1.Genazzani, AR, Petraglia, F, Purdy, RH, eds. The Brain: Source and Target for Sex Steroid 1. American Heart Association. Heart Disease and Stroke Statistics–2003 Update. Dallas, Tex: American Heart Association; 2002.
2.Bogousslavsky, J, Van Melle, G, Regli, F. The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke. 1988;19:1083–1092.
3.Ezekowitz, MD, Bridgers, SL, James, KE, et al.Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med. 1992;327:1406–1412.
4.Fisher, CM. Lacunes: small, deep cerebral infarcts. Neurology. 1965;15:774–778.
5.Fisher, CM, Gore, I, Okabe, N, White, PD. Atherosclerosis of the carotid and vertebral arteries. Extracranial and intracranial. J Neuropath Exp Neurol. 1965;24:455–476.
6.Sacco, RL, Kargman, DE, Gu, Q, Zamanillo, MC. Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. Stroke. 1995;26:14–20.
7.Elmore, EM, Mosquera, A, Weinberger, J. The prevalence of asymptomatic intracranial large-vessel occlusive disease: the role of diabetes. J Neuroimaging, 2003;13:224–22.
8.Tunick, PA, Culliford, AT, Lamparello, PJ, Kronzon, I. Atheromatosis of the aortic arch as an occult source of multiple systemic emboli. Ann Intern Med. 1991;114:391–392.
9.Fuster, V. Coronary artery disease: a clinical-pathological correlation. In: Fuster, V, ed. Syndromes of Atherosclerosis: Correlations of Clinical Imaging and Pathology. Armonk, NY: Futura Publishing Co.; 1996:1–15.
10.Zarins, CK, Giddens, DP, Bharadvaj, BK, Sottiurai, VS, Mabon, RF, Glagov, S. Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ Res. 1983;53:502–514.
11.O'Brien, ER, Schwartz, SM. A new view of restenosis. In: Fuster, V, ed. Syndromes of Atherosclerosis: Chelations of Clinked imaging and Pathology. Armonk, NY: Futura Publishing Co.; 1996:485–505.
12.Bond, MG, Barnes, RW, Riley, WA, et al.High-resolution B-mode ultrasound scanning methods in the Atherosclerosis Risk in Communities (ARIC) cohort. J Neuroimaging. 1991;1:168–172.
13.Falk, E. Plaque rupture with severe pre-existing coronary stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusion thrombi. Br Heart J. 1983;50:127–134.
14.Imparato, AM, Riles, TS, Gorstein, F. The carotid bifurcation plaque: pathologic findings associated with cerebral ischemia. Stroke. 1979;10:238–245.
15.Imparato, AM, Riles, TS, Mintzer, R, Baumann, FG. The importance of hemorrhage in the relationship between gross morphologic characteristics and cerebral symptoms in 376 carotid artery plaques. Ann Surg. 1983;1979:195–203.
16.Lusby, RJ, Ferrell, LD, Ehrenfeld, WK, Stoney, RJ, Wylie, EJ. Carotid plaque hemorrhage. Its role in production of cerebral ischemia. Arch Surg. 1982;117:1479–1488.
17.Reilly, LM, Lusby, RJ, Hughes, L, Ferrell, LD, Stoney, RJ, Ehrenfeld, WK. Carotid plaque histology using real-time ultrasonography. Clinical and therapeutic implications. Am J Surg. 1983;146:188–193.
18.Steffen, CM, Gray-Weale, AC, Byrne, KE, Lusby, RJ. Carotid artery atheroma. Ultrasound appearance in symptomatic and asymptomatic vessels. Aust NZ J Surg. 1989;59:529–534.
19.Weinberger, J, Marks, SJ, Gaul, JJ, et al. Atherosclerotic plaque at the carotid artery bifurcation. Correlation of ultrasonographic imaging with morphology. J Ultrasound Med. 1987;6:363–366.
20.Langsfeld, M, Gray-Weale, AC, Lusby, RJ. The role of plaque morphology and diameter reduction in the development of new symptoms in asymptomatic carotid arteries. J Vasc Surg. 1989;9:548–557.
