐related cardiovascular and endocrine effects of transdermal nicotine. Clin Pharmacol Ther. 1998;64:87–95.
    1. Pilz H, Oguogho A, Chehne F, Lupattelli G, Palumbo B, Sinzinger H. Quitting cigarette smoking results in a fast improvement of in vivo oxidation injury (determined via plasma, serum and urinary isoprostane). Thromb Res. 2000;99:209–221.
    1. Benowitz NL, Fitzgerald GA, Wilson M, Zhang Q. Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking. J Am Coll Cardiol. 1993;22:1159–1167.
    1. Singh KP, Lawyer G, Muthumalage T, Maremanda KP, Khan NA, McDonough SR, Ye D, McIntosh S, Rahman I. Systemic biomarkers in electronic cigarette users: implications for noninvasive assessment of vaping‐associated pulmonary injuries. ERJ Open Res. 2019;5:00182‐2019.
    1. Sakamaki‐Ching S, Williams M, Hua M, Li J, Bates SM, Robinson AN, Lyons TW, Goniewicz ML, Talbot P. Correlation between biomarkers of exposure, effect and potential harm in the urine of electronic cigarette users. BMJ Open Respir Res. 2020;7:e000452.
    1. Shahab L, Goniewicz ML, Blount BC, Brown J, McNeill A, Alwis KU, Feng J, Wang L, West R. Nicotine, carcinogen, and toxin exposure in long‐term e‐cigarette and nicotine replacement therapy users: a cross‐sectional study. Ann Intern Med. 2017;166:390–400.
    1. Filippini P, Cesario A, Fini M, Locatelli F, Rutella S. The yin and yang of non‐neuronal alpha7‐nicotinic receptors in inflammation and autoimmunity. Curr Drug Targets. 2012;13:644–655.
    1. Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS, Iwamoto Y, Thompson B, Carlson AL, Heidt T, et al. Myocardial infarction accelerates atherosclerosis. Nature. 2012;487:325–329.
    1. Benowitz NL, Jacob P III, Yu L. Daily use of smokeless tobacco: systemic effects. Ann Intern Med. 1989;111:112–116.
    1. Sgambato JA, Jones BA, Caraway JW, Prasad GL. Inflammatory profile analysis reveals differences in cytokine expression between smokers, moist snuff users, and dual users compared to non‐tobacco consumers. Cytokine. 2018;107:43–51.
    1. Arimilli S, Madahian B, Chen P, Marano K, Prasad GL. Gene expression profiles associated with cigarette smoking and moist snuff consumption. BMC Genom. 2017;18:156.
    1. Bitzer ZT, Goel R, Reilly SM, Foulds J, Muscat J, Elias RJ, Richie JP Jr. Effects of solvent and temperature on free radical formation in electronic cigarette aerosols. Chem Res Toxicol. 2018;31:4–12.
    1. Reilly SM, Bitzer ZT, Goel R, Trushin N, Richie JP. Free radical, carbonyl, and nicotine levels produced by Juul electronic cigarettes. Nicotine Tob Res. 2019;21:1274–1278.
    1. Sleiman M, Logue JM, Montesinos VN, Russell ML, Litter MI, Gundel LA, Destaillats H. Emissions from electronic cigarettes: key parameters affecting the release of harmful chemicals. Environ Sci Technol. 2016;50:9644–9651.
    1. Suskin N, Sheth T, Negassa A, Yusuf S. Relationship of current and past smoking to mortality and morbidity in patients with left ventricular dysfunction. J Am Coll Cardiol. 2001;37:1677–1682.
    1. Farsalinos K, Cibella F, Caponnetto P, Campagna D, Morjaria JB, Battaglia E, Caruso M, Russo C, Polosa R. Effect of continuous smoking reduction and abstinence on blood pressure and heart rate in smokers switching to electronic cigarettes. Intern Emerg Med. 2016;11:85–94.
    1. Polosa R, Morjaria JB, Caponnetto P, Battaglia E, Russo C, Ciampi C, Adams G, Bruno CM. Blood pressure control in smokers with arterial hypertension who switched to electronic cigarettes. Int J Environ Res Public Health. 2016;13:1123.
    1. Hansson J, Galanti MR, Hergens M‐P, Fredlund P, Ahlbom A, Alfredsson L, Bellocco R, Eriksson M, Hallqvist J, Hedblad B, et al. Use of snus and acute myocardial infarction: pooled analysis of eight prospective observational studies. Eur J Epidemiol. 2012;27:771–779.
    1. Arefalk G, Hambraeus K, Lind L, Michaelsson K, Lindahl B, Sundstrom J. Discontinuation of smokeless tobacco and mortality risk after myocardial infarction. Circulation. 2014;130:325–332.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj