Skip to main content
SpringerLink
Log in

Very Low Nicotine Content Cigarettes and Potential Consequences on Cardiovascular Disease

  • Tobacco Use and Lifestyle (HA Tindle, Section Editor)
  • Published:
Current Cardiovascular Risk Reports Aims and scope Submit manuscript

Abstract

Cigarette smoking remains highly prevalent in the U.S. and contributes significantly to cardiovascular disease (CVD). Tobacco control policies, including product regulation, can reduce smoking-related harm. One approach being considered in the U.S. is for the FDA to set a low nicotine standard for cigarettes. Such a standard could result in multiple beneficial outcomes including reduced cardiovascular toxicity related to nicotine, reduced smoking intensity in current smokers, increased cessation rates, decreased development of smoking dependence in youth, and decreased passive smoke exposure. Consequently, CVD risk in the U.S. could be dramatically improved by nicotine reduction in cigarettes. Possible pathways linking nicotine reduction in cigarettes to decreased CVD risk are discussed, while potential unintended consequences that could offset expected gains are also presented. Gaps in the literature, including limited data on CVD biomarkers and long-term CVD outcomes following the use of very low nicotine cigarettes, are discussed to highlight areas for new research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

  1. Centers for Disease Control and Prevention. Vital signs: current cigarette smoking among adults aged >/=18 years--United States, 2005–2010. MMWR Morb Mortal Wkly Rep. 2011;60:1207–12.

    Google Scholar 

  2. Centers for Disease Control and Prevention. Smoking-attributable mortality, years of potential life lost, and productivity losses--United States, 2000–2004. MMWR Morb Mortal Wkly Rep. 2008;57:1226–8.

    Google Scholar 

  3. Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease: an update. J Am Coll Cardiol. 2004;43:1731–7.

    Article  PubMed  CAS  Google Scholar 

  4. U.S. Department of Health and Human Services. The Health Consequences of Smoking: 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 2004.

  5. Bazzano LA, He J, Muntner P, Vupputuri S, Whelton PK. Relationship between cigarette smoking and novel risk factors for cardiovascular disease in the United States. Ann Intern Med. 2003;138:891–7.

    PubMed  Google Scholar 

  6. • 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. This report describes the mechanisms by which cigarette smoking contributes to the development of cardiovascular disease.

  7. Zhang L, Curhan GC, Hu FB, Rimm EB, Forman JP. Association between passive and active smoking and incident type 2 diabetes in women. Diabetes Care. 2011;34:892–7.

    Article  PubMed  Google Scholar 

  8. U.S. Congress: Family smoking prevention and tobacco control and federal reform act. Pub. Law No. 111–31, 1776 (Jun 22, 2009), Washington, D.C.

  9. U.S. Department of Health and Human Services. The Health Consequences of Smoking: Nicotine addiction: A Report of the Surgeon General. U.S. Department of Health and Human Service, Center for Health Promotion and Education, Office of Smoking and Health 1988.

  10. Benowitz NL, Henningfield JE. Establishing a nicotine threshold for addiction. The implications for tobacco regulation. N Engl J Med. 1994;331:123–5.

    Article  PubMed  CAS  Google Scholar 

  11. Benowitz NL, Jacob 3rd P. Daily intake of nicotine during cigarette smoking. Clin Pharmacol Ther. 1984;35:499–504.

    Article  PubMed  CAS  Google Scholar 

  12. National Cancer Institute: Risks Associated with Smoking Cigarettes with Low Machine-Measured Yields of Tar and Nicotine; Report of the NCI Expert Committee. Smoking and Tobacco Control Monograph. vol. 13. Bethesda, MD; 2001.

  13. Kozlowski LT, Goldberg ME, Yost BA, White EL, Sweeney CT, Pillitteri JL. Smokers' misperceptions of light and ultra-light cigarettes may keep them smoking. Am J Prev Med. 1998;15:9–16.

    Article  PubMed  CAS  Google Scholar 

  14. Tindle HA, Rigotti NA, Davis RB, Barbeau EM, Kawachi I, Shiffman S. Cessation among smokers of "light" cigarettes: results from the 2000 national health interview survey. Am J Public Health. 2006;96:1498–504.

    Article  PubMed  Google Scholar 

  15. Zeller M, Hatsukami D. The Strategic Dialogue on Tobacco Harm Reduction: a vision and blueprint for action in the US. Tob Control. 2009;18:324–32.

