Abstract
Platelet activation, impairment of fibrinolysis, activation of the coagulation pathway, and dyslipidemia are important factors in the pathogenesis and progression of ischemic heart disease, and patients generally need to use an antiplatelet agent. Lipid-lowering cerivastatin, a novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, was administered to 20 patients with primary mixed hyperlipidemia for the assessment of the effect of cerivastatin on lipid levels, plasma fibrinogen concentration, factor VII, VIII, and X levels, plasminogen and antiplasmin concentrations, platelet count, and aggregation (adenosine diphosphate [ADP], collagen, and epinephrine induced). Assessments were made immediately after 2 months of a standard lipid-lowering diet, 4 weeks of placebo administration, and 4 weeks of cerivastatin treatment. Cerivastatin achieved significant reductions in triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels. The significant improvement of the lipid profile was associated with platelet aggregation reduction in vitro stimulated by ADP, collagen, and epinephrine (P > .05,P = .05,P > .005, respectively). Significantly lower levels of factor VII and fibrinogen were observed (P = .001,P > .0001) immediately after cerivastatin treatment. No significant differences were detected in factor VIII level, plasminogen and antiplasmin concentrations, and platelet count after cerivastatin treatment. It was concluded that cerivastatin in mixed hyperlipidemia can exert beneficial changes on specific hemostatic variables and platelet aggregation in addition to its positive effects on plasma lipid values.
Similar content being viewed by others
References
Goldstein JL, Kita T, Brown MS. Defective lipoprotein receptors and atherosclerosis.N Engl J Med. 1983;309:288–296.
Arad Y, Ramakrishnan E, Ginsberg HN. Lovastatin therapy reduces low density lipoprotein apo B levels in subjects with combined hyperlipidemia by reducing production of apoB-containing lipoproteins: implications for pathophysiology of apoB production.J Lipid Res. 1990;31:567–582.
Stephard J, Cobbe SM, Ford I. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.N Engl J Med. 1995;333:1301–1307.
Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).Lancet. 1994;3441:383–389.
Beigel Y, Fuchs J, Snir M, Lurie Y, Green P, Djaldetti M. Lovastatin therapy in heterozygous familial hypercholesterolemic patients: effect on blood rheology and fibrinogen levels.J Intern Med. 1991; 230:23–27.
Osamah H, Mira R, Sorina S, Shlomo K, Michael A. Reduced platelet aggregation after fluvastatin therapy is associated with altered platelet lipid composition and drug binding to the platelets.Br J Clin Pharmacol. 1997;44:77–83.
Sandset PM, Lund H, Norseth J, Abildguard U, Ose L. Treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors in hypercholesterolemia induces changes in the components of the extrinsic coagulation system.Arterioscler Thromb. 1991;11: 138–145.
Silveria A, Karpe F, Blomback M. Activation of coagulation factor VII during alimentary lipidemia.Arterioscler Thromb. 1994;14: 60–69.
Mitropoulos KA, Miller GJ, Reeves BEA,Wilkes HC, Cruickshank JK. Factor VII coagulant activity is strongly associated with the plasma concentration of large lipoprotein particles in middle-aged men.Atherosclerosis. 1989;76:203–208.
Farnier M. Cerivastatin in the treatment of mixed hyperlipidemia: the RIGHT Study. The Cerivastatin Study Group.Am J Cardiol. 1998;82:515–525.
Mabuchi H, Koizumi J, Kajinami K. Clinical efficacy and safety of cerivastatin in the treatment of heterozygous familial hypercholes-terolemia.Am J Cardiol. 1998;82:525–555.
Friedwald WT, Levy RI, Frederikson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preoperative ultracentrifuge.Clin Chem. 1972;18: 499–502.
Kisiel W, McMullen BA. Isolation and characterization of human factor VIIa.Thromb Res Suppl. 1981;22:375–380.
Zacharski LR, Rosenstein R. Standardization of the one-stage assay for factor VIII.Am J Clin Pathol. 1978;70:280–286.
Fair DS, Edgington TS. Heterogeneity of hereditary and acquired factor X deficiencies by combined immunochemical and functional analyses.Br J Haematol. 1985;59:235–248.
Koepke JA, Gilmer PR, Jr Filip DJ, et al. Studies of fibrinogen measurement in the CAP survey program.Am J Clin Pathol. 1975; 63:984–989.
Wohl RC, Sinio L, Robbins KC. Methods for studying fibrinolytic pathway components in human plasma.Thromb Res Suppl. 1982; 27:525–535.
Reddy KNN, Marcus G. Mechanisms of activation of human plasminogen by streptokinase: presence of active center in streptoki-nase-plasminogen complex.J Biol Chem. 1972;247:1683.
