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Early Cardiovascular Risk in E-cigarette Users: the Potential Role of Metals

  • Metals and Health (R Fry, Section Editor)
  • Published:
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A Correction to this article was published on 16 December 2020

This article has been updated

Abstract

Purpose of Review

Electronic cigarettes (e-cigs) are a source of metals. Epidemiologic and experimental evidence support that metals are toxic to the cardiovascular system. Little is known, however, about the role that e-cig metals may play as toxicants for the possible cardiovascular effects of e-cig use. The goal of this narrative review is to summarize the evidence on e-cig use and metal exposure and on e-cig use and cardiovascular toxicity and discuss the research needs.

Recent Findings

In vitro studies show cytotoxicity and increased oxidative stress in myocardial cells and vascular endothelial cells exposed to e-liquids and e-cig aerosols, with effects partially reversed with antioxidant treatment. There is some evidence that the heating coil plays a role in cell toxicity. Mice exposed to e-cigs for several weeks showed higher levels of oxidative stress, inflammation, platelet activation, and thrombogenesis. Cross-over clinical experiments show e-cig use alters nitric oxide–mediated flow-mediated dilation, endothelial progenitor cells, and arterial stiffness. Cross-sectional evidence from large nationally representative samples in the USA support that e-cig use is associated with self-reported myocardial infarction. Smaller studies found associations of e-cig use with higher oxidized low-density protein and heart variability compared to healthy controls. Numerous studies have measured elevated levels of toxic metals in e-cig aerosols including lead, nickel, chromium, and manganese. Arsenic has been measured in some e-liquids. Several of these metals are well known to be cardiotoxic.

Summary

Numerous studies show that e-cigs are a source of cardiotoxic metals. Experimental studies (in vitro, in vivo, and clinical studies) show acute toxicity of e-cigs to the vascular system. Studies of long-term toxicity in animals and humans are missing. Longitudinal studies with repeated measures of metal exposure and subclinical cardiovascular outcomes (e.g., coronary artery calcification) could contribute to determine the long-term cardiovascular effects of e-cigs and the potential role of metals in those effects.

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Change history

  • 16 December 2020

    A Correction to this paper has been published: <ExternalRef><RefSource>https://doi.org/10.1007/s40572-020-00302-4</RefSource><RefTarget Address="10.1007/s40572-020-00302-4" TargetType="DOI"/></ExternalRef>

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Villarroel MA, Cha AE, Vahratian A. Electronic cigarette use among U.S. adults, 2018. NCHS Data Brief. 2020;365:1–8.

  2. Gentzke AS, Creamer M, Cullen KA, Ambrose BK, Willis G, Jamal A, et al. Vital signs: tobacco product use among middle and high school students — United States, 2011–2018. MMWR Morb Mortal Wkly Rep. 2019;68:157–64.

    PubMed  PubMed Central  Google Scholar 

  3. Creamer MR, Wang TW, Babb S, et al. Tobacco product use and cessation indicators among adults — United States, 2018. MMWR Morb Mortal Wkly Rep. 2019;68:1013–9.

    PubMed  PubMed Central  Google Scholar 

  4. Cullen KA, Gentzke AS, Sawdey MD, Chang JT, Anic GM, Wang TW, et al. e-cigarette use among youth in the United States, 2019. Jama. 2019;322:2095–103.

    PubMed  PubMed Central  Google Scholar 

  5. Wang TW, Neff LJ, Park-Lee E, Ren C, Cullen KA, King BA. E-cigarette use among middle and high school students — United States, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:1310–2.

