Effect of Lipid-Lowering Treatment on Factor VII Profile in Hyperlipidemic Patients

Summary

A link has been suggested between blood lipids and hemostatic activation. Factor VII (FVII) is a coagulation factor which plays a pivotal role in fibrin generation and thrombus formation. Clinical trials have demonstrated that inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase greatly reduce cardiovascular events in patients with and without coronary artery disease but few data, at this time, are available on the effects of lipid-lowering treatment on factor VII levels. We studied thirty-six IIA and IIB type hyperlipidemic patients who, after a preliminary period of lipid-lowering diet, added atorvastatin (20 mg/daily) or continued dietary treatment alone until they achieved LDL-C recommended levels (< 4 mmol/L). Four to six weeks of lipid lowering treatment with diet plus atorvastatin, produced a significant reduction in FVII coagulant activity (FVIIc) and antigen (FVIIAg). No significant changes were observed in activated FVII (FVIIa). The lipid-lowering treatment with diet alone induced an improved lipid pattern, but no significant changes in FVII profile. Our study suggests a significant effect of lipid-lowering treatment on FVII levels. A possibile nonlipid mechanism that modifies FVII pathway may be suggested.

Key words

Factor VII - hyperlipdemia - statins

• References

• 1 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WR, Haines AP, Stirling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 02: 533-7.
• 2 Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342: 1076-9.
• 3 Hoffman CJ, Miller RH, Lawson WE, Hultin MB. Elevation of factor VII activity and mass in young adults at risk of ischemic heart disease. J Am Coll Cardiol 1989; 14: 941-6.
• 4 Suzuki T, Yamauchi K, Matsushita T, Furumichi T, Furui H, Tsuzuki J, Saito H. Elevation of factor VII activity and mass in coronary artery disease of varying severity. Clin Cardiol 1991; 14: 731-6.
• 5 Broadhurst P, Kelleher C, Hughes L, Imeson JD, Raftery EB. Fibrinogen, factor VII clotting activity and coronary artery disease severity. Atherosclerosis 1990; 85: 169-73.
• 6 Folsom AR, Wu KK, Rosamund WD, Sharret AR, Chambless LE. Prospective study of hemostatic factors and the incidence of coronary heart disease. The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1997; 96: 1102-8.
• 7 Heinrich J, Balleisen L, Schulte H, Assmann G, van de Loo J. Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM study in healthy men. Arterioscler Thromb 1994; 14: 54-9.
• 8 Miller GJ, Bauer KA, Barzegar S, Cooper JA, Rosenberg RD. Increased activation of the haemostatic system in men at high risk of fatal coronary heart disease. Thromb Haemost 1996; 75: 767-71.
• 9 Junker R, Heinrich J, Schulte H, van de Loo J, Assmann G. Coagulation factor VII and the risk of coronary heart disease in healthy men. Arterioscler Thromb Vasc Biol 1997; 17: 1539-44.
• 10 Scarabin PY, Vissac AM, Kirzin JM, Bourgeat P, Amiral J, Agher R, Guize L. Population correlates of coagulation factor VII. Importance of age, sex, and menopausal status as determinants of activated factor VII Arterioscler Thromb Vasc Biol 1996; 16: 1170-6.
• 11 Miller GJ, Martin JC, Mitropoulos KA. et al Plasma factor VII is activated by postprandial triglyceridemia, irrespective of dietary fat composition. Atherosclerosis 1991; 86: 163-71.
• 12 Carvalho de Souza J, Bruckert E, Giral P. et al Coagulation factor VII and plasma tryglicerides. Decreased catabolism as a possible mechanism of factor VII hyperactivity. Haemostasis 1989; 19: 125-30.
