The levels of inflammatory markers in the treatment of stroke study (limits): Inflammatory biomarkers as risk predictors after lacunar stroke

International Journal of Stroke

Volumn 5, Issue 2, 2010, Pages 117-125

  Elkind, M S V ^a,b   Luna, J M ^c   Coffey, C S ^d   McClure, L A ^d   Liu, K M ^a   Spitalnik, S ^a   Paik, M C ^c   Roldan, A ^e   White, C ^e   Hart, R ^e   Benavente, O ^e  

^a Columbia University College of Physicians and Surgeons ^*  (United States)

^b Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H Sergievsky Center   (United States)

^c Mailman School of Public Health ^*  (United States)

^d UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^e Mays Cancer Center at UT Health San Antonio   (United States)

Author keywords

Antiplatelet therapy; Aspirin; Cerebral infarction; Epidemiology; Ischaemic stroke; Prevention; Protocols; Risk factors

Indexed keywords

ACETYLSALICYLIC ACID; BIOLOGICAL MARKER; C REACTIVE PROTEIN; CD40 ANTIGEN; CLOPIDOGREL; INTERLEUKIN 6; MONOCYTE CHEMOTACTIC PROTEIN 1; PLACEBO; SERUM AMYLOID A; TUMOR NECROSIS FACTOR ALPHA RECEPTOR;

ADULT; ARTICLE; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CLINICAL TRIAL; COGNITION; COMBINATION CHEMOTHERAPY; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE MARKER; DOUBLE BLIND PROCEDURE; FOLLOW UP; HUMAN; INFLAMMATION; MAJOR CLINICAL STUDY; MONOTHERAPY; PATIENT CARE; PATIENT SAFETY; PATIENT SELECTION; PREDICTION; PRIORITY JOURNAL; PROGNOSIS; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; RECURRENCE RISK; RECURRENT DISEASE; RISK ASSESSMENT; RISK FACTOR; SECONDARY PREVENTION; TREATMENT OUTCOME;

BLOOD SPECIMEN COLLECTION; C-REACTIVE PROTEIN; CD40 LIGAND; CHEMOKINE CCL2; HUMANS; INFLAMMATION; INTERLEUKIN-6; PREDICTIVE VALUE OF TESTS; RECEPTORS, TUMOR NECROSIS FACTOR, TYPE I; RISK REDUCTION BEHAVIOR; SAFETY; SERUM AMYLOID A PROTEIN; STROKE; TREATMENT OUTCOME;

EID: 77951218980     PISSN: 17474930     EISSN: 17474949     Source Type: Journal    
DOI: 10.1111/j.1747-4949.2010.00420.x     Document Type: Article

References (83)

