E-cigs Hurt Vascular Function as Much as Traditional Cigarettes

Patrice Wendling

April 29, 2020

Chronic e-cigarette use, alone or with traditional cigarettes, was associated with vascular and endothelial impairment similar to that of traditional cigarette smoking, a cross-sectional study suggests.

"There's been a lot of discussion about whether electronic cigarettes might be a less harmful product for people that are currently using tobacco cigarettes and are addicted to nicotine," senior author Naomi Hamburg, MD, Boston University School of Medicine, told theheart.org | Medscape Cardiology. "There's nothing in our data that suggests electronic cigarettes are healthier than traditional cigarettes."

Commenting on the results, Holly Middlekauff, MD, University of California Los Angeles, said: "It's a really interesting and timely study because it's looking at a comparison between tobacco and electronic cigarettes, and that's an important question we all want to know. Like all good studies, it probably raises more questions than it answers."

The new analysis, published today in the Journal of the American Heart Association, focused on the vascular effects of chronic e-cigarette use among healthy, young adults, ages 21 to 45 years, who smoked e-cigarettes exclusively at least 5 days a week for a minimum of 3 months.

As part of the Cardiovascular Injury due to Tobacco Use (CITU) study, noninvasive vascular function testing was performed in 94 nonsmokers, 285 cigarette smokers, 36 e-cigarette users, and 52 dual users, who were free of cardiovascular disease risk factors or CVD. All e-cigarette users were former smokers.

Most e-cigarettes were second-generation devices, not the pod mods more recently popularized by Juul; most e-cigarette and dual users reported using flavored e-liquids.

Combustible cigarette and dual users were older than nonsmokers and e-cigarette users. E-cigarette users were more likely to be younger, male, and white.

Before considering relevant confounders, baseline brachial diameter and flow velocity, flow-mediated dilation (FMD), shear stress, reactive hyperemia, and heart rate were similar across the tobacco product users and the nonsmokers.

However, carotid-femoral pulse wave velocity (PWV), carotid-radial PWV, and augmentation indexes were significantly different across the groups, suggestive of alterations in vascular stiffness, Hamburg and colleagues note. Central systolic and diastolic blood pressures were also different across the groups.

After adjustment for baseline differences in age, sex, race, and study site among nonsmokers, cigarette smokers, e-cigarette users, and dual users, the association remained significant only for augmentation index (118.4, 129.8, 126.2, 134.9, respectively; P =.0008) and systolic blood pressure (105 mm Hg, 110 mm Hg,106 mm Hg, 114 mm Hg, respectively; P = .007).

Augmentation index is an indirect measure of arterial stiffness and has been shown in previous studies to decline with smoking cessation in healthy tobacco users.

"We do see it as a perhaps more sensitive detector of the effects of smoking tobacco products, so it's not unexpected that that's what we saw with both the cigarette smokers and electronic cigarette users," Hamburg said.

"I would say that all of these measures can be categorized broadly as measures of vascular aging, and so it suggests there may be early vascular aging in the tobacco users, both electronic and traditional cigarettes."

Although the augmentation index was similarly abnormal in the combustible and e-cigarette users, the analysis compared very different groups, did not adjust for socioeconomic status, and had only 36 e-cigarette users, all of whom were former smokers; some had quit only weeks earlier, Middlekauff observed.

"Who knows how much of this vascular effect is residual from their prior smoking compared to is it really just the electronic cigarette [that's] a factor," she said. "So I think there are some limitations."

Also notable is that, even after adjustment, there was no difference in FMD between tobacco smokers and nonsmokers, and "that's a little bit surprising," Middlekauff said. Impaired FMD is more widely regarded as the first sign of future atherosclerosis, and has been shown in many populations to be predictive of cardiovascular events.

Further, a recent randomized study by George et al showed that mean FMD improved within 1 month of switching from tobacco cigarettes to e-cigarettes, and concluded that such a switch "could be considered a vascular harms reduction measure."

The FMD finding was "unexpected, but it may be that our cohort was younger and had less pack-years smoking than in previous studies," study coauthor Aruni Bhatnagar, MD, also with Boston University, said in an interview.

Post hoc analyses of freshly collected endothelial cells from 57 participants showed that A23187-stimulated nitric oxide production was similar between combustible and e-cigarette users, suggesting similar impairment in nitric oxide signaling, the researchers said. E-cigarette users also had lower endothelial nitric oxide synthase levels, compared with combustible cigarette smokers (10.7 AU vs 22.1 AU; P = .03).

"It's hard to know how to piece that in because, again, the abnormal FMD is thought to be mediated by impairment of the nitric oxide release…and there was no difference in FMD, no matter how you statistically looked at it," Middlekauff said.

Taken together, "it's by far from the final word on vascular effects of electronic cigarettes compared to tobacco cigarettes," she concluded. "So I wouldn't change my recommendations to people that I would prefer they use electronic cigarettes compared to tobacco cigarettes. I'd rather that they switch, based on the George study, and hope that they would eventually wean themselves off e-cigarettes."

Hamburg said there is still a lot of controversy in this area, and that first-line therapy for smoking cessation are tools currently approved by the US Food and Drug Administration, which does not include electronic cigarettes.

"I would just emphasize that both smoking and vaping have effects on the lungs that may put people at risk for having a more severe COVID infection," she said. "So we're emphasizing the importance of quitting even more during this current moment."

The researchers are one of three groups to receive nearly $17 million in research funding from the American Heart Associaton as part of its campaign to end youth vaping. Their research will include evaluating blood vessel health in teenagers and young adults, use of mobile health technology to measure cardiovascular impacts of e-cigarettes on youth, and development of a smoking cessation program, Hamburg said.

This work was supported by awards from the National Heart, Lung, and Blood Institute of the National Institutes of Health and by an American Heart Association Mentored Clinical and Population Research Award. The authors and Middlekauff report no relevant disclosures.

J Am Heart Assoc. Published online April 29, 2020. Full text

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