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Stroke Risk Significantly Elevated for Smokers Who Also Vape, Early Data Suggest

Dual use of e-cigarettes and combustible cigarettes were associated with a more than double higher odds of stroke versus nonsmokers. The findings, though preliminary, bear additional study in longitudinal studies with prospective risk factors, the study authors and independent stroke experts said.

The risk of stroke could be almost three times higher for cigarette smokers who also use e-cigarettes or other vaping devices than for those who have never smoked, and double that of current smokers, regardless of other potential factors, according to an analysis of data collected by phone interviews with young adults between 2016 and 2019.

Although stroke incidence and hospitalizations have been increasing in young adults who vape, the association between e-cigarette use and stroke remains largely unknown, said lead author Tarang Parekh, MBBS, MSc, a researcher in the department of health administration and policy at George Mason University in Fairfax, VA.

Analysis of data—pooled responses from the Behavior Risk Factor Surveillance System (BRFSS), a nationally representative telephone survey—showed the risk of stroke was 2.9 times higher in users of both cigarettes and e-cigarettes, and 1.83 times higher than for those who just smoked combustible cigarettes. No difference in stoke incidence was observed between nonsmokers and individuals who only vaped, however, Dr. Parekh noted.

Data for just 2017 showed that the odds of having a stroke were almost three times higher in current dual cigarette/vape users, even after being adjusted for such well-known stroke risk factors as hypertension and poor cholesterol levels, according to the study, which was published online January 7 in the American Journal of Preventive Medicine.

“Switching from cigarettes to e-cigarettes does not confer any stroke benefits,” Dr. Parekh told Neurology Today. “To our knowledge, this is the first study to report a stroke association with e-cigarette use in young adults and whether or not switching from cigarettes to e-cigarettes confers any benefits, using national survey data.”

He continued, “Sole e-cigarette use is not associated with greater odds of stroke in young adults, however if young adults also reported former or current combustible cigarette use, the odds of stroke are significantly increased even compared with current sole combustible cigarette use.”

Study Design, Findings

Dr. Parekh and his colleagues reviewed response from the BRFSS, which included 161,529 participants between the ages of 18 and 44 years. In terms of ethnicity, gender, and socioeconomics, the responses were representational of the status quo in this age bracket, and included 53.1 percent women; 50.6 percent Caucasian; 23.9 percent Hispanic; 47.9 percent with an average annual income of $50,000 or more; and 50.3 percent unmarried.

Among sole e-cigarette users, about 70 percent were between 18 and 24 years of age, while almost half of current sole combustible cigarette users were aged 35—44 years, the researchers found. Compared with nonsmoking, current sole e-cigarette use and current dual use were associated with higher rates of college dropout or high school graduation, unmarried status, and obesity, as well as with regular binge drinking.

At the American Heart Association’s 2019 Scientific Sessions last November, he and his colleagues presented findings from the same data set about stroke risk among marijuana smokers. Concurrently published in Stroke, the investigators reported that, compared to respondents who had never smoked cannabis, those who were regular users had an adjusted odds ratio (AOR) of 2.75. The odds ratio is the association between exposure and an outcome, and represents the odds that a particular exposure will result in a certain outcome, compared to the odds of the outcome happening without such exposure.

‘Cocktail Effect’

For individuals who only reported using e-cigarettes, the investigators did not find significantly different odds compared with dual users, however the odds were lower for such individuals when compared to respondents who were currently only smoking combustible cigarettes. The odds of stroke in current sole e-cigarette users were nearly half those of current cigarette smokers, potentially due to the relatively younger age of sole e-cigarette users, their lower health risk, higher insurance coverage, and higher socioeconomic status, the researchers noted.

The AOR for stroke among those with current sole combustible cigarette use compared with never-smokers was 1.59 and 2.54 for e-cigarette users who had a history of smoking cigarettes. Compared with combustible cigarette smokers, current sole e-cigarette users had an AOR of 0.43, or lower odds of stroke, but current users of both combustible and e-cigarettes had 83 percent higher odds of experiencing a stroke.

