Elevated plasma levels of free-form of TFPI antigen in hypercholesterolemic patients

Several studies have previously reported high levels of total tissue factor pathway inhibitor (TFPI) antigen in patients with hypercholesterolemia. Th e relationship between serum lipid concentrations and total and free-form T FPI antigen in 32 patients with primary type II hypercholesterolemia and 38 age- and gender-matched normolipemic control subjects was studied (Study G roup I). Plasma concentrations of total TFPI (tTFPI) antigen, free-form TFP I (fTFPI) antigen, tissue factor antigen, factor VII activity (FVIIc), and prothrombin Fragment 1 + 2 (F1 + 2) were measured. The median levels of tTF PI, fTFPI, FVIIc, and Fl + 2 were higher in hyperlipidemic patients compare d with those in healthy subjects. The effect of lowering total cholesterol on hypercoagulability in 25 patients with type II hyperlipoproteinemia (Stu dy Group II) were also studied. The median levels of tTFPI, FVIIc, and F1 2 decreased significantly after 6 months of 3-hydroxy-3-methylglutaryl coe nzyme A (HMG-CoA) reductase inhibitor therapy in the hypercholesterolemic p atients. On the other hand, fTFPI did not change after therapy. Plasma tTFP I was strongly correlated with total cholesterol and low density lipoprotei n (LDL)-cholesterol in hyperlipidemic patients. In contrast to the strong c orrelation between tTFPI and total cholesterol, the correlation between pla sma fTFPI and total cholesterol was relatively poor. These results suggest that the activation of the anticoagulant system as well as the activation o f the coagulation system may occur in association with hypercholesterolemia . Furthermore, the results of this study may suggest that lowering of total cholesterol in hyperlipidemic patients reduces the thrombin generation in plasma and that down-regulation of LDL does not affect the anticoagulant po tency of TFPI in plasma. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.