Differential metabolic actions of specific statins: Clinical and therapeutic considerations

Antioxidants and Redox Signaling

Volumn 20, Issue 8, 2014, Pages 1286-1299

  Lim, Soo ^a   Sakuma, Ichiro ^b   Quon, Michael J ^c   Koh, Kwang Kon ^d  

^a Seoul National University Bundang Hospital   (South Korea)

^b Hokko Memorial Clinic   (Japan)

^c UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^d Gachon University College of Medicine   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMALS; DIABETES MELLITUS, TYPE 2; ENDOTHELIAL CELLS; ENDOTHELIUM, VASCULAR; GENE EXPRESSION REGULATION; HEMOSTASIS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INFLAMMATION; INSULIN; INSULIN RESISTANCE; OXIDATIVE STRESS;

EID: 84892957896     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2013.5531     Document Type: Review

References (120)

1. Albert MA, Danielson E, Rifai N, and Ridker PM. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 286: 64-70, 2001.
2. Albertini R, Moratti R, and De LG Oxidation of Lowdensity Lipoprotein in Atherosclerosis from Basic Biochemistry to Clinical Studies. Curr Mol Med 2: 579-592, 2002.
3. Antoniades C, Bakogiannis C, Tousoulis D, Reilly S, Zhang MH, Paschalis A, Antonopoulos AS, Demosthenous M, Miliou A, Psarros C, Marinou K, Sfyras N, Economopoulos G, Casadei B, Channon KM, and Stefanadis C. Preoperative atorvastatin treatment in CABG patients rapidly improves vein graft redox state by inhibition of Rac1 and NADPHoxidase activity. Circulation 122: S66-S73, 2010.
4. Aviram M, Rosenblat M, Bisgaier CL, and Newton RS. Atorvastatin and gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation. Atherosclerosis 138: 271-280, 1998.
5. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, and Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376: 1670-1681, 2010.
6. Bayturan O, Kapadia S, Nicholls SJ, Tuzcu EM, Shao M, Uno K, Shreevatsa A, Lavoie AJ, Wolski K, Schoenhagen P, and Nissen SE. Clinical predictors of plaque progression despite very low levels of low-density lipoprotein cholesterol. J Am Coll Cardiol 55: 2736-2742, 2010.
7. Bellia A, Rizza S, Lombardo MF, Donadel G, Fabiano R, Andreadi K, Quon MJ, Sbraccia P, Federici M, Tesauro M, Cardillo C, and Lauro D. Deterioration of glucose homeostasis in type 2 diabetic patients one year after beginning of statins therapy. Atherosclerosis 223: 197-203, 2012.
8. Boekholdt SM, Arsenault BJ, Mora S, Pedersen TR, LaRosa JC, Nestel PJ, Simes RJ, Durrington P, Hitman GA, Welch KM, DeMicco DA, Zwinderman AH, Clearfield MB, Downs JR, Tonkin AM, Colhoun HM, Gotto AM, Jr., Ridker PM, and Kastelein JJ. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA 307: 1302-1309, 2012.
9. Bokoch GM and Prossnitz V. Isoprenoid metabolism is required for stimulation of the respiratory burst oxidase of HL-60 cells. J Clin Invest 89: 402-408, 1992.
10. Breen DM and Giacca A. Effects of insulin on the vasculature. Curr Vasc Pharmacol 9: 321-332, 2011.
11. Buldak L, Dulawa-Buldak A, Labuzek K, and Okopien B. Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose. Int J Clin Pharmacol Ther 50: 805-813, 2012.
12. Calnek DS, Mazzella L, Roser S, Roman J, and Hart CM. Peroxisome proliferator-activated receptor gamma ligands increase release of nitric oxide from endothelial cells. Arterioscler Thromb Vasc Biol 23: 52-57, 2003.
13. Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, and Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ 346: f2610, 2013.
14. Ceriello A, Assaloni R, Da RR, Maier A, Piconi L, Quagliaro L, Esposito K, and Giugliano D. Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation 111: 2518-2524, 2005.
15. Cersosimo E and DeFronzo RA. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev 22: 423-436, 2006.
16. Chamberlain LH. Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes. FEBS Lett 507: 357-361, 2001.
17. Cheng SM, Lai JH, Yang SP, Tsao TP, Ho LJ, Liou JT, and Cheng CC. Modulation of human T cells signaling transduction by lovastatin. Int J Cardiol 140: 24-33, 2010.