21.Johnson, JM, Kennelly, MM, Decesare, D, Morgan, S, Sparrow, A. Natural history of asymptomatic carotid plaque. Arch Surg. 1985;120:1010–1012.
22.Weinberger, J, Ramos, L, Ambrose, JA, Fuster, V. Morphologic and dynamic changes of atherosclerotic plaque at the carotid artery bifurcation: Sequential imaging by real time imaging by real time B-mode ultrasonography. J Am Coll Cardiol. 1988;12:1515–1521.
23.Moore, WS, Hall, AD. Importance of emboli from carotid bifurcation in pathogenesis of cerebral ischemic attacks. Arch Surg. 1970;101:708–711.
24.Mitusch, R, Doherty, C, Wucherpfenning, H, et al.Vascular events during follow-up in patients with aortic arch atherosclerosis. Stroke. 1997;28:36–39.
25.Weinberger, J, Papamitsakis, N, Newfield, A, Godbold, J, Goldman, M. Plaque morphology correlates with cerebrovascular symptoms in patients with complex aortic arch plaque. Arch Neurol. 2000;57:81–84.
26.Jorge, RE, Robinson, RG, Arndt, S, Starkstein, S. Mortality and poststroke depression: a placebo controlled trial of antidepressants. Am J Psychiatry. 2003;160:1823–1829.
27.The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch intern Med. 1997;157:2413–2444.
28.Gueyffier, F, Boutitie, F, Boisel, JP, et al.Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men. A meta-analysis of individual patient data from randomized, controlled trials. The INDANA Investigators. Ann intern Med. 1997;126:761–767.
29.Insua, JT, Sacks, HS, Lau, TS, et al.Drug treatment of hypertension in the elderly: a meta-analysis. Ann Intern Med. 1994;121:355–362.
30.Perry, HM, Davis, BR, Price, TR, et al.Effect of treating isolated systolic hypertension on the risk of developing various types and subtypes of stroke: the Systolic Hypertension, in the Elderly Program (SHEP). JAMA. 2000;284:465–471.
31.Gueyffier, F, Bulpitt, C, Boissel, JP, et al.Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group. Lancet. 1999;353:793–796.
32.Voko, Z, Bots, ML, Hofman, A, Koudstaal, PJ, Witteman, JC, Breteler, MM. J-shaped relation between blood pressure and stroke in treated hypertensives. Hypertension. 1999;34:1181–1185.
33.Alex, M, Baron, EK, Goldenberg, S, Blumenthal, HT. An autopsy study of cerebrovascular accident in diabetes melilitus. Circulation. 1962;25:663–667.
34.Merimee, TJ. Diabetic retinopathy. A synthesis of perspectives. N Engl J Med. 1990;322:978–983.
35.Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317:703–713.
36.Woo, J, Lam, CW, Kay, R, Wong, AH, Teoh, R, Nicholls, MG. The influence of hyperglycemia and diabetes mellitus on immediate and 3-month morbidity and mortality after acute stroke. Arch Neurol. 1990;47:1174–1177.
37.Yusuf, S, Sleight, P, Pogue, J, Bosch, J, Davtes, R, Dagenais, G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:145–153.
38.Ibsen, H, Lindholm, LH, Pedersen, OL, Dahlof, B, Kjeldsen, S. The effect of losartan versus atenolol on cardiovascular morbidity and mortality in patients with diabetes mellitus in the LIFE-study [Danish]. Ugeskr Laeger. 2003;165:459–462.
39.Dahlof, B, Devereux, RB, Kjeldsen, SE, et al.Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:995–1003.
40.Kjeldsen, SE, Dahlof, B, Devereux, RB, et al.Effects of Iosartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy. JAMA. 2002;288:1491–1498.
41.Kannel, WB, Wolf, PA. Epidemiology of cerebrovascular disease. In Ross-Russell, RW, ed. Vascular Disease of the Central Nervous System. New York, NY: Churchill Livingstone; 1983:1–24.
