Pleiotropic effects of statins: Stabilization of the vulnerable atherosclerotic plaque?

Current Pharmaceutical Design

Volumn 13, Issue 10, 2007, Pages 1003-1012

  Akdim, Fatima ^a   van Leuven, Sander I ^a   Kastelein, John J P ^a   Stroes, Erik S G ^a  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

HMG CoA reductase inhibitors; Plaque vulnerability; Pleiotropic; Statins

Indexed keywords

ATORVASTATIN; CHOLESTEROL; EZETIMIBE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LIPID; PLACEBO; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN;

ACUTE CORONARY SYNDROME; ANGIOGRAPHY; ATHEROSCLEROTIC PLAQUE; CARDIOVASCULAR DISEASE; CAUSE OF DEATH; CHOLESTEROL SYNTHESIS; CLINICAL TRIAL; CORONARY ARTERY DISEASE; CORONARY ARTERY OBSTRUCTION; DEATH; DEVELOPING COUNTRY; DRUG MECHANISM; ENDOTHELIUM; HEART INFARCTION; HUMAN; INFLAMMATION; NONHUMAN; PRIORITY JOURNAL; REVIEW; RISK REDUCTION; UNSTABLE ANGINA PECTORIS;

ANTI-INFLAMMATORY AGENTS; ATHEROSCLEROSIS; C-REACTIVE PROTEIN; CARDIOVASCULAR DISEASES; CORONARY ARTERIOSCLEROSIS; DENDRITIC CELLS; ENDOTHELIUM, VASCULAR; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LIPIDS; MACROPHAGES; RUPTURE, SPONTANEOUS; T-LYMPHOCYTES; TREATMENT OUTCOME;

EID: 34247884512     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161207780487548     Document Type: Review

References (110)

