Quantitative and qualitative pleiotropic differences between Simvastatin single and Vytorin combination therapy in hypercholesterolemic subjects

Atherosclerosis

Volumn 231, Issue 2, 2013, Pages 411-420

  Sternberg, Zohara ^a   Chichelli, Trevor ^a   Sternberg, Daniel ^a   Hojnacki, David ^a   Drake, Allison ^a   Liu, Song ^b   Hu, Qiang ^b   Munschauer, Frederick ^a  

^a Buffalo General Medical Center   (United States)

^b ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

Dyslipidemia; Ezetimibe; Inflammation; Microarray; Mononuclear cells; Platelet adhesion; Statin; Thrombosis

Indexed keywords

C REACTIVE PROTEIN; EZETIMIBE PLUS SIMVASTATIN; GLUTATHIONE PEROXIDASE 1; INTERLEUKIN 10; SIMVASTATIN; SUPEROXIDE DISMUTASE;

ADULT; APOPTOSIS; ARTICLE; CELL PROLIFERATION; CLINICAL ARTICLE; FEMALE; GENE EXPRESSION; HUMAN; HYPERCHOLESTEROLEMIA; IMMUNOMODULATION; MALE; MICROARRAY ANALYSIS; MONOTHERAPY; PERIPHERAL BLOOD MONONUCLEAR CELL; PLEIOTROPY; PRIORITY JOURNAL; QUALITATIVE ANALYSIS; QUANTITATIVE ANALYSIS; THROMBOCYTE ADHESION;

ACE; ACS; ACUTE CORONARY SYNDROME; ALANINE AMINOTRANSFERASE; ALT; ANGIOTENSIN RECEPTOR BLOCKERS; ANGIOTENSIN-CONVERTING ENZYME; ARB; ASPARTATE AMINOTRANSFERASE; AST; BLOOD PRESSURE; BP; C-REACTIVE PROTEIN; CAROTID INTIMA-MEDIA THICKNESS; CHD; CIMT; CORONARY HEART DISEASE; CRP; DYSLIPIDEMIA; EZETIMIBE; HDL; HIGH-DENSITY LIPOPROTEIN CHOLESTEROL; IL; INFLAMMATION; INTERLEUKIN; LDL; LOW-DENSITY LIPOPROTEIN CHOLESTEROL; MICROARRAY; MONONUCLEAR CELLS; NFK-B; NUCLEAR FACTOR KAPPAB; PBMCS; PERIPHERAL BLOOD MONONUCLEAR CELLS; PLATELET ADHESION; REACTIVE OXYGEN SPECIES; ROS; STATIN; TC; THROMBOSIS; TNF; TOTAL CHOLESTEROL; TRG; TRIGLYCERIDE; TUMOR NECROSIS FACTOR; VON WILLEBRAND FACTOR; VWF;

ADULT; AZETIDINES; C-REACTIVE PROTEIN; CROSS-OVER STUDIES; CROSS-SECTIONAL STUDIES; DRUG COMBINATIONS; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HUMANS; HYPERCHOLESTEROLEMIA; IMMUNE SYSTEM; LEUKOCYTES, MONONUCLEAR; MALE; MIDDLE AGED; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PLATELET ADHESIVENESS; SIMVASTATIN; THROMBOSIS;

EID: 84888085490     PISSN: 00219150     EISSN: 18791484     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2013.09.031     Document Type: Article

References (60)