    PubMed  PubMed Central  Google Scholar 

  6. Leventhal AM, Strong DR, Kirkpatrick MG, Unger JB, Sussman S, Riggs NR, et al. Association of electronic cigarette use with initiation of combustible tobacco product smoking in early adolescence. Jama. 2015;314:700–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Audrain-McGovern J, Strasser AA, Wileyto EP. The impact of flavoring on the rewarding and reinforcing value of e-cigarettes with nicotine among young adult smokers. Drug Alcohol Depend. 2016;166:263–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Kim H, Davis AH, Dohack JL, Clark PI. E-cigarettes use behavior and experience of adults: qualitative research findings to inform E-cigarette use measure development. Nicotine Tob Res. 2017;19:190–6.

    CAS  PubMed  Google Scholar 

  9. Patel D, Davis KC, Cox S, Bradfield B, King BA, Shafer P, et al. Reasons for current E-cigarette use among U.S. adults. Prev Med. 2016;93:14–20.

    PubMed  PubMed Central  Google Scholar 

  10. Soule EK, Lopez AA, Guy MC, Cobb CO. Reasons for using flavored liquids among electronic cigarette users: a concept map** study. Drug Alcohol Depend. 2016;166:168–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Clark EM, Jones CA, Williams JR, Kurti AN, Norotsky MC, Danforth CM, et al. Vaporous marketing: uncovering pervasive electronic cigarette advertisements on twitter. PLoS One. 2016;11:e0157304.

    PubMed  PubMed Central  Google Scholar 

  12. Dai H, Hao J. Exposure to advertisements and susceptibility to electronic cigarette use among youth. J Adolesc Health. 2016;59:620–6.

    PubMed  Google Scholar 

  13. Jarmul S, Aherrera A, Rule AM, Olmedo P, Chen R, Navas-Acien A. Lost in E-cigarette clouds: a culture on the rise. Am J Public Health. 2017;107:265–6.

    PubMed  PubMed Central  Google Scholar 

  14. Padon AA, Maloney EK, Cappella JN. Youth-targeted E-cigarette marketing in the US. Tob Regul Sci. 2017;3:95–101.

    PubMed  PubMed Central  Google Scholar 

  15. Barrington-Trimis JL, Urman R, Leventhal AM, et al. E-cigarettes, cigarettes, and the prevalence of adolescent tobacco use. Pediatrics. 2016;138:e20153983.

  16. Margolis KA, Nguyen AB, Slavit WI, King BA. E-cigarette curiosity among U.S. middle and high school students: findings from the 2014 national youth tobacco survey. Prev Med. 2016;89:1–6.

    PubMed  PubMed Central  Google Scholar 

  17. Sussan TE, Shahzad FG, Tabassum E, Cohen JE, Wise RA, Blaha MJ, et al. Electronic cigarette use behaviors and motivations among smokers and non-smokers. BMC Public Health. 2017;17:686.

    PubMed  PubMed Central  Google Scholar 

  18. Chadi N, Hadland SE, Harris SK. Understanding the implications of the “va** epidemic” among adolescents and young adults: a call for action. Subst Abus. 2019;40:7–10.

    PubMed  PubMed Central  Google Scholar 

  19. Gottlieb MA. Regulation of E-cigarettes in the United States and its role in a youth epidemic. Children (Basel). 2019;6:40.

  20. Jenssen BP, Boykan R. Electronic cigarettes and youth in the United States: a call to action (at the local, national and global levels). Children (Basel). 2019;6:30.

  21. Cobb CO, Hendricks PS, Eissenberg T. Electronic cigarettes and nicotine dependence: evolving products, evolving problems. BMC Med. 2015;13:119.

    PubMed  PubMed Central  Google Scholar 

  22. Sleiman M, Logue JM, Montesinos VN, Russell ML, Litter MI, Gundel LA, et al. Emissions from electronic cigarettes: key parameters affecting the release of harmful chemicals. Environ Sci Technol. 2016;50:9644–51.

    CAS  PubMed  Google Scholar 

  23. • Zhao D, Aravindakshan A, Hilpert M, Olmedo P, Rule AM, Navas-Acien A, et al. Metal/metalloid levels in electronic cigarette liquids, aerosols, and human biosamples: a systematic review. Environ Health Perspect. 2020;128:36001. This systematic review summarizes the main studies evaluating metals in e-cigarette solutions and aerosol emissions, as well as in human biosamples, supporting that e-cigarettes are a major source of metal exoposure.