• 13 Constantino M, Merskey C, Kudzma DJ, Zucher MB. Increased activity of vitamin K dependent clotting factors in human hyperlipoproteinemia association with cholesterol and tryglicerides levels. Thromb Haemost 1977; 38: 465-74.
• 14 Marchioli R, Marfisi RM, Carinci F, Tognoni G. Meta-analysis, clinical trials, and transferability of research results into practice. The case of cholesterol-lowering interventions in the secondary prevention of coronary artery disease. Arch Intern Med 1996; 156: 1158-72.
• 15 Scandinavian Simvastatin Survival Group. Randomized trial of cholesterol lowering in 4444 patients with coronary disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-9.
• 16 Kearney D, Fitzgerald D. The anti-thrombotic effects of statins. J Am Coll Cardiol 1999; 33: 1305-7.
• 17 Colli S, Eligini S, Lalli M, Camera M, Paoletti R, Tremoli E. Vastatins inhibit tissue factor in cultured human macrophages. Arterioscler Thromb Vasc Biol 1997; 17: 265-72.
• 18 Mussoni L, Banfi C, Sironi L, Baldassarre D, Tremoli E. Plasminogen activator inhibitor type 1 secretion by HepG2 cells: opposite effects of two fibric acid derivatives. Blood Coagul Fibrinolysis 1996; Jun; 07: 503-5.
• 19 National Cholesterol Education Program. Second Report of the Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II). Circulation 1994; 89: 1329-445.
• 20 Morrissey JH, Macik BG, Neuenschwander PF, Comp PC. Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation. Blood 1993; 03: 734-44.
• 21 Friedwald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of ultracentrifuge. Clin Chim Acta 1972; 71: 397-402.
• 22 SAS Institute Inc. SAS/STAT Users Guide, Version 6. Cary, NC: SAS Institute Inc; 1989
• 23 Sandset PM, Lund H, Norseth J, Abildgaard U, Ose L. Treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors in hypercholesterolemia induces changes in the components of the extrinsic coagulation system. Arteriosclerosis Thrombosis 1991; 11: 138-45.
• 24 Dangas G, Badimon JJ, Smith DA, Unger AH, Levine D, Shao BS, Meraj P, Fier C, Fallon JT, Ambrose JA. Pravastatin therapy in hyperlipidemia: effects on thrombus formation and systemic hemostatic profile. J Am Coll Cardiol 1999; 33: 1294-304.
• 25 Hamelin BA, Turgeon J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci 1998; 19: 26-36.
• 26 Knopp RH. Drug treatment of lipid disorders. N Engl J Med 1999; 341 (07) 498-511.
• 27 Vaughan CJ, Murphy MB, Buckley BM. Statin do more than just lower cholesterol. Lancet 1996; 348: 1079-2.
• 28 Scarabin PY, Vissac AM, Kirzin JM, Bourgeat P, Amiral J, Agher R, Guize L. Population correlates of coagulation factor VII Importance of age, sex and menopausal status as determinants of activated factor VII Arterioscl. Thromb Vasc Biol 1996; 16: 1170-6.
• 29 Zitoun D, Bara L, Basdevant A, Samama MM. Levels of Factor VIIc associated with decreased tissue factor pathway inhibitor and increased plasminogen activator inhibitor-1 in dyslipidemias. Arterioscler Thromb Vasc Biol 1996; 01: 77-81.
• 30 Ferro D, Basile S, Alessandri C, Mantovani B, Cordova C, Violi F. Simvastatin reduces monocyte-tissue factor expression in type IIa hypercholesterolemia. Lancet 1997; 350: 1222.
• 31 Branchi A, Rovellini A, Sommariva D, Gugliandolo AG, Fasoli A. Effect of three fibrate derivatives and two HMG-CoA reductase inhibitors on plasma fibrinogen level in patients with primary hypercholesterolemia. Thromb Haemost 1993; 70: 241-3.
• 32 Tsuda Y, Satoh K, Kitadi M. Effects of pravastatin sodium and simvastatin on plasma fibrinogen level and blood rheology in type II hyperlipoproteinemia. Atherosclerosis 1996; 122: 225-33.
• 33 Wierzbicki AS, Lumb PJ, Semra YK, Crook MA. Effect of atorvastatin on plasma fibrinogen. Lancet 1998; 351: 569-70.