본문 바로가기
KERD
논문KCI 등재

Biomarkers for Stroke

2

조회

0

다운로드

3

인용

0

참고문헌

키워드

주제분류신경과학

초록

Background Major stroke clinical trials have failed during the past decades. The failures suggest the presence of heterogeneity among stroke patients. Biomarkers refer to indicators found in the blood, other body fluids or tissues that predicts physiologic or disease states, increased disease risk, or pharmacologic responses to a therapeutic intervention. Stroke biomarkers could be used as a guiding tool for more effective personalized therapy. Main Contents Three aspects of stroke biomarkers are explored in detail. First, the possible role of biomarkers in patients with stroke is discussed. Second, the limitations of conventional biomarkers (especially protein biomarkers) in the area of stroke research are presented with the reasons. Lastly, various types of biomarkers including traditional and novel genetic,microvesicle, and metabolomics-associated biomarkers are introduced with their advantages and disadvantages. We especially focus on the importance of comprehensive approaches using a variety of stroke biomarkers. Conclusion Although biomarkers are not recommended in practice guidelines for use in the diagnosis or treatment of stroke, many efforts have been made to overcome the limitations of biomarkers. The studies reviewed herein suggest that comprehensive analysis of different types of stroke biomarkers will improve the understanding of individual pathophysiologies and further promote the development of screening tools for of high-risk patients, and predicting models of stroke outcome and rational stroke therapy tailored to the characteristics of each case.

Abstract

Background Major stroke clinical trials have failed during the past decades. The failures suggest the presence of heterogeneity among stroke patients. Biomarkers refer to indicators found in the blood, other body fluids or tissues that predicts physiologic or disease states, increased disease risk, or pharmacologic responses to a therapeutic intervention. Stroke biomarkers could be used as a guiding tool for more effective personalized therapy. Main Contents Three aspects of stroke biomarkers are explored in detail. First, the possible role of biomarkers in patients with stroke is discussed. Second, the limitations of conventional biomarkers (especially protein biomarkers) in the area of stroke research are presented with the reasons. Lastly, various types of biomarkers including traditional and novel genetic,microvesicle, and metabolomics-associated biomarkers are introduced with their advantages and disadvantages. We especially focus on the importance of comprehensive approaches using a variety of stroke biomarkers. Conclusion Although biomarkers are not recommended in practice guidelines for use in the diagnosis or treatment of stroke, many efforts have been made to overcome the limitations of biomarkers. The studies reviewed herein suggest that comprehensive analysis of different types of stroke biomarkers will improve the understanding of individual pathophysiologies and further promote the development of screening tools for of high-risk patients, and predicting models of stroke outcome and rational stroke therapy tailored to the characteristics of each case.

참고문헌 (119)