    CAS  PubMed  Google Scholar 

  24. Laine JE, Bailey KA, Olshan AF, Smeester L, Drobná Z, Stýblo M, et al. Neonatal metabolomic profiles related to prenatal arsenic exposure. Environ Sci Technol. 2017;51:625–33.

    CAS  PubMed  Google Scholar 

  25. Lee WH, Ong SG, Zhou Y, Tian L, Bae HR, Baker N, et al. Modeling cardiovascular risks of E-cigarettes with human-induced pluripotent stem cell-derived endothelial cells. J Am Coll Cardiol. 2019;73:2722–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Muthumalage T, Prinz M, Ansah KO, Gerloff J, Sundar IK, Rahman I. Inflammatory and oxidative responses induced by exposure to commonly used e-cigarette flavoring chemicals and flavored e-liquids without nicotine. Front Physiol. 2017;8:1130.

    PubMed  Google Scholar 

  27. Fetterman JL, Weisbrod RM, Feng B, Bastin R, Tuttle ST, Holbrook M, et al. Flavorings in tobacco products induce endothelial cell dysfunction. Arterioscler Thromb Vasc Biol. 2018;38:1607–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Taylor M, Jaunky T, Hewitt K, Breheny D, Lowe F, Fearon IM, et al. A comparative assessment of e-cigarette aerosols and cigarette smoke on in vitro endothelial cell migration. Toxicol Lett. 2017;277:123–8.

    CAS  PubMed  Google Scholar 

  29. Anderson C, Majeste A, Hanus J, Wang S. E-cigarette aerosol exposure induces reactive oxygen species, DNA damage, and cell death in vascular endothelial cells. Toxicol Sci. 2016;154:332–40.

    CAS  PubMed  Google Scholar 

  30. • Lerner CA, Sundar IK, Yao H, Gerloff J, Ossip DJ, McIntosh S, et al. Vapors produced by electronic cigarettes and e-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung. PLoS One. 2015;10:e0116732. This experimental in vitro study showed that e-cigarettes can induce toxicity, oxidative stress, and inflammation in lung epithelial cells as well as in an animal model. These mechanisms are consistent with metal-induced toxcity.

    PubMed  PubMed Central  Google Scholar 

  31. Lerner CA, Rutagarama P, Ahmad T, Sundar IK, Elder A, Rahman I. Electronic cigarette aerosols and copper nanoparticles induce mitochondrial stress and promote DNA fragmentation in lung fibroblasts. Biochem Biophys Res Commun. 2016;477:620–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Hwang JH, Lyes M, Sladewski K, Enany S, McEachern E, Mathew DP, et al. Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. J Mol Med (Berl). 2016;94:667–79.

    CAS  Google Scholar 

  33. Lim HB, Kim SH. Inhallation of e-cigarette cartridge solution aggravates allergen-induced airway inflammation and hyper-responsiveness in mice. Toxicol Res. 2014;30:13–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Qasim H, Karim ZA, Silva-Espinoza JC, Khasawneh FT, Rivera JO, Ellis CC, et al. Short-term E-cigarette exposure increases the risk of thrombogenesis and enhances platelet function in mice. J Am Heart Assoc. 2018;7:e009264.

  35. Rao P, Liu J, Springer ML. JUUL and combusted cigarettes comparably impair endothelial function. Tob Regul Sci. 2020;6:30–7.

    PubMed  PubMed Central  Google Scholar 

  36. Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim JH, Sudini K, et al. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model. PLoS One. 2015;10:e0116861.

    PubMed  PubMed Central  Google Scholar 

  37. Kuntic M, Oelze M, Steven S, Kröller-Schön S, Stamm P, Kalinovic S, et al. Short-term e-cigarette vapour exposure causes vascular oxidative stress and dysfunction: evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX-2). Eur Heart J. 2020;41:2472–83.