    Article  PubMed  Google Scholar 

  16. Benowitz NL. Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog Cardiovasc Dis. 2003;46:91–111.

    Article  PubMed  CAS  Google Scholar 

  17. Woolf KJ, Zabad MN, Post JM, McNitt S, Williams GC, Bisognano JD. Effect of nicotine replacement therapy on cardiovascular outcomes after acute coronary syndromes. Am J Cardiol. 2012, In press.

  18. Kimmel SE, Berlin JA, Miles C, Jaskowiak J, Carson JL, Strom BL. Risk of acute first myocardial infarction and use of nicotine patches in a general population. J Am Coll Cardiol. 2001;37:1297–302.

    Article  PubMed  CAS  Google Scholar 

  19. Joseph AM, Norman SM, Ferry LH, et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med. 1996;335:1792–8.

    Article  PubMed  CAS  Google Scholar 

  20. Tzivoni D, Keren A, Meyler S, Khoury Z, Lerer T, Brunel P. Cardiovascular safety of transdermal nicotine patches in patients with coronary artery disease who try to quit smoking. Cardiovasc Drugs Ther. 1998;12:239–44.

    Article  PubMed  CAS  Google Scholar 

  21. Escobedo LG, Zack MM. Comparison of sudden and nonsudden coronary deaths in the United States. Circulation. 1996;93:2033–6.

    Article  PubMed  CAS  Google Scholar 

  22. Dinas PC, Koutedakis Y, Flouris AD. Effects of active and passive tobacco cigarette smoking on heart rate variability. Int J Cardiol. 2012, In press.

  23. Csonka E, Somogyi A, Augustin J, Haberbosch W, Schettler G, Jellinek H. The effect of nicotine on cultured cells of vascular origin. Virchows Arch A Pathol Anat Histopathol. 1985;407:441–7.

    Article  PubMed  CAS  Google Scholar 

  24. Cucina A, Corvino V, Sapienza P, et al. Nicotine regulates basic fibroblastic growth factor and transforming growth factor beta1 production in endothelial cells. Biochem Biophys Res Commun. 1999;257:306–12.

    Article  PubMed  CAS  Google Scholar 

  25. Villablanca AC. Nicotine stimulates DNA synthesis and proliferation in vascular endothelial cells in vitro. J Appl Physiol. 1998;84:2089–98.

    PubMed  CAS  Google Scholar 

  26. Puranik R, Celermajer DS. Smoking and endothelial function. Prog Cardiovasc Dis. 2003;45:443–58.

    Article  PubMed  CAS  Google Scholar 

  27. Wang S, Zhang C, Zhang M, et al. Activation of AMP-activated protein kinase alpha2 by nicotine instigates formation of abdominal aortic aneurysms in mice in vivo. Nat Med. 2012;18:902–10.

    Article  PubMed  CAS  Google Scholar 

  28. Li ZZ, Dai QY. Pathogenesis of abdominal aortic aneurysms: role of nicotine and nicotinic acetylcholine receptors. Mediat Inflamm. 2012;1–8.

  29. Burns DM. Epidemiology of smoking-induced cardiovascular disease. Prog Cardiovasc Dis. 2003;46:11–29.

    Article  PubMed  Google Scholar 

  30. Girdhar G, Xu S, Bluestein D, Jesty J. Reduced-nicotine cigarettes increase platelet activation in smokers in vivo: a dilemma in harm reduction. Nicotine Tob Res. 2008;10:1737–44.

    Article  PubMed  CAS  Google Scholar 

  31. Ramachandran J, Rubenstein D, Bluestein D, Jesty J. Activation of platelets exposed to shear stress in the presence of smoke extracts of low-nicotine and zero-nicotine cigarettes: the protective effect of nicotine. Nicotine Tob Res. 2004;6:835–41.

    Article  PubMed  CAS  Google Scholar 

  32. Benowitz NL, Hall SM, Stewart S, Wilson M, Dempsey D, Jacob 3rd P. Nicotine and carcinogen exposure with smoking of progressively reduced nicotine content cigarette. Cancer Epidemiol Biomarkers Prev. 2007;16:2479–85.

    Article  PubMed  CAS  Google Scholar 

  33. Donny EC, Houtsmuller E, Stitzer ML. Smoking in the absence of nicotine: behavioral, subjective and physiological effects over 11 days. Addiction. 2007;102:324–34.

    Article  PubMed  Google Scholar 

  34. •• Hatsukami DK, Kotlyar M, Hertsgaard LA, et al. Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation. Addiction. 2010;105:343–55. This article demonstrates the effectiveness of very low nicotine content cigarettes at reducing smoking intensity and cigarette dependence for treatment-seeking smokers.

