title: Cigarette smoking is independently associated with markers of endothelial dysfunction and hyperinsulinaemia in nondiabetic individuals with coronary artery disease.
abstract: BACKGROUND
  Oxidative stress and endothelial dysfunction have been introduced as a unifying pathological mechanism for early atherosclerotic disease. They are caused by a variety of stimuli including cigarette smoking (environmental) and type 2 diabetes (disease factor). However, the role of hyperinsulinemia, a marker of insulin resistance, as a risk factor for atherosclerosis remains to be clarified.
  
  
  OBJECTIVE
  To study the relationship of smoking, hyperinsulinaemia and biochemical markers of oxidative stress and endothelial dysfunction, in patients with coronary artery disease.
  
  
  METHODS
  Case-control study of 5-year survivor status in smokers, former smokers and nonsmokers with angiographically documented stable coronary artery disease classified by self-reporting of smoking status together with plasma cotinine measurements.
  
  
  METHODS
  Cardiology and cardiac surgery unit of a tertiary care referral centre.
  
  
  METHODS
  Plasma levels of vitamins C, E and selenium, and the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were assessed in 214 patients at baseline together with the glucose and insulin response to an oral glucose challenge. Sixty known or newly diagnosed type 2 diabetic patients (28%) were identified and excluded from further analysis.
  
  
  RESULTS
  E-selectin and ICAM-1, serving as markers of endothelial dysfunction, significantly correlated with hyperinsulinaemia (p < 0.05). Circulating immunoreactive insulin was elevated in active smokers and former smokers as compared to non-smokers after an oral glucose load (p < 0.05 for the area under the insulin time curve), despite a similar glucose response. Smoking was associated with a decrease in antioxidant vitamins C (p = 0.02) and E (p = 0.03), and an increase of E-selectin (p < 0.05) and ICAM-1 (p < 0.001). Low baseline ICAM-1 and high vitamin C levels emerged as the most significant multivariate predictors of 5-year survival (p < 0.001).
  
  
  CONCLUSIONS
  Hyperinsulinaemia in smokers is linked with markers of endothelial dysfunction. Impaired vascular reactivity can thus be a new possible mechanism linking insulin resistance and smoking.
authors.affiliation: Kooperationseinheit Pharmakogenomik/Angewandte Genomforschung, Universitätsklinikum Heidelberg, Germany. winkbr@gmx.de
authors.forename: B R
authors.initials: BR
authors.lastname: Winkelmann
authors.forename: B O
authors.initials: BO
authors.lastname: Boehm
authors.forename: M
authors.initials: M
authors.lastname: Nauck
authors.forename: P
authors.initials: P
authors.lastname: Kleist
authors.forename: W
authors.initials: W
authors.lastname: März
authors.forename: N K
authors.initials: NK
authors.lastname: Verho
authors.forename: N
authors.initials: N
authors.lastname: Ranjith
authors.forename: G
authors.initials: G
authors.lastname: Kneissl
mesh_terms: D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality*; D003367:Cotinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005858:Germany / Q000453:epidemiology; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D015996:Survival Rate; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D003367:Cotinine