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Compared to nonsmoking, non-e-cigarette user controls, healthy, habitual users of e-cigarettes also showed evidence of increased systemic oxidative stress.
The findings were not attributable to the transient pharmacological effect of nicotine, Holly R. Middlekauff, MD, of the University of California Los Angeles, and colleagues wrote in JAMA Cardiology, published online Feb. 1.
The study, one of the first to show regular e-cigarette use to be associated with physiologic effects associated with cardiovascular risk, suggest that e-cigarette use is not harmless, as many vaping proponents claim, Middlekauff said.
"Use of e-cigarettes, especially among young people, has increased dramatically in recent years and many users do not smoke cigarettes," Middlekauff told MedPage Today. "There is a perception among teens and young adults that e-cigarettes are safe. But this study shows that there are real physiologic adverse effects."
The cross-sectional case-control study included 23 self-identified habitual users of e-cigarettes and 19 non-smoking controls ages 21-45 with no known health problems and who were not taking any prescription medications.
In a controlled setting, the researchers measured two main mechanisms by which traditional smoking is known to promote cardiovascular disease: shift in the cardiac sympathovagal balance toward sympathetic predominance as assessed by heart rate variability (HRV) and increased systemic oxidative stress and inflammation.
Heart rate variability components were analyzed for the high frequency component (o.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, the researchers wrote.
To avoid the potential influence of circadian rhythm and menstrual cycle phases on autonomic tone, participants were studied midday (between 10 a.m. and 2 p.m.), and women were studied during their early follicular phase, confirmed by plasma estrogen and progesterone levels. E-cigarette users were also asked to abstain from use on the day of the study, to avoid measurement of transient nicotine effects.
Plasma measures of oxidative stress included low-density lipoprotein oxidizability, high-density lipoprotein antioxidant/anti-inflammatory capacity and paraoxonase-1-activity.
Of the 42 total study participants, 35% were women, 35% were white, and the mean age was 27.6 years.
Compared with non-smoking, non-e-cigarette user controls:
- The high-frequency component was significantly decreased in the e-cigarette users (mean [SEM] 46.5 [3.7] nu versus 57.8 [3.6] nu, P=0.04)
- The low-frequency component (mean [SEM], 52. [4.0] nu versus 39.9 [3.8] nu, P=0.03) and the low frequency to high frequency ratio (mean, [SEM], 1.37 [0.19] versus 0.85 [0.18], P=0.05) were significantly increased in the e-cigarette users, 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 (mean [SEM], 3801.0 [415.7] U versus 2413.3[325.0] U, P=0.01), consistent with increased oxidative stress
- Differences in high-density antioxidant/anti-inflammatory capacity and paraoxonase-1 activity were not significant
In an editorial published with the study, Aruni Bhatnagar, PhD, of the University of Louisville in Kentucky, wrote that while the findings suggest habitual e-cigarette use may increase cardiovascular risk, "changes in HRV and low-density lipoprotein oxidizability are indirect indices of cardiovascular injury, and it remains unclear to what extend these changes present an increase in cardiovascular risk."
Likewise, Bhatnagar wrote, the predictive value of change in low frequency and low frequency to high frequency ratio as a marker of cardiac influences is not clear.
Bhatnagar noted that the mechanisms by which e-cigarettes induce oxidative stress "in the absence of tar and other long-lived radicals" also remains unclear, and he concluded that additional research into the potential cardiovascular impact of e-cigarette use is needed.
"Such investigations are critical for evaluating how harmful e-cigarettes are and whether their widespread acceptance will decrease the incidence of cardiovascular disease, or, by renormalizing smoking and promoting nicotine addiction, erode public health gains made by evidence-based tobacco control and regulation," Bhatnagar wrote.
The researchers declared no relevant relationships with media related to this study.