Vaping Harms Vasculature, Even Without Nicotine

Marlene Busko

August 20, 2019

In a small group of healthy young people who did not smoke or vape, vaping one nicotine-free electronic cigarette (e-cigarette) produced transient changes in blood vessels similar to those seen in early atherosclerosis, a study found.

The acute changes seen after one-time vaping — inhaling and exhaling the vaporized aerosol mist from the heated liquid in a battery-operated e-cigarette — suggest that repeated vaping would lead to chronic vascular endothelial dysfunction, the authors of this MRI study say.

The study, by Alessandra Caporale, PhD, a postdoctoral researcher from the Laboratory for Structural, Physiologic and Functional Imaging, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues, was published online August 20 in Radiology.

The study used nicotine-free e-cigarettes; therefore, the findings shatter any mistaken belief that it is only the nicotine in e-cigarettes that is harmful to health.

"Endothelial dysfunction — the inability or reduced ability of the vasculature to expand to allow for increase in blood flow when needed — is the earliest stage of atherosclerosis pathogenesis," senior study author Felix W. Wehrli, PhD, director of the Laboratory for Structural, Physiologic and Functional Imaging and professor at the University of Pennsylvania, told Medscape Medical News in a joint interview with Caporale.

"The harms of cigarettes are obviously well known," Wehrli summarized, "but what was not well known [and what was shown in this study] was that e-cigarettes — even though advertised as comparatively unharmful — may actually ultimately cause harm similar to cigarettes and unrelated to nicotine."

Parents of middle school and high school students, whose e-cigarette use has increased dramatically, should be aware of these harms, Wehrli and Caporale stressed.

The many flavors that e-cigarettes come in "attract young people and potentially attract them to potential life-long addiction," Caporale said. She noted that some e-cigarettes contain more nicotine than what is stated on the label.

Not as Benign as Some Believe

Similarly, Karen M. Wilson, MD, MPH, a pediatrician at Icahn School of Medicine at Mount Sinai, New York City, who was not involved with the study, told Medscape Medical News that "there has been this narrative that electronic cigarettes create this harmless 'water vapor,' " thereby making them useful for adults who want to quit smoking.

But "what we're really starting to understand" is that in addition to nicotine, the aerosol contains other potentially toxic particles, she said.

According to Wilson, although it is unknown what the effects will be after 20 or 30 years, this study suggests that, as with smoking, "we are likely to see an increase in cardiovascular disease" from vaping.

Importantly, "some of these vascular changes in the lungs or the direct irritation from those toxins and particulates in the aerosol [may be] what's precipitating" the recently seen cluster of cases of severe lung disease in young people who had been vaping, Wilson said.

As recently reported, from July through August 8, there were 12 confirmed cases and 13 cases under investigation of teens and young adults in Wisconsin who were hospitalized for severe lung problems after vaping.

Newer e-cigarette models, such as the Juul (Juul Labs), that have nicotine salt make it easier to inhale higher concentrations of nicotine, Wilson pointed out. "By the time [young people] recognize that it's dangerous, they're already addicted."

Importantly, the current study shows that "even without the nicotine, [e-cigarettes are] still harmful," she stressed, adding that there is no need to inhale anything except air or, if needed, a medication, such as albuterol for asthma.

Similarly, Deepak L. Bhatt, MD, MPH, a cardiologist at Brigham and Women's Hospital and a professor at Harvard Medical School in Boston, Massachusetts, told Medscape Medical News, "Vaping is growing among young people at an alarming rate, and the widespread belief among them is that this is safe for health." Bhatt was not involved with the study.

However, "this study demonstrates that these aerosols do negatively impact markers of endothelial function as assessed by MRI and adds to the growing literature that vaping is bad for cardiovascular health.

"Unfortunately, the full clinical impact of vaping will not be known for several years," he noted.

Effect of Aerosols on Blood Vessels

The e-liquid in e-cigarettes contains propylene glycol, glycerin, flavorings, and different amounts of nicotine. When heated, the aerosol that is formed contains formaldehyde and acetaldehyde (probable carcinogens) and tiny metal particles (likely from the heating element).

Once inhaled, these substances reach the lung alveoli, where they are taken up by blood vessels and can cause systemic oxidative stress and inflammation, as reported in studies of e-cigarettes that contain nicotine, the researchers write.

To investigate this in e-cigarettes without nicotine, Caporale and colleagues performed an MRI study in 17 men and 14 women who were 18 to 35 years old. The participants had never smoked or vaped. Their body mass index was 18 to 35 kg/m2, and they had no overt cardiovascular or neurovascular disease.

Under supervision, the participants took part in a "vaping challenge" in which they inhaled for 3 seconds (with no coughing or swallowing of the vapor) 16 times, using a disposable e-cigarette (Eco series; Epuffer) that contained propylene glycol, glycerol, and flavor but no nicotine. A 3.7-volt battery operated the e-cigarettes.

The participants underwent MRI scanning of the superficial femoral artery and vein, the superior sagittal sinus, and the aorta before and after the vaping challenge.

The researchers determined flow-mediated femoral artery dilation and femoral vein oxygen saturation by constricting the blood vessels of the upper leg using a cuff, and then releasing the cuff.

"The blood flow is completely disrupted for the femoral artery and vein for a few minutes, and then it is released, and then blood will shoot through the artery and return to the heart through the veins," Wehrli explained.

The researchers also assessed the cerebrovascular reactivity of the sagittal sinus using a breath-hold test, in which the participants held their breath for 30 seconds and breathed normally for 2 minutes three times.

MRI imaging was used to determine aortic pulse wave velocity.

A comparison of pre- and post-vaping MRI data after a single vaping challenge yielded the following results:

  • a 34% reduction in femoral artery flow–mediated dilation and a 25.8% reduction in blood flow acceleration (P <. 001 for both), indicating endothelial dysfunction;

  • a 20% reduction in oxygen saturation of the femoral vein (P < .001), indicating microvascular impairment; and

  • a 3% increase in aortic pulse-wave velocity (P = .05), suggesting aortic stiffening.

There were no statistically significant differences in the cerebrovascular reactivity of the sagittal sinus (P = .08).

"Even though 31 is not a very big number [of participants], the effects we observed [were] highly statistically significant," Wehrli emphasized.

Related Studies Support Current Findings

It would be unethical to perform this experiment using tobacco cigarettes in nonsmokers, Wehrli noted.

However, the team previously conducted a study that showed similar harmful vascular effects in long-term cigarette smokers.

In addition, another study they recently conducted demonstrated that nicotine-free e-cigarette vaping caused a transient increase in serum markers of inflammation (C-reactive protein) and oxidative stress, which peaked 1 to 2 hours after vaping and returned to baseline within 6 hours. These results support the imaging findings in the current study.

The research was funded by the National Heart, Lung, and Blood Institute. The authors have disclosed no relevant financial relationships.

Radiology. Published online August 20, 2019. Full text

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