Effects of Ezetimibe, Simvastatin, and Vytorin on Reducing L5 a Subfraction of LDL in Patients With Metabolic Syndrome.

Summary

The purpose of this study is: * To identify the common factor for L5 prevalence in patients with Metabolic Syndrome. * To determine whether Ezetimibe, Simvastatin, and Vytorin can correct the L5- promoting factor and reduce L5 in Metabolic Syndrome patients.

Timeline

Start

2007-03

Primary completion

2008-02

Completion

2008-02

Publications

• Background Avogaro P, Cazzolato G, Bittolo-Bon G. Some questions concerning a small, more electronegative LDL circulating in human plasma. Atherosclerosis. 1991 Nov;91(1-2):163-71. doi: 10.1016/0021-9150(91)90198-c.
• Background Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, Sun S, LeBeaut AP, Sager PT, Veltri EP; Ezetimibe Study Group. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003 May 20;107(19):2409-15. doi: 10.1161/01.CIR.0000068312.21969.C8. Epub 2003 Apr 28.
• Background Ballantyne CM, Hoogeveen RC, Bang H, Coresh J, Folsom AR, Heiss G, Sharrett AR. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 2004 Feb 24;109(7):837-42. doi: 10.1161/01.CIR.0000116763.91992.F1. Epub 2004 Feb 2.
• Background Chan DC, Watts GF, Barrett PH, Mamo JC, Redgrave TG. Markers of triglyceride-rich lipoprotein remnant metabolism in visceral obesity. Clin Chem. 2002 Feb;48(2):278-83.
• Background Chen CH, Jiang T, Yang JH, Jiang W, Lu J, Marathe GK, Pownall HJ, Ballantyne CM, McIntyre TM, Henry PD, Yang CY. Low-density lipoprotein in hypercholesterolemic human plasma induces vascular endothelial cell apoptosis by inhibiting fibroblast growth factor 2 transcription. Circulation. 2003 Apr 29;107(16):2102-8. doi: 10.1161/01.CIR.0000065220.70220.F7. Epub 2003 Apr 14.
• Background Chen CH, Pace PW, Karakoc ND, Lu J, Chen HH, Henry PD, Pownall HJ Foreyt JP, Ballantyne CM, Yang CY. Effective reduction of novel atherogenic LDL subfraction by atorvastatin in patients with hypercholesteremia. J AM Coll Cardiol. 2004:43(suppl A):486A (Abstract)
• Background Chappey B, Myara I, Benoit MO, Maziere C, Maziere JC, Moatti N. Characteristics of ten charge-differing subfractions isolated from human native low-density lipoproteins (LDL). No evidence of peroxidative modifications. Biochim Biophys Acta. 1995 Dec 7;1259(3):261-70. doi: 10.1016/0005-2760(95)00172-7.
• Background De Castellarnau C, Sanchez-Quesada JL, Benitez S, Rosa R, Caveda L, Vila L, Ordonez-Llanos J. Electronegative LDL from normolipemic subjects induces IL-8 and monocyte chemotactic protein secretion by human endothelial cells. Arterioscler Thromb Vasc Biol. 2000 Oct;20(10):2281-7. doi: 10.1161/01.atv.20.10.2281.
• Background Demuth K, Myara I, Chappey B, Vedie B, Pech-Amsellem MA, Haberland ME, Moatti N. A cytotoxic electronegative LDL subfraction is present in human plasma. Arterioscler Thromb Vasc Biol. 1996 Jun;16(6):773-83. doi: 10.1161/01.atv.16.6.773.
• Background Kleinman Y, Krul ES, Burnes M, Aronson W, Pfleger B, Schonfeld G. Lipolysis of LDL with phospholipase A2 alters the expression of selected apoB-100 epitopes and the interaction of LDL with cells. J Lipid Res. 1988 Jun;29(6):729-43.
• Background La Belle M, Blanche PJ, Krauss RM. Charge properties of low density lipoprotein subclasses. J Lipid Res. 1997 Apr;38(4):690-700.
• Background Lee SJ, Campos H, Moye LA, Sacks FM. LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients. Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):853-8. doi: 10.1161/01.ATV.0000066131.01313.EB. Epub 2003 Mar 13.
• Background Libby P. Inflammation in atherosclerosis. Nature. 2002 Dec 19-26;420(6917):868-74. doi: 10.1038/nature01323.
• Background Sanchez-Quesada JL, Benitez S, Ordonez-Llanos J. Electronegative low-density lipoprotein. Curr Opin Lipidol. 2004 Jun;15(3):329-35. doi: 10.1097/00041433-200406000-00014.
• Background Sevanian A, Bittolo-Bon G, Cazzolato G, Hodis H, Hwang J, Zamburlini A, Maiorino M, Ursini F. LDL- is a lipid hydroperoxide-enriched circulating lipoprotein. J Lipid Res. 1997 Mar;38(3):419-28.
• Background Steinberg D. Lewis A. Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis. Circulation. 1997 Feb 18;95(4):1062-71. doi: 10.1161/01.cir.95.4.1062. No abstract available.
• Background Simons L, Tonkon M, Masana L, Maccubbin D, Shah A, Lee M, Gumbiner B. Effects of ezetimibe added to on-going statin therapy on the lipid profile of hypercholesterolemic patients with diabetes mellitus or metabolic syndrome. Curr Med Res Opin. 2004 Sep;20(9):1437-45. doi: 10.1185/030079904x2321.
• Background van Heek M, Austin TM, Farley C, Cook JA, Tetzloff GG, Davis HR. Ezetimibe, a potent cholesterol absorption inhibitor, normalizes combined dyslipidemia in obese hyperinsulinemic hamsters. Diabetes. 2001 Jun;50(6):1330-5. doi: 10.2337/diabetes.50.6.1330.
• Background Yang CY, Raya JL, Chen HH, Chen CH, Abe Y, Pownall HJ, Taylor AA, Smith CV. Isolation, characterization, and functional assessment of oxidatively modified subfractions of circulating low-density lipoproteins. Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1083-90. doi: 10.1161/01.ATV.0000071350.78872.C4. Epub 2003 Apr 10.
• Background Yang CY, Chen HH, Huang MT, Raya JL, Yang JH, Chen CH, Gaubatz JW, Pownall HJ, Taylor AA, Ballantyne CM, Jenniskens FA, Smith CV. Pro-apoptotic low-density lipoprotein subfractions in type II diabetes. Atherosclerosis. 2007 Aug;193(2):283-91. doi: 10.1016/j.atherosclerosis.2006.08.059. Epub 2006 Oct 9.

Drugs

Indications