Effects of cigarettes, e-cigarettes and Swedish snus on vascular function

Sammanfattning: Cigarette smoking is considered one of the leading causes of preventable morbidity and premature death worldwide. A large portion of this is attributable to cardiovascular disease such as ischemic heart disease and stroke. However, with the public’s increasing awareness of the harm and diseases related directly to cigarette smoke, alternative combustion-free nicotine delivery products have gained in popularity. Two of the products which have seen substantial market growths during the last few years are Swedish snus and electronic cigarettes. In recent years, an increasing number of studies have demonstrated a correlation between snus usage and increased mortality in coronary heart disease and stroke. Although there are studies with contradictory results, regarding the general underlying increase of cardiovascular risk. So far, there is limited data available on the potential negative health effects of e-cigarette smoking. The overall aim of this thesis was to investigate vascular health effects caused by acute cigarette and e-cigarette inhalation as well as chronic snus usage. Methods and Results: In Paper I, twelve healthy volunteers were subjected to cigarette smoking or not-smoking in a cross-over study. Microvesicles and endothelial progenitor cells were analyzed in collected blood samples at baseline and 1h, 4h and 24h following exposure. Cigarette smoking caused an acute increase in endothelial progenitor cells and in microvesicles of platelet, leukocyte and endothelial origin. Paper II was a randomized, cross-over study where 16 healthy volunteers were exposed to electronic cigarette inhalation with nicotine vs non-inhalation. Biomarkers were analyzed in the same approach as in Paper I. E-cigarette inhalation caused an acute increase in endothelial progenitor cells. Microvesicles, with the exception of endothelial derived microvesicles, were unaffected. In Paper III, seventeen healthy volunteers inhaled e-cigarette vapor with and without nicotine. In this double-blinded, randomized, cross-over study arterial stiffness was analyzed at baseline and at predetermined intervals for 4 hours following exposure. E-cigarette vapor inhalation containing nicotine caused a transient acute increase in heart rate and arterial stiffness. Paper IV was a cross-sectional study investigating healthy long-term snus users (mean age 44.8 years) and age-matched controls. Arterial stiffness, forearm blood flow as well as fibrinolytic function and endothelial progenitor cells in blood samples were analyzed. Snus users had significantly higher arterial stiffness as well as impaired endothelial function, i.e. decreased forearm blood flow upon glyceryl tri-nitrate infusion. There was no difference in fibrinolytic function and endothelial progenitor cells between the two groups. Discussion: Smoking a single cigarette causes a rapid activation of endothelial cells, platelets and leukocytes. As cigarette smoking has known detrimental effects on vascular health, our results were not unexpected. However, e-cigarette inhalation as well as smoking a conventional cigarette, causes a similar swift mobilization of endothelial progenitor cells. This may be interpreted as an acute endothelial stress caused by nicotine. Furthermore, inhaled nicotine is linked to increases in arterial stiffness, which is chronically altered in daily snus users. This elucidates that nicotine alone may alter endothelial function, both upon acute and chronic exposure. Snus users also display an attenuated effect of glyceryl tri-nitrate which further strengthens the findings that snus use is associated with increased mortality following myocardial infarction. In summary, we demonstrate that the nicotine content in combustion-free nicotine delivering products may alter vascular function. E-cigarettes and snus should therefore not be considered as harmless recreational products.