  1. Chimowitz MI, "Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis", N Engl J Med, 352, pp.1305~1316 (2005)
  2. Diener HC, "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, 364, pp.331~337 (2004)
  3. Bhatt DL, "Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events", N Engl J Med, 354, pp.1706~1717 (2006)
  4. Hacke W, "Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study", Lancet Neurol, 8, pp.141~150 (2009)
  5. Davis SM, "Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial", Lancet Neurol, 7, pp.299~309 (2008)
  6. Shuaib A, "NXY-059 for the treatment of acute ischemic stroke", N Engl J Med, 357, pp.562~571 (2007)
  7. Albers GW, "Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies", Stroke, 42, pp.2645~2650 (2011)
  8. Schulz KF, "CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials", PLoS Med, 7, pp.1000251~ (2010)
  9. Maasland L, "Patients enrolled in large randomized clinical trials of antiplatelet treatment for prevention after transient ischemic attack or ischemic stroke are not representative of patients in clinical practice: the Netherlands Stroke Survey", Stroke, 40, pp.2662~2668 (2009)
  10. Saver JL, "Novel end point analytic techniques and interpreting shifts across the entire range of outcome scales in acute stroke trials", Stroke, 38, pp.3055~3062 (2007)
  11. Saver JL, "Treatment effects for which shift or binary analyses are advantageous in acute stroke trials", Neurology, 72, pp.1310~1315 (2009)
  12. Casper ML, "The shifting stroke belt. Changes in the geographic pattern of stroke mortality in the United States, 1962 to 1988", Stroke, 26, pp.755~760 (1995)
  13. El-Saed A, "Geographic variations in stroke incidence and mortality among older populations in four US communities", Stroke, 37, pp.1975~1979 (2006)
  14. Howard G, "Racial and geographic differences in awareness, treatment, and control of hypertension: the REasons for Geographic And Racial Differences in Stroke study", Stroke, 37, pp.1171~1178 (2006)
  15. Ridker PM, "Established and emerging plasma biomarkers in the prediction of first atherothrombotic events", Circulation, 109 (2004)
  16. Woodward M, "Associations of inflammatory and hemostatic variables with the risk of recurrent stroke", Stroke, 36, pp.2143~2147 (2005)
  17. Ridker PM, "Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein", N Engl J Med, 359, pp.2195~2207 (2008)
  18. Welsh P, "Associations of proinflammatory cytokines with the risk of recurrent stroke", Stroke, 39, pp.2226~2230 (2008)
  19. Pikula A, "Association of plasma ADMA levels with MRI markers of vascular brain injury: Framingham offspring study", 40, pp.2959~2964 (2009)
  20. Park CS, "Relation between C-reactive protein, homocysteine levels, fibrinogen, and lipoprotein levels and leukocyte and platelet counts, and 10-year risk for cardiovascular disease among healthy adults in the USA", Am J Cardiol, 105, pp.1284~1288 (2010)
  21. Wieberdink RG, "High von Willebrand factor levels increase the risk of stroke: the Rotterdam study", Stroke, 41, pp.2151~2156 (2010)
  22. Pikula A, "Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the Framingham Offspring Study", Circulation, 125, pp.2100~2107 (2012)
  23. Yamada Y, "Identification of CELSR1 as a susceptibility gene for ischemic stroke in Japanese individuals by a genome-wide association study", Atherosclerosis, 207, pp.144~149 (2009)
  24. Penttila K, "Myoglobin, creatine kinase MB isoforms and creatine kinase MB mass in early diagnosis of myocardial infarction in patients with acute chest pain", Clin Biochem, 35, pp.647~653 (2002)
  25. Gibler WB, "Evaluation of chest pain and heart failure in the emergency department: impact of multimarker strategies and b-type natriuretic peptide", Rev Cardiovasc Med, 4, pp.47~55 (2003)
  26. Stein PD, "D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review", Ann Intern Med, 140, pp.589~602 (2004)
  27. Laskowitz DT, "Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study", Stroke, 40, pp.77~85 (2009)
  28. Hanson E, "Plasma levels of von Willebrand factor in the etiologic subtypes of ischemic stroke", J Thromb Haemost, 9, pp.275~281 (2011)
  29. Bang OY, "Inflammatory markers, rather than conventional risk factors, are different between carotid and MCA atherosclerosis", J Neurol Neurosurg Psychiatry, 76, pp.1128~1134 (2005)
  30. Rodriguez-Yanez M, "Early biomarkers of clinical-diffusion mismatch in acute ischemic stroke", Stroke, 42, pp.2813~+2818 (2011)
  31. Kernagis DN, "Evolving role of biomarkers in acute cerebrovascular disease", Ann Neurol, 71, pp.289~303 (2012)
  32. Kalow W, "Hypothesis: comparisons of inter- and intra-individual variations can substitute for twin studies in drug research", Pharmacogenetics, 8, pp.283~289 (1998)
  33. Higashi MK, "Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy", JAMA, 287, pp.1690~1698 (2002)
  34. Sconce EA, "The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen", Blood, 106, pp.2329~2333 (2005)
  35. Heo JH, "Increase in plasma matrix metalloproteinase-9 in acute stroke patients with thrombolysis failure", Stroke, 34, pp.48~50 (2003)
  36. Montaner J, "Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke", Circulation, 107, pp.598~603 (2003)
  37. Foerch C, "Elevated serum S100B levels indicate a higher risk of hemorrhagic transformation after thrombolytic therapy in acute stroke", Stroke, 38, pp.2491~2495 (2007)
  38. Marti-Fabregas J, "Hemostatic markers of recanalization in patients with ischemic stroke treated with rt-PA", Neurology, 65, pp.366~370 (2005)
  39. Vila N, "Proinflammatory cytokines and early neurological worsening in ischemic stroke", Stroke, 31, pp.2325~2329 (2000)
  40. Whiteley W, "Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6", PLoS Med, 6, pp.1000145~ (2009)
  41. Yoon CW, "Premorbid warfarin use and lower D-dimer levels are associated with spontaneous early improvement in atrial fibrillationrelated stroke", J Thromb Haemost (2012)[DOI]
  42. Roldan V, "Plasma von Willebrand factor levels are an independent risk factor for adverse events including mortality and major bleeding in anticoagulated atrial fibrