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

Abstract

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.

Figure 1. Heart Rate Variability Components

A, The high-frequency (HF) component, an indicator of vagal activity, was significantly decreased in the e-cigarette users compared with nonuser control individuals (mean [SEM], 46.5 [3.7] nu vs 57.8 [3.6] nu, P = .04). B and C, The low-frequency (LF) component (mean [SEM], 52.7 [4.0] nu vs 39.9 [3.8] nu, P = .03), and the LF to HF ratio (1.37 [0.19] vs 0.85 [0.18], P = .05), were significantly increased in the e-cigarette users compared with nonuser controls, consistent with sympathetic predominance. These findings were present even in the absence of recent e-cigarette use, as verified by the absence of detectable nicotine in the plasma.

Figure 2. Heart Rate Variability During Controlled Breathing

A, Within each group (e-cigarette users and nonuser control participants), the high-frequency (HF) component was significantly increased during controlled breathing compared with spontaneous breathing. Similarly, within each group, the low frequency (LF) (B), and LF to HF ratio (C) were decreased during controlled compared with spontaneous breathing, consistent with a relative increase in cardiac vagal and decline in cardiac sympathetic influence. However, between e-cigarette user and nonuser groups, the magnitude of the increase in HF and decrease in LF and LF to HF ratio during controlled breathing were not different. ^aP = .05, within-group difference between controlled breathing and spontaneous breathing.

Figure 3. Oxidative Stress

Low-density lipoprotein oxidizability, indicative of susceptibility of apoB-containing lipoproteins to oxidation, was significantly increased in e-cigarette users (n = 12) compared with nonuser (n = 18) control participants (mean [SEM], 3801.0 [415.7] U vs 2413.3 [325.0] U, P = .01), consistent with increased oxidative stress.