1. Ambrose JA, Almeida OD, Sharma SK, Dangas G, Ratner DE. Angiographic evolution of intracoronary thrombus and dissection following percutaneous transluminal coronary angioplasty (the Thrombolysis and Angioplasty in Unstable Angina TAUSA trial). Am J Cardiol 1997; 79: 559-63.
2. Little WC. Angiographic assessment of the culprit coronary artery lesion before acute myocardial infarction. Am J Cardiol 1990; 66: 44G-7G.
3. Giroud D, Li JM, Urban P, Meier B, Rutishauer W. Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography. Am J Cardiol 1992; 69: 729-32.
4. Pasterkamp G, Schoneveld AH, van der Wal AC, Hijnen DJ, van Wolveren WJ, Plomp S, et al. Inflammation of the atherosclerotic cap and shoulder of the plaque is a common and locally observed feature in unruptured plaques of femoral and coronary arteries. Arterioscler Thromb Vasc Biol 1999; 19: 54-8.
5. Gertz SD, Roberts WC. Hemodynamic shear force in rupture of coronary arterial atherosclerotic plaques. Am J Cardiol 1990; 66: 1368-72.
6. Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation 1994; 90: 775-8.
7. Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J. Risk of thrombosis in human atherosclerotic plaques: Role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 1993; 69: 377-81.
8. Loree HM, Tobias BJ, Gibson LJ, Kamm RD, Small DM, Lee RT. Mechanical properties of model atherosclerotic lesion lipid pools. Arterioscler Thromb 1994; 14: 230-4.
9. Grodos D, Tonglet R. Scandinavian simvastatin study (4S). Lancet 1994; 344(8939-8940): 1768.
10. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001-9
11. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998; 339: 1349-57.
12. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronaAy syndromes: The MIRACL study: a randomized controlled trial. JAMA 2001; 285: 1711-8.
13. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350: 1495-504.
14. Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 1998; 97: 1440-5.
15. Ridker PM, Morrow DA, Rose LM, Rifai N, Cannon CP, Braunwald E. Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density lipoprotein cholesterol <70 mg/dl and C-reactive protein <2 mg/l: An analysis of the PROVE-IT TIMI-22 trial. J Am Coll Cardiol 2005; 45: 1644-8.
16. Libby P, Aikawa M. Mechanisms of plaque stabilization with statins. Am J Cardiol 2003; 91: 4B-8B.
17. Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000; 101: 948-54.
18. Targonski PV, Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Lerman A. Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events. Circulation 2003; 107: 2805-9.
19. Gokce N, Keaney JF, Jr Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, et al. Predictive value of noninvasivelydetermined endothelial dysfunction for long-term cardiovascular events inpatients with peripheral vascular disease. J Am Coll Cardiol 2003; 41: 1769-75.
20. Stroes ES, van Faassen EE, van Londen GJ, Rabelink TJ. Oxygen radical stress in vascular disease: The role of endothelial nitric oxide synthase. J Cardiovasc Pharmacol 1998; 32(Suppl 3): S14-21.
21. Wolfrum S, Jensen KS, Liao JK. Endothelium-dependent effects of statins. Arterioscler Thromb Vasc Biol 2003; 23: 729-36.
22. Monnink SH, van Haelst PL, van Boven AJ, Stroes ES, Tio RA, Plokker TW, et al. Endothelial dysfunction in patients with coronary artery disease: A comparison of three frequently reported tests. J Investig Med 2002; 50: 19-24.
23. Doshi SN, Naka KK, Payne N, Jones CJ, Ashton M, Lewis MJ, et al. Flow-mediated dilatation following wrist and upper arm occlusion in humans: The contribution of nitric oxide. Clin Sci (Lond) 2001; 101: 629-35.
24. Mullen MJ, Kharbanda RK, Cross J, Donald AE, Taylor M, Vallance P, et al. Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo: Relevance to endothelial dysfunction in hypercholesterolemia. Circ Res 2001; 88: 145-51.
25. Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, et al. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 1995; 91: 1314-9.
26. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111-5.
27. Schroeder S, Enderle MD, Ossen R, Meisner C, Baumbach A, Pfohl M, et al. Noninvasive determination of endotheliummediated vasodilation as a screening test for coronary artery disease: Pilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging. Am Heart J 1999; 138: 731-9.
28. Dupuis J, Tardif JC, Cernacek P, Theroux P. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial. Circulation 1999; 99: 3227-33.
