Studies show that the cardiovascular effects of cigarettes and e-cigarettes are strikingly similar

Studies show that the cardiovascular effects of cigarettes and e-cigarettes are strikingly similar

Two related studies, one in humans and the other in rats, found that the cardiovascular effects of cigarettes and e-cigarettes are strikingly similar and that these deleterious effects on blood vessel function are likely caused by respiratory irritation due to inhalation of a foreign substance. rather than a specific component of cigarette smoke or e-cigarette vapor (aerosol), according to new research published today in the American Heart Association's peer-reviewed journal Arteriosclerosis, Thrombosis and Vascular Biology (ATVB).

Both cigarette smoking and e-cigarette vaping are known to cause endothelial dysfunction, the inability of major blood vessels to open sufficiently to supply adequate blood to the heart and other tissues. This can be an early indicator of cardiovascular disease. Endothelial cells line the interior of all blood vessels and regulate the opening of blood vessels, the exchange of substances between the bloodstream and the surrounding tissue, and immune and inflammatory reactions.

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. Thousands of chemicals have been identified in tobacco smoke, some of which are also present in e-cigarette aerosols, either as the original ingredient or as a chemical reaction product of the heating process. “We tried to figure out what specific component of smoke or e-cigarette vapor might be responsible for impairing the ability of blood vessels to function efficiently.”

Matthew L. Springer, Ph.D., principal investigator of both studies, professor of medicine, department of cardiology, University of California, San Francisco

Springer and colleagues conducted two studies to examine the effects of smoking and vaping on cardiovascular function in both rats and humans.

Impairment of endothelial function by cigarette smoke is not caused by a specific smoke component, but rather by vagal entry from the respiratory tract

In the rat study, arterial flow-mediated dilatation (FMD), i.e. h. measured the ability of blood vessels to dilate before and after exposure to smoke from four types of conventional combustible cigarettes: conventional nicotine, reduced nicotine, conventional nicotine with added menthol, and reduced nicotine with added menthol. Menthol is added to many tobacco products, and it can reduce the irritation caused by smoking, especially in new smokers, and can play an important role in easing nicotine addiction.

The results of the study found that blood vessel dilation was reduced after using all four types of cigarettes, with the magnitude of reduction ranging from 20 to 46% depending on the cigarette type. Nicotine was not required for impairment of vascular function, but higher nicotine levels were associated with a greater decrease in FMD than lower nicotine levels, and menthol was associated with a smaller decrease in FMD than non-menthol products.

Springer emphasized that the finding that the addition of menthol resulted in less severity of flow-induced dilation impairment should not be overinterpreted to suggest that menthol is a beneficial additive in smoking and vape products, as the impairment was still significant and menthol has other deleterious effects.

The rats were also exposed to two of the main gases found in both smoke and e-cigarette aerosols, as well as clean carbon nanoparticles, to evaluate the effects of these types of components on blood vessel dilation. The gases and carbon particles had similar adverse effects as whole tobacco smoke, even though they represented completely different chemical and physical components of the smoke.

“Because flow-mediated dilation was affected by smoke, gas phase components of smoke, and simple carbon particles, with no single component being solely responsible, we then investigated whether the mechanism involved a common respiratory stimulus response involving the vagus nerve.” Springer said.

The vagus nerve is a major component of the parasympathetic nervous system, which controls involuntary internal organ functions. It is responsible for regulating digestion, heart rate, respiratory rate, vasodilation, inflammatory responses and lung functions such as the cough reflex and mucus production.

To test this hypothesis, the researchers exposed anesthetized rats to smoke after cutting the vagus nerves. They found that preventing nerve signals in the rats' lungs from reaching the rest of the body completely prevented smoke from affecting vascular function. These findings suggest that endothelial dysfunction may be caused by a vagus nerve-dependent mechanism resulting from irritation of the airway and sensory nerves of the lung.

"We were surprised to discover that it is not a specific inhaled foreign material that causes adverse cardiovascular effects - it is the fact that some type of irritant is inhaled at all, regardless of what it was," Springer said. “All inhaled products are likely to have similar deleterious effects on vascular function.”

Springer noted that the absence of a specific toxin responsible for vascular damage means regulators cannot rely on banning specific ingredients to prevent adverse effects from inhaled products.

Co-authors are Pooneh Nabavizadeh, MD; Jiangtao Liu, MD; Poonam Rao, MD; Sharina Ibrahim, M.Sc.; Daniel D. Han, BA; Ronak Derakhshandeh, M.Sc.; Huiliang Qiu, MD; Xiaoyin Wang, MD; Stanton A. Glantz, Ph.D.; and Suzaynn F. Schick, Ph.D. The authors' details are listed in the manuscript.

This work was supported by grants from the National Heart, Lung, and Blood Institute, a division of the National Institutes of Health (NIH), and the US Food and Drug Administration Center for Tobacco Products; the National Cancer Institute at NIH and with support from the Elfenworks Foundation (in memory of Deb O’Keefe) and the Roy E Thomas Medical Foundation.

