Very Low Nicotine Content Cigarettes and Potential Consequences on Cardiovascular Disease
Tobacco Use and Lifestyle (HA Tindle, Section Editor)
First Online: 01 September 2012 DOI:
10.1007/s12170-012-0266-9 Cite this article as: Joel, D.L., Denlinger, R.L., Dermody, S.S. et al. Curr Cardiovasc Risk Rep (2012) 6: 534. doi:10.1007/s12170-012-0266-9 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.
Keywords Smoking Cigarette Nicotine Cardiovascular disease Tobacco policy Nicotine reduction References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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.
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.
Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease: an update. J Am Coll Cardiol. 2004;43:1731–7.
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.
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.
• 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.
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.
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.
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.
Benowitz NL, Henningfield JE. Establishing a nicotine threshold for addiction. The implications for tobacco regulation. N Engl J Med. 1994;331:123–5.
Benowitz NL, Jacob 3rd P. Daily intake of nicotine during cigarette smoking. Clin Pharmacol Ther. 1984;35:499–504.
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.
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.
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.
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.
Benowitz NL. Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog Cardiovasc Dis. 2003;46:91–111.
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.
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.
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.
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.
Escobedo LG, Zack MM. Comparison of sudden and nonsudden coronary deaths in the United States. Circulation. 1996;93:2033–6.
Dinas PC, Koutedakis Y, Flouris AD. Effects of active and passive tobacco cigarette smoking on heart rate variability. Int J Cardiol. 2012, In press.
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.
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.
Villablanca AC. Nicotine stimulates DNA synthesis and proliferation in vascular endothelial cells in vitro. J Appl Physiol. 1998;84:2089–98.
Puranik R, Celermajer DS. Smoking and endothelial function. Prog Cardiovasc Dis. 2003;45:443–58.
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.
Li ZZ, Dai QY. Pathogenesis of abdominal aortic aneurysms: role of nicotine and nicotinic acetylcholine receptors. Mediat Inflamm. 2012;1–8.
Burns DM. Epidemiology of smoking-induced cardiovascular disease. Prog Cardiovasc Dis. 2003;46:11–29.
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.
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.
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.
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.
•• 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
•• 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
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.
Donny EC, Jones M. Prolonged exposure to denicotinized cigarettes with or without transdermal nicotine. Drug Alcohol Depend. 2009;104:23–33.
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.
Hatsukami DK, Kotlyar M, Allen S, et al. Effects of cigarette reduction on cardiovascular risk factors and subjective measures. Chest. 2005;128:2528–37.
Bjartveit K, Tverdal A. Health consequences of smoking 1–4 cigarettes per day. Tob Control. 2005;14:315–20.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Critchley J, Capewell S. Smoking cessation for the secondary prevention of coronary heart disease. Cochrane Database Syst Rev. 2004:CD003041.
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.
Glantz SA, Parmley WW. Passive smoking and heart disease. Epidemiology, physiology, and biochemistry. Circulation. 1991;83:1–12.
Venn A, Britton J. Exposure to secondhand smoke and biomarkers of cardiovascular disease risk in never-smoking adults. Circulation. 2007;115:990–5.
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.
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.
• 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
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.
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.
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.
Benowitz NL. Smokeless Tobacco as a Nicotine Delivery Device: Harm or Harm Reduction? Clin Pharmacol Ther. 2011;90:491–3.
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