29. O'Driscoll G, Green D, Taylor RR. Simvastatin, an HMGcoenzyme A reductase inhibitor, improves endothelial function within 1 month. Circulation 1997; 95: 1126-31.
30. Omori H, Nagashima H, Tsurumi Y, Takagi A, Ishizuka N, Hagiwara N, et al. Direct in vivo evidence of a vascular statin: A single dose of cerivastatin rapidly increases vascular endothelial responsiveness in healthy normocholesterolaemic subjects. Br J Clin Pharmacol 2002; 54: 395-9.
31. Landmesser U, Bahlmann F, Mueller M, Spiekermann S, Kirchhoff N, Schulz S, et al. Simvastatin versus ezetimibe: Pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation 2005; 111: 2356-63.
32. Laufs U, Liao JK. Targeting Rho in cardiovascular disease. Circ Res 2000; 87: 526-8.
33. Hattori Y, Nakanishi N, Akimoto K, Yoshida M, Kasai K. HMGCoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells. Arterioscler Thromb Vasc Biol 2003; 23: 176-82.
34. Solem J, Levin M, Karlsson T, Grip L, Albertsson P, Wiklund O. Composition of coronary plaques obtained by directional atherectomy in stable angina: Its relation to serum lipids and statin treatment. J Intern Med 2006; 259: 267-75.
35. Libby P. Inflammation in atherosclerosis. Nature 2002; 420: 868-74.
36. Li H, Cybulsky MI, Gimbrone MA Jr, Libby P. An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscler Thromb 1993; 13: 197-204.
37. Ramos CL, Huo Y, Jung U, Ghosh S, Manka DR, Sarembock IJ, et al. Direct demonstration of P-selectin- and VCAM-1-dependent mononuclear cell rolling in early atherosclerotic lesions of apolipoprotein E-deficient mice. Circ Res 1999; 84: 1237-44.
38. Edfeldt K, Swedenborg J, Hansson GK, Yan ZQ. Expression of toll-like receptors in human atherosclerotic lesions: A possible pathway for plaque activation. Circulation 2002; 105: 1158-61.
39. de KD, Pasterkamp G. Toll-like receptors in cardiovascular diseases. Cardiovasc Res 2003; 60: 58-67.
40. Cook DN, Pisetsky DS, Schwartz DA. Toll-like receptors in the pathogenesis of human disease. Nat Immunol 2004; 5: 975-9.
41. Aliprantis AO, Yang RB, Weiss DS, Godowski P, Zychlinsky A. The apoptotic signaling pathway activated by Toll-like receptor-2. EMBO J 2000; 19: 3325-36.
42. Kucharczak J, Simmons MJ, Fan Y, Gelinas C. To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis. Oncogene 2003; 22: 8961-82.
43. Vink A, de Kleijn DP, Pasterkamp G. Functional role for toll-like receptors in atherosclerosis and arterial remodeling. Curr Opin Lipidol 2004; 15: 515-21.
44. Pasterkamp G, Schoneveld AH, Hijnen DJ, de Kleijn DP, Teepen H, van der Wal AC, et al. Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery. Atherosclerosis 2000; 150: 245-53.
45. Newby AC. Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates. Cardiovasc Res 2006; 69: 614-24.
46. Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest 1996; 98: 2572-9
47. Dimitrova Y, Dunoyer-Geindre S, Reber G, Mach F, Kruithof EK, de MP. Effects of statins on adhesion molecule expression in endothelial cells. J Thromb Haemost 2003; 1: 2290-9.
48. Chung HK, Lee IK, Kang H, Suh JM, Kim H, Park KC, et al. Statin inhibits interferon-gamma-induced expression of intercellular adhesion molecule-1 (ICAM-1) in vascular endothelial and smooth muscle cells. Exp Mol Med 2002; 34: 451-61.
49. Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005; 45: 89-118.
50. Methe H, Kim JO, Kofler S, Nabauer M, Weis M. Statins decrease Toll-like receptor 4 expression and downstream signaling in human CD14+ monocytes. Arterioscler Thromb Vasc Biol 2005; 25: 1439-45.
51. Wojciak-Stothard B, Williams L, Ridley AJ. Monocyte adhesion and spreading on human endothelial cells is dependent on Rhoregulated receptor clustering. J Cell Biol 1999; 145: 1293-307.
52. Kwak BR, Mach F. Statins inhibit leukocyte recruitment: New evidence for their anti-inflammatory properties. Arterioscler Thromb Vasc Biol 2001; 21: 1256-8.
53. Wong B, Lumma WC, Smith AM, Sisko JT, Wright SD, Cai TQ. Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation. J Leukoc Biol 2001; 69: 959-62.
54. Luan Z, Chase AJ, Newby AC. Statins inhibit secretion of metalloproteinases-1, -2, -3, and -9 from vascular smooth muscle cells and macrophages. Arterioscler Thromb Vasc Biol 2003; 23: 769-75.
55. Furman C, Copin C, Kandoussi M, Davidson R, Moreau M, McTaggiart F, et al. Rosuvastatin reduces MMP-7 secretion by human monocyte-derived macrophages: Potential relevance to atherosclerotic plaque stability. Atherosclerosis 2004; 174: 93-8.