1. Pearson TA, Mensah GA, Alexander RW. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003, 107:499-511.
2. Di Napoli M, Schwaninger M, Cappelli R. Evaluation of C-reactive protein measurement for assessing risk and prognosis in ischemic stroke: a statement for healthcare professional from the CRP pooling project member. Stroke 2005, 36:1316-29.
3. Chamorro A, Sacco R, Mohr JP. Clinical-computed tomographic correlations of lacunar infarction in the stroke data bank. Stroke 1991, 22:175-81.
4. Rothrock JF, Lyden PD, Brody ML. Analysis of ischemic stroke in an urban southern California population. Arch Intern Med 1993, 153:619-24.
5. Wolfe CDA, Rudd AG, Howard R. Incidence and case fatality rates of stroke subtypes in a multiethnic population: the south London stroke register. J Neurol Neurosurg Psychiatry 2002, 72:211-16.
6. Ross G, Petrovitch H, White L. Characterization of risk factors for vascular dementia: The Honolulu-Asia aging study. Neurology 1999, 53:337-43.
7. Tatemichi TK, Desmond D, Paik M. Clinical determinants of dementia related to stroke. Ann Neurol 1993, 33:568-75.
8. Bamford JM, Sandercock P, Jones L, Warlow C. The natural history of lacunar infarction: the Oxfordshire Community Stroke Project. Stroke 1987, 18:545-51.
9. Mohr JP, Thompson JLP, Lazar RM. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001, 345:1444-51.
10. Petty GW, Brown RDJ, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence. Stroke 2000, 31:1062-8.
11. Salgado AV, Ferro JM, Gouveia-Oliveira A. Long-term prognosis of first-ever lacunar stroke. Stroke 1996, 27:661-6.
12. Samuelsson M, Lindell D, Norrving B. Presumed pathogenetic mechanisms of recurrent stroke after lacunar infarction. Cerebrovasc Dis 1996, 6:128-36.
13. de Jong G, Kessels F, Lodder J. Two types of lacunar infarct. Further arguments from a study on prognosis. Stroke 2002, 33:2072-6.
14. Miyao S, Takano A, Teramoto J, Takahashi A. Leukoaraiosis in relation to prognosis for patients with lacunar infarction. Stroke 1992, 23:1434-8.
15. Arboix A, Marti-Vilalta JL, Garcia JH. Clinical study of 227 patients with lacunar infarcts. Stroke 1990, 21:842-7.
16. Mohr JP, Caplan LR, Melski JW. The Harvard cooperative stroke registry. Neurology 1978, 28:754-62.
17. Lammie AG, Brannan F. Nonhypertensive cerebral small-vessel disease. Stroke 1997, 28:2222-9.
18. Mast H, Thompson AJ, Lee SH, Mohr JP, Sacco R. Hypertension and diabetes mellitus as determinants of multiple lacunar infarcts. Stroke 1995, 26:30-3.
19. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003, 348:1215-22.
20. Wright CB, Paik MC, Brown TR. Total homocysteine is associated with white matter hyperintensity volume: the Northern Manhattan Study. Stroke 2005, 36:1207-11.
21. Young G, Halliday GM, Kril JJ. Neuropathologic correlates of white matter hyperintensities. Neurology 2008, 71:804-11.
22. Lammie GA, Brannan F, Slattery J, Warlow C. Nonhypertensive cerebral small-vessel disease. An autopsy study. Stroke 1997, 11:2222-9.
23. Gan R, Sacco RL, Kargman DE, Roberts JK, Boden-Albala B, Gu Q. Testing the validity of the lacunar hypothesis: the Northern Manhattan Stroke study experience. Neurology 1997, 48:1204-11.
24. Revilla M, Obach V, Cervera A, Davalos A, Castillo J, Chamorro A. A -174G/C polymorphism of the interleukin-6 gene in patients with lacunar infarction. Neurosci Lett 2002, 324:29-32.
25. Rundek T, Elkind MS, Pittman JG, Boden-Albala B, Humphries SE, Sacco RL. Increased carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6 and hepatic lipase genes: the Northern Manhattan Prospective Cohort Study. Stroke 2002, 33:1420-3.
26. Castellanos M, Castillo J, Garcia MM. Inflammation-mediated damage in progressing lacunar infarctions: a potential therapeutic target. Stroke 2002, 33:982-7.
27. Elkind MSV, Sciacca RR, Tondella MLC. Seropositivity to chlamydia pneumoniae is associated with risk of first ischemic stroke. Stroke 2006, 37:790-5.
28. Elkind MSV, Cheng J, Rundek T, Boden-Albala B, Sacco RL. Leukocyte count predicts outcome after ischemic stroke: the Northern Manhattan Stroke Study. J Stroke Cerebrovasc Dis 2004, 13:220-7.
29. Pérgola PE, White CL, Graves JW. Reliability and validity of blood pressure measurement in the secondary prevention of small subcortical strokes study. Blood Press Monit 2007, 1:1-8. SPS3 investigators.
30. http://www.clinicaltrials.gov/ct2/show/NCT00059306?term=SPS3&rank=1, Secondary Prevention of Small Subcortical Strokes Trial (SPS3)., Available at, (accessed 25 May 2009)
