One reason why dual use of ecigs and cigs is worse than using either product alone

Once upon a time, people – including me – thought eicgs were just cigarettes without the combustion, so they had to be less toxic.  By this logic, dual users (people who used e-cigs and cigs at the same time) were probably no worse off than smokers.

Now we know that is wrong.  While they do not deliver combustion products, e-cigarettes expose users to some toxicants at higher levels than cigarettes.  This means that dual users are exposing themselves to a wider range of toxicants than people who just use cigarette or e-cigarettes.  Consistent with this fact, epidemiological studies consistently show dual use is worse than smoking.

Leila Mohammadi, Matt Springer and colleagues at UCSF and elsewhere have just published “Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels” that helps explain how and why dual use has worse cardiovascular effects than just smoking. 

Your arteries are constantly adjusting how big they are based on how much blood flow you need.  When you are resting, and the arteries are narrow (to maintain blood pressure).  When you start exercising, the need for blood flow increases and arteries get wider to accommodate the increased flow.  This phenomenon is called flow mediated dilation (FMD).  When blood flow speeds up it causes friction against the cells lining the artery (called the vascular endothelium) and that friction stimulates the production of nitric oxide (NO) that diffuses into the muscle that comprises the artery wall and makes it relax, so the artery gets bigger. 

Mohammadi and colleagues collected blood samples people who were established e-cigarette users, established cigarette smokers, and people who didn’t use either product.   They then exposed cultured human artery (endothelial) cells in the laboratory to the different blood samples and measured the release of nitric oxide, the chemical endothelial cells emit to cause blood vessels to dilate (enlarge) when they need to accommodate higher rates of blood flow.

They also tested cell permeability, the ability of molecules to pass through a layer of cells to the other side. Too much permeability makes vessels leaky, which impairs function and increases the risk for cardiovascular disease.

They found that blood from established e-cigarette users and established smokers caused a significantly greater decrease in nitric oxide production by the isolated endothelial cells than the blood of nonusers. Notably, they found that blood from those who used e-cigarettes also caused more permeability in the blood vessel cells than the blood from both those who smoked cigarettes and nonusers. Blood from those that used e-cigarettes also caused a greater release of hydrogen peroxide by the blood vessel cells than the blood of the nonusers. Each of these three factors can contribute to impairing blood vessel function in people who use e-cigarettes.

Mohammadi and colleagues also found that e-cigarettes had harmful cardiovascular effects in ways that were different from those caused by tobacco smoke. Specifically, they found that blood from people who smoked cigarettes had higher levels of certain circulating biomarkers (biological indicators) of cardiovascular risks, and the blood people who used e-cigarettes had elevated levels of other circulating biomarkers of cardiovascular risks.

The bottom line: Both e-cigarettes and cigarettes compromise blood vessel function in ways that increase the risk of cardiovascular disease, but potentially through different mechanisms.  Dual users (people who use both products) suffer both sets of adverse effects, which is worse than either alone.

Here is the abstract:

Background: The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function.

Methods: Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured effects of participants’ sera, or e-cigarette aerosol condensate, on NO and H2O2 release and cell permeability in cultured endothelial cells (ECs).

Results: E-cigarette users and smokers had lower flow-mediated dilation (FMD) than nonusers. Sera from e-cigarette users and smokers reduced VEGF (vascular endothelial growth factor)-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera caused increased endothelial release of H2O2, and more permeability than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the receptor for advanced glycation end products (RAGE) ligands S100A8 and HMGB1 (high mobility group box 1) than smoker and nonuser sera, and receptor for advanced glycation end product inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production.

Conclusions: Chronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function.

The full citation is: Mohammadi L, Han DD, Xu F, Huang A, Derakhshandeh R, Rao P, Whitlatch A, Cheng J, Keith RJ, Hamburg NM, Ganz P, Hellman J, Schick SF, Springer ML. Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels. Arterioscler Thromb Vasc Biol. 2022 Nov;42(11):1333-1350. doi: 10.1161/ATVBAHA.121.317749. Epub 2022 Oct 26. PMID: 36288290.  It is available here.

Here are press releases from NIH and AHA about the paper and its implications:

https://www.nih.gov/news-events/news-releases/nih-funded-studies-show-damaging-effects-vaping-smoking-blood-vessels

https://newsroom.heart.org/news/smoking-and-vaping-had-overlapping-adverse-health-effects-dual-product-use-may-be-worse

Published by Stanton Glantz

Stanton Glantz is a retired Professor of Medicine who served on the University of California San Francisco faculty for 45 years. He conducts research on tobacco and cannabis control and cardiovascular disease/

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: