Healthy nonsmokers may experience increased adrenaline levels in their heart after one electronic cigarette (e-cigarette) with nicotine, according to new research in Journal of the (AHA), the Open Access Journal of the American Heart Association (AHA)/American Stroke Association.

Nerve endings in the sympathetic nervous system release both adrenaline (epinephrine) and noradrenalin (norepinephrine), both of which play a role in the fight or flight response. Perpetually increased activity of the sympathetic nervous system contributes to increased cardiac risk.

“While e-cigarettes typically deliver fewer carcinogens than are found in the tar of tobacco cigarette smoke, they also usually deliver nicotine. Many believe that the tar — not the nicotine — is what leads to increased cancer and heart attack risks,” said Holly R. Middlekauff, M.D., senior study author and professor of medicine (cardiology) and physiology at the David Geffen School of Medicine at UCLA. “So, we asked the question, are e-cigarettes safe?”

Middlekauff and her team used a technique called “heart rate variability” obtained from a prolonged, non-invasive heart rhythm recording. Heart rate variability is calculated from the degree of variability in the time between heart beats. This variability may be indicative of the amount of adrenaline on the heart.

Prior studies have used a heart rate variability test to link increased adrenaline activity in the heart with increased cardiac risk. People with known heart disease and people without known heart disease who have this pattern of high adrenaline levels in the heart have increased risk of death, Middlekauff said.

In what Middlekauff said is the first study to separate the nicotine from the non-nicotine components when looking at the heart impact of e-cigarettes on humans, researchers studied 33 healthy adults who were not current e-cigarette or tobacco cigarette smokers. On different days, each participant used an e-cigarette with nicotine, an e-cigarette without nicotine or a sham device. Researchers measured cardiac adrenaline activity by assessing heart rate variability, and oxidative stress in blood samples by measuring the enzyme plasma paraoxonase (PON1).

They found:

  • Exposure to e-cigarettes with nicotine, but not e-cigarettes without nicotine, led to increased adrenaline levels to the heart, as indicated by abnormal heart rate variability.
  • Oxidative stress, which increases risks for atherosclerosis and heart attack, showed no changes after exposure to e-cigarettes with and without nicotine. The number of markers they studied for oxidative stress were minimal, however and more studies are warranted, according to Middlekauff.

“While it’s reassuring that the non-nicotine components do not have an obvious effect on adrenaline levels to the heart, these findings challenge the concept that inhaled nicotine is benign, or safe. Our study showed that acute electronic cigarette use with nicotine increases cardiac adrenaline levels. And it’s in the same pattern that is associated with increased cardiac risk in patients who have known cardiac disease, and even in patients without known cardiac disease,” Middlekauff said. “I think that just seeing this pattern at all is very concerning and it would hopefully discourage nonsmokers from taking up electronic cigarettes.”

The (AHA) believes that e-cigarettes, like all tobacco products, pose risk. The association supports FDA regulation of e-cigarettes that address marketing, youth access, characterizing flavors, free sampling, labeling, quality control over manufacturing and product standards for contaminants and other ingredients. The association also supports including e-cigarettes in comprehensive smoke-free air laws, taxation and comprehensive cessation programs.

Future studies should look more closely at oxidative stress and e-cigarette use, using a broader number of cardiac markers, in a larger population of people, researchers said.

Co-authors are Roya S. Moheimani, B.S.; May Bhetraratana, M.H.S.; Kacey M. Peters, B.S.; Benjamin K. Yang; Fen Yin, Ph.D.; Jeffrey Gornbein, Dr.PH; and Jesus A. Araujo, M.D., Ph.D. Author disclosures are on the manuscript.

The Tobacco-Related Disease Research Program; (AHA), Western States Affiliate; National Institute of Environmental Health Sciences, National Institutes of Health; Irma and Norman Switzer Dean's Leadership in Health and Science Scholarship; and UCLA Clinical and Translational Science Institute funded the study.

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