Stein E. Cerivastatinin primary hyperlipidemia: a multicenter analysis of efficacy and safety.Am J Cardiol. 1998;82:40J-46J.
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;324:1076–1079.
Harker LA, Ritchie JL. The role of platelets in acute vascular events.Circulation. 1980;62:V13-V18.
Fuster V, Chesebro JH, Frye RL, Elveback LR. Platelet survival and the development of coronary artery disease in the young adult: effects of cigarette smoking, strong family history and medical therapy.Circulation. 1981;63:546–551.
Shastri KM, Carvlho ACA, Lees RS. Platelet function and platelet lipid composition in the dyslipoproteinemias.J Lipid Res. 1980;21: 467–478.
Mort G, Bulgarelli A, Casseder M, Pagaso G. Effect of short term treatment with bezafibrate on plasma fibrinogen, fibrinopeptide A, platelet activation and blood filterability in atherosclerotic hyperfibrinogenemic patients.Atherosclerosis. 1988;71:113–119.
Nordoy A, Simonsen T, Ytre-Arne K, Lyngmo V, Svensson B. The effect of two cholesterol lowering agents on platelets in patients with hypercholesterolemia.Thromb Haemost. 1987;58:1002.
Brook G, Winterstein G, Aviram M. Platelet function and lipoprotein levels after plasma exchange in patients with familial hypercholesterolemia.Clin Sci (Lond). 1983;64:637–642.
Aviram M, Brook JG. Selective release from platelet granules induced by plasma lipoproteins.Biochem Med. 1984;32:30–33.
Aviram M, Brook JG. Platelet interaction with high and low density lipoproteins.Atherosclerosis. 1983;46:259–268.
Nordoy A, Refsum N, Thelle D, Jaeger S. Platelet function and serum high density lipoproteins.Thromb Haemost. 1979;42: 1181–1186.
Desai K, Bruckdorfer KR, Hutton RA, Owen JS. Binding of apoE-rich high density lipoprotein particles by saturable sites on human blood platelets inhibits agonist-induced platelet aggregation.J Lipid Res. 1989;30:831–840.
Dajani EZ, Shahwan TG, Dajani NE. Statins, platelet aggregation and coronary heart disease.J Assoc Acad Minor Phys. 2002;13: 27–31.
Ma LP, Nie DN, Hsu SX, Yin SM, Xu LZ, Nunes JV. Inhibition of platelet aggregation and expression of alpha granule membrane protein 140 and thromboxane B2 with pravastatin therapy for hypercholesterolemia.J Assoc Acad Minor Phys. 2002;13:23–26.
Owen J, Grossman BA, Palmer RH. Hyperlipidemia and in vivo hemostatic system activation.Semin Thromb Hemost. 1988;14: 241–245.
Kannel WB, Wolf P, Castelli WP, D’Agostino R. Fibrinogen and risk of cardiovascular disease: the Framingham Study.JAMA. 1987;258: 1183–1186.
Branchi A, Rovellini A, Sommariva D, Gugliandolo AG, Fasoli A. Effect of three fibrate derivatives and of two HMG-CoA reductase inhibitors on plasma fibrinogen level in patients with primary hyper cholesterolemia.Thromb Haemost. 1993;70:241–243.
Jay RH, Rampling MW, Betteridge DJ. Abnormalities of blood rheology in familial hypercholesterolemia: effects of treatment.Atherosclerosis. 1990;85:249–256.
Zambrana JL, Velasco F, Castro P, et al. Comparison of bezafibrate versus lovastatin for lowering plasma insulin, fibrinogen, and plasminogen activator inhibitor-1 concentrations in hyperlipidemic heart transplant patients.Am J Cardiol. 1997;80:836–840.
Meade TW, Mellows S, Brozovic M. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study.Lancet. 1986;2:533–537.
Mitropoulos KA, Miller GJ, Martin JC, Reeves BEA, Cooper J. Dietary fat induces changes in factor VII coagulant activity through effects on plasma free stearic acid concentration.Arterioscler Thromb. 1994;14:214–222.
Mitropoulos KA, Armitage JM, Collins R, et al. Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids. Oxford Cholesterol Study Group.Eur Heart J. 1997;18:235–241.
Hamsten A, Wiman B, Faire deU, Blomback M.Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction.N Engl J Med. 1985;313:1557–1563.
Bourcier T, Libby P. HMG CoA reductase inhibitors reduce plasminogen activator-1 expression by human vascular smooth muscle and endothelial cells.Arterioscler ThrombVasc Biol. 2000;20:556–562.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Ural, A.U., Yilmaz, M.I., Avcu, F. et al. Treatment with Cerivastatin in Primary Mixed Hyperlipidemia Induces Changes in Platelet Aggregation and Coagulation System Components. Int J Hematol 76, 279–283 (2002). https://doi.org/10.1007/BF02982799
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02982799