Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program

Ignatios Ikonomidis, Margarita Marinou, Dimitrios Vlastos, Kallirhoe Kourea, Ioanna Andreadou, Nikolaos Liarakos, Helen Triantafyllidi, George Pavlidis, Elias Tsougos, John Parissis, John Lekakis


Background and aims

The effects of medically-aided smoking cessation on vascular function and oxidative stress are not fully clarified.


One hundred eighty-eight current smokers were randomized to varenicline or nicotine replacement treatment (NRT) for a 3-month period. We assessed: (a) augmentation index (Aix) and pulse wave velocity (PWV); (b) perfusion boundary region (PBR) of sublingual microvasculature (range:5–25 μm), an index of the endothelial glycocalyx thickness, using Sideview, Darkfield imaging; (c) the exhaled CO; and (d) the malondialdehyde (MDA) and protein carbonyls (PC) plasma levels, as markers of oxidative stress, at baseline and after 3 and 12 months.


After 3 months of treatment, CO, MDA, PC and Aix were decreased in all subjects (median CO: 25 vs. 6 ppm, MDA: 0.81 vs. 0.63 nmol/L, PC: 0.102, vs. 0.093 nmol/mg protein, Aix: 13% vs. 9%, p < 0.05) while PWV remained unchanged. Endothelial glycocalyx integrity showed a greater improvement in the varenicline than the NRT treatment (PBR range 5–9 μm: 1.07 ± 0.02 vs. 1.17 ± 0.02 μm, p = 0.03) in parallel with the greater CO reduction (5 vs. 7 ppm, p = 0.02). At 1-year follow-up, MDA, PC, Aix and PBR at 5–25 μm range were further improved in subjects who abstained from smoking (n = 84 out of 188), while the above markers and PWV deteriorated in relapsed smokers (p < 0.05).


A smoking cessation program using varenicline or NRT for 3 months resulted in a decrease of CO, oxidative stress, arterial stiffness and restored endothelial glycocalyx. These effects were more evident after varenicline treatment, likely because of a greater CO reduction, and were maintained after 1 year only in subjects who abstained from smoking.