The Effect of Ezetimibe on Plasma Viscosity, Fibrinogen and Lipid Profile

Abstract

Objectives: The aim of this study is to reveal the effect of ezetimibe monotherapy on plasma viscosity and fibrinogen levels in hyperlipidemia.

Material and Methods: A study group of 31 hyperlipidemic patients was treated for twelve weeks with a monotherapy of ezetimibe 10 mg/day. A healthy control group of 31 individuals with normal plasma lipid profile was also  admitted to the study. PV, fibrinogen and fasting lipid parameters were evaluated. PV was measured by Harkness Capillary Viscometer.

Results: PV and fibrinogen levels decreased significantly with ezetimibe monotherapy (p<0.01). Total cholesterol and low density lipoprotein (LDL) levels were statistically significantly lower than ezetimibe monotherapy group (p<0.001), whereas high density lipoprotein (HDL) level was significantly higher than ezetimibe monotherapy group (p<0.01). HDL level increased significantly in ezetimibe monotherapy group (p<0.01). PV and fibrinogen levels of the control group were lower than ezetimibe monotherapy group before treatment (p<0.01 and p<0.001; respectively). Besides, fibrinogen level of control group was significantly lower than ezetimibe monotherapy group after treatment (p<0.01). Total cholesterol and LDL levels of control group was lower than ezetimibe monotherapy group before and after treatment (p<0.001 and p<0.01; p<0.001, respectively). HDL level of  control group was significantly higher than ezetimibe monotherapy group before treatment (p<0.01).

Conclusions: Ezetimibe monotherapy ameliorates lipid profile and PV parameters in hyperlipidemic individuals. Increased PV and deteriorations in lipid profile may induce endothelial damage in cardiovascular diseases. Being a biophysical mechanical marker, PV may be useful for diagnosis, treatment and follow-up of hyperlipidemic patients treated with ezetimibe monotherapy.

 

Keywords

• Ezetimibe; viscosity; fibrinogen; hyperlipidemia

The Effect of Ezetimibe on Plasma Viscosity, Fibrinogen and Lipid Profile

Öz

Kaynakça

1. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269:3015-23.
2. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-97.
3. Dujovne CA, Ettinger MP, McNeer JF, Lipka LJ, Le Beaut AP, Suresh R, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol. 2002;90:1092-7. doi: 10.1016/S0002-9149(02)02798-4.
4. Kikuchi K, Nezu U, Inazumi K, Miyazaki T, Ono K, Orime K, et al. Double-blind randomized clinical trial of the effects of ezetimibe on postprandial hyperlipidemia and hyperglycaemia. J Atheroscler Thromb. 2012;19(12):1093-1101. doi: doi.org/10.5551/jat.12427.
5. Krysiak R, Zmuda W, Okopien B. The effect of ezetimibe and simvastatin on hemostasis in patients with isolated hypercholesterolemia. Fundam and Clin Pharm. 2012;26:424-31. doi: 10.1111/j.1472-8206.2011.00932.x.
6. Sudhop T, Lutjohann D, Kodal A, Tribble DL, Shah S, Perevozskaya I, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 2002;106:1943-8. doi: 10.1161/01.CIR.0000034044.95911.DC.
7. Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003;107:2409-15. doi: 10.1161/01.CIR.0000068312.21969.C8.
8. Woodward M, Rumley A, Tunstall-Pedoe H, Lowe GDO. Associations of blood rheology and interleukin-6 with cardiovascular risk factors and prevalent cardiovascular disease. Br J Haematol. 1999;104:246–57. doi: 10.1046/j.1365-2141.1999.01158.x.

