Three more studies show how e-cigs increase heart disease risk

The paper “Short-term e-cigarette vapour exposure causes vascular oxidative stress and dysfunction: evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX-2)” recently published by Marin Kuntic and colleagues in the European Heart Journal is a real-tour de force that includes human, mouse, and isolated cell studies to not only show that e-cigarette use has adverse effects on blood vessels (in several places throughout the body), but defines the cellular and molecular pathways responsible for these effects. 

Consistent with earlier studies, they founds that e-cigarette smoking immediately compromised the ability of arteries to dilate (expand) in response to increases in the need for blood flow (called flow-mediated dilation).  Significantly, they found this effect in smokers, which is consistent with our (paper 1, paper 2) and others’ epidemiological findings that e-cigarettes pose an independent risk of having had a heart attack (myocardial infarction) in smokers.

Kuntic and colleagues also found that e-cigarette aerosol causes oxidative stress in the brain, the lung and in vessels, induces inflammation, and adversely affects lipids and tracked down the biological pathway for these effects (NADPH oxidase, NOX-2). They found that the e-cigarette product acrolein, a reactive aldehyde, was causing these changes in isolated blood vessels.  They also found that heated aerosol was more toxic than the unheated e-liquid. 

Here is the abstract:

Aims.  Electronic (e)-cigarettes have been marketed as a ‘healthy’ alternative to traditional combustible cigarettes and as an effective method of smoking cessation. There are, however, a paucity of data to support these claims. In fact, e-cigarettes are implicated in endothelial dysfunction and oxidative stress in the vasculature and the lungs. The mechanisms underlying these side effects remain unclear. Here, we investigated the effects of e-cigarette vapour on vascular function in smokers and experimental animals to determine the underlying mechanisms.

Methods and results.  Acute e-cigarette smoking produced a marked impairment of endothelial function in chronic smokers determined by flow-mediated dilation. In mice, e-cigarette vapour without nicotine had more detrimental effects on endothelial function, markers of oxidative stress, inflammation, and lipid peroxidation than vapour containing nicotine. These effects of e-cigarette vapour were largely absent in mice lacking phagocytic NADPH oxidase (NOX-2) or upon treatment with the endothelin receptor blocker macitentan or the FOXO3 activator bepridil. We also established that the e-cigarette product acrolein, a reactive aldehyde, recapitulated many of the NOX-2-dependent effects of e-cigarette vapour using in vitro blood vessel incubation.

Conclusions.  E-cigarette vapour exposure increases vascular, cerebral, and pulmonary oxidative stress via a NOX-2-dependent mechanism. Our study identifies the toxic aldehyde acrolein as a key mediator of the observed adverse vascular consequences. Thus, e-cigarettes have the potential to induce marked adverse cardiovascular, pulmonary, and cerebrovascular consequences. Since e-cigarette use is increasing, particularly amongst youth, our data suggest that aggressive steps are warranted to limit their health risks.

Reinforcing this finding, Mohamad Rashida and colleagues will be presenting a paper at the American Heart Association Annual Scientific sessions, “ Chronic E-Cigarette Users Exhibit Abnormal Myocardial Blood Flow with Stress,”  that showed that In the Smidt Heart Institute study, the team of researchers in healthy, young-adult smokers aged 18 to 38 who were regular users of e-cigarettes or tobacco cigarettes, e-cigarettes depressed blood flow to their hearts more than cigarettes. The researchers measured blood flow to the heart muscle before and after sessions of either e-cigarette use or cigarette smoking, while participants were at rest and also after they performed a handgrip exercise which simulates physiologic stress.  In smokers who used combusted cigarettes, blood flow increased modestly after traditional cigarette inhalation and then decreased with subsequent stress. However, in smokers who used e-cigarettes, blood flow decreased after both inhalation at rest and after handgrip stress.

Also at the AHA meeting, Poonam Rao, ,Jiangtao Liu, and Matthew L Springer presented “Juul and Previous Generation E-cigarette Exposure Comparably Impair Vascular Endothelial Function.”  This paper did a head-to-head comparison of a Juul, and a  Marlboro Red combusted cigarette in terms of vascular function (flow mediated dilation) and found they were essentially the same.  (They also found the same thing for older generation e-cigs.)

Overall, the evidence that e-cigarettes increase cardiovascular risk has now reached the overwhelming level.  We have all this biology – down to what molecules and biological pathways are involved – together with consistent population-level epidemiology.

The full cite for the first paper is:  Kuntic M, et al.  Short-term e-cigarette vapour exposure causes vascular oxidative stress and dysfunction: evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX-2).  European Heart Journal, ehz772, https://doi.org/10.1093/eurheartj/ehz772