42.Arenillas, JF, Molina, CA, Chacon, P, et al.High lipoprotein (a), diabetes and the extent of symptomatic intracranial atherosclerosis. Neurology. 2004;63:27–32.
43.Welch, GN, Loscalzo, J. Homocysteine and atherothtombosis. N Engl J Med. 1998;338:1042–1050.
44.Ridker, PM, Rifai, N, Pfeffer, MA, Sacks, F, Braunwald, E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1999;100:230–235.
45.Brown, BG, Zhao, X-Q, Poulin, D, Albers, JJ. Coronary angiographic changes, lipid-lowering therapy and their relationship to clinical cardiac events, In: Fuster, V, ed. Syndromes of Atherosclerosis: Correlations of Clinical Imaging and Pathobgy. Armonk, NY: Futura Publishing Co.; 1996:471–482.
46.Randomised trial of cholesterol lowering in 4444 patients with coronary, heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–1389.
47.Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet. 1994;344:633–638.
48.Shepherd, J, Cobbe, SM, Ford, I, et al.Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301–1307.
49.Schwartz, GG, Olsson, AG, Ezekowitz, MD, et al.Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285:1711–1718
50.Jukema, JWBruschke, AVG, van Boven, AJ, et al.Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS). Circulation. 1995;91:2528–2540.
51.Furberg, CD, Adams, HP Jr, Applegate, WB, et al.Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Gradation. 1994;90:1679–1687.
52.Crouse, JR 3rd, Byington, RP, Bond, MG, et al.Pravastatin, lipids, and atherosclerosis in the carotid arteries (PLAC-II) Am J Cardiol. 1995;75:455–459.
53.Collins, R, Armitage, J, Parish, S, Sleight, P, Peto, R; Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet. 2004;363:757–766.
54.Corti, R, Fuster, V, Fayad, ZA, et al.Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years' follow-up by high-resolution noninvasive magnetic resonance imaging. Circulation. 2002;106:2884–2887.
55.Kushi, LH, Folsom, AR, Prineas, RJ, Mink, PJ, Wu, Y, Bostick, RM. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med. 1996;334:1156–1162.
56.Stephens, NG, Parsons, A, Schofield, PM, Kelly, F; Cheeseman, K, Mitchinson, MJ. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996;347:781–786.
57.Salonen, JT, Salonen, R. Ultrasound B-mode imaging in observational studies of atherosclerotic progression. Circulation. 1993;87(3 suppl):I156–I165.
58.Tell, GS, Howard, G, McKinney, WM, Toole, JF. Cigarette smoking cessation and extracranial carotid atherosclerosis. JAMA. 1989;261:1178–1180.
59.ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-convert-ing enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Loweting Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981–2997.
60.PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033–1041.
61.Papademetriou, V, Farsang, C, Elmfeldt, D, et al.Stroke prevention with the angiotensin II type 1-receptor blocker candesartan in elderly patients with isolated systolic hypertension: the Study on Cognition and Prognosis in the Elderly (SCOPE). J Am Coll Cardiol. 2004;44:1175–1180.
62.Fernandez-Ortiz, A, Badimon, JJ, Falk, E, et al.Characterization of the relative thrombo-genicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol. 1994;23:1562–1569.
63.Badimon, L, Badimon, JJ. Mechanisms of arterial thrombosis in nonparallel streamlines: platelet thrombi grow on the apex of stenotic severely injured vessel wall. Experimental study in the pig model. J Clin Invest. 1989;84:1134–1144.
64.Ruggeri, ZM. Mechanisms of shear-induced platelet adhesion and aggregation. Thromb Haemost. 1993;70:119–123.
65.Sinzinger, H, Rodrigues, M, Kritz, H. Radioisotopic imaging of atheroma. In: Fuster, V, ed. Syndromes of Atherosclerosis: Correlations of Clinical Imagingand Pathology. Armonk, NY: Futura Publishing Co.; 1996:369–383.
66.Roth, GJ, Majerus, PW. The mechanism of the effect of aspirin on human platelet. I. Acetylation of a particular fraction protein. J Clin Invest. 1975;56:624–632.
67.Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71–86.