9. Ercan M, Konukoglu D, Yesim NT. Association of plasma viscosity with cardiovascular risk factors in obesity: An old marker, a new insight. Clin Hemorheol Microcirc. 2006;35:441–6.
10. Sloop GD. A critical analysis of the role of cholesterol in atherogenesis. Clin Hemorheol Microcirc. 1999;142:265–8.
11. Cunnigham KS, Gotlieb AI. The role of shear stress in the pathogenesis of atherosclerosis. Lab Invest. 2005;85:9-23. doi:10.1038/labinvest.3700215.
12. Gori T, Dragoni S, Di Stalfo G, Fonconi S. Endothelium and hemorheology. Ann 1st Super Sanita. 2007;43:124-9.
13. Ikeda S, Maemura K. Ezetimibe and vascular endothelial function. Curr Vasc Pharmacol. 2011;9:87-98. doi: http://dx.doi.org/10.2174/157016111793744797.
14. Kensey KR. Rheology: An overlooked component of vascular disease. Clin App Thromb-Hemost. 2003;9:93-9. doi: 10.1177/107602960300900201.
15. Rampling MW. Haemorheological disturbances in hypertension: the influence of diabetes and smoking. Clin Hemorheol Microcir. 1999;21(3-4):183-7.
16. Landin K, Stigendal L, Eriksson E, Krotkiewski M, Risberg B, Tengborn L, et al. Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1. Metabolism. 1990;39:1044–8. doi: http://dx.doi.org/10.1016/0026-0495(90)90164-8.
17. Landin K, Tengborn L, Smith U. Elevated fibrinogen and plasminogen activator inhibitor (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular diseases. J Intern Med. 1990;227:273–8.
18. Baskurt OK, Boynard M, Cokelet GC, Connes P, Cooke BM, Forconi S et, al. New guidelines for hemorheological laboratory techniques. Clin Hemorheol Microcirc. 2009;42(2):75-97. doi: 10.3233/CH-2009-1202.
19. Miyashita Y, Endo K, Saiki A, Ban N, Nagumo A, Yamaguchi T, et al. Effect of ezetimibe monotherapy on lipid metabolism and arterial stiffness assessed by cardio-ankle vascular index in type 2 diabetic patients. J Atheroscler Thromb. 2010;17:1070-6. doi: 10.5551/jat.4465.
20. Van der Loo B, Spring S, Koppensteiner R. High-dose atorvastatine treatment in patients with peripheral arterial disease: Effects on platelet aggregation, blood rheology and plasma homocysteine. Clin Hemorheol Microcirc. 2011;47:241-51. doi: 10.3233/CH-2011-1386.
21. Lowe GD, Lee AJ, Rumley A, Price JF, Fowkes FG. Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study. Br J Haematol 1997; 96: 168–73.
22. Shimada S, Hasegawa K, Wada H, Terashima S, Satoh-Asahara N, Yamakage H, et al. High blood viscosity is closely associated with cigarette smoking and markedly reduced by smoking cessation. Circ J. 2011;75:185–9. doi: 10.1253/circj.CJ-10-0335.
23. Laszlo S, Beata H, Zsolt M, Gergely M, Kalman T, Samuel K. Effect of atorvastatin treatment on the hemorheological and hemostaseological parameters I chronic cerebrovascular patients. Orvosi Hetilap. 2008;149:1117-23. doi: http://dx.doi.org/10.1556/OH.2008.28267.
24. Yano K, Grove J, Chen R, Rodríguez BL, Curb JD, Tracy RP. Plasma fibrinogen as a predictor of total and cause-specific mortality in elderly Japanese-American men. Arterio Throm Vascul Biol. 2001;21:1065-70. doi: 10.1161/01.ATV.21.6.1065.
25. Turfaner N, Uzun H, Balci H, Ercan M, Karter YH, Caner M, et al. Ezetimibe therapy and its influence on oxidative stres and fibrinolytic activity. The South Med J. 2010;103:428-33. doi: 10.1097/SMJ.0b013e3181d83374.
26. Ercan M, Koksal C, Konukoglu D, Bozkurt AK, Onen S. Impaired plasma viscosity via increased cholesterol levels in peripheral occlusive arterial diseases. Clin Hemorheol Microcirc. 2003;29(1):3-9.
27. Kannel WB. Overview of hemostatic factors involved in atherosclerotic cardiovascular disease. Lipids. 2005;40:1215-20.