18. Cholesterol Treatment Trialists' Ctt Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 380: 581-590, 2012.
19. Coleman CI, Reinhart K, Kluger J, and White CM. The effect of statins on the development of new-onset type 2 diabetes: a meta-analysis of randomized controlled trials. Curr Med Res Opin 24: 1359-1362, 2008.
20. Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, and Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation 103: 926-933, 2001.
21. Culver AL, Ockene IS, Balasubramanian R, Olendzki BC, Sepavich DM, Wactawski-Wende J, Manson JE, Qiao Y, Liu S, Merriam PA, Rahilly-Tierny C, Thomas F, Berger JS, Ockene JK, Curb JD, and Ma Y. Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med 172: 144-152, 2012.
22. Danaei G, Garcia Rodriguez LA, Fernandez CO, and Hernan MA. Statins and risk of diabetes: an analysis of electronic medical records to evaluate possible bias due to differential survival. Diabetes Care 36: 1236-1240, 2013.
23. Dechend R, Fiebler A, Lindschau C, Bischoff H, Muller D, Park JK, Dietz R, Haller H, and Luft FC. Modulating angiotensin II-induced inflammation by HMG Co-A reductase inhibition. Am J Hypertens 14: 55S-61S, 2001.
24. Di AE, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, and Danesh J. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 302: 1993-2000, 2009.
25. Dichtl W, Dulak J, Frick M, Alber HF, Schwarzacher SP, Ares MP, Nilsson J, Pachinger O, and Weidinger F. HMGCoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 23: 58-63, 2003.
26. Diep QN, Amiri F, Touyz RM, Cohn JS, Endemann D, Neves MF, and Schiffrin EL. PPARalpha activator effects on Ang II-induced vascular oxidative stress and inflammation. Hypertension 40: 866-871, 2002.
27. Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, and Cobbe SM. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med 357: 1477-1486, 2007.
28. Freeman DJ Norrie J, Sattar N, Neely RD, Cobbe SM, Ford I, Isles C, Lorimer AR, Macfarlane PW, McKillop JH, Packard CJ, Shepherd J, and Gaw A. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 103: 357-362, 2001.
29. Girona J, La Ville AE, Sola R, Plana N, and Masana L. Simvastatin decreases aldehyde production derived from lipoprotein oxidation. Am J Cardiol 83: 846-851, 1999.
30. Goldfine AB. Statins: is it really time to reassess benefits and risks? N Engl J Med 366: 1752-1755, 2012.
31. Han SH, Quon MJ, and Koh KK. Reciprocal relationships between abnormal metabolic parameters and endothelial dysfunction. Curr Opin Lipidol 18: 58-65, 2007.
32. Hauck L, Harms C, Grothe D, An J, Gertz K, Kronenberg G, Dietz R, Endres M, and von HR. Critical role for FoxO3adependent regulation of p21CIP1/WAF1 in response to statin signaling in cardiac myocytes. Circ Res 100: 50-60, 2007.
33. Holvoet P. Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease. Verh K Acad Geneeskd Belg 70: 193-219, 2008.
34. Hong H, Zeng JS, Kreulen DL, Kaufman DI, and Chen AF. Atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in ischemic stroke. Am J Physiol Heart Circ Physiol 291: H2210-H2215, 2006.
35. Jialal I, Stein D, Balis D, Grundy SM, ms-Huet B, and Devaraj S. Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation 103: 1933-1935, 2001.
36. Jo H, Otani H, Jo F, Shimazu T, Okazaki T, Yoshioka K, Fujita M, Kosaki A, and Iwasaka T. Inhibition of nitric oxide synthase uncoupling by sepiapterin improves left ventricular function in streptozotocin-induced diabetic mice. Clin Exp Pharmacol Physiol 38: 485-493, 2011.
37. Joo SJ. Anti-inflammatory effects of statins beyond cholesterol lowering. Korean Circ J 42: 592-594, 2012.
38. Kai T, Arima S, Taniyama Y, Nakabou M, and Kanamasa K. Comparison of the effect of lipophilic and hydrophilic statins on serum adiponectin levels in patients with mild hypertension and dyslipidemia: Kinki Adiponectin Interventional (KAI) Study. Clin Exp Hypertens 30: 530-540, 2008.
39. Kanda M, Satoh K, and Ichihara K. Effects of atorvastatin and pravastatin on glucose tolerance in diabetic rats mildly induced by streptozotocin. Biol Pharm Bull 26: 1681-1684, 2003.
