Association between electronic nicotine delivery systems use and risk of stroke: A systematic review and meta-analysis of observational studies with 822,162 participants

Abstract

Abstract Background The use of electronic nicotine delivery systems (ENDS) is becoming increasingly prevalent. Yet, its association with risk of stroke is still uncertain and not well-established. Purpose To synthesize more conclusive evidence about the association between ENDS use and risk of stroke through a systematic review and meta-analysis of available observational studies. Methods PubMed, Scopus, and Web of Science databases were searched from inception until February 20, 2023, to identify observational studies (either cross sectional, cohort, or case-control studies) that assessed the association of ENDS use with risk of stroke compared with non-users. Adjusted risk estimates of stroke form each relevant study were extracted and pooled as odds ratio (OR) with 95% confidence interval (CI) under the random-effects meta-analysis model. We also performed a leave-one-out sensitivity analysis to evaluate the robustness of the combined result. The I2 statistic was used to quantify heterogeneity. Results Six studies (four cross-sectional and two prospective cohort studies) with a total of 822,162 participants (ENDS users=38,539 and non-users=783,623) matched our criteria and were included in this meta-analysis. The analysis revealed that ENDS use was associated with a statistically significant increased risk of stroke (OR: 1.48 [95% CI: 1.07 to 2.05]; I2: 82%; Figure 1A) compared with non-users. This result was sensitive (i.e., became statistically insignificant) to the removal of one study by Bricknell and co-authors l (OR: 1.44 [95% CI: 0.96 to 2.18]; I2: 85%; Figure 1B). Conclusion The usage of ENDS appears to be associated with a greater risk of stroke when compared with a lack of use. Further well-designed longitudinal investigations are needed to validate these findings and investigate the potential mechanisms implicated with this association. Figure 1: (A) results of meta-analysis of the included studies that assessed the association of ENDS use with risk of stroke (B) results of the leave-one-out sensitivity analysis.