February 4, 2017

Stanton A. Glantz, PhD

The evidence that e-cigs increase cardiovascular risk keeps piling up: Effects on heart rhythm and oxidative stress

While e-cigarette advocates keep stressing the widely-accepted fact that e-cigarettes deliver lower levels of most cancer-causing chemicals, they remain silent on the growing and quite consistent evidence that e-cigarette use increases the risk of cardiovascular (and non-cancer lung) disease.
 
The latest contribution to this literature is “Increased Cardiac Sympathetic Activity and Oxidative Stress in Habitual Electronic Cigarette Users: Implications for Cardiovascular Risk” by Roya S. Moheimani and colleagues at UCLA in JAMA Cardiology.  This paper examined heart rhythms and oxidative loads in chronic e-cigarette only users.  They found reduced heart rate variability, the variation in the time between heart beats.  Reductions in heart rate variability are a well-established predictor of future heart attacks. 
 
They also found increases in oxidized LDL cholesterol, the bad cholesterol which increases the risk of atherosclerosis.  This increased oxidant load is also tied to reductions in normal function of arteries, an effect previously shown in cigarette smokers and e-cigarette users. 
 
The paper is accompanied by an accompanying editorial by Aruni Bhatnagar that points both the reasons that one would expect e-cigarettes  to increase cardiovascular risk and the many remaining questions about underlying mechanisms.  This developing literature, however, is rapidly filling out the picture of how and why e-cigarettes increase risk of cardiovascular disease and heart attacks. 
 
These effects are important because heart and vascular disease kills about the same number of US smokers (160,000) as all cancers (163,000).   (Noncancer lung disease, which is probably increased by e-cigarettes  kills another 113,000 smokers.)  That is why I think ecigs are about 30-50% as dangerous as cigarettes.
 
Here are the Key Points and Abstract from the paper:
 
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.
 
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. [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.
 
The full citation is Roya S. Moheimani, May Bhetraratana,  Fen Yin, Kacey M. Peters,  Jeffrey Gornbein, Jesus A. Araujo,  Holly R. Middlekauff.  Increased Cardiac Sympathetic Activity and Oxidative Stress in Habitual Electronic Cigarette Users” Implications for Cardiovascular Risk. JAMA Cardiol. Published online February 1, 2017. doi:10.1001/jamacardio.2016.5303

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