1. Law M.R., Wald N.J., Rudnicka A.R. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003, 326:1423.
2. Spagnoli L.G., Bonanno E., Sangiorgi G., Mauriello A. Role of inflammation in atherosclerosis. JNucl Med 2007, 48:1800-1815.
3. Ishigaki Y., Oka Y., Katagiri H. Circulating oxidized LDL: a biomarker and a pathogenic factor. Curr Opin Lipidol 2009, 20:363-369.
4. Park H., Shima T., Yamaguchi K., et al. Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease. JGastroenterol 2011, 46:101-107.
5. Sudhop T., Reber M., Tribble D., et al. Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men. JLipid Res 2009, 50:2117-2123.
6. Zhou Q., Liao J.K. Pleiotropic effects of statins. Basic research and clinical perspectives. Circ J 2010, 74:818-826.
7. Hattori S., Hattori Y. Efficacy and safety of ezetimibe in patients undergoing hemodialysis. Endocr J 2010, 57:1001-1005.
8. Kuhlencordt P.J., Padmapriya P., Rutzel S., et al. Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice. Atherosclerosis 2009, 202:48-57.
9. Yagi S., Akaike M., Aihara K., et al. Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia. JAtheroscler Thromb 2010, 17:173-180.
10. Tamaki N., Ueno H., Morinaga Y., Shiiya T., Nakazato M. Ezetimibe ameliorates atherosclerotic and inflammatory markers, atherogenic lipid profiles, insulin sensitivity, and liver dysfunction in Japanese patients with hypercholesterolemia. JAtheroscler Thromb 2012, 19:532-538.
11. Krysiak R., Okopien B. The effect of ezetimibe and simvastatin on monocyte cytokine release in patients with isolated hypercholesterolemia. JCardiovasc Pharmacol 2011, 57:505-512.
12. Sager P.T., Capece R., Lipka L., et al. Effects of ezetimibe coadministered with simvastatin on C-reactive protein in a large cohort of hypercholesterolemic patients. Atherosclerosis 2005, 179:361-367.
13. Araujo D.B., Bertolami M.C., Ferreira W.P., et al. Pleiotropic effects with equivalent low-density lipoprotein cholesterol reduction: comparative study between simvastatin and simvastatin/ezetimibe coadministration. JCardiovasc Pharmacol 2010, 55:1-5.
14. Pesaro A.E., Serrano C.V., Katz M., et al. Increasing doses of simvastatin versus combined Ezetimibe/Simvastatin: effect on circulating endothelial progenitor cells. JCardiovasc Pharmacol Ther 2013.
15. Powell E.E., Kroon P.A. Low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression in human mononuclear leukocytes is regulated coordinately and parallels gene expression in human liver. JClin Invest 1994, 93:2168-2174.
16. Gentleman R.C., Carey V.J., Bates D.M., et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 2004, 5:R80.
17. Du P., Kibbe W.A., Lin S.M. lumi: a pipeline for processing Illumina microarray. Bioinformatics 2008, 24:1547-1548.
18. Allain C.C., Poon L.S., Chan C.S., Richmond W., Fu P.C. Enzymatic determination of total serum cholesterol. Clin Chem 1974, 20:470-475.
19. Smyth G.K. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 2004, 3. Article3.
20. Jeanmougin M., de Reynies A., Marisa L., Paccard C., Nuel G., Guedj M. Should we abandon the t-test in the analysis of gene expression microarray data: a comparison of variance modeling strategies. PLoS One 2010, 5:e12336.
21. Wibaut-Berlaimont V., Randi A.M., Mandryko V., Lunnon M.W., Haskard D.O., Naoumova R.P. Atorvastatin affects leukocyte gene expression in dyslipidemia patients: invivo regulation of hemostasis, inflammation and apoptosis. JThromb Haemost 2005, 3:677-685.
22. Gelosa P., Cimino M., Pignieri A., Tremoli E., Guerrini U., Sironi L. The role of HMG-CoA reductase inhibition in endothelial dysfunction and inflammation. Vasc Health Risk Manag 2007, 3:567-577.
23. Landmesser U., Bahlmann F., Mueller M., et al. Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation 2005, 111:2356-2363.
24. Dabek J., Kulach A., Gasior Z. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB): a new potential therapeutic target in atherosclerosis?. Pharmacol Rep 2010, 62:778-783.
25. Cude K., Wang Y., Choi H.J., et al. Regulation of the G2-M cell cycle progression by the ERK5-NFkappaB signaling pathway. JCell Biol 2007, 177:253-264.
26. Miranda C., Roccato E., Raho G., Pagliardini S., Pierotti M.A., Greco A. The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF-kappaB pathway. JCell Physiol 2006, 208:154-160.
27. Collins A.R., Lyon C.J., Xia X., et al. Age-accelerated atherosclerosis correlates with failure to upregulate antioxidant genes. Circ Res 2009, 104:e42-e54.
28. Zhao M.M., Xu M.J., Cai Y., et al. Mitochondrial reactive oxygen species promote p65 nuclear translocation mediating high-phosphate-induced vascular calcification invitro and invivo. Kidney Int 2011, 79:1071-1079.
29. Wagner A.H., Kautz O., Fricke K., et al. Upregulation of glutathione peroxidase offsets stretch-induced proatherogenic gene expression in human endothelial cells. Arteriosc Thromb Vasc Biol 2009, 29:1894-1901.
30. Undas A., Machnik A., Potaczek D.P., Wypasek E., Zmudka K., Tracz W. Ezetimibe combined with simvastatin compared with simvastatin alone results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients after acute coronary events. JCardiovasc Pharmacol 2011, 58:167-172.
31. Han X., Kitamoto S., Wang H., Boisvert W.A. Interleukin-10 overexpression in macrophages suppresses atherosclerosis in hyperlipidemic mice. FASEB J 2010, 24:2869-2880.
