Biological basis for statin therapy in stroke prevention

Current Opinion in Neurology

Volumn 13, Issue 1, 2000, Pages 57-62

  Rosenson, Robert S ^a  

^a RUSH UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FLUINDOSTATIN; MEVINOLIN; PRAVASTATIN; SIMVASTATIN; STATIN; WARFARIN; ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR;

ATHEROSCLEROSIS; BRAIN BLOOD FLOW; HYPERCHOLESTEROLEMIA; ISCHEMIC HEART DISEASE; REVIEW; RISK FACTOR; STROKE; THROMBOEMBOLISM; ANIMAL EXPERIMENT; ANIMAL MODEL; AORTA ATHEROSCLEROSIS; ARTERY EMBOLISM; CARDIOVASCULAR RISK; CAROTID ARTERY OBSTRUCTION; CLINICAL TRIAL; FEMALE; HEART LEFT VENTRICLE; HUMAN; MALE; MOUSE; NONHUMAN;

ANIMALS; CEREBROVASCULAR ACCIDENT; HUMANS; LOVASTATIN; PRAVASTATIN; SIMVASTATIN;

EID: 0034007692     PISSN: 13507540     EISSN: None     Source Type: Journal    
DOI: 10.1097/00019052-200002000-00011     Document Type: Review

References (68)