40. Kietadisorn R, Juni RP, and Moens AL. Tackling endothelial dysfunction by modulating NOS uncoupling: new insights into its pathogenesis and therapeutic possibilities. Am J Physiol Endocrinol Metab 302: E481-E495, 2012.
41. Kim JA, Koh KK, and Quon MJ. The union of vascular and metabolic actions of insulin in sickness and in health. Arterioscler Thromb Vasc Biol 25: 889-891, 2005.
42. Kim JA, Montagnani M, Koh KK, and Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 113: 1888-1904, 2006.
43. Kimura Y, Hyogo H, Yamagishi S, Takeuchi M, Ishitobi T, Nabeshima Y, Arihiro K, and Chayama K. Atorvastatin decreases serum levels of advanced glycation endproducts (AGEs) in nonalcoholic steatohepatitis (NASH) patients with dyslipidemia: clinical usefulness of AGEs as a biomarker for the attenuation of NASH. J Gastroenterol 45: 750-757, 2010.
44. Koh KK. Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability. Cardiovasc Res 47: 648-657, 2000.
45. Koh KK. Effects of HMG-CoA reductase inhibitor on hemostasis. Int J Cardiol 76: 23-32, 2000.
46. Koh KK. How to balance cardiometabolic benefits & risks of statins. J Am Coll Cardiol 61: 1932-1933, 2013.
47. Koh KK, Han SH, Oh PC, Shin EK, and Quon MJ. Combination therapy for treatment or prevention of atherosclerosis: focus on the lipid-RAAS interaction. Atherosclerosis 209: 307-313, 2010.
48. Koh KK, Han SH, and Quon MJ. Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions. J Am Coll Cardiol 46: 1978-1985, 2005.
49. Koh KK, Lim S, Sakuma I, and Quon MJ. Caveats to aggressive lowering of lipids by specific statins. Int J Cardiol 154: 97-101, 2012.
50. Koh KK, Oh PC, and Quon MJ. Does reversal of oxidative stress and inflammation provide vascular protection? Cardiovasc Res 81: 649-659, 2009.
51. Koh KK and Quon MJ. Targeting converging therapeutic pathways to overcome hypertension. Int J Cardiol 132: 297-299, 2009.
52. Koh KK, Quon MJ, Han SH, Ahn JY, Jin DK, Kim HS, Kim DS, and Shin EK. Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. Hypertension 45: 1088-1093, 2005.
53. Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH, Choi IS, and Shin EK. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol 45: 1649-1653, 2005.
54. Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH, Kang MH, Ahn TH, Choi IS, and Shin EK. Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Circulation 110: 3687-3692, 2004.
55. Koh KK, Quon MJ, Han SH, Lee Y, Ahn JY, Kim SJ, Koh Y, and Shin EK. Simvastatin improves flow-mediated dilation but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients. Diabetes Care 31: 776-782, 2008.
56. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Park JB, and Shin EK. Differential metabolic effects of pravastatin and simvastatin in hypercholesterolemic patients. Atherosclerosis 204: 483-490, 2009.
57. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Park JB, and Shin EK. Differential metabolic effects of rosuvastatin and pravastatin in hypercholesterolemic patients. Int J Cardiol 166: 509-515, 2011.
58. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, and Shin EK. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J Am Coll Cardiol 55: 1209-1216, 2010.
59. This reference has been deleted.
60. Koh KK, Quon MJ, Rosenson RS, Chung WJ, and Han SH. Vascular and metabolic effects of treatment of combined hyperlipidemia: focus on statins and fibrates. Int J Cardiol 124: 149-159, 2008.
61. Koh KK, Sakuma I, and Quon MJ. Differential metabolic effects of distinct statins. Atherosclerosis 215: 1-8, 2011.
62. Koh KK, Schenke WH, Waclawiw MA, Csako G, and Cannon RO, III. Statin attenuates increase in C-reactive protein during estrogen replacement therapy in postmenopausal women. Circulation 105: 1531-1533, 2002.
63. Koh KK, Son JW, Ahn JY, Choi YM, Jin DK, Park GS, Choi IS, Sohn MS, and Shin EK. Non-lipid effects of statin on hypercholesterolemic patients established to have coronary artery disease who remained hypercholesterolemic while eating a step-II diet. Coron Artery Dis 12: 305-311, 2001.
