Association of electronic cigarette use with circulating angiogenic cell levels in healthy young adults: Evidence for chronic systemic injury

Background: Circulating angiogenic cells (CACs) are indicative of vascular health and repair capacity; however, their relationship with chronic e-cigarette use is unclear. This study aims to assess the association between e-cigarette use and CAC levels. Methods: We analyzed CAC levels in 324 healthy participants aged 21-45 years from the cross-sectional Cardiovascular Injury due to Tobacco Use study in four groups: never tobacco users (n = 65), sole e-cigarette users (n = 19), sole combustible cigarette users (n = 212), and dual users (n = 28). A total of 15 CAC subpopulations with four cell surface markers were measured using flow cytometry: CD146 (endothelial), CD34 (stem), CD45 (leukocyte), and AC133 (early progenitor/stem). Generalized linear models with gamma distribution and log-link were generated to assess association between CACs and smoking status. Benjamini-Hochberg were used to adjust p-values for multiple comparisons. Results: The cohort was 47% female, 51% Black/African American, with a mean (+/- SD) age of 31 +/- 7 years. Sole cigarette use was significantly associated with higher levels of two endothelial marker CACs (Q <= 0.05). Dual users had higher levels of four endothelial marker CACs and one early progenitor/stem marker CAC (Q <= 0.05). Sole e-cigarette users had higher levels of one endothelial and one leukocyte marker CAC (Q <= 0.05). Conclusion: Dual use of e-cigarettes and combustible cigarettes was associated with higher levels of endothelial origin CACs, indicative of vascular injury. Sole use of e-cigarettes was associated with higher endothelial and inflammatory CACs, suggesting ongoing systemic injury. Distinct patterns of changes in CAC subpopulations suggest that CACs may be informative biomarkers of changes in vascular health due to tobacco product use.