According to new research published today in the American Heart Association's peer-reviewed journal Arte, the cardiovascular effects of cigarettes and e-cigarettes are strikingly similar, and these harmful effects on blood vessel function are likely caused by airway irritation due to inhalation of a foreign substance, rather than a specific component of the cigarette smoke or e-cigarette vapor (aerosol) (ATVB).
Both cigarette smoking and e-cigarette vaping are known to promote endothelial dysfunction, which is the inability of big blood arteries to open sufficiently to give enough blood to the heart and other tissues. This has the potential to be an early indicator of cardiovascular disease.
Endothelial cells line the inside of all blood vessels and control blood vessel opening, material exchange between the bloodstream and surrounding tissues, and immunological and inflammatory responses.
"The goal of this project was to determine why a growing number of inhaled tobacco products, including combustible cigarettes, heated tobacco products, and e-cigarettes, all impair endothelial function despite fundamental differences in these products," said the lead researcher of both studies Matthew L. Springer, Ph.D., a professor of medicine in the division of cardiology at the University of California, San Francisco.
"Thousands of chemicals have been identified in tobacco smoke, some of which are also present in e-cigarette aerosols, either as an original ingredient or as a chemical reaction product of the heating process. We sought to find which specific component of smoke or e-cigarette vapor may be responsible for interfering with blood vessels' ability to function efficiently."
Springer and colleagues conducted two experiments in rats and humans to investigate the effects of smoking and vaping on cardiovascular function.
Cigarette smoke impairs endothelial function due to vagal input from the airway rather than a specific smoke constituent
The ability of blood vessels to widen was examined in the rat study before and after exposure to smoke from four types of classic combustible cigarettes: conventional nicotine, reduced nicotine, conventional nicotine with added menthol, and reduced nicotine with added menthol.
Menthol is found in many tobacco products, and it may reduce irritation experienced by smoking, particularly among novice smokers, as well as play a significant role in fostering nicotine addiction.
The study's findings revealed that blood vessel dilatation was reduced after smoking all four types of cigarettes, with the magnitude of the reduction varying from 20-46% depending on the cigarette type. Although nicotine was not necessary for vascular function impairment, higher nicotine levels were linked with a greater decrease in FMD than lower nicotine levels, and menthol products were related to a lesser decrease in FMD than non-menthol products.
Springer stressed that the discovery that menthol reduced the severity of flow-mediated dilation impairment should not be taken as menthol is a useful component in smoking and vaping products because the impairment was still significant and menthol has additional adverse consequences.
The rats were also given two of the primary gases found in both smoke and e-cigarette aerosol, as well as clean carbon nanoparticles, to see how they affected blood vessel dilatation. Despite being fundamentally different chemical and physical components of smoke, the gases and carbon particles displayed identical impairment effects to whole tobacco smoke.
"Because flow-mediated dilation was impaired by whole smoke, gas phase components of smoke, and plain carbon particles, with no single constituent uniquely responsible, we then explored whether the mechanism involved a common irritation response from the airway involving the vagus nerve," Springer said.
The vagus nerve is an important part of the parasympathetic nervous system, which regulates involuntary organ activities. It regulates digestion, heart rate, respiratory rate, vascular dilation, inflammatory reactions, and pulmonary functions like cough reflex and mucus formation.
Researchers tested this idea by exposing anesthetized rats to smoke after cutting the vagus nerves. They discovered that stopping nerve signals from reaching the rest of the body from the rats' lungs fully avoided any vascular functional impairment caused by smoke.
Endothelial dysfunction may be triggered by a vagus nerve-dependent process caused by respiratory irritation and pulmonary sensory nerves, according to these studies.
"We were surprised to discover that it's not a specific foreign material being inhaled that causes harmful cardiovascular effects - it's the fact that some kind of irritant is being inhaled in the first place, regardless of what it was," Springer said. "All inhaled products are likely to have similar harmful effects on vascular function."
Springer stated that because there is no single toxin that accounts for vascular damage, regulatory bodies cannot rely on forbidding specific chemicals to minimize the negative consequences of inhaled products.
The National Heart, Lung, and Blood Institute, a division of the National Institutes of Health (NIH), and the U.S. Food and Drug Administration Center for Tobacco Products funded this research, as did the National Cancer Institute at the NIH and the Elfenworks Foundation (in memory of Deb O'Keefe) and the Roy E Thomas Medical Foundation.