1. Salonen JT, Yla-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, et al. Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 1992; 339:883-887.
2. Prospective Studies Collaboration. Cholesterol, diastolic blood pressure, and stroke: 13,000 strokes in 450,000 people in 45 prospective cohorts. Lancet 1995; 346:1647-1653.
3. Atkins D, Psaty BM, Koepsell TD, Longstreth WT Jr, Larson EB. Cholesterol reduction and risk for stroke in men. A meta-analysis of randomized, controlled trials. Ann Intern Med 1993; 119:136-145.
4. Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. JAMA 1997; 278:313-321.
5. Crouse JR III, Byington RP, Hoen HM, Furberg CD. Reductase inhibitor monotherapy and stroke prevention. Arch Intern Med 1997; 157:1305-1310.
6. Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins. Implications for cardiovascular event reduction. JAMA 1998; 279:1643-1650. •• A review article that describes the effects of statins on atherosclerosis and thrombosis.
7. Rosenson RS. Non-lipid-lowering effects of statins on atherosclerosis. Curr Cardiol Rep 1999; 1:225-232. •• A review article on non-lipid mechanisms of statins that emphasizes the anti-inflammatory properties of these agents.
8. Delanty N, Vaughan CJ. Vascular effects of statins in stroke. Stroke 1997; 28:2315-2320.
9. Rosenson RS. Basic mechanisms of stroke prevention with lipid lowering therapy. Curr Atheroscler Rep 2000; (in press).
10. Martin R, Bogousslavsky J. Mechanisms of late stroke after myocardial infarct: the Lausanne Stroke Registry. J Neurol Neurosurg Psychiatry 1993; 56:760-764.
11. Franco R, Alam M, Ausman J, Pickard SD, Goldstein S. Echocardiography in cerebrovascular accidents and cerebral transient ischemic attacks [abstract]. Circulation 1980; 62 (Suppl. III):22.
12. Loh E, St John Sutton M, Wun C-CC, Rouleau JL, Flaker GC, Gottlieb SS, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 1997; 336:251-257.
13. Kjekshus J, Pedersen TR, Olsson AG, Faergeman O, Pyorala K. The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease. J Card Fail 1997; 3:249-254.
14. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Group (4S). Lancet 1994; 344:1383-1389.
15. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339:1349-1357.
16. 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; 335:1001-1009.
17. The French Study of Aortic Plaques in Stroke Group. Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke. N Engl J Med 1996; 334:1216-1221.
18. Tunnick PA, Perez JL, Kronzon I. Protruding atheromas in the thoracic aorta and systemic embolization. Ann Intern Med 1991; 115:423-427.
19. Karalis DG, Chandrasekaran K, Victor MF, Ross JJ Jr, Mintz GS. Recognition and embolic potential of intraaortic atherosclerotic debris. J Am Coll Cardiol 1991; 17:73-78.
20. Dressler FA, Craig WR, Castello R, Labovitz AJ. Mobile aortic atheroma and systemic emboli: efficacy of anticoagulation and influence of plaque morphology on recurrent stroke. J Am Coll Cardiol 1998; 31:134-138.
21. Amarenco P, Cohen A, Tzourio C, Bertrand B, Hommel M, Besson G, et al. Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. N Engl J Med 1994; 331:1474-1479.
22. Pitsavos CE, Aggeli KI, Barbetseas JD, Skoumas IN, Lambrou SG, Frogoudaki AA, et al. Effects of pravastatin on thoracic aortic atherosclerosis in patients with heterozygous familial hypercholesterolemia. Am J Cardiol 1998; 82:1484-1888.
23. Furberg CD, Adams HP Jr, Applegate WB, Byington RP, Espeland MA, Hartwell T, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation 1994; 90:1679-1687.
24. Crouse JR III, Byington RP, Bond MG, Espeland MA, Craven TE, Sprinkle JW, et al. Pravastatin, lipids, and atherosclerosis in the carotid arteries (PLAC-II). Am J Cardiol 1995; 75:455-459.
25. Salonen R, Nyyssonen K, Porkkala E, Rummukainen J, Belder R, Park J-S, Salonen JT. Kuopio Atherosclerosis Prevention Study (KAPS): a population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation 1995; 92:1758-1764.
26. Salonen JT, Nyyssonen K, Salonen R, Porkkala-Sarataho E, Tuomainen T-P, Diczfalusy U, Bjorkhem I. Lipoprotein oxidation and progression of carotid atherosclerosis. Circulation 1997; 95:840-845.
27. Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 1997; 272:20963-20966.
28. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med 1999; 340:115-126.
29. Diaz MN, Frei B, Vita JA, Keaney JF Jr. Antioxidants and atherosclerotic heart disease. N Engl J Med 1997; 337:408-416.
30. Salonen R, Nyyssonen K, Porkkala-Sarataho E, Salonen JT. The Kuopio Atherosclerosis Prevention Study (KAPS): effect of pravastatin treatment on lipids, oxidation resistance of lipoproteins, and atherosclerotic progression. Am J Cardiol 1995; 76:34C-39C.
31. Byington RP, Evans GW, Espeland MA, Applegate WB, Hunninghake DB, Probstfield J, Furberg CD. For the Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Effects of lovastatin and warfarin on early carotid atherosclerosis. Sex-specific analyses. Circulation 1999; 100:e14-e17.
32. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92:657-871.
33. Farb A, Burke AP, Tang AL, Liang TY, Mannan P, Smialek J, Virmani R. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996; 93:1354-1363.
34. Carr S, Farb A, Pearce WH, Virmani R, Yao ST. Atherosclerotic plaque rupture in symptomatic carotid artery stenosis. J Vasc Surg 1996; 23:755-766.
35. Van Damme H, Vivario M, Boniver J, Limet R. Histologic characterization of carotid plaques. Cardiovasc Pathol 1994; 3:9-17.
36. Davies, MJ. Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995. Circulation 1996; 94:2013-2020.
37. Libby P. Molecular basis of acute coronary syndromes. Circulation 1995; 91:2844-2850.
38. Lee RT, Libby P. The unstable atheroma. Arterioscler Thromb Vasc Biol 1997; 17:1859-1867.
39. Rabbani R, Topol EJ. Strategies to achieve coronary arterial plaque stabilization. Cardiovasc Res 1999; 41:402-417.
40. Arroyo LH, Lee RT. Mechanisms of plaque rupture: mechanical and biologic interactions. Cardiovasc Res 1999; 41:369-375.
