title: Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction.
abstract: BACKGROUND
  The association of plasma fibrinogen with myocardial infarction (MI) may (like that of C-reactive protein, CRP) be a marker of subclinical inflammation, mediated by cytokines such as interleukin-6 (IL-6). There are well-recognized discrepancies between commonly performed fibrinogen assays. Increased ratio of clottable fibrinogen to intact fibrinogen (measured by a recently developed immunoassay) has been proposed as a measure of hyperfunctional fibrinogen, and is elevated in acute MI.
  
  
  OBJECTIVE
  To compare the associations of intact fibrinogen and four routine fibrinogen assays (two von Clauss assays; one prothrombin-time derived; and one immunonephelometric) in a case-control study of previous MI.
  
  
  METHODS
  Cases (n=399) were recruited 3-9 months after their event; 413 controls were age- and sex- matched from the case-control study local population. Intact fibrinogen was measured in 50% of subjects.
  
  
  RESULTS
  All routine fibrinogen assays showed high intercorrelations (r=0.82-0.93) and significant (P<0.0001) increased mean levels in cases vs. controls. These four routine assays correlated only moderately with intact fibrinogen (r=0.45-0.62), while intact fibrinogen showed only a small, nonsignificant increase in cases vs. controls. Consequently, the ratio of each of the four routine assays to the intact fibrinogen assay was significantly higher (P<0.0003) in cases vs. controls. Each fibrinogen assay correlated with plasma levels of CRP and IL-6 (which were also elevated in cases vs. controls). Each routine fibrinogen assay remained significantly elevated in cases vs. controls after further adjustment for C-reactive protein and interleukin-6.
  
  
  CONCLUSIONS
  These data provide evidence for acquired, increased hyperfunctional plasma fibrinogen in MI survivors, which is not associated with markers of inflammatory reactions. The causes and significance of these results remain to be established in prospective studies.
authors: University Department of Medicine, Royal Infirmary, Glasgow, UK. gdl1j@clinmed.gla.ac.uk
authors: G D O
authors: GD
authors: Lowe
authors: M
authors: M
authors: Woodward
authors: A
authors: A
authors: Rumley
authors: C E
authors: CE
authors: Morrison
authors: W
authors: W
authors: Nieuwenhuizen
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis*; D016022:Case-Control Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis* / Q000502:physiology; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D012307:Risk Factors; D017741:Survivors
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D005340:Fibrinogen; D002097:C-Reactive Protein