56. Sugiyama S, Okada Y, Sukhova GK, Virmani R, Heinecke JW, Libby P. Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. Am J Pathol 2001; 158: 879-91.
57. Shishehbor MH, Brennan ML, Aviles RJ, Fu X, Penn MS, Sprecher DL, et al. Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation 2003; 108: 426-31.
58. Kumar AP, Reynolds WF. Statins downregulate myeloperoxidase gene expression in macrophages. Biochem Biophys Res Commun 2005; 331: 442-51.
59. Nachtigal P, Kopecky M, Solichova D, Zdansky P, Semecky V. The changes in the endothelial expression of cell adhesion molecules and iNOS in the vessel wall after the short-term administration of simvastatin in rabbit model of atherosclerosis. J Pharm Pharmacol 2005; 57: 197-203.
60. Liuzzo G, Goronzy JJ, Yang H, Kopecky SL, Holmes DR, Frye RL, et al. Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes. Circulation 2000; 101: 2883-8.
61. Stemme S, Rymo L, Hansson GK. Polyclonal origin of T lymphocytes in human atherosclerotic plaques. Lab Invest 1991; 65: 654-60.
62. Hansson GK, Holm J, Jonasson L. Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol 1989; 135: 169-75.
63. de Boer OJ, van der Wal AC, Houtkamp MA, Ossewaarde JM, Teeling P, Becker AE. Unstable atherosclerotic plaques contain Tcells that respond to Chlamydia pneumoniae. Cardiovasc Res 2000; 48: 402-8.
64. Stemme S, Faber B, Holm J, Wiklund O, Witztum JL, Hansson GK. T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci USA 1995; 92: 3893-7.
65. Xu Q. Role of heat shock proteins in atherosclerosis. Arterioscler Thromb Vasc Biol 2002; 22: 1547-59.
66. Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature 1996; 383: 787-93.
67. Mosmann TR, Coffman RL. TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7: 145-73.
68. Methe H, Brunner S, Wiegand D, Nabauer M, Koglin J, Edelman ER. Enhanced T-helper-1 lymphocyte activation patterns in acute coronary syndromes. J Am Coll Cardiol 2005; 45: 1939-45.
69. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352: 1685-95.
70. Hakamada-Taguchi R, Uehara Y, Kuribayashi K, Numabe A, Saito K, Negoro H, et al. Inhibition of hydroxymethylglutaryl-coenzyme a reductase reduces Th1 development and promotes Th2 development. Circ Res 2003; 93: 948-56.
71. Aktas O, Waiczies S, Smorodchenko A, Dorr J, Seeger B, Prozorovski T, et al. Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin. J Exp Med 2003; 197: 725-33.
72. Youssef S, Stuve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002; 420: 78-84.
73. Ortego M, Bustos C, Hernandez-Presa MA, Tunon J, Diaz C, Hernandez G, et al. Atorvastatin reduces NF-kappaB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells. Atherosclerosis 1999; 147: 253-61.
74. Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, et al. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 2001; 7: 687-92
75. Salomon B, Bluestone JA. LFA-1 interaction with ICAM-1 and ICAM-2 regulates Th2 cytokine production. J Immunol 1998; 161: 5138-42.
76. Blanco-Colio LM, Munoz-Garcia B, Martin-Ventura JL, Lorz C, Diaz C, Hernandez G, et al. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors decrease Fas ligand expression and cytotoxicity in activated human T lymphocytes. Circulation 2003; 108: 1506-13.
77. Cipollone F, Fazia M, Iezzi A, Zucchelli M, Pini B, De CD, et al. Suppression of the functionally coupled cyclooxygenase- 2/prostaglandin E synthase as a basis of simvastatin-dependent plaque stabilization in humans. Circulation 2003; 107: 1479-85.
78. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392: 245-52.
79. Bobryshev YV, Lord RS. Ultrastructural recognition of cells with dendritic cell morphology in human aortic intima. Contacting interactions of vascular dendritic cells in athero-resistant and athero-prone areas of the normal aorta. Arch Histol Cytol 1995; 58: 307-22.
80. Bobryshev YV. Dendritic cells in atherosclerosis: Current status of the problem and clinical relevance. Eur Heart J 2005; 26: 1700-4.
81. Yilmaz A, Lochno M, Traeg F, Cicha I, Reiss C, Stumpf C, et al. Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques. Atherosclerosis 2004; 176: 101-10.
82. Bobryshev YV, Lord RS. Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immuneinflammatory reactions. Cardiovasc Res 1998; 37: 799-810.