68.Johnson, M, Walton, PL, Cotton, RC, Strachan, CJL. Pharmacological evaluation of ticlopidine, a novel inhibitor of platelet function. Thromb Haemost. 1977;38:64–69.
69.Hass, WK, Easton, JD, Adams, HP Jr, et al.A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med. 1988;321:501–507
70.Grotta, JC, Norris, JW, Kamm, B. Prevention of stroke with ticlopidine: who benefits most? TASS Baseline and Angiographic Data Subgroup. Neurology. 1992;42:1111–1115.
71.Gorelick, P, Richardson, De J, Kelly, M, et al.Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized clinical trial. JAMA. 2003;289:2947–2957.
72.Bennett, CL, Weinberg, PD, Rozenberg-Ben-Dror, K, Yarnold, PR, Kwaan, HC, Green, D. Thrombotic thrombocytopenic purpura associated with ticlopidine. A review of 60 cases. Ann Intern Med. 1998;128:541–544.
73.A randomised, blinded, trial of Clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348:1329–1339.
74.Yusuf, S, Zhao, F, Mehta, SR, et al.Effects of Clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502.
75.Dienet, HC, Bogousslavsky, J, Brass, LM, et al.Aspirin and Clopidogrel compared with Clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364:331–337.
76.Fitzgerald, GA. Dipyridamole. N Engl J Med. 1987;316:1247–1257.
77.Acheson, J, Danta, G, Hutchinson, EC. Controlled trial of dipyridamole in cerebral vascular disease. Br Med J. 1969;1:614–615
78.Persantine Aspirin Trial in cerebral ischemia. Part II: Endpoint results. The American-Canadian Co-Operative Study group. Stroke. 1985;16:406–415.
79.European Stroke Prevention Study. ESPS Group. Stroke. 1990;21:1122–1130.
80.Diener, HC, Cunha, L, Forbes, C, et al.European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143:1–13.
81.Mohr, JP, Thompson, JL, Lazar, RM, et al.A comparison of warfarin and aspirin for the ptevention of recurrent ischemic stroke. N Engl J Med. 2001;345:1444–1451.
82.Hankey, GJ. Ongoing and planned trials of antiplatelet therapy in the acute and long-term management of patients with ischaemic brain syndromes: setting a new standard of care. Cerebrovasc Dis. 2004;17:11–16.
83.Weinberger, J, Biscarra, V, Weitzner, I Jr, Sacher, M. Noninvasive carotid artery testing: role in the management of patients with transient ischemic attacks. N Y State J Med. 1981;81:1463–1468.
84.Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. 1991;325;445–453.
85.Barnett, HJM, Taylor, DW, Eliasziw, M, et al.Benefit of carotid endarterectomy in patients with symptomatic moderate to severe stenosis. N Engl J Med. 1998;339:1415–1425.
86.Polak, JF, Bajakian, RL, O'Leary, DH, Anderson, MR, Donaldson, MC, Jolesz, FA. Detection of internal carotid artery stenosis: comparison of MR angiography, color Doppler sonography and arteriography. Radiology. 1992;182:35–40.
87.Wennberg, DE, Lucas, FL, Birkmeyer, JD, et al.Variation in carotid endarterectomy mortality in the Medicare population. Trial hospitals, volume and patient characteristics. JAMA 1998;270:1278–1281
88.Cebul, RD, Snow, RJ, Pine, R, Hertzer, NR, Norris, DG. Indications, outcomes and provider volumes for carotid endarterectomy. JAMA. 1998;279:1282–1287.
89.Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995;273:1421–1428.
90.Halliday, A, Mansfield, A, Marro, J, et al.Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004;363:1491–1502.
91.Norris, JW, Zhu, CZ, Bornstein, NM, Chambers, BR. Vascular risks of asymptomatic carotid stenosis. Stroke. 1991;22:1485–1490.
92.Diethrich, EB, Ndiaye, M, Reid, DB. Stenting in the carotid artery: initial experience in 110 patients. J Endovasc Surg. 1996;3:42–62.