    CAS  PubMed  Google Scholar 

  38. • Espinoza-Derout J, Hasan KM, Shao XM, Jordan MC, Sims C, Lee DL, et al. Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice. Am J Phys Heart Circ Phys. 2019;317:H445–h59. This study showed that e-cig use can induce cardiovascular outcomes, including cardiac dysfunction and atherosclerosis, endpoints that are consistent with metal cardiotoxicity, in an animal model commonly used to study cardiovascular disease.

    CAS  Google Scholar 

  39. Orzabal MR, Lunde-Young ER, Ramirez JI, Howe SYF, Naik VD, Lee J, et al. Chronic exposure to e-cig aerosols during early development causes vascular dysfunction and offspring growth deficits. Transl Res. 2019;207:70–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Farsalinos K, Cibella F, Caponnetto P, Campagna D, Morjaria JB, Battaglia E, et al. 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.

    PubMed  PubMed Central  Google Scholar 

  41. Farsalinos KE, Tsiapras D, Kyrzopoulos S, Savvopoulou M, Voudris V. Acute effects of using an electronic nicotine-delivery device (electronic cigarette) on myocardial function: comparison with the effects of regular cigarettes. BMC Cardiovasc Disord. 2014;14:78.

    PubMed  PubMed Central  Google Scholar 

  42. Szoltysek-Boldys I, Sobczak A, Zielinska-Danch W, Barton A, Koszowski B, Kosmider L. Influence of inhaled nicotine source on arterial stiffness. Przegl Lek. 2014;71:572–5.

    PubMed  Google Scholar 

  43. Yan XS, D'Ruiz C. Effects of using electronic cigarettes on nicotine delivery and cardiovascular function in comparison with regular cigarettes. Regul Toxicol Pharmacol. 2015;71:24–34.

    CAS  PubMed  Google Scholar 

  44. Cossio R, Cerra ZA, Tanaka H. Vascular effects of a single bout of electronic cigarette use. Clin Exp Pharmacol Physiol. 2020;47:3–6.

    CAS  PubMed  Google Scholar 

  45. Franzen KF, Willig J, Cayo Talavera S, et al. E-cigarettes and cigarettes worsen peripheral and central hemodynamics as well as arterial stiffness: a randomized, double-blinded pilot study. Vasc Med. 2018;23:419–25.

    PubMed  Google Scholar 

  46. Kerr DMI, Brooksbank KJM, Taylor RG, et al. Acute effects of electronic and tobacco cigarettes on vascular and respiratory function in healthy volunteers: a cross-over study. J Hypertens. 2019;37:154–66.

    CAS  PubMed  Google Scholar 

  47. Antoniewicz L, Bosson JA, Kuhl J, Abdel-Halim SM, Kiessling A, Mobarrez F, et al. Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers. Atherosclerosis. 2016;255:179–85.

    CAS  PubMed  Google Scholar 

  48. Carnevale R, Sciarretta S, Violi F, Nocella C, Loffredo L, Perri L, et al. Acute impact of tobacco vs electronic cigarette smoking on oxidative stress and vascular function. Chest. 2016;150:606–12.

    PubMed  Google Scholar 

  49. Antoniewicz L, Brynedal A, Hedman L, Lundback M, Bosson JA. Acute effects of electronic cigarette inhalation on the vasculature and the conducting airways. Cardiovasc Toxicol. 2019;19:441–50.

    PubMed  PubMed Central  Google Scholar 

  50. Vlachopoulos C, Ioakeimidis N, Abdelrasoul M, Terentes-Printzios D, Georgakopoulos C, Pietri P, et al. Electronic cigarette smoking increases aortic stiffness and blood pressure in young smokers. J Am Coll Cardiol. 2016;67:2802–3.

