LEVELS OF FACTOR-VIIC ASSOCIATED WITH DECREASED TISSUE FACTOR PATHWAYINHIBITOR AND INCREASED PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN DYSLIPIDEMIAS

Tissue factor pathway inhibitor (TFPI), a kunitz-type inhibitor of the extrinsic coagulation pathway, factor VII coagulant (FVIIc), FVIIa, a nd the fibrinolytic factors plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (TPA) have been studied in various hy perlipidemias. Compared with a normal lipidic group, mean TFPI activit y 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 hyperli pidemia (P=.05). TFPI was correlated with LDL cholesterol (P<.001), to tal cholesterol (P<.001); HDL cholesterol (P<.01), apolipoproteins (ap e) AI (P<.001) and B (P<.001) and lipoprotein a (P<.01). TFPI was nega tively correlated with the triglyceride level (P<.05); the correlation was dependent on LDL cholesterol and HDL cholesterol levels, which we re decreased in type IV hyperlipidemia. FVIIc activity (P<.001) was in creased by 30% in both type IV and type IIb hyperlipidemia and was cor related with triglyceride levels. FVIla was not significantly increase d 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 t he hypothesis that higher FVIIc concentrations in hyperlipidemic patie nts 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 I Ia hyperlipidemia, threefold higher (P<.001) in type IIb hyperlipidemi a, and fourfold higher in type IV hyperlipidemia (P<.001). PAI-1 activ ity correlated with triglyceride levels (P<.001), apoB levels (P<.001) and total cholesterol levels (P<.05). These correlations were depende nt 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 lipo protein carriers: LDL, HDL, and Lp (a). The association in hypertrigly cemic patients of hypercoagulability (increased FVIIc and decreased TF PI) and hypofibrinolysis (increased PAI-1) may explain thrombosis pred isposition of some of these patients. However, it would be interesting to study the increased levels of endothelium-derived TFPI in plasma i nduced by the injection of heparin.