    Article  PubMed  Google Scholar 

  35. •• Benowitz NL, Dains KM, Hall SM, et al. Smoking behavior and exposure to tobacco toxicants during 6 months of smoking progressively reduced nicotine content cigarettes. Cancer Epidemiol Biomarkers Prev. 2012;21:761–9. This article demonstrates that smokers can switch to reduced nicotine cigarettes and reduce their smoking intensity without compensating for lower nicotine.

    Article  PubMed  CAS  Google Scholar 

  36. Strasser AA, Lerman C, Sanborn PM, Pickworth WB, Feldman EA. New lower nicotine cigarettes can produce compensatory smoking and increased carbon monoxide exposure. Drug Alcohol Depend. 2007;86:294–300.

    Article  PubMed  CAS  Google Scholar 

  37. Donny EC, Jones M. Prolonged exposure to denicotinized cigarettes with or without transdermal nicotine. Drug Alcohol Depend. 2009;104:23–33.

    Article  PubMed  CAS  Google Scholar 

  38. Eliasson B, Hjalmarson A, Kruse E, Landfeldt B, Westin A. Effect of smoking reduction and cessation on cardiovascular risk factors. Nicotine Tob Res. 2001;3:249–55.

    Article  PubMed  CAS  Google Scholar 

  39. Hatsukami DK, Kotlyar M, Allen S, et al. Effects of cigarette reduction on cardiovascular risk factors and subjective measures. Chest. 2005;128:2528–37.

    Article  PubMed  Google Scholar 

  40. Bjartveit K, Tverdal A. Health consequences of smoking 1–4 cigarettes per day. Tob Control. 2005;14:315–20.

    Article  PubMed  CAS  Google Scholar 

  41. Pope 3rd CA, Burnett RT, Krewski D, et al. Cardiovascular mortality and exposure to airborne fine particulate matter and cigarette smoke: shape of the exposure-response relationship. Circulation. 2009;120:941–8.

    Article  PubMed  CAS  Google Scholar 

  42. Walker N, Howe C, Bullen C, et al. The combined effect of very low nicotine content cigarettes, used as an adjunct to usual Quitline care (nicotine replacement therapy and behavioural support), on smoking cessation: a randomized controlled trial. Addiction. 2012, In press.

  43. Allen SS, Hatsukami D, Gorsline J. Cholesterol changes in smoking cessation using the transdermal nicotine system. Transdermal Nicotine Study Group. Prev Med. 1994;23:190–6.

    Article  PubMed  CAS  Google Scholar 

  44. Gepner AD, Piper ME, Johnson HM, Fiore MC, Baker TB, Stein JH. Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial. Am Heart J. 2011;161:145–51.

    Article  PubMed  CAS  Google Scholar 

  45. Johnson HM, Gossett LK, Piper ME, et al. Effects of smoking and smoking cessation on endothelial function: 1-year outcomes from a randomized clinical trial. J Am Coll Cardiol. 2010;55:1988–95.

    Article  PubMed  CAS  Google Scholar 

  46. Johnson HM, Piper ME, Baker TB, Fiore MC, Stein JH. Effects of smoking and cessation on subclinical arterial disease: a substudy of a randomized controlled trial. PLoS One. 2012;7:1–6.

    Article  Google Scholar 

  47. Bakhru A, Erlinger TP. Smoking cessation and cardiovascular disease risk factors: results from the Third National Health and Nutrition Examination Survey. PLoS Med. 2005;2:528–36.

    Article  Google Scholar 

  48. Ockene JK, Kuller LH, Svendsen KH, Meilahn E. The relationship of smoking cessation to coronary heart disease and lung cancer in the Multiple Risk Factor Intervention Trial (MRFIT). Am J Public Health. 1990;80:954–8.

    Article  PubMed  CAS  Google Scholar 

  49. Kondo T, Osugi S, Shimokata K, et al. Smoking and smoking cessation in relation to all-cause mortality and cardiovascular events in 25,464 healthy male Japanese workers. Circ J. 2011;75:2885–92.

    Article  PubMed  Google Scholar 

  50. Critchley J, Capewell S. Smoking cessation for the secondary prevention of coronary heart disease. Cochrane Database Syst Rev. 2004:CD003041.

  51. Committee on Secondhand Smoke Exposure and Acute Coronary Events, Institute of Medicine. Secondhand Smoke Exposure and Cardiovascular Effects: Making Sense of the Evidence. Washington, D.C.; 2010.