83. Weis M, Schlichting CL, Engleman EG, Cooke JP. Endothelial determinants of dendritic cell adhesion and migration: New implications for vascular diseases. Arterioscler Thromb Vasc Biol 2002; 22: 1817-23.
84. Yilmaz A, Reiss C, Tantawi O, Weng A, Stumpf C, Raaz D, et al. HMG-CoA reductase inhibitors suppress maturation of human dendritic cells: New implications for atherosclerosis. Atherosclerosis 2004; 172: 85-93.
85. Sun D, Fernandes G. Lovastatin inhibits bone marrow-derived dendritic cell maturation and upregulates proinflammatory cytokine production. Cell Immunol 2003; 223: 52-62.
86. Ridker PM. Cardiology Patient Page. C-reactive protein: A simple test to help predict risk of heart attack and stroke. Circulation 2003; 108: e81-5.
87. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102: 2165-8.
88. Pasceri V, Cheng JS, Willerson JT, Yeh ET. Modulation of Creactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 2001; 103: 2531-4.
89. Verma S, Wang CH, Li SH, Dumont AS, Fedak PW, Badiwala MV, et al. A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 2002; 106: 913-9.
90. Devaraj S, Xu DY, Jialal I. C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: Implications for the metabolic syndrome and atherothrombosis. Circulation 2003; 107: 398-404.
91. Ballou SP, Lozanski G. Induction of inflammatory cytokine release from cultured human monocytes by C-reactive protein. Cytokine 1992; 4: 361-8.
92. Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993; 82: 513-20.
93. Danenberg HD, Szalai AJ, Swaminathan RV, Peng L, Chen Z, Seifert P, et al. Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice. Circulation 2003; 108: 512-5.
94. Griselli M, Herbert J, Hutchinson WL, Taylor KM, Sohail M, Krausz T, et al. C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med 1999; 190: 1733-40.
95. Meuwissen M, van der Wal AC, Niessen HW, Koch KT, de Winter RJ, van der Loos CM, et al. Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction. J Clin Pathol 2006; 59: 196-201.
96. Ray KK, Cannon CP, McCabe CH, Cairns R, Tonkin AM, Sacks FM, et al. Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: Results from the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 2005; 46: 1405-10.
97. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001; 344: 1959-65.
98. Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels: The pravastatin inflammation/CRP evaluation (PRINCE): A randomized trial and cohort study. JAMA 2001; 286: 64-70.
99. Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels: The pravastatin inflammation/CRP evaluation (PRINCE): A randomized trial and cohort study. JAMA 2001; 286: 64-70.
100. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: Results of AFCAPS/ TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279: 1615-22.
101. Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, et al. Effect of intensive compared with moderate lipidlowering therapy on progression of coronary atherosclerosis: A randomized controlled trial. JAMA 2004; 291: 1071-80.
102. Arntzenius AC, Kromhout D, Barth JD, Reiber JH, Bruschke AV, Buis B, et al. Diet, lipoproteins, and the progression of coronary atherosclerosis. The Leiden Intervention Trial. N Engl J Med 1985; 312: 805-11.
103. Nikkila EA, Viikinkoski P, Valle M, Frick MH. Prevention of progression of coronary atherosclerosis by treatment of hyperlipidaemia: A seven year prospective angiographic study. Br Med J (Clin Res Ed) 1984; 289: 220-3.
104. Blankenhorn DH, Azen SP, Kramsch DM, Mack WJ, Cashin-Hemphill L, Hodis HN, et al. Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med 1993; 119: 969-76.
105. Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990; 323: 1289-98.
106. Buchwald H, Varco RL, Matts JP, Long JM, Fitch LL, Campbell GS, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med 1990; 323: 946-55.
107. Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, et al. Effect of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis: The ASTEROID Trial. JAMA 2006; 13: 1556-65.
108. Gazi IF, Liberopoulos EN, Athyros VG, Elisaf M, Mikhailidis DP. Statins and solid organ transplantation. Curr Pharm Des 2006; 12(36): 4771-83.
109. Neubauer H, Mugge A. Thienopyridines and statins: Assessing a potential drug-drug interaction. Curr Pharm Des 2006; 12(10): 1271-80.
110. Yamagishi S, Nakamura K, Takenaka K, Matsui T, Inoue H. Pleiotropic effects of nifedipine on atherosclerosis. Curr Pharm Des 2006; 12(12): 1543-7.