Like Tobacco, Long-term E-Cigarettes Harm Vascular Function

E-cigarettes appear to strain the cardiovascular system as much as tobacco cigarettes do in long-term smokers, according to a new study. Both are equally associated with more signs of vascular stiffness and less production of nitric oxide compared with not smoking, calling into question whether e-cigarettes should be employed as cessation aids.

Intuitively, it would seem to make sense that e-cigarettes are safer for the heart, in that their use doesn’t involve burning substances that release toxins and carcinogens. But preliminary research has suggested this isn’t the case—a 2018 review, for example, cited adverse changes involving endothelial function, vascular stiffness, vasoconstriction, heart rate, blood pressure, inflammation, oxidative stress, and platelet function seen in more than a dozen studies conducted in high-income countries.

“A lot of the other studies that have come out so far have looked at what happens to blood vessels just after someone uses an electronic cigarette,” said Jessica L. Fetterman, PhD (Boston University School of Medicine, MA), the new paper’s lead author. “They haven’t really looked at: what are the cardiovascular impacts associated with e-cigarette use over a longer period?”

Smokers in their study, published online earlier this week in the Journal of the American Heart Association, had established habits dating back at least 3 months prior to enrolling.

Holly R. Middlekauff, MD (UCLA Health, Los Angeles, CA), told TCTMD a “real strength” of the study is its focus on chronic smokers rather than the acute effects of use. But it also looked at a heterogeneous group in terms of demographics, with differences that could affect vascular function, and all of the e-cigarette users were former smokers.

“It’s an interesting study. It’s intriguing. But there’s still a lot more that needs to be done before we accept [that e-cigarettes are no better]. I think the data’s just not there yet” to draw a final answer, she commented.

Differences and Similarities in Vascular Stiffness

For the Cardiovascular Injury due to Tobacco Use (CITU) study, the investigators enrolled a total of 467 people without CVD or risk factors for the disease. Among them, 61% used combustible cigarettes, 8% used e-cigarettes (all were former tobacco smokers), 11% were dual users, and 20% were nonsmokers. Notably, the mean number of cigarettes and years spent smoking were similar for the conventional-cigarette smokers and dual users.

Smokers of regular cigarettes and dual users tended to be older than both e-cigarette users and nonsmokers. Overall, the people who used e-cigarettes were younger and were more likely to be male and to be white.

In unadjusted analyses, baseline brachial diameter and flow velocity, flow-mediated dilation, shear stress, reactive hyperemia, and heart rate all were similar across the three groups. Various measures of arterial stiffness including carotid femoral pulse-wave velocity (PWV), carotid radial PWV, augmentation index, and central blood pressures, on the other hand, differed.

After accounting for age, sex, race, and study site, multivariable models showed that augmentation index in particular was significantly higher among smokers of combustible cigarettes (129.8 ± 1.5) compared with nonsmokers (118.8 ± 2.7, P = 0.003), but similar to what was seen in e-cigarette users (134.9 ± 4.0, P = 1.00).

Additionally, the researchers analyzed endothelial cells that were freshly collected from study participants and found that “stimulated nitric oxide production was diminished in both combustible and e-cigarette users, suggesting the presence of endothelial cell dysfunction.”

Digesting the Data

Middlekauff pointed out that these findings are “a little bit at odds” with a 114-patient randomized trial, published late last year in Journal of the American Heart Association, that found significant improvement in flow-mediated dilation within 1 month of switching from tobacco cigarettes to e-cigarettes.

Flow-mediated dilation, she said, is “highly validated to be predictive. It’s one of the earliest signs of atherosclerosis or hardening of the arteries.” Augmentation index, a measure of vascular stiffness, “is less studied and less frequently used, . . . but it is valid. And it is interesting that it is different but only after they adjusted for all these differences in the populations. It’s a statistical approach that takes away some of the transparency and you just wish that the groups were better matched upfront . . . rather than have to do that mathematically.”

Asked about how these two studies fit together, Fetterman said, “We looked at slightly different measurements. And I think it is challenging to know both from their study and our study how many of the e-cigarette users truly switched completely to e-cigarettes because we don’t have a good biomarker to look at.”

Urine tests that measure cotinine pick up nicotine exposure, no matter whether that nicotine comes from combustible or e-cigarettes, she explained. “That’s been a real challenge. So how do you really validate that someone has only been using electronic cigarettes and been cheating with a cigarette here and there? We just don’t have that yet. I think there are some possible new ones coming. There’s been a lot of different studies trying to identify new biomarkers, but we don’t currently have a validated one yet.”

We just don’t know what the chronic effects are. I don’t want to say that they’re safe or harmless. Holly R. Middlekauff

On the whole, though, the literature shows that e-cigarettes aren’t any safer than tobacco cigarettes for vascular health, Fetterman said. “I think the evidence is growing that it’s not good for you.”

What it “suggests is that there’s no vascular improvement with switching to electronic cigarettes if you’re a smoker, and there are some studies suggesting there’s even harm in people that have never used tobacco [then] try using an e-cigarette, showing vascular impairments,” she noted.

Much needed now are long-term studies, Fetterman urged. “Heart disease takes decades to develop so it’s going to be a while before we really know [e-cigarettes’ safety].”

Even so, e-cigarettes can’t fully be ruled out as a safer alternative, Middlekauff said. For instance, she pointed out, they have “far fewer carcinogens.” Complicating matters is the fact that their effect on the lungs also isn’t known, but reports of e-cigarette or vaping-related lung injury (EVALI) seem largely related to contaminated THC.

“Again, we just don’t know what the chronic effects are. I don’t want to say that they’re safe or harmless” at this point, she concluded.

As for what clinicians can tell patients who ask about their options, Fetterman had some advice on how to handle the uncertainty over e-cigarettes. “If that patient has tried all of the traditional nicotine replacement therapies and tried behavioral therapy and not been successful in quitting, I think it’s worth a shot,” she acknowledged. “But it has to be done with the guidance of a physician, and if possible a cessation team, to help that patient step down on the nicotine and really create a plan to get them off of all tobacco products. Maybe e-cigarettes could play a role in that process, but I think it’s really important for patients to work with a physician to do that.”