31. Ford ES, Giles WH. Serum C-reactive protein and self-reported stroke: findings from the third national health and nutrition examination survey. Thromb Vasc Biol 2000, 20:1052-6.
32. Gussekloo J, Schaap MC, Frolich M, Blauw GJ, Westendorp RG. C-reactive protein is a strong but nonspecific risk factor of fatal stroke in elderly persons. Arterioscler Thromb Vasc Biol 2000, 20:1047-51.
33. Rost NS, Wolf PA, Kase CS. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack. Stroke 2001, 32:2575-9.
34. Curb JD, Abbott RD, Rodriguez BL. C-reactive protein and the future risk of thromboembolic stroke in healthy men. Circulation 2003, 107:2016-20.
35. Elkind MS, Sciacca RR, Boden-Albala B. Leukocyte count is associated with reduced endothelial reactivity. Atherosclerosis 2005, 181:329-38.
36. Elkind MSV, Tai W, Coates K, Paik MC, Sacco RL. Lipoprotein-associated phospholipase A2, C-reactive protein, and outcome after ischemic stroke. Arch Int Med 2006, 166:2073-80.
37. Poole S, Walker D, Gaines Das RE, Gallimore JR, Pepys MB. The first international standard for serum amyloid A protein (SAA). Evaluation in an international collaborative study. J Immunol Methods 1998, 214:1-10.
38. Ridker PM, Hennekens CH, Buring JE. C-Reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000, 342:836-43.
39. Johnson BD, Kip KE, Marroquin OC. Serum amyloid A as a predictor of coronary artery disease and cardiovascular outcome in women: the National Heart Lung and Blood Institute - Sponsored Women's Ischemia Syndrome Evaluation (WISE). Circulation 2004, 109:726-32.
40. Morrow DA, Rifai N, Antman EM. Serum amyloid A predicts early mortality in acute coronary syndromes: a TIMI 11A substudy. J Am Coll Cardiol 1999, 35:358-62.
41. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000, 101:1767-72.
42. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998, 98:731-3.
43. Kinlay S, Schwartz GG, Olsson AG. Effect of atorvastatin on risk of recurrent cardiovascular events after an acute coronary syndrome associated with high soluble CD40 ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study. Circulation 2004, 110:386-91.
44. Hollenbaugh D, Mischel-Petty N, Edwards CP. Expression of functional CD40 by vascular endothelial cells. J Exp Med 1995, 182:33-40.
45. Mach F, Schonbeck U, Bonnefoy J-Y, Pober JS. Libby activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor. Circulation 1997, 96:396-9.
46. Schönbeck U, Mach F, Bonnefoy J-Y, Loppnow H, Flad H-D. Libby ligation of CD40 activates interleukin 1(beta)-converting enzyme (caspase-1) activity in vascular smooth muscle and endothelial cells and promotes elaboration of active interleukin 1(beta). J Biol Chem 1997, 272:569-74.
47. Mach F, Schönbeck U, Sukhova GK, Atkinson E. Libby reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 1998, 394:200-3.
48. Schönbeck U, Varo N, Libby P, Buring J, Ridker PM. Soluble CD40L and cardiovascular risk in women. Circulation 2001, 104:2266-68.
49. Heeschen C, Dimmeler S, Hamm CW. Soluble CD40 ligand in acute coronary syndromes. N Engl J Med 2003, 348:1104-11.
50. Varo N, de Lemos JA, libby P. Soluble CD40L: risk prediction after acute coronary syndromes. Circulation 2003, 108:1049-52.
51. Kinlay S, Schwartz GG, Olsson AG. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study investigators. Effect of atorvastatin on risk of recurrent cardiovascular events after an acute coronary syndrome associated with high soluble CD40 ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study. Circulation 2004, 110:386-91. Epub 2004 July 19
52. Garlichs CD, Kozina S, Fateh-Moghadam S. Upregulation of CD40-CD40 Ligand (CD154) in patients with acute cerebral ischemia. Stroke 2003, 34:1412-8.
53. Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhoj P, Pedersen BK. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol Ser A Biol Sci Med Sci 1999, 54:M357-64.
54. Elkind MS, Cheng J, Boden-Albala B. Tumor necrosis factor receptor levels are associated with carotid atherosclerosis. Stroke 2002, 33:31-8.
55. Blann AD, McCollum CN. Increased levels of soluble tumor necrosis factor receptors in atherosclerosis: no clear relationship with levels of tumor necrosis factor. Inflammation 1998, 22:483-91.
56. Valgimigli M, Ceconi C, Malagutti P. Tumor necrosis factor-alpha receptor 1 is a major predictor of mortality and new-onset heart failure in patients with acute myocardial infarction: the Cytokine-Activation and Long-Term Prognosis in Myocardial Infarction (C-ALPHA) study. Circulation 2005, 111:863-70.
