title: Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden?
abstract: BACKGROUND
  Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease.
  
  
  OBJECTIVE
  To determine the relationship between inflammatory markers and the angiographic severity of CAD.
  
  
  METHODS
  We measured inflammatory markers in consecutive patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay.
  
  
  RESULTS
  There was a significant correlation between TNFalpha and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFalpha; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P< 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFalpha (P< 0.05) and combined levels of TNFalpha and IL-6 (P< 0.05). IL-6 levels were independently predictive of Gensini coronary score (P< 0.05).
  
  
  CONCLUSIONS
  TNFalpha and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.
authors.affiliation: Heart Institute, Department of Cardiology, Hadassah-Hebrew University Medical Center, Ierusalem, Israel. igotsman@bezeqint.net
authors.forename: Israel
authors.initials: I
authors.lastname: Gotsman
authors.forename: Ayala
authors.initials: A
authors.lastname: Stabholz
authors.forename: David
authors.initials: D
authors.lastname: Planer
authors.forename: Thea
authors.initials: T
authors.lastname: Pugatsch
authors.forename: Ludmila
authors.initials: L
authors.lastname: Lapidus
authors.forename: Yelena
authors.initials: Y
authors.lastname: Novikov
authors.forename: Siham
authors.initials: S
authors.lastname: Masrawa
authors.forename: Aubrey
authors.initials: A
authors.lastname: Soskolne
authors.forename: Chaim
authors.initials: C
authors.lastname: Lotan