64. Koh KK, Son JW,Ahn JY, Jin DK,KimHS,ChoiYM, Ahn TH, Kim DS, and Shin EK. Vascular effects of diet and statin in hypercholesterolemic patients. Int J Cardiol 95: 185-191, 2004.
65. Koh KK, Son JW, Ahn JY, Jin DK, Kim HS, Choi YM, Kim DS, Jeong EM, Park GS, Choi IS, and Shin EK. Comparative effects of diet and statin on NO bioactivity and matrix metalloproteinases in hypercholesterolemic patients with coronary artery disease. Arterioscler Thromb Vasc Biol 22: e19-e23, 2002.
66. Koh KK, Son JW, Ahn JY, Kim DS, Han SH, Ahn TH, Choi IS, Park GS, and Shin EK. Comparative effects of diet and simvastatin on markers of thrombogenicity in patients with coronary artery disease. Am J Cardiol 91: 1231-1234, 2003.
67. Laakso M, Edelman SV, Brechtel G, and Baron AD. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. J Clin Invest 85: 1844-1852, 1990.
68. Laufs U and Liao JK. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 273: 24266-24271, 1998.
69. Lee BS, Choi JY, Kim JY, Han SH, and Park JE. Simvastatin and losartan differentially and synergistically inhibit atherosclerosis in apolipoprotein e(-/-) mice. Korean Circ J 42: 543-550, 2012.
70. Lee WJ, Lee WL, Tang YJ, Liang KW, Chien YH, Tsou SS, and Sheu WH. Early Improvements in insulin sensitivity and inflammatory markers are induced by pravastatin in nondiabetic subjects with hypercholesterolemia. Clin Chim Acta 390: 49-55, 2008.
71. Li L, Chen W, Rezvan A, Jo H, and Harrison DG. Tetrahydrobiopterin deficiency and nitric oxide synthase uncoupling contribute to atherosclerosis induced by disturbed flow. Arterioscler Thromb Vasc Biol 31: 1547-1554, 2011.
72. Lim S, Despres JP, and Koh KK. Prevention of atherosclerosis in overweight/obese patients.-In need of novel multi-targeted approaches. Circ J 75: 1019-1027, 2011.
73. Lim S, Park YM, Sakuma I, and Koh KK. How to control residual cardiovascular risk despite statin treatment: focusing on HDL-cholesterol. Int J Cardiol 166: 8-14, 2013.
74. Lim S, Sakuma I, Quon MJ, and Koh KK. Potentially important considerations in choosing specific statin treatments to reduce overall morbidity and mortality. Int J Cardiol 167: 1696-1702, 2013.
75. Matsubara T, Naruse K, Arakawa T, Nakao M, Yokoi K, Oguri M, Marui N, Amano T, Ichimiya S, Ohashi T, Imai K, Sakai S, Sugiyama S, Ishii H, and Murohara T. Impact of pitavastatin on high-sensitivity C-reactive protein and adiponectin in hypercholesterolemic patients with the metabolic syndrome: the PREMIUM Study. J Cardiol 60: 389-394, 2012.
76. McKenney JM. Pharmacologic characteristics of statins. Clin Cardiol 26: III32-III38, 2003.
77. Mora S, Wenger NK, Demicco DA, Breazna A, Boekholdt SM, Arsenault BJ, Deedwania P, Kastelein JJ, and Waters DD. Determinants of residual risk in secondary prevention patients treated with high-versus low-dose statin therapy: the Treating to New Targets (TNT) study. Circulation 125: 1979-1987, 2012.
78. Moutzouri E, Liberopoulos E, Mikhailidis DP, Kostapanos MS, Kei AA, Milionis H, and Elisaf M. Comparison of the effects of simvastatin vs. rosuvastatin vs. simvastatin/ezetimibe on parameters of insulin resistance. Int J Clin Pract 65: 1141-1148, 2011.
79. Nakagami H, Jensen KS, and Liao JK. A novel pleiotropic effect of statins: prevention of cardiac hypertrophy by cholesterol-independent mechanisms. Ann Med 35: 398-403, 2003.
80. Nickenig G, Baumer AT, Temur Y, Kebben D, Jockenhovel F, and Bohm M. Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men. Circulation 100: 2131-2134, 1999.
81. Oguz A and Uzunlulu M. Short term fluvastatin treatment lowers serum asymmetric dimethylarginine levels in patients with metabolic syndrome. Int Heart J 49: 303-311, 2008.