    PubMed  Google Scholar 

  51. Caporale A, Langham MC, Guo W, Johncola A, Chatterjee S, Wehrli FW. Acute effects of electronic cigarette aerosol inhalation on vascular function detected at quantitative MRI. Radiology. 2019;293:97–106.

    PubMed  Google Scholar 

  52. Chaumont M, de Becker B, Zaher W, et al. Differential effects of E-cigarette on microvascular endothelial function, arterial stiffness and oxidative stress: a randomized crossover trial. Sci Rep. 2018;8:10378.

    PubMed  PubMed Central  Google Scholar 

  53. Mobarrez F, Antoniewicz L, Hedman L, Bosson JA, Lundbäck M. Electronic cigarettes containing nicotine increase endothelial and platelet derived extracellular vesicles in healthy volunteers. Atherosclerosis. 2020;301:93–100.

    CAS  PubMed  Google Scholar 

  54. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems. Public Health Consequences of E-Cigarettes. Eaton DL, Kwan LY, Stratton K, editors. Washington (DC): National Academies Press (US); 2018 Jan 23.

  55. • Bhatta DN, Glantz SA. Electronic cigarette use and myocardial infarction among adults in the US population assessment of tobacco and health. J Am Heart Assoc. 2019;8:e012317. This population-based study from the Population Assessment of Tobacco and Health Wave 1 survey found that e-cigarette use is associated with a higher risk of myocardial infarction. A limitation of the study is that there are few participants who solely used e-cigarettes in the absence of past or current traditional smoking. This manuscript has been retracted but understanding the limitations of the study remains relevant.

    PubMed  PubMed Central  Google Scholar 

  56. Alzahrani T, Pena I, Temesgen N, Glantz SA. Association between electronic cigarette use and myocardial infarction. Am J Prev Med. 2018;55:455–61.

    PubMed  PubMed Central  Google Scholar 

  57. Vindhyal MR, Ndunda P, Munguti C, Vindhyal S, Okut H. Impact on cardiovascular outcomes among E-cigarette users: a review from National Health Interview Surveys. J Am Coll Cardiol. 2019;73:11.

    Google Scholar 

  58. • Osei AD, Mirbolouk M, Orimoloye OA, et al. Association between E-cigarette use and cardiovascular disease among never and current combustible-cigarette smokers. Am J Med. 2019;132:949–54.e2. This population-based study used data from the Behavioral Risk Factor Surveillance System (BRFSS) survey to show that e-cigarette use is associated with a higher risk of myocardial infarction (MI). Dual use of e-cigarettes and smoking was associated with higher risk of MI than the sum of their independent effects.

    CAS  PubMed  Google Scholar 

  59. Moheimani RS, Bhetraratana M, Yin F, et al. Increased cardiac sympathetic activity and oxidative stress in habitual electronic cigarette users: implications for cardiovascular risk. JAMA Cardiol. 2017;2:278–84.

    PubMed  PubMed Central  Google Scholar 

  60. Kosmider L, Sobczak A, Fik M, et al. Carbonyl compounds in electronic cigarette vapors: effects of nicotine solvent and battery output voltage. Nicotine Tob Res. 2014;16:1319–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Goniewicz ML, Knysak J, Gawron M, et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control. 2014;23:133–9.

    PubMed  Google Scholar 

  62. Pagano T, DiFrancesco AG, Smith SB, et al. Determination of nicotine content and delivery in disposable electronic cigarettes available in the United States by gas chromatography-mass spectrometry. Nicotine Tob Res. 2016;18:700–7.

    PubMed  Google Scholar 

  63. Tayyarah R, Long GA. Comparison of select analytes in aerosol from e-cigarettes with smoke from conventional cigarettes and with ambient air. Regul Toxicol Pharmacol. 2014;70:704–10.