32. Smallie T., Ricchetti G., Horwood N.J., Feldmann M., Clark A.R., Williams L.M. IL-10 inhibits transcription elongation of the human TNF gene in primary macrophages. JExp Med 2010, 207:2081-2088.
33. Geng Y.J. Biologic effect and molecular regulation of vascular apoptosis in atherosclerosis. Curr Atheroscler Rep 2001, 3:234-242.
34. Kiener P.A., Davis P.M., Murray J.L., Youssef S., Rankin B.M., Kowala M. Stimulation of inflammatory responses invitro and invivo by lipophilic HMG-CoA reductase inhibitors. Int Immunopharmacol 2001, 1:105-118.
35. Mason J.C. Statins and their role in vascular protection. Clin Sci (Lond) 2003, 105:251-266.
36. Mikael L.G., Rozen R. Homocysteine modulates the effect of simvastatin on expression of ApoA-I and NF-kappaB/iNOS. Cardiovasc Res 2008, 80:151-158.
37. Austin R.C., Lentz S.R., Werstuck G.H. Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease. Cell Death Differ 2004, 11(Suppl.1):S56-S64.
38. Szeplaki G., Prohaszka Z., Duba J., et al. Association of high serum concentration of the third component of complement (C3) with pre-existing severe coronary artery disease and new vascular events in women. Atherosclerosis 2004, 177:383-389.
39. N'Diaye M., Le Ferrec E., Kronenberg F., Dieplinger H., Le Vee M., Fardel O. TNFalpha- and NF-kappaB-dependent induction of the chemokine CCL1 in human macrophages exposed to the atherogenic lipoprotein(a). Life Sci 2009, 84:451-457.
40. Knopp R.H., Gitter H., Truitt T., et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J 2003, 24:729-741.
41. van Wissen S., Smilde T.J., Trip M.D., de Boo T., Kastelein J.J., Stalenhoef A.F. Long term statin treatment reduces lipoprotein(a) concentrations in heterozygous familial hypercholesterolaemia. Heart 2003, 89:893-896.
42. Fichtlscherer S., Schmidt-Lucke C., Bojunga S., et al. Differential effects of short-term lipid lowering with ezetimibe and statins on endothelial function in patients with CAD: clinical evidence for 'pleiotropic' functions of statin therapy. Eur Heart J 2006, 27:1182-1190.
43. Pesaro A.E., Serrano C.V., Fernandes J.L., et al. Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin. Int J Cardiol 2012, 158:400-404.
44. Voleti B., Agrawal A. Statins and nitric oxide reduce C-reactive protein production while inflammatory conditions persist. Mol Immunol 2006, 43:891-896.
45. Kastelein J.J., Akdim F., Stroes E.S., et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. NEngl J Med 2008, 358:1431-1443.
46. Fleg J.L., Mete M., Howard B.V., et al. Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. JAm Coll Cardiol 2008, 52:2198-2205.
47. Guyton J.R., Betteridge D.J., Farnier M., et al. Achievement of recommended lipid and lipoprotein levels with combined ezetimibe/statin therapy versus statin alone in patients with and without diabetes. Diab Vasc Dis Res 2011, 8:160-172.
48. Abramson B.L., Benlian P., Hanson M.E., Lin J., Shah A., Tershakovec A.M. Response by sex to statin plus ezetimibe or statin monotherapy: a pooled analysis of 22,231 hyperlipidemic patients. Lipids Health Dis 2011, 10:146.
49. Shigematsu E., Yamakawa T., Taguri M., et al. Efficacy of ezetimibe is associated with gender and baseline lipid levels in patients with type 2 diabetes. JAtheroscler Thromb 2012, 19:846-853.
50. Meaney A., Ceballos G., Asbun J., et al. The VYtorin on Carotid intima-media thickness and overall arterial rigidity (VYCTOR) study. JClin Pharmacol 2009, 49:838-847.
51. Katsiki N., Lioudaki E., Ganotakis E.S., Mikhailidis D.P. Impact of ezetimibe coadministered with statins on cardiovascular events following acute coronary syndrome: a 3-year population-based retrospective cohort study in taiwan. Clin Ther 2011, 33:2091. [author reply 2092].
52. Rossebo A.B., Pedersen T.R., Boman K., et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. NEngl J Med 2008, 359:1343-1356.
53. Baigent C., Landray M.J., Reith C., et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011, 377:2181-2192.
54. Simon T., Boutouyrie P., Gompel A., et al. Rationale, design and methods of the CASHMERE study. Fundam Clin Pharmacol 2004, 18:131-138.
55. Waehre T., Yndestad A., Smith C., et al. Increased expression of interleukin-1 in coronary artery disease with downregulatory effects of HMG-CoA reductase inhibitors. Circulation 2004, 109:1966-1972.
56. Smilde T.J., van Wissen S., Wollersheim H., Trip M.D., Kastelein J.J., Stalenhoef A.F. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial. Lancet 2001, 357:577-581.
57. Roeters van Lennep H.W., Liem A.H., Dunselman P.H., Dallinga-Thie G.M., Zwinderman A.H., Jukema J.W. The efficacy of statin monotherapy uptitration versus switching to ezetimibe/simvastatin: results of the EASEGO study. Curr Med Res Opin 2008, 24:685-694.
58. Robinson J.G., Ballantyne C.M., Hsueh W., et al. Achievement of specified low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol apolipoprotein B, and high-sensitivity C-reactive protein levels with ezetimibe/simvastatin or atorvastatin in metabolic syndrome patients with and without atherosclerotic vascular disease (from the VYMET study). JClin Lipidol 2011, 5:474-482.
59. Cannon C.P., Giugliano R.P., Blazing M.A., et al. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J 2008, 156:826-832.
60. van der Weide K., de Jonge-Peeters S., Huls G., et al. Treatment with high-dose simvastatin inhibits geranylgeranylation in AML blast cells in a subset of AML patients. Exp Hematol 2012, 40:177-186 e176.