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

Atherosclerosis. 2017 Jul;262:123-130. doi: 10.1016/j.atherosclerosis.2017.05.012. Epub 2017 May 13.

Abstract

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

Methods: 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.

Results: 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).

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT02307045.

Keywords: Arterial stiffness; Augmentation index; Glycocalyx; Nicotine replacement therapy; Nitric oxide; Pulse wave velocity; Smoking cessation; Varenicline.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Breath Tests
  • Carbon Monoxide / metabolism
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Glycocalyx / drug effects*
  • Glycocalyx / metabolism
  • Glycocalyx / pathology
  • Greece
  • Humans
  • Male
  • Malondialdehyde / metabolism
  • Middle Aged
  • Nicotinic Agonists / adverse effects
  • Nicotinic Agonists / therapeutic use*
  • Oxidative Stress / drug effects*
  • Protein Carbonylation / drug effects
  • Pulse Wave Analysis
  • Smoking / drug therapy*
  • Smoking / metabolism
  • Smoking / pathology
  • Smoking / physiopathology
  • Smoking Cessation / methods*
  • Time Factors
  • Tobacco Use Cessation Devices* / adverse effects
  • Tobacco Use Disorder / drug therapy*
  • Tobacco Use Disorder / metabolism
  • Tobacco Use Disorder / pathology
  • Tobacco Use Disorder / physiopathology
  • Treatment Outcome
  • Varenicline / adverse effects
  • Varenicline / therapeutic use*
  • Vascular Stiffness / drug effects*

Substances

  • Nicotinic Agonists
  • Malondialdehyde
  • Carbon Monoxide
  • Varenicline

Associated data

  • ClinicalTrials.gov/NCT02307045