Moreover, greater intensity/frequency (everyday versus someday use) of e-cigarettes was slightly associated with higher stroke odds than among nonsmokers, with an AOR of 2.96 for everyday users compared with an AOR of 2.87 for occasional vapers. There was no significant difference between respondents who said they were currently exclusively combustible cigarette smokers versus current e-cigarette users who were former smokers.

“Recently, e-cigarettes have been linked to causing endothelial dysfunction, aortic stiffness, increasing diastolic blood pressure and heart rate, all of which are factors for stroke risk,” Dr. Parekh told Neurology Today.

“These findings have clear implications for physicians, public health agencies, and tobacco product regulation authorities. The increased risk of stroke in current e-cigarette users who were former or current combustible cigarette users possibly indicates an additional cerebrovascular effect by-cigarette ingredients apart from nicotine.”

He noted that a recent study described the role of the “splenocardiac axis,” an inflammatory signaling network underlying ischemic heart disease in the escalating risk of future cardiovascular events in e-cigarette users.

Another factor is called “the cocktail effect,” he continued, explaining that this refers to the unknown interaction(s) of multiple inhaled substances, such as flavorings, in addition to nicotine.

“There is a possibility of the cocktail effect of e-cigarettes in current combustible cigarette users,” Dr. Parekh said. “Those who are currently using combustible e-cigarettes have already a higher level of nicotine in their blood. And the addition of e-cigarettes could significantly increase that level along with the delivery of other harmful chemical components, such as glycerol, formaldehyde and other aldehydes. Such chemical components have shown an association with oxidative stress and cell death.”

Expert Commentary

Fan Z. Caprio, MD, assistant professor of neurology and medical director of the Comprehensive Stroke Center at Northwestern University in Chicago, told Neurology Today that young adults who have had a stroke need to be asked about their cigarette/vaping history, and any other risks they may have.

Findings derived from the BRFSS, presented as an oral abstract last January at the International Stroke Conference, showed a similar relationship between the use of e-cigarettes and elevated risk of cardiovascular events, including stroke, she said.

“The current findings dig a little bit deeper to assess the risk of stroke. As mentioned in the paper, e-cigarettes may potentiate or increase risk of stroke via additional ingredients other than nicotine. Another possibility, which was not directly addressed here, is the total amount of smoking—we don’t know if there is a dose-effect or additive effect, or if people smoking combustible and e-cigarettes are simply smoking in larger amounts.”

Dr. Caprio noted that data from self-reported, cross-sectional surveys like the BRFSS are often challenging in terms of [identifying] other possible confounding factors, such as concurrent illegal drug use, even though the researchers did incorporate factors such as hypertension, comorbidities, and cholesterol. Other variables to consider might include duration of smoking and amount of smoking, she said, adding: “The trend is certainly believable and concerning.”

She added that further epidemiologic studies are warranted to better delineate the association between the long-term risk of stroke and e-cigarette smoking, with or without combustible cigarette smoking.

“I would also be interested knowing more about the severity and types of stroke, as well as other cardiovascular disease and events, in these individuals. A prospective, controlled, longitudinal study might better help us understand the potential additive risks and benefits of e-cigarette smoking versus cigarette use.”

Larry B. Goldstein, MD, FAAN, professor and chair of the department of neurology and interim director of the University of Kentucky-Norton Stroke Care Network, in Lexington, pointed to another recent study from the same cohort that supports the findings.

Dr. Goldstein told Neurology Today that it remains unclear why the new study found the risk of stroke to be so much higher in younger persons who smoked both cigarettes and e-cigarettes/vaping devices, but one factor might be greater exposure to nicotine in users of both delivery systems or other components of e-cigarettes that increase the impact of combustible tobacco.

All of the researchers, including the study authors, cautioned that it is too soon to draw specific conclusions about these risks.

“There is uncertainty in risk calculations based on this [new] study design because of unmeasured confounding,” said Dr. Goldstein. “Longitudinal studies with prospective risk factors, as well as outcome assessments and inclusion of appropriate controls, would be needed to better address the question.”

Kurt Samson/Neurology Today