    CAS  PubMed  Google Scholar 

  64. Allen JG, Flanigan SS, LeBlanc M, et al. Flavoring chemicals in E-cigarettes: diacetyl, 2,3-pentanedione, and acetoin in a sample of 51 products, including fruit-, candy-, and cocktail-flavored E-cigarettes. Environ Health Perspect. 2016;124:733–9.

    CAS  PubMed  Google Scholar 

  65. Fuoco FC, Buonanno G, Stabile L, Vigo P. Influential parameters on particle concentration and size distribution in the mainstream of e-cigarettes. Environ Pollut. 2014;184:523–9.

    CAS  PubMed  Google Scholar 

  66. Williams M, Villarreal A, Bozhilov K, Lin S, Talbot P. Metal and silicate particles including nanoparticles are present in electronic cigarette cartomizer fluid and aerosol. PLoS One. 2013;8:e57987.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Saffari A, Daher N, Ruprecht A, et al. Particulate metals and organic compounds from electronic and tobacco-containing cigarettes: comparison of emission rates and secondhand exposure. Environ Sci Process Impacts. 2014;16:2259–67.

    CAS  PubMed  Google Scholar 

  68. Hess CA, Olmedo P, Navas-Acien A, Goessler W, Cohen JE, Rule AM. E-cigarettes as a source of toxic and potentially carcinogenic metals. Environ Res. 2017;152:221–5.

    CAS  PubMed  Google Scholar 

  69. • Olmedo P, Goessler W, Tanda S, et al. Metal concentrations in e-cigarette liquid and aerosol samples: the contribution of metallic coils. Environ Health Perspect. 2018;126:027010. This study showed that metal levels are much higher in the aerosol generated by e-cigarettes compared to the original e-liquid that had not been in contact with the coil, supporting that the coil is a major source of metals.

    PubMed  PubMed Central  Google Scholar 

  70. 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;16:4450.

  71. Zhao D, Navas-Acien A, Ilievski V, et al. Metal concentrations in electronic cigarette aerosol: effect of open-system and closed-system devices and power settings. Environ Res. 2019;174:125–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Stayner L, Smith R, Thun M, Schnorr T, Lemen R. A dose-response analysis and quantitative assessment of lung cancer risk and occupational cadmium exposure. Ann Epidemiol. 1992;2:177–94.

    CAS  PubMed  Google Scholar 

  73. Beauval N, Howsam M, Antherieu S, et al. Trace elements in e-liquids - development and validation of an ICP-MS method for the analysis of electronic cigarette refills. Regul Toxicol Pharmacol. 2016;79:144–8.

    CAS  PubMed  Google Scholar 

  74. Nordberg GF, Fowler BA, Nordberg M, Friberg LT. Handbook on the toxicology of metals. Amsterdam: Elsevier; 2007.

    Google Scholar 

  75. Goyer RA, Clarkson TW. Chapter 23. Toxic effects of metals. In: Klaassen CD, editor. Casarett and Doull’s toxicology The basic science of poisons. 6th ed. New York: McGraw-Hill; 2001.

    Google Scholar 

  76. Pappas RS, Gray N, Halstead M, Valentin-Blasini L, Watson C. Toxic metal-containing particles in aerosols from pod-type electronic cigarettes. J Anal Toxicol. 2020:bkaa088. https://doi.org/10.1093/jat/bkaa088.

  77. Schraufnagel DE. The health effects of ultrafine particles. Exp Mol Med. 2020;52:311–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Wiseman KD, Cornacchione J, Wagoner KG, et al. Adolescents’ and young adults’ knowledge and beliefs about constituents in novel tobacco products. Nicotine Tob Res. 2016;18:1581–7.

    PubMed  PubMed Central  Google Scholar 

  79. Wagoner KG, Cornacchione J, Wiseman KD, Teal R, Moracco KE, Sutfin EL. E-cigarettes, Hookah pens and vapes: adolescent and young adult perceptions of electronic nicotine delivery systems. Nicotine Tob Res. 2016;18:2006–12.