  52. Glantz SA, Parmley WW. Passive smoking and heart disease. Epidemiology, physiology, and biochemistry. Circulation. 1991;83:1–12.

    Article  PubMed  CAS  Google Scholar 

  53. Venn A, Britton J. Exposure to secondhand smoke and biomarkers of cardiovascular disease risk in never-smoking adults. Circulation. 2007;115:990–5.

    Article  PubMed  CAS  Google Scholar 

  54. Whincup PH, Gilg JA, Emberson JR, et al. Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement. BMJ. 2004;329:200–5.

    Article  PubMed  CAS  Google Scholar 

  55. Khuder SA, Milz S, Jordan T, Price J, Silvestri K, Butler P. The impact of a smoking ban on hospital admissions for coronary heart disease. Prev Med. 2007;45:3–8.

    Article  PubMed  Google Scholar 

  56. • Lippert WC, Gustat J. Clean Indoor Air Acts reduce the burden of adverse cardiovascular outcomes. Public Health. 2012;126:279–85. This article provides an example of how a smoking policy can reduce tobacco smoke exposure and thus decrease cardiovascular disease risk.

    Article  PubMed  CAS  Google Scholar 

  57. Bartecchi C, Alsever RN, Nevin-Woods C, et al. Reduction in the incidence of acute myocardial infarction associated with a citywide smoking ordinance. Circulation. 2006;114:1490–6.

    Article  PubMed  Google Scholar 

  58. Sargent RP, Shepard RM, Glantz SA. Reduced incidence of admissions for myocardial infarction associated with public smoking ban: before and after study. BMJ. 2004;328:977–80.

    Article  PubMed  Google Scholar 

  59. Piano MR, Benowitz NL, Fitzgerald GA, et al. Impact of smokeless tobacco products on cardiovascular disease: implications for policy, prevention, and treatment: a policy statement from the American Heart Association. Circulation. 2010;122:1520–44.

    Article  PubMed  Google Scholar 

  60. Benowitz NL. Smokeless Tobacco as a Nicotine Delivery Device: Harm or Harm Reduction? Clin Pharmacol Ther. 2011;90:491–3.

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

This work was supported by grants from the National Institute on Drug Abuse, DA02277 and U54 DA031659.

Disclosure

D.L. Joel: none; R.L. Denlinger: none; S. Dermody: none; D.K. Hatsukami: Funded by Nabi Biopharmaceuticals and NIDA to be a site for a nicotine immunotherapy trial, had travel/accommodations expenses covered or reimbursed by Selecta Biosciences; N.L. Benowitz: consultant to several pharmaceutical companies that have developed or market smoking cessation medications; E.C. Donny: none.

Author information

Authors and Affiliations

  1. Department of Psychology, University of Pittsburgh, 4311 Sennott Square, 201 S. Bouquet Street, Pittsburgh, PA, 15260, USA

    Danielle L. Joel

  2. Departments of Psychology & Behavioral Community Health Sciences, University of Pittsburgh, 4120 Sennott Square, 201 S. Bouquet Street, Pittsburgh, PA, 15260, USA

    Rachel L. Denlinger

  3. Department of Psychology, University of Pittsburgh, 4118 Sennott Square, 201 S. Bouquet Street, Pittsburgh, PA, 15260, USA

    Sarah S. Dermody

  4. Department of Psychiatry, University of Minnesota, 717 Delaware Street, SE, Minneapolis, MN, 55414, USA

    Dorothy K. Hatsukami

  5. Departments of Medicine and Bioengineering & Therapeutic Sciences, Division of Clinical Pharmacology and Experimental Therapeutics, University of California San Francisco, Box 1220, San Francisco, CA, 94143, USA

    Neal L. Benowitz

  6. Departments of Psychology & Psychiatry, University of Pittsburgh, 4119 Sennott Square, 201 S. Bouquet Street, Pittsburgh, PA, 15260, USA

    Eric C. Donny

Authors
  1. Danielle L. Joel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel L. Denlinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah S. Dermody
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dorothy K. Hatsukami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Neal L. Benowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eric C. Donny
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric C. Donny.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Joel, D.L., Denlinger, R.L., Dermody, S.S. et al. Very Low Nicotine Content Cigarettes and Potential Consequences on Cardiovascular Disease. Curr Cardiovasc Risk Rep 6, 534–541 (2012). https://doi.org/10.1007/s12170-012-0266-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12170-012-0266-9

Keywords

Search

Navigation