Heated tobacco products cause increased endothelial and platelet derived extracellular vesicles in healthy young adults

<bold>Background and aims:</bold> Heated tobacco products (HTPs) are novel alternative tobacco products being promoted as a healthier option to cigarettes. To evaluate use of HTPs on vascular function, we investigated the effects of brief HTP use on extracellular vesicles (EVs) of endothelial and platelet origin in healthy volunteers. <bold>Methods:</bold> This randomised crossover study included 24 healthy young adults with occasional tobacco use. Exposure was smoking 28 puffs of the HTP IQOS 3 Multi (Phillip Morris Int.) and “no-exposure” was control, with a wash-out of one week in-between. Blood samples, collected at baseline and 4 hours following exposure, were analysed with flow cytometry to measure EVs of endothelial and platelet origin. <bold>Results:</bold> HTP exposure caused heightened levels of EVs derived from endothelial cells (+149 EVs/µl, 95% CI: +115 to 182; p<0.001) as well as increased levels of EVs from platelets expressing the CD41 ligand and activation marker P-selectin (+366EVs/µl, 95% CI: +216 to 517; p<0.001), compared to the no-exposure control 4 hours after exposure. <bold>Conclusions:</bold> Our study shows that brief HTP use increases endothelial and platelet extracellular vesicles in healthy adults, indicating vascular dysfunction and platelet activation. This challenges HTPs as a safer alternative to cigarettes, highlighting the need for further evaluation of their long-term cardiovascular impact.