E-cigarette use may not be harmless

Increased Cardiac Sympathetic Activity and Oxidative Stress in Habitual Electronic Cigarette Users Implications for Cardiovascular Risk

Literature - Moheimani RS, Bhetraratana M, Yin F, et al. - JAMA Cardiol. 2017; published online ahead of print


Electronic (e)-cigarettes contain nicotine, flavourings and a moisturising substance instead of tobacco, they are seen as a safer alternative to tobacco cigarettes and are very popular [1-5]. However, there are no data about the impact of their use on the cardiovascular (CV) system or on the mechanisms by which tobacco cigarettes increase CV risk.

In this study, the effects of e-cigarettes use on heart rate (HR) variability, systemic oxidative stress, and inflammation were evaluated in e-cigarette smokers and compared with non-smokers.

Main results

  • The high frequency (HF, 0.15-0.4 Hz) spectral component of HR variability, an indicator of vagal activity, was significantly decreased in the e-cigarette users compared with controls (mean ± SEM 46.5 ± 3.7 n.u. vs. 57.8 ± 3.6 n.u, P = 0.04).
  • The low frequency component (LF, 0.04-0.15 Hz) and LF:HF ratio were significantly increased in the e-cigarette users compared with controls, suggesting sympathetic predominance (mean ± SEM 52.7 ± 4.0 n.u. vs. 39.9 ± 3.8 n.u, P = 0.03 and 1.37 ± 0.19 n.u. vs. 0.85 ± 0.18 n.u, P = 0.05, respectively).
  • Plasma cotinine levels, an estimate of e-cigarette use, were inversely related to the HF component (r = −0.34, P = 0.04) and directly related to the LF component (r = 0.35, P = 0.03) and to the LF:HF ratio (r = 0.36, P = 0.03).
  • Controlled Breathing (Vagal Maneuver): Within each group, the HF component was significantly increased during controlled breathing compared with spontaneous breathing, and the LF and LF:HF ratio were decreased during controlled breathing compared with spontaneous breathing, suggesting a relative increase in cardiac vagal tone and decline in cardiac sympathetic influence.
  • Low-density lipoprotein oxidizability, indicative of susceptibility of apolipoprotein B–containing lipoproteins to oxidation, was significantly increased in e-cigarette users (n=12) compared with controls (n=18, mean ± SEM 3801.0 ± 415.7 U vs. 2413.3 ± 325.0 U, P = 0.01), suggesting increased oxidative stress.
  • Paraoxonase-1 activity tended to be lower in e-cigarette users compared with controls (mean ± SEM 649.9 ± 125.7 nmol p-nitrophenol/min/mL vs. 892.8 ± 110.0 nmol p-nitrophenol/min/mL, P = 0.17), suggesting decreased protection against oxidative stress.
  • The high-density lipoprotein antioxidant index as well as inflammatory markers, including fibrinogen and C-reactive protein levels, were not different between e-cigarette users and controls.
  • Plasma cotinine levels were directly related to LDL oxidizability (r = 0.35; P = 0.05).


In a small cross-sectional study, habitual e-cigarette use was associated with a shift in cardiac autonomic balance toward sympathetic predominance and increased oxidative stress, both indicative of increased CV risk. These data suggest that habitual e-cigarette use is associated with physiologic effects and that e-cigarette use is not harmless.

Editorial comment

In his editorial article [6], Bhatnagar briefly discusses the e-cigarette debate. Subsequently, he shares some interesting comments regarding the endpoints used in the study of Moheimani et al, suggesting that they may not reflect accurately the extend of increased CVD risk. The author concludes: ‘How e-cigarettes can induce oxidative stress in the absence of tar and other long-lived radicals remains unclear, and further studies are required not only to fully explore the reasons for the interesting observations of Moheimani et al but also to assess in greater depth the CV effects of e-cigarettes. Such investigations are critical for evaluating how harmful e-cigarettes are and whether their widespread acceptance will decrease the incidence of CVD or, by renormalizing smoking and promoting nicotine addiction, erode public health gains made by evidence-based tobacco control and regulation.’


1. Bhatnagar A, Whitsel LP, Ribisl KM, et al; American Heart Association Advocacy Coordinating Committee, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Quality of Care and Outcomes Research. Electronic cigarettes: a policy statement from the American Heart Association. Circulation. 2014;130:(16):1418-1436.

2. Singh T, Marynak K, Arrazola RA. Vital signs: exposure to electronic cigarette advertising among middle school and high school students: United States, 2014. MMWR Morb Mortal Wkly Rep. 2016;64(52):1403-1408.

3. Avdalovic MV, Murin S. POINT: does the risk of electronic cigarettes exceed potential benefits? Yes. Chest. 2015;148(3):580-582.

4. Middlekauff HR. COUNTERPOINT: does the risk of electronic cigarettes exceed potential benefits? No. Chest. 2015;148(3):582-584.

5. Green SH, Bayer R, Fairchild AL. Evidence, policy, and e-cigarettes: will England reframe the debate? N Engl J Med. 2016;374(14):1301-1303.

6. Bhatnagar A. Are Electronic Cigarette Users at Increased Risk for Cardiovascular Disease? JAMA Cardiol. 2017; published online ahead of print

Find this article online at JAMA cardiol

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