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Higher cardiovascular risk for habitual e-cigarette users

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, found a small University of California study.

A study undertaken by Dr Holly R Middlekauff, of the David Geffen School of Medicine, University of California – Los Angeles, and colleagues has examined whether habitual users of electronic cigarettes (e-cigarettes) are more likely to have risk factors associated with increased cardiovascular risk.

Electronic cigarettes, first marketed in the US in 2006, have gained unprecedented popularity, especially among young people, but virtually nothing is known about their cardiovascular risks. This study included 23 habitual e-cigarette users (used most days for a minimum of one year) and 19 non-e-cigarette user control participants between the ages of 21 and 45 years who met study criteria, which included no current tobacco cigarette smoking and no known health problems.

The researchers found that habitual e-cigarette users were more likely than the non-smoking control participants to have increased cardiac sympathetic activity (increased adrenaline levels in the heart) and increased oxidative stress, known mechanisms by which tobacco cigarettes increase cardiovascular risk.

The authors write that these findings have critical implications for the long-term cardiac risks associated with habitual e-cigarette use and mandate a re-examination of aerosolised nicotine and its metabolites. “Nicotine, which is the major bioactive ingredient in e-cigarette aerosol, with its metabolites, may harbour unrecognised, sustained adverse physiologic effects that lead to an increased cardiovascular risk profile in habitual e-cigarette users.”

The researchers note that they cannot confirm causality on the basis of a single, small study, and that further research into the potential adverse cardiovascular health effects of e-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.

Authors
Roya S Moheimani; May Bhetraratana; Fen Yin; Kacey M Peters; Jeffrey Gornbein; Jesus A Araujo; Holly R Middlekauff

[link url="http://media.jamanetwork.com/news-item/habitual-e-cigarette-use-associated-with-risk-factors-linked-to-increased-cardiovascular-risk/"]JAMA material[/link]
[link url="http://jamanetwork.com/journals/jamacardiology/article-abstract/2600166"]JAMA Cardiology abstract[/link]
[link url="http://jamanetwork.com/journals/jamacardiology/article-abstract/2600160"]JAMA Cardiology editorial[/link]

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