Serum lipids and regulation of tissue factor-induced coagulation in middle-aged men

Formation of an occlusive thrombus by exposure of tissue factor (TF) to cir culating blood and subsequent triggering of coagulation by TF-activated fac tor VII (FVIIa) complexes on ruptured atherosclerotic plaques is thought to be a key event in myocardial infarction. Tissue factor pathway inhibitor ( TFPI) is a potent inhibitor of TF-induced coagulation in which the anticoag ulant function most probably is restricted to free TFPI in human plasma. Th e present study was undertaken to assess the interrelations between serum l ipids and components of TF-induced coagulation in 234 apparently healthy me n aged 36-56 years recruited from the general population. Plasma free TFPI antigen (Ag) was positively correlated (P<.001) with total cholesterol, low -density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B (ap oB-100), fibrinogen, total amount of FVII (FVIIam), coagulation activity of factor VII (FVIIc), and FVTIa. The significant predictors for free TFPI Ag were total cholesterol, triglycerides, fibrinogen, FVIIc, and age, which e xplained 33% of the plasma variation in free TFPI Ag assessed by multiple r egression analysis. A highly significant (P<.0001) linear trend for increas e in atherogenic lipids (i.e., total cholesterol and triglycerides), FVII ( i.e., FVIIc and FVIIa), and fibrinogen across quartiles of TFPI Ag was demo nstrated after adjustment for confounders. These findings may indicate a co mpensatory increase in plasma free TFPI with lipid and hemostatic risk fact ors for atherothrombotic diseases in healthy middle-aged men. (C) 2001 Else vier Science Ltd. All rights reserved.