    PubMed  PubMed Central  Google Scholar 

  80. Cosselman KE, Navas-Acien A, Kaufman JD. Environmental factors in cardiovascular disease. Nat Rev Cardiol. 2015;12:627–42.

    CAS  PubMed  Google Scholar 

  81. Lamas GA, Navas-Acien A, Mark DB, Lee KL. Heavy metals, cardiovascular disease, and the unexpected benefits of chelation therapy. J Am Coll Cardiol. 2016;67:2411–8.

    PubMed  PubMed Central  Google Scholar 

  82. Bhatnagar A. Environmental cardiology: studying mechanistic links between pollution and heart disease. CircRes. 2006;99:692–705.

    CAS  Google Scholar 

  83. Navas-Acien A, Guallar E, Silbergeld EK, Rothenberg SJ. Lead exposure and cardiovascular disease--a systematic review. Environ Health Perspect. 2007;115:472–82.

    CAS  PubMed  Google Scholar 

  84. Nigra AE, Ruiz-Hernandez A, Redon J, Navas-Acien A, Tellez-Plaza M. Environmental metals and cardiovascular disease in adults: a systematic review beyond lead and cadmium. Curr Environ Health Rep. 2016;3:416–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Menke A, Muntner P, Batuman V, Silbergeld EK, Guallar E. Blood lead below 0.48 micromol/L (10 microg/dL) and mortality among US adults. Circulation. 2006;114:1388–94.

    CAS  PubMed  Google Scholar 

  86. Moon K, Guallar E, Navas-Acien A. Arsenic exposure and cardiovascular disease: an updated systematic review. Curr Atheroscler Rep. 2012;14:542–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Moon KA, Guallar E, Umans JG, et al. Association between exposure to low to moderate arsenic levels and incident cardiovascular disease. A prospective cohort study. Ann Intern Med. 2013;159:649–59.

    PubMed  PubMed Central  Google Scholar 

  88. Lippmann M, Ito K, Hwang JS, Maciejczyk P, Chen LC. Cardiovascular effects of nickel in ambient air. Environ Health Perspect. 2006;114:1662–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Navas-Acien A, Silbergeld EK, Sharrett R, Calderon-Aranda E, Selvin E, Guallar E. Metals in urine and peripheral arterial disease. Environ Health Perspect. 2005;113:164–9.

    CAS  PubMed  Google Scholar 

  90. Lamas GA, Goertz C, Boineau R, et al. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. Jama. 2013;309:1241–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Arenas I, Ujueta F, Diaz D, et al. Limb preservation using edetate disodium-based chelation in patients with diabetes and critical limb ischemia: an open-label pilot study. Cureus. 2019;11:e6477.

    PubMed  PubMed Central  Google Scholar 

  92. Ujueta FAI, Yates T, Beasley R, Diaz D, Lamas GL. Edetate disodium-based treatment in a patient with diabetes and critical limb ischemia after unsuccessful peripheral arterial revascularization: a case report. Clin Diabetes. 2019;37:294–7.

    PubMed  PubMed Central  Google Scholar 

  93. Polonsky TS, McClelland RL, Jorgensen NW, et al. Coronary artery calcium score and risk classification for coronary heart disease prediction. Jama. 2010;303:1610–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. McClelland RL, Jorgensen NW, Budoff M, et al. 10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study). J Am Coll Cardiol. 2015;66:1643–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Aikawa E, Nahrendorf M, Figueiredo J-L, et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation. 2007;116:2841–50.

    CAS  PubMed  Google Scholar 

  96. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15:827–32.

    CAS  PubMed  Google Scholar 

  97. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med. 2008;358:1336–45.

    CAS  PubMed  Google Scholar 

  98. Folsom AR, Kronmal RA, Detrano RC, et al. Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA). Arch Intern Med. 2008;168:1333–9.

    PubMed  PubMed Central  Google Scholar 

  99. Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2935–59.