Chronic e-cigarette use impairs endothelial function on the physiological and cellular levels
The second study was conducted at different locations and included people who said they smoked combustible cigarettes on a regular basis, people who said they used e-cigarette products on a regular basis, and people who said they didn't use any nicotine products at all. Researchers measured endothelial function and performed cell culture studies to investigate the association of chronic e-cigarette use on levels of vascular impairment in all subjects at a specific point in time. Nitric oxide production, a vital component for correctly functioning blood arteries, and endothelial cell permeability, which shows how easily chemicals can leak out of blood vessels, were among the measures taken.
Increased vessel permeability leads to the leakage of larger molecules and may contribute to edema, or swelling caused by excess fluid in tissues, inflammation, heart disease, and other diseases such as cancer.
"Because the combustible cigarette smoke and e-cigarette aerosol that people inhale doesn't have direct contact with the blood vessels, and the blood does, we took blood serum (the clear liquid in the blood that remains after it clots) from every participant and put it in contact with endothelial cells in a culture dish to evaluate how the different serum samples affected the functional behavior of those cells," Springer said. "This enabled us to investigate the effects on endothelial cells of substances in smoke/aerosol that are absorbed through the lungs and enter the bloodstream, and also any other circulating molecules that the body might produce in response to inhaling the smoke and/or aerosol, including proteins involved in the inflammatory response."
The study recruited 120 adults between the ages of 21 and 50 who were free of cardiovascular disease. People who smoked more than 5 combustible cigarettes per day for a year or longer; people who used electronic cigarette devices 5 or more times per week for 3 months or longer; and people who did not now smoke or vape were eligible to participate.
The study discovered that both long-term vaping and cigarette smoking generate blood alterations that impact endothelial function, albeit in different ways.
* Endothelial cells submerged in blood serum from people who smoked regularly and those who vaped regularly generated less nitric oxide, indicating that the endothelial cells were functionally compromised.
* Condensed e-cigarette aerosol did not directly inhibit nitric oxide synthesis, indicating that the chemicals in the blood that affected nitric oxide generation did not come directly from the aerosol and were instead created by the body in reaction to inhalation.
* Blood serum from participants who regularly vaped, but not those who regularly smoked, increased endothelial cell permeability, allowing more substances to pass through the cells and causing them to behave more like those in leaky blood vessels, which can cause tissue edoema.
* Blood serum from participants who regularly vaped also caused endothelial cells to produce molecules that cause oxidative stress, which is the imbalance of free radicals and antioxidants.
* When compared to persons who did not routinely smoke or vape, people who used e-cigarettes or smoked combustible cigarettes had changes in circulating indicators of inflammation, blood clotting factors, and cell adhesion.
* Certain inflammatory indicators were enhanced in the blood serum of those who smoked combustible cigarettes on a regular basis, but not in those who used e-cigarettes. Other inflammatory indicators were raised in the blood serum of those who vaped regularly but not in those who smoked combustible cigarettes.
"The distinct patterns of these heart disease risk biomarkers in blood serum of frequent users of combustible cigarettes and e-cigarette products indicate that, despite the similar physiological effects, e-cigarette use and smoking trigger fundamentally different molecular responses. Our findings suggest that vaping, although not smoking combustible cigarettes, causes changes in the blood that increase the potential for leakage in the blood vessels and that both smoking and vaping cause changes in the blood that lead to endothelial dysfunction and an increased risk of future cardiovascular events in otherwise healthy people," Springer said.
The study also discovered that flow-mediated dilatation was significantly smaller (by more than 5%) among those who used e-cigarettes on a regular basis and those who smoked combustible cigarettes on a regular basis compared to people who neither smoked nor vaped. Previous research has linked a 2% decrease in artery dilation to a 15% increase in heart disease risk, indicating that smoking and vaping have a clinically significant influence.
"It's important for regulators, clinicians, and the public to realize that vaping is not harmless," Springer said.
"Smoking and vaping can have similar harmful cardiovascular effects but each condition causes some potentially harmful effects that the other does not. These differences indicate that dual product use, meaning smoking combustible cigarettes and also using e-cigarette products, may actually be worse for vascular health than either smoking or vaping alone."
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