41. Nikkari ST, O'Brien KD, Ferguson M, Hatsukami T, Welgus HG, Alpers CE, et al. Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis. Circulation 1995; 92:1393-1398.
42. Dollery CM, McEwan JR, Henney AM. Matrix metalloproteinases and cardiovascular disease. Circ Res 1995; 77:863-868.
43. George SJ. Tissue inhibitors of metalloproteinases and metalloproteinases in atherosclerosis. Curr Opin Lipidol 1998; 9:413-423.
44. Shiomi M, Ito T, Tsukada T, Yata T, Watanabe Y, Tsujita Y, et al. Reduction of serum cholesterol levels alters lesional composition of atherosclerotic plaques. Effect of pravastatin sodium on atherosclerosis in mature WHHL rabbits. Arterioscler Thromb Vasc Biol 1995; 15:1938-1944.
45. Bustos C, Hernandez-Presa MA, Ortego M, Tunon J, Ortega L, Perez F, et al. HMGCoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis. J Am Coll Cardiol 1998; 32:2057-2064. • An animal model of cholesterol lowering with atorvastatin that showed a decrease in lesion size and neointimal MCP-1
46. Williams JK, Sukhova GK, Herrington DM, Libby P. Pravastatin has cholesterol-lowering independent effects on the artery wall of atherosclerotic monkeys. J Am Coll Cardiol 1998; 31:684-691. •• An animal model that evaluated the mode of LDL cholesterol-lowering therapy (diet versus pravastatin) on plaque composition, and reported significant group differences despite the same cholesterol level. This study provides the most support for the non-lipid lowering properties of statin therapy.
47. Crisby M. Community risk factors: pravastatin treatment decreases lipid content, inflammation and cell death in human carotid plaques [Abstract]. Presented at the American Heart Association 24th International Conference on Stroke and Cerebral Circulation, 4-6 February 1999. Nashville, TN.
48. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336:973-979.
49. Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR. C-reactive protein and outcome after ischemic stroke. Stroke 1999; 30:981-985. •• This study showed that elevated CRP levels predict survival in stroke patients.
50. Hak AE, Stehouwer CDA, Bots ML, Polderman KH, Schalkwijk CG, Westendorp ICD, et al. Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. Arterioscler Thromb Vasc Biol 1999; 19:1986-1991.
51. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. For the Cholesterol and Recurrent Events (CARE) Investigators. Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation 1999; 100:230-235. •• A nested case - control study showed that pravastatin reduced long-term (5 year) high-sensitivity CRP levels in post myocardial infarction patients.
52. Baumann H, Gauldie J. The acute phase response. Immunol Today 1994; 15:74-80.
53. Steel DM, Whitehead AS. The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein. Immunol Today 1994; 15:81-88.
54. Rosenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytokine production by pravastatin. Lancet 1999; 353:983-984. • A clinical study that showed a reduction in proinflammatory cytokine production (TNF-α and IL-6) with pravastatin.
55. Strandberg TE, Vanhanen H, Tikkanen MJ. Effect of statins on C-reactive protein in patients with coronary artery disease. Lancet 1999; 353:118-119. • A clinical study that showed a reduction in CRP levels with statins.
56. Rosenson RS, Lowe GDO. Effects of lipids and lipoproteins on thrombosis and rheology. Atherosclerosis 1998; 140:271-280. • This review discusses the interactions of lipoproteins with coagulation factors, fibrinogen and viscosity. The effects of several classes of lipid-lowering therapies on thrombosis are discussed.
57. Lacoste L, Lam JYT, Hung J, Letchacovski G, Solymoss CB, Waters D. Hyperlipidemia and coronary disease: correction of the increased thrombogenic potential with cholesterol reduction. Circulation 1995; 92:3172-3177.
58. Colli S, Eligini S, Lalli M, Camera M, Paoletti R, Tremoli E. Vastatins inhibit tissue factor in cultured human macrophages. Arterioscler Thromb Vasc Biol 1997; 17:265-272.
59. Isaacsohn J, Setaro JF, Nicholas C, Davey JA, Diotalevi LJ, Christianson DS, et al. Effects of lovastatin therapy on plasminogen activator inhibitor-1 antigen levels. Am J Cardiol 1994; 74:735-737.
60. Avellone G, Di Garbo V, Cordova R, Raneli G, De Simone R, Bompiani G. Changes induced by pravastatin treatment on hemostatic and fibrinolytic patterns in patients with type IIB hyperlipoproteinemia. Curr Ther Res Clin Exp 1994; 55:1335-1344.
61. Wada H, Mori Y, Kaneko T, Wakita Y, Minamikawa K, Ohiwa M, et al. Hypercoagulable state in patients with hypercholesterolemia: effects of pravastatin. Clin Ther 1992; 14:829-834.
62. Mitropoulos KA, Armitage JM, Collins R, Meade TW, Reeves BE, Wallendszus KR, et al. Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids. Eur Heart J 1997; 18:235-241.
63. Liao JK, Shin WS, Lee WY, Clark SL. Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase. J Biol Chem 1995; 270:319-324.
64. Kugiyama K, Kerns SA, Morrisett JK, Roberts R, Henry PD. Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature 1990; 344:160-162.
65. John S, Schlaich M, Langenfeld M, Weihprecht H, Schmitz G, Weidinger G, et al. Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients. A randomized, placebo-controlled, double-blind study. Circulation 1998; 98:211-216.
66. Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMGCoA reductase inhibitors. Circulation 1998; 97:1129-1135.
67. Kaesemeyer WH, Caldwell RB, Huang J, Caldwell RW. Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions. J Am Coll Cardiol 1999; 33:234-241. • A differential effect of statins (pravastatin versus simvastatin) on vasorelaxation and eNOS production was shown in an ex-vivo study of pre-constructed aortic rings.
68. Endres M, Laufs U, Huang Z, Nakamura T, Huang P, Moskowitz MA, et al. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci USA 1998; 95:8880-8885. • An experimental animal model of cerebral infarotion showed that simvastatin improved cerebral blood flow that was mediated by an upregulation of eNOS and reduced infarct size.