    PubMed  Google Scholar 

  100. Liang CJ, Budoff MJ, Kaufman JD, Kronmal RA, Brown ER. An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA). BMC Med Imaging. 2012;12:14.

    PubMed  PubMed Central  Google Scholar 

  101. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999;340:115–26.

    CAS  PubMed  Google Scholar 

  102. Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005;111:363–8.

    PubMed  Google Scholar 

  103. Newby DE, Wright RA, Labinjoh C, et al. Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking: a mechanism for arterial thrombosis and myocardial infarction. Circulation. 1999;99:1411–5.

    CAS  PubMed  Google Scholar 

  104. Shimbo D, Muntner P, Mann D, et al. Endothelial dysfunction and the risk of hypertension: the multi-ethnic study of atherosclerosis. Hypertension. 2010;55:1210–6.

    CAS  PubMed  Google Scholar 

  105. Barr RG, Mesia-Vela S, Austin JH, et al. Impaired flow-mediated dilation is associated with low pulmonary function and emphysema in ex-smokers: the Emphysema and Cancer Action Project (EMCAP) Study. Am J Respir Crit Care Med. 2007;176:1200–7.

    PubMed  PubMed Central  Google Scholar 

  106. VanWijk MJ, VanBavel E, Sturk A, Nieuwland R. Microparticles in cardiovascular diseases. Cardiovasc Res. 2003;59:277–87.

    CAS  PubMed  Google Scholar 

  107. Boulanger CM, Amabile N, Tedgui A. Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. Hypertension. 2006;48:180–6.

    CAS  PubMed  Google Scholar 

  108. Nieri D, Neri T, Petrini S, Vagaggini B, Paggiaro P, Celi A. Cell-derived microparticles and the lung. Eur Respir Rev. 2016;25:266–77.

    PubMed  Google Scholar 

  109. Lynch SF, Ludlam CA. Plasma microparticles and vascular disorders. Br J Hematol. 2007;137:36–48.

    CAS  Google Scholar 

  110. Berezin AE, Kremzer AA, Martovitskaya YV, Berezina TA, Gromenko EA. Pattern of endothelial progenitor cells and apoptotic endothelial cell-derived microparticles in chronic heart failure patients with preserved and reduced left ventricular ejection fraction. EBioMedicine. 2016;4:86–94.

    PubMed  PubMed Central  Google Scholar 

  111. Pirro M, Schillaci G, Bagaglia F, et al. Microparticles derived from endothelial progenitor cells in patients at different cardiovascular risk. Atherosclerosis. 2008;197:757–67.

    CAS  PubMed  Google Scholar 

  112. Antoniewicz L, Kiessling A, Mobarrez F, Lundback M. Reply to: “Endothelial progenitor cell release is usually considered a beneficial effect: problems in interpreting the acute effects of e-cigarette use”. Atherosclerosis. 2017;258:164–5.

    CAS  PubMed  Google Scholar 

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National Institute of Environmental Health Sciences (NIEHS) - R01ES029967, R01ES030025, R21ES029777, P30ES009089, P42ES010349.

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Correspondence to Nancy J. LoIacono.

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The original online version of this article was revised: The description of reference 55 should be changed to: This population-based study from the Population Assessment of Tobacco and Health Wave 1 survey found that e-cigarette use is associated with a higher risk of myocardial infarction. A limitation of the study is that there are few participants who solely used e-cigarettes in the absence of past or current traditional smoking. This manuscript has been retracted but understanding the limitations of the study remains relevant.

This article is part of the Topical Collection on Metals and Health

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Navas-Acien, A., Martinez-Morata, I., Hilpert, M. et al. Early Cardiovascular Risk in E-cigarette Users: the Potential Role of Metals. Curr Envir Health Rpt 7, 353–361 (2020). https://doi.org/10.1007/s40572-020-00297-y

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  • DOI: https://doi.org/10.1007/s40572-020-00297-y

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