This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zitoun, D. Articles by Samama, M. M. Search for Related Content PubMed PubMed Citation Articles by Zitoun, D. Articles by Samama, M. M.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:77-81.)
© 1996 American Heart Association, Inc.

Articles

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

Danièle Zitoun; Lucienne Bara; Arnaud Basdevant; Meyer Michel Samama

From the Laboratoire de Thrombose Expérimentale (D.Z., L.B., M.M.S.), Université Pierre et Marie Curie-Paris VI, and the Service de Nutrition du Pr Guy-Grand (A.B.), Hôtel-Dieu, Paris.

Correspondence to Dr L. Bara, Laboratoire de Thrombose Expérimentale, Université Pierre et Marie Curie-Paris VI, Institut Biomédical des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France.

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.

Key Words: hyperlipidemia • tissue factor pathway inhibitor • factor VIIa • plasminogen activator inhibitor type 1 • tissue-type plasminogen activator

This article has been cited by other articles:

				L. Calabresi, M. Gomaraschi, and G. Franceschini Endothelial Protection by High-Density Lipoproteins: From Bench to Bedside Arterioscler Thromb Vasc Biol, October 1, 2003; 23(10): 1724 - 1731. [Abstract] [Full Text] [PDF]

				J. D Mills and P. J Grant Insulin resistance, haemostatic factors and cardiovascular risk The British Journal of Diabetes & Vascular Disease, January 1, 2002; 2(1): 19 - 26. [Abstract] [PDF]

				Y. Arai, N. Hirose, K. Yamamura, M. Kimura, A. Murayama, I. Fujii, and M. Tsushima Long-Term Effect of Lipid-Lowering Therapy on Atherosclerosis of Abdominal Aorta in Patients with Hypercholesterolemia: Noninvasive Evaluation by a New Image Analysis Program Angiology, January 1, 2002; 53(1): 57 - 68. [Abstract] [PDF]

				B. J. O'Connell and J. Genest Jr High-Density Lipoproteins and Endothelial Function Circulation, October 16, 2001; 104(16): 1978 - 1983. [Abstract] [Full Text] [PDF]

				R. S. Rosenson and C. C. Tangney Antiatherothrombotic Properties of Statins: Implications for Cardiovascular Event Reduction JAMA, May 27, 1998; 279(20): 1643 - 1650. [Abstract] [Full Text] [PDF]

				R. Junker, J. Heinrich, H. Schulte, J. van de Loo, and G. Assmann Coagulation Factor VII and the Risk of Coronary Heart Disease in Healthy Men Arterioscler Thromb Vasc Biol, August 1, 1997; 17(8): 1539 - 1544. [Abstract] [Full Text]

				J. C. LaRosa Triglycerides and Coronary Risk in Women and the Elderly Arch Intern Med, May 12, 1997; 157(9): 961 - 968. [Abstract] [PDF]