82. Potenza MA, Marasciulo FL, Chieppa DM, Brigiani GS, Formoso G, Quon MJ, and Montagnani M. Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. Am J Physiol Heart Circ Physiol 289: H813-H822, 2005.
83. Potenza MA, Marasciulo FL, Tarquinio M, Quon MJ, and Montagnani M. Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance. Diabetes 55: 3594-3603, 2006.
84. Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, Braunwald E, Kastelein JJ, de Lemos JA, Blazing MA, Pedersen TR, Tikkanen MJ, Sattar N, and Ray KK. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 305: 2556-2564, 2011.
85. Pueyo ME, Gonzalez W, Nicoletti A, Savoie F, Arnal JF, and Michel JB. Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress. Arterioscler Thromb Vasc Biol 20: 645-651, 2000.
86. Rezaie-Majd A, Maca T, Bucek RA, Valent P, Muller MR, Husslein P, Kashanipour A, Minar E, and Baghestanian M. Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 22: 1194-1199, 2002.
87. Rice JB, Stoll LL, Li WG, Denning GM, Weydert J, Charipar E, Richenbacher WE, Miller FJ, Jr., and Weintraub NL. Low-level endotoxin induces potent inflammatory activation of human blood vessels: inhibition by statins. Arterioscler Thromb Vasc Biol 23: 1576-1582, 2003.
88. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, Pfeffer MA, and Braunwald E. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 352: 20-28, 2005.
89. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Jr., Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, Mac-Fadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, and Glynn RJ. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 359: 2195-2207, 2008.
90. This reference has been deleted.
91. Rikitake Y, Kawashima S, Takeshita S, Yamashita T, Azumi H, Yasuhara M, Nishi H, Inoue N, and Yokoyama M. Antioxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits. Atherosclerosis 154: 87-96, 2001.
92. Rodriguez-Porcel M, Lerman LO, Herrmann J, Sawamura T, Napoli C, and Lerman A. Hypercholesterolemia and hypertension have synergistic deleterious effects on coronary endothelial function. Arterioscler Thromb Vasc Biol 23: 885-891, 2003.
93. Sakamoto T, Kojima S, Ogawa H, Shimomura H, Kimura K, Ogata Y, Sakaino N, and Kitagawa A. Usefulness of hydrophilic vs lipophilic statins after acute myocardial infarction: subanalysis of MUSASHI-AMI. Circ J 71: 1348-1353, 2007.
94. Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di AE, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, and Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375: 2215-2222, 2010.
95. Sasaki J, Ikeda Y, Kuribayashi T, Kajiwara K, Biro S, Yamamoto K, Ageta M, Kobori S, Saikawa T, Otonari T, and Kono S. A 52-week, randomized, open-label, parallelgroup comparison of the tolerability and effects of pitavastatin and atorvastatin on high-density lipoprotein cholesterol levels and glucose metabolism in Japanese patients with elevated levels of low-density lipoprotein cholesterol and glucose intolerance. Clin Ther 30: 1089-1101, 2008.
96. Sathyapalan T, Shepherd J, Coady AM, Kilpatrick ES, and Atkin SL. Atorvastatin reduces malondialdehyde concentrations in patients with polycystic ovary syndrome. J Clin Endocrinol Metab 97: 3951-3955, 2012.
97. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, Tognoni G, Kjekshus J, Pedersen TR, Cook TJ, Gotto AM, Clearfield MB, Downs JR, Nakamura H, Ohashi Y, Mizuno K, Ray KK, and Ford I. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 375: 735-742, 2010.
98. Schonbeck U, Gerdes N, Varo N, Reynolds RS, Horton DB, Bavendiek U, Robbie L, Ganz P, Kinlay S, and Libby P. Oxidized low-density lipoprotein augments and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors limit CD40 and CD40L expression in human vascular cells. Circulation 106: 2888-2893, 2002.
99. Seshasai SR, Kaptoge S, Thompson A, Di AE, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njolstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, and Danesh J. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 364: 829-841, 2011.
100. Sparrow CP, Burton CA, Hernandez M, Mundt S, Hassing H, Patel S, Rosa R, Hermanowski-Vosatka A, Wang PR, Zhang D, Peterson L, Detmers PA, Chao YS, and Wright SD. Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering. Arterioscler Thromb Vasc Biol 21: 115-121, 2001.
101. Stoll LL, McCormick ML, Denning GM, and Weintraub NL. Antioxidant effects of statins. Drugs Today (Barc) 40: 975-990, 2004.
