title: Role of risk factors in the modulation of tissue factor activity and blood thrombogenicity.
abstract: BACKGROUND
  Several studies suggest a role for an increased circulating pool of tissue factor (TF) in atherothrombotic diseases. Furthermore, certain cardiovascular risk factors, such as diabetes, hyperlipemia, and smoking, are associated with a higher incidence of thrombotic complications. We hypothesized that the observed increased blood thrombogenicity (BT) observed in patients with type 2 diabetes mellitus may be mediated via an increased circulating tissue factor activity. We have extended our study to smokers and hyperlipidemic subjects.
  
  
  RESULTS
  Poorly controlled patients with type 2 diabetes mellitus (n=36), smokers (n=10), and untreated hyperlipidemic subjects (n=10) were studied. Circulating TF was immunocaptured from plasma, relipidated, and quantified by factor Xa (FXa) generation in the presence of factor VIIa. BT was assessed as thrombus formation on the Badimon perfusion chamber. Patients with improvement in glycemic control showed a reduction in circulating TF (362+/-135 versus 243+/-74 pmol/L per min FXa, P=0.0001). A similar effect was observed in BT (15 445+/-1130 versus 12 072+/-596 microm/mm2, P=0.01). Two hours after smoking 2 cigarettes, TF was increased (217+/-72 versus 283+/-106 pmol/L per min FXa, P=0.003). Hyperlipidemic subjects showed higher TF (237+/-63 versus 195+/-44 pmol/L per min FXa, P=0.035) than healthy volunteers.
  
  
  CONCLUSIONS
  These findings suggest that high levels of circulating TF may be the mechanism of action responsible for the increased thrombotic complications associated with the presence of these cardiovascular risk factors. These observations strongly emphasize the usefulness of the management of the patients based on their global risk assessment.
authors.affiliation: Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Antonia
authors.initials: A
authors.lastname: Sambola
authors.forename: Julio
authors.initials: J
authors.lastname: Osende
authors.forename: James
authors.initials: J
authors.lastname: Hathcock
authors.forename: Michael
authors.initials: M
authors.lastname: Degen
authors.forename: Yale
authors.initials: Y
authors.lastname: Nemerson
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.forename: Jill
authors.initials: J
authors.lastname: Crandall
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Badimon
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000097:blood*; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology
chemical_list: D013925:Thromboplastin