title: Effects of smoking and cessation on subclinical arterial disease: a substudy of a randomized controlled trial.
abstract: BACKGROUND
  The mechanisms by which smoking cessation reduces cardiovascular disease risk are unclear. We evaluated longitudinal changes in carotid intima-media thickness among current smokers enrolled in a prospective, randomized smoking cessation clinical trial.
  
  
  RESULTS
  Subjects were enrolled in a randomized, double-blind, placebo-controlled trial of 5 smoking cessation pharmacotherapies and underwent carotid ultrasonography with carotid intima-media thickness measurement. Subjects were classified as continuously abstinent (biochemically confirmed abstinence at 6 months, 1 year, and 3 years post-quit attempt), intermittently abstinent (reported smoking at one of the three time points), or smoked continuously (reported smoking at all three time points). The primary endpoint was the absolute change (mm) in carotid intima-media thickness (ΔCIMT(max)) before randomization and 3 years after the target quit date. Pearson correlations were calculated and multivariable regression models (controlling for baseline CIMT(max) and research site) were analyzed. Among 795 subjects (45.2 ± 10.6 years old, 58.5% female), 189 (23.8%) were continuously abstinent, 373 (46.9%) smoked continuously, and 233 (29.3%) were abstinent intermittently. There was a greater increase in carotid intima-media thickness among subjects who were continuously abstinent than among those who smoked continuously (p = 0.020), but not intermittently (p = 0.310). Antihypertensive medication use (p = 0.001) and research site (p<0.001) independently predicted ΔCIMTmax--not smoking status. The greatest increase in carotid intima-media thickness among continuous abstainers was related to increases in body-mass index (p = 0.043).
  
  
  CONCLUSIONS
  Smoking status did not independently predict ΔCIMT(max); increasing body-mass index and antihypertensive medication use were the most important independent predictors. The rapid reduction in cardiovascular disease events observed with smoking cessation is unlikely to be mediated by changes in subclinical atherosclerosis burden.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00332644.
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Johnson
authors.forename: Megan E
authors.initials: ME
authors.lastname: Piper
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Baker
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fiore
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000453:epidemiology; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000453:epidemiology*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000453:epidemiology; D059168:Carotid Intima-Media Thickness; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000453:epidemiology*; D016540:Smoking Cessation / Q000706:statistics & numerical data*; D016896:Treatment Outcome; D017539:Tunica Intima / Q000000981:diagnostic imaging
chemical_list: D000959:Antihypertensive Agents