title: Increased tissue factor pathway inhibitor activity is associated with myocardial infarction in young women: results from the RATIO study.
abstract: BACKGROUND
  The tissue factor pathway inhibitor (TFPI)/protein S anticoagulant system is a potent inhibitor of blood coagulation. TFPI and protein S are major determinants of thrombin generation (TG) tests determined at low tissue factor (TF) and at high TF concentrations in the presence of activated protein C (APC). Both TFPI and protein S protect against venous thrombosis, but the importance of the TFPI/protein S system in arterial thrombosis remains unclear.
  
  
  OBJECTIVE
  To investigate the influence of the TFPI/protein S anticoagulant system on the risk of myocardial infarction (MI) in young women.
  
  
  METHODS
  The RATIO study is a case-control study in women under 50 years of age, including 205 patients and 638 controls. TFPI and protein S were quantified using ELISA. The TFPI/protein S activity (nTFPIr) and the APC sensitivity ratio (nAPCsr) were determined using TG tests. Odds ratios (ORs) adjusted for putative confounders and corresponding 95% confidence intervals (95% CI) were determined.
  
  
  RESULTS
  Women with MI had higher TFPI levels than controls (135.9 ± 40% vs. 124.2 ± 41%), resulting in increased TFPI/protein S activities and increased APC sensitivity. Furthermore, an increased TFPI activity was associated with MI [nTFPIr: adjusted OR Q1 vs. Q4 = 2.1 (95%CI 1.1-4.1)]. Additionally, an increased APC sensitivity was associated with MI [nAPCsr: adjusted OR Q1 vs. Q4 = 1.7 (95% CI 0.9-3.2)]
  
  
  CONCLUSIONS
  Women with MI had increased TFPI levels compared with controls. Consequently, the TFPI/protein S activity and APC sensitivity are increased in women with MI. Whether this increase in TFPI activity acts as a compensating mechanism for an increased procoagulant state or is a marker of endothelial damage remains to be investigated.
authors: Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands. kristien.winckers@maastrichtuniversity.nl
authors: K
authors: K
authors: Winckers
authors: B
authors: B
authors: Siegerink
authors: C
authors: C
authors: Duckers
authors: L F
authors: LF
authors: Maurissen
authors: G
authors: G
authors: Tans
authors: E
authors: E
authors: Castoldi
authors: H M H
authors: HM
authors: Spronk
authors: H
authors: H
authors: Ten Cate
authors: A
authors: A
authors: Algra
authors: T M
authors: TM
authors: Hackeng
authors: F R
authors: FR
authors: Rosendaal
mesh_terms: D000328:Adult; D000925:Anticoagulants; D002316:Cardiotonic Agents; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D016017:Odds Ratio; D017293:Protein S / Q000032:analysis; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D002316:Cardiotonic Agents; D008074:Lipoproteins; D017293:Protein S; C051928:lipoprotein-associated coagulation inhibitor