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Original Investigation
March 2017

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

Author Affiliations
  • 1David Geffen School of Medicine, University of California, Los Angeles
  • 2Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles
  • 3Department of Biomathematics, David Geffen School of Medicine, University of California, Los Angeles
  • 4Department of Environmental Health Sciences, School of Public Health, University of California, Los Angeles
JAMA Cardiol. 2017;2(3):278-284. doi:10.1001/jamacardio.2016.5303
Key Points

Question  Do habitual electronic cigarette users have increased cardiac sympathetic activity and oxidative stress, both risk factors for future adverse cardiac events?

Findings  In this cross-sectional case-control study of 42 otherwise healthy habitual electronic cigarette users and nonuser control individuals, heart rate variability was shifted toward increased sympathetic predominance, with the low frequency to high frequency ratio significantly increased. Furthermore, low-density lipoprotein oxidizability, which is a measure of oxidative stress, was significantly increased in habitual electronic cigarette users.

Meaning  Habitual electronic cigarette use is associated with physiologic effects. Further research into potential adverse health effects of electronic cigarettes is warranted.


Importance  Electronic cigarettes (e-cigarettes) have gained unprecedented popularity, but virtually nothing is known about their cardiovascular risks.

Objective  To test the hypothesis that an imbalance of cardiac autonomic tone and increased systemic oxidative stress and inflammation are detectable in otherwise healthy humans who habitually use e-cigarettes.

Design, Setting, and Participants  Cross-sectional case-control study of habitual e-cigarette users and nonuser control individuals from 2015 to 2016 at the University of California, Los Angeles. Otherwise healthy habitual e-cigarette users between the ages of 21 and 45 years meeting study criteria, including no current tobacco cigarette smoking and no known health problems or prescription medications, were eligible for enrollment. Healthy volunteers meeting these inclusion criteria who were not e-cigarette users were eligible to be enrolled as control individuals. A total of 42 participants meeting these criteria were enrolled in the study including 23 self-identified habitual e-cigarette users and 19 self-identified non–tobacco cigarette, non–e-cigarette user control participants.

Main Outcomes and Measures  Heart rate variability components were analyzed for the high-frequency component (0.15-0.4 Hz), an indicator of vagal activity, the low-frequency component (0.04-0.15 Hz), a mixture of both vagal and sympathetic activity, and the ratio of the low frequency to high frequency, reflecting the cardiac sympathovagal balance. Three parameters of oxidative stress were measured in plasma: (1) low-density lipoprotein oxidizability, (2) high-density lipoprotein antioxidant/anti-inflammatory capacity, and (3) paraoxonase-1 activity.

Results  Of the 42 participants, 35% were women, 35% were white, and the mean age was 27.6 years. The high-frequency component was significantly decreased in the e-cigarette users compared with nonuser control participants (mean [SEM], 46.5 [3.7] nu vs 57.8 [3.6] nu; P = .04). The low-frequency component (mean [SEM], 52.7 [4.0] nu vs 39.9 [3.8] nu; P = .03) and the low frequency to high frequency ratio (mean [SEM], 1.37 [0.19] vs 0.85 [0.18]; P = .05) were significantly increased in the e-cigarette users compared with nonuser control participants, consistent with sympathetic predominance. Low-density lipoprotein oxidizability, indicative of the susceptibility of apolipoprotein B–containing lipoproteins to oxidation, was significantly increased in e-cigarette users compared with nonuser control individuals (mean [SEM], 3801.0 [415.7] U vs 2413.3 [325.0] U; P = .01) consistent with increased oxidative stress, but differences in high-density antioxidant/anti-inflammatory capacity and paraoxonase-1 activity were not significant.

Conclusions and Relevance  In this study, habitual e-cigarette use was associated with a shift in cardiac autonomic balance toward sympathetic predominance and increased oxidative stress, both associated with increased cardiovascular risk.