57. Iosif RE, Ahlenius H, Ekdahl CT. Suppression of stroke-induced progenitor proliferation in adult subventricular zone by tumor necrosis factor receptor 1. J Cereb Blood Flow Metab 2008, 28:1574-87.
58. Störk S, Baumann K, von Schacky C, Angerer P. The effect of 17 beta-estradiol on MCP-1 serum levels in postmenopausal women. Cardiovasc Res 2002, 53:642-9.
59. Ikeda U, Matsui K, Murakami Y, Shimada K. Monocyte chemoattractant protein-1 and coronary artery disease. Clin Cardiol 2002, 25:143-7.
60. Di Napoli M, Papa F, Bocola V. Prognostic influence of increased C-reactive protein and fibrinogen levels in ischemic stroke. Stroke 2001, 32:133-8.
61. Dhamoon MS, Tai W, Boden-Albala B. Risk of myocardial infarction or vascular death after first ischemic stroke: the Northern Manhattan Study. Stroke 2007, 381:752-8.
62. Hlatky MA, Greenland P, Arnett D. Criteria for evaluation of novel markers of cardiovascular risk. Circulation 2009, 119:2408-16.
63. Mendall MA, Strachan DP, Butland BK. C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men. Eur Heart J 2000, 21:1584-90.
64. Jager A, van Hinsbergh VWM, Kostense PJ. Von Willebrand factor, C-reactive protein and 5-year mortality in diabetic and nondiabetic subjects: The Hoorn study. Arterioscler Thromb Vasc Biol 1999, 19:3071-8.
65. Lowe GDO, Yarnell JWG, Rumley A, Bainton D, Sweetnam PM. C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the speedwell study: are inflammation and fibrin turnover linked in pathogenesis? Arterioscler Thromb Vasc Biol 2001, 21:603-10.
66. Pirro M, Bergeron J, Dagenais GR. Age and duration of follow-up as modulators of the risk for ischemic heart disease associated with high plasma C-reactive protein levels in men. Arch Intern Med 2001, 161:2474-80.
67. Ridker PM, Danielson E, Fonseca FA. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008, 359:2195-207. The JUPITER Study Group.
68. Imhof A, Fröhlich M, Loewel H. Distributions of C-reactive protein measured by high-sensitivity assays in apparently healthy men and women from different populations in Europe. Clin Chem 2003, 49:669-72.
69. Yamada S, Gotoh T, Nakashima Y. Distribution of serum C-reactive protein and its association with atherosclerotic risk factors in a Japanese population. Am J Epidemiol 2001, 153:1183-90.
70. Elkind MS, Cheng J, Boden-Albala B, Paik MC, Sacco RL. Elevated white blood cell count and carotid plaque thickness: the Northern Manhattan Stroke Study. Stroke 2001, 32:842-9.
71. Zweifler R, Lyden P, Taft B, Kelly N, Rothrock J. Impact of race and ethnicity on ischemic stroke: the University of California at San Diego stroke data bank. Stroke 1995, 26:245-8.
72. Ross R. Atherosclerosis - an inflammatory disease. N Engl J Med 1999, 340:115-26.
73. Canova CR, Courtin C, Reinhart WH. C-reactive protein (CRP) in cerebro-vascular events. Atherosclerosis 1999, 147:49-53.
74. Ridker PM, Rifai N, Clearfield M. 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. for the air force/Texas coronary atherosclerosis prevention study investigators.
75. The feasibility of a collaborative double-blind study using an anticoagulant: the Warfarin-Aspirin Recurrent Stroke Study (WARSS), the Antiphospholipid Antibodies and Stroke Study (APASS), the Patent foramen ovale In Cryptogenic Stroke Study (PICSS), and the Haemostatic System Activation Study (HAS). Cerebrovasc Dis 1997, 7:100-12. WARSS, APASS, PICSS, and HAS Study Groups.
76. Johnston KC, Li JY, Lyden PD. Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. Stroke 1999, 29:447-53. for the RANTTAS investigators.
77. Langhorne Stott DJ, Robertson L, MacDonald J. Medical complications after stroke: a multicenter study. Stroke 2000, 31:1223-9.
78. Sacco RL, DeRosa JT, Haley EC. Glycine antagonist in neuroprotection for patients with acute stroke. GAIN Americas: a randomized controlled trial. JAMA 2001, 285:1719-28. for the GAIN Americas Investigators.
79. Davenport RJ, Dennis MS, Wellwood I, Warlow C. Complications after acute stroke. Stroke 1996, 27:415-20.
80. Prentice RL, Szatrowski TP, Fujikura T, Kato H, Mason MW, Hamilton HH. Leukocyte counts and coronary heart disease in a Japanese cohort. Am J Epidemiol 1982, 116:496-509.
81. Friedman GD, Klatsky AL, Siegelaub AB. The leukocyte count as a predictor of myocardial infarction. N Eng J Med 1974, 290:1275-8.
82. Grau AJ, Buggle F, Schnitzler P, Spiel M, Lichy C, Hacke W. Fever and infection early after ischemic stroke. J Neurol Sci 1999, 171:115-20.
83. Zalokar JB, Richard JL, Claude JR. Leukocyte count, smoking, and myocardial infarction. N Engl J Med 1981, 304:465-8.