93.Wholey, MH, Wholey, MH, Jarmolowski, CR, Eles, G, Levy, D, Buecthel, J. Endovascular stents fot carotid artery occlusive disease. J Endovasc Surg. 1997;4:326–328.
94.Qureshi, AI, Luft, AR, Janardhan, V, et al.Identification of patients at risk for peripro-cedural neurological deficits associated with carotid angioplasty and stenting. Stroke. 2000;31:376–382.
95.Alazzaz, A, Thornton, J, Aletich, VA, Debrun, GM, Ausman, JI, Charbel, F. intracranial percutaneous transluminal angioplasty fot arteriosclerotic stenosis. Arch Neurol. 2000;57:1625–1630.
96.Malek, AM, Higashida, RT, Phatouros, CC, et al.Stent angioplasty for cervical carotid artery stenosis in high-risk symptomatic NASCET-ineligible patients. Stroke. 2000;31:3029–3033
97.Cremonesi, A, Manetti, R, Setacci, F, Setacci, C, Castriota, F. Protected carotid stenting. Clinical advantages and complications of embolic protection devices in 442 consecutive patients. Stroke. 2003;34:1936–1943.
98.Yadav, J, Wholey, MH, Kuntz, RE, et al.Protected carotid-artery stenting versus endarterectomy in high risk patients. N Engl J Med. 2004;351:493–501.
99.Hilton, TC, Menke, DBlackshear, JL. Variable effect of anticoagulation in the treatment of severe protruding atherosclerotic debris. Am Heart J. 1994;127:1645–1647.
100.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.
101.Fredberg, RS, Tunick, PA, Culliform, AT, et al.Disappearance of a large intraaortic mass in a patient with prior systemic embolization. Am Heart J. 1993:25(5 pt 1):1445–1447.
102.Tunick, PA, Nayar, AC, Goodkin, GM, et al.Effect of treatment on the incidence of stroke and other emboli in 519 patients with severe thoracic aortic plaque. Am J Cardiol. 2002;90:1320–1325.
103.Tunick, PA, Culliford, AT, Lamparello, PJ, Kronzon, I. Atheromatosis of the aortic arch as an occult source of multiple systemic emboli. Ann Intern Med. 1991;114:391–392.
104.Geraci, A, Weinberger, J. Natural history of aortic arch plaque. Neurology. 2000;54:749–751.
105.Chimowitz, MI, Kokkinos, J, Strong, J, et al.The wararin-aspirin symptomatic intracranial disease study. Neurology. 1995;45:1488–1493.
106.Caplan, LR. Advances in stroke research: basic science, treatment, and clinical trial outcomes. Highlights of the 29th International Stroke Conference. Rev Neurol Dis. 2004;1:91–94.
107.Bhatt, DL, Marso, SP, Hirsch, AT, Ringleb, PA, Hacke, W, Topol, EJ. Amplified benefit of clopidogrel versus aspirin in patients with diabetes mellitus. Am J Cardiol. 2002;90:625–628.
108.Gupta, R, Shumacher, HC, Magla, S, et al.Urgent endovascular revascularization for symptomatic intracranial atherosclerotic stenosis. Neurology. 2003;61:1729–1735.
109.Chaturvedi, S, Caplan, LP. Angioplasty for intracranial atherosclerosis: is the treatment worse than the disease? Neurobgy. 2003;61:1647–1658.
110.Weinberger, J, Rothlauf, E, Materese, E, Halperin, J. Noninvasive evaluation of the extracranial carotid arteries in patients with cerebrovascular events and atrial fibrillations. Arch Int Med. 1990;150:458–460.
111.Kanter, MC, Tegeler, CH, Pearce, LA, Weinberger, J, et al.Carotid stenosis in patients with atrial fibrillation. Prevalence, risk factors, and relationship to stroke in the Stroke Prevention in Atrial Fibrillation Study. Arch Int Med. 1994;154:1372–1377.
112.Horowitz, DR, Tuhrim, S, Weinberger, JM, Rudolph, SH. Mechanisms in lacunar infarction. Stroke. 1992;23:325–327.