Levels of Factor VIIc Associated With Decreased Tissue Factor Pathway Inhibitor and Increased Plasminogen Activator Inhibitor-1 in Dyslipidemias

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Abstract
Abstract Tissue factor pathway inhibitor (TFPI), a kunitz-type inhibitor of the extrinsic coagulation pathway, factor VII coagulant (FVIIc), FVIIa, and the fibrinolytic factors plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (TPA) have been studied in various hyperlipidemias. Compared with a normal lipidic group, mean TFPI activity was 70% higher ( P <.001) and 36% higher ( P <.001) in type IIa and IIb hyperlipidemias, respectively, and was lower by 13% in type IV hyperlipidemia ( P =.05). TFPI was correlated with LDL cholesterol ( P <.001), total cholesterol ( P <.001), HDL cholesterol ( P <.01), apolipoproteins (apo) AI ( P <.001) and B ( P <.001) and lipoprotein a ( P <.01). TFPI was negatively correlated with the triglyceride level ( P <.05); the correlation was dependent on LDL cholesterol and HDL cholesterol levels, which were decreased in type IV hyperlipidemia. FVIIc activity ( P <.001) was increased by 30% in both type IV and type IIb hyperlipidemia and was correlated with triglyceride levels. FVIIa was not significantly increased in any group compared with control group. FVIIc was correlated with triglyceride level ( P <.001), while FVIIa was not. Interestingly, FVIIa was correlated with FVIIc ( r =.5, P <.001) in the control group as well as in the hyperlipidemic groups ( r =.32, P <.01). These results favor the hypothesis that higher FVIIc concentrations in hyperlipidemic patients are likely due to enhancement of synthesis of FVII and that a part of this FVII circulates in an activated chemical form. Compared with the control group, PAI-1 activity was twofold higher ( P <.08) in type IIa hyperlipidemia, threefold higher ( P <.001) in type IIb hyperlipidemia, and fourfold higher in type IV hyperlipidemia ( P <.001). PAI-1 activity correlated with triglyceride levels ( P <.001), apoB levels ( P <.001) and total cholesterol levels ( P <.05). These correlations were dependent on apoB and probably reflect the correlation between PAI-1 and VLDL. In contrast, TPA level was normal in the different hyperlipidemias. No correlation was found between TFPI, FVIIc, and PAI-1. Variation of TFPI activity appears to be related to the variations of its main lipoprotein carriers: LDL, HDL, and Lp (a). The association in hypertriglycemic patients of hypercoagulability (increased FVIIc and decreased TFPI) and hypofibrinolysis (increased PAI-1) may explain thrombosis predisposition of some of these patients. However, it would be interesting to study the increased levels of endothelium-derived TFPI in plasma induced by the injection of heparin.