Chronic e-cigarette use impairs endothelial function at physiological and cellular levels

The second study was conducted at multiple centers and included people who reported regularly smoking combustible cigarettes, people who reported regularly using e-cigarette products, and people who reported not using nicotine products. The cardiovascular health of all participants was assessed at a single time point, with researchers measuring endothelial function and conducting cell culture experiments to assess the association between chronic e-cigarette use and the degree of vascular impairment. Measures included production of nitric oxide, a key molecule for well-functioning blood vessels, and endothelial cell permeability, which reflects how easily substances can leak out of blood vessels. Increased vascular permeability leads to the leakage of larger molecules and can 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 do not have direct contact with blood vessels, we took blood serum (the clear liquid in the blood that remains after clotting) from each participant and exposed it to endothelial cells in a culture dish to evaluate how the different serum samples affected the functional behavior of these cells." Springer said. "This allowed us to study the effect on endothelial cells of substances in smoke/aerosol that are absorbed through the lungs and enter the bloodstream, as well as other circulating molecules that the body may produce in response to smoke and/or aerosol inhalation, including proteins involved in the inflammatory response."

120 adults between the ages of 21 and 50 without cardiovascular disease took part in the study. Participants included individuals who had smoked more than 5 combustible cigarettes per day for a year or more; People who have used electronic cigarettes at least 5 times per week for 3 months or more; and people who have not currently smoked or vaped.

The analysis found that prolonged vaping and cigarette smoking both cause changes in the blood that affect endothelial function, although in different ways.

• In Blutserum getauchte Endothelzellen sowohl von Menschen, die regelmäßig geraucht hatten, als auch von denen, die regelmäßig dampften, setzten weniger Stickoxid frei, was bedeutet, dass die Endothelzellen funktionell beeinträchtigt waren.
• Kondensiertes E-Zigaretten-Aerosol reduzierte die Stickoxidproduktion nicht direkt, was darauf hinweist, dass die Substanzen im Blut, die die Stickoxidproduktion beeinträchtigten, nicht direkt aus dem Aerosol stammten, sondern vom Körper als Reaktion auf die Inhalation produziert wurden.
• Das Blutserum von Menschen, die regelmäßig dampften, aber nicht von denen, die regelmäßig rauchten, erhöhte die Durchlässigkeit der Endothelzellen, wodurch mehr Substanzen durch die Zellen dringen konnten und sie sich eher wie in undichten Blutgefäßen verhalten, was zu Gewebeödemen führen kann.
• Das Blutserum der Teilnehmer, die regelmäßig dampften, veranlasste auch Endothelzellen, Moleküle zu produzieren, die oxidativen Stress verursachen, der das Ungleichgewicht von freien Radikalen und Antioxidantien im Körper darstellt und zu Zell- und Gewebeschäden führen kann.
• Menschen, die regelmäßig E-Zigaretten benutzten, und solche, die brennbare Zigaretten rauchten, zeigten Veränderungen bei zirkulierenden Biomarkern für Entzündungen, Blutgerinnungsfaktoren und Zelladhäsion im Vergleich zu Menschen, die nicht regelmäßig rauchten oder dampften.
• Bestimmte entzündliche Biomarker waren im Blutserum von Menschen erhöht, die regelmäßig brennbare Zigaretten rauchten, jedoch nicht bei denen, die E-Zigaretten verwendeten. Andere entzündliche Biomarker waren jedoch im Blutserum der Menschen erhöht, die regelmäßig dampften, nicht jedoch bei denen, die regelmäßig brennbare Zigaretten rauchten.

"The different patterns of these heart disease risk biomarkers in the 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 results suggest that vaping, despite 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 found that flow-mediated dilation was significantly lower (by more than 5%) in participants who regularly used e-cigarettes and those who regularly smoked combustible cigarettes compared to those who neither smoked nor vaped. In previous research, a 2% reduction in vasodilation was associated with a 15% increase in the risk of heart disease, suggesting that the effects of smoking and vaping are clinically significant.

“It is important that regulators, doctors and the public recognize 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 suggest that using two products, i.e. smoking combustible cigarettes and also using e-cigarette products, may actually be worse for vascular health than either just smoking or vaping."

Source:

American Heart Association

References:

Nabavizadeh, P., et al. (2022) Impairment of endothelial function by cigarette smoke is not caused by a specific smoke component but by vagal input from the respiratory tract. Arteriosclerosis, thrombosis and vascular biology. doi.org/10.1161/ATVBAHA.122.318051.

Mohammadi, L., et al. (2022) Chronic e-cigarette use impairs endothelial function at physiological and cellular levels. Arteriosclerosis, thrombosis and vascular biology. doi.org/10.1161/ATVBAHA.121.317749.

.