Increased Cardiac Sympathetic Activity and Oxidative Stress in Habitual Electronic Cigarette Users: Implications for Cardiovascular Risk.
Electronic cigarettes (e-cigarettes) have gained unprecedented popularity, but virtually nothing is known about their cardiovascular risks.



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.



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.



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.



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.



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.
David Geffen School of Medicine, University of California, Los Angeles.
Roya S
RS
Moheimani
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles.
May
M
Bhetraratana
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles.
Fen
F
Yin
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles.
Kacey M
KM
Peters
Department of Biomathematics, David Geffen School of Medicine, University of California, Los Angeles.
Jeffrey
J
Gornbein
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles4Department of Environmental Health Sciences, School of Public Health, University of California, Los Angeles.
Jesus A
JA
Araujo
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles.
Holly R
HR
Middlekauff
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003367:Cotinine / Q000097:blood; D003430:Cross-Sectional Studies; D066300:Electronic Nicotine Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D012307:Risk Factors; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D000072137:Vaping / Q000009:adverse effects* / Q000503:physiopathology; D055815:Young Adult
D015415:Biomarkers; D003367:Cotinine