102. Sugawara A, Takeuchi K, Uruno A, Ikeda Y, Arima S, Kudo M, Sato K, Taniyama Y, and Ito S. Transcriptional suppression of type 1 angiotensin II receptor gene expression by peroxisome proliferator-activated receptor-gamma in vascular smooth muscle cells. Endocrinology 142: 3125-3134, 2001.
103. Sydow K, Mondon CE, Schrader J, Konishi H, and Cooke JP. Dimethylarginine dimethylaminohydrolase overexpression enhances insulin sensitivity. Arterioscler Thromb Vasc Biol 28: 692-697, 2008.
104. Teixeira AA, Buffani A, Tavares A, Ribeiro AB, Zanella MT, Kohlmann O, Jr., and Batista MC. Effects of fluvastatin on insulin resistance and cardiac morphology in hypertensive patients. J Hum Hypertens 25: 492-499, 2011.
105. ter AE, Abbink EJ, de GJ, Tack CJ, and Stalenhoef AF. Effect of rosuvastatin on insulin sensitivity in patients with familial combined hyperlipidaemia. Eur J Clin Invest 35: 558-564, 2005.
106. Tham DM, Martin-McNulty B, Wang YX, Wilson DW, Vergona R, Sullivan ME, Dole W, and Rutledge JC. Angiotensin II is associated with activation of NF-kappaBmediated genes and downregulation of PPARs. Physiol Genomics 11: 21-30, 2002.
107. Vincent MA, Montagnani M, and Quon MJ. Molecular and physiologic actions of insulin related to production of nitric oxide in vascular endothelium. Curr Diab Rep 3: 279-288, 2003.
108. Wagner AH, Kohler T, Ruckschloss U, Just I, and Hecker M. Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol 20: 61-69, 2000.
109. Wassmann S, Laufs U, Baumer AT, Muller K, Konkol C, Sauer H, Bohm M, and Nickenig G. Inhibition of geranylgeranylation reduces angiotensin II-mediated free radical production in vascular smooth muscle cells: involvement of angiotensin AT1 receptor expression and Rac1 GTPase. Mol Pharmacol 59: 646-654, 2001.
110. Wassmann S, Laufs U, Muller K, Konkol C, Ahlbory K, Baumer AT, Linz W, Bohm M, and Nickenig G. Cellular antioxidant effects of atorvastatin in vitro and in vivo. Arterioscler Thromb Vasc Biol 22: 300-305, 2002.
111. Wassmann S and Nickenig G. Interrelationship of free oxygen radicals and endothelial dysfunction-modulation by statins. Endothelium 10: 23-33, 2003.
112. Waters DD, Ho JE, Boekholdt SM, DeMicco DA, Kastelein JJ, Messig M, Breazna A, and Pedersen TR. Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes. J Am Coll Cardiol 61: 148-152, 2013.
113. Waters DD, Ho JE, DeMicco DA, Breazna A, Arsenault BJ, Wun CC, Kastelein JJ, Colhoun H, and Barter P. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol 57: 1535-1545, 2011.
114. Wei Y, Whaley-Connell AT, Chen K, Habibi J, Uptergrove GM, Clark SE, Stump CS, Ferrario CM, and Sowers JR. NADPH oxidase contributes to vascular inflammation, insulin resistance, and remodeling in the transgenic (mRen2) rat. Hypertension 50: 384-391, 2007.
115. Yada T, Nakata M, Shiraishi T, and Kakei M. Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca2 + signalling and insulin secretion due to blockade of L-type Ca2 + channels in rat islet beta-cells. Br J Pharmacol 126: 1205-1213, 1999.
116. This reference has been deleted.
117. Yamamoto A, Ichihara K, and Hoshi K. Antioxidative effect of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on peroxidation of phospholipid liposomes. J Pharm Pharmacol 53: 227-232, 2001.
118. Yang P, Cao Y, and Li H. Hyperglycemia induces inducible nitric oxide synthase gene expression and consequent nitrosative stress via c-Jun N-terminal kinase activation. Am J Obstet Gynecol 203: 185.e5-e11, 2010.
119. YoshikawaM,NakamuraK,Nagase S, Sakuragi S,KusanoKF, Matsubara H, and Ohe T. Effects of combined treatment with angiotensin II type 1 receptor blocker and statin on stent restenosis. J Cardiovasc Pharmacol 53: 179-186, 2009.
120. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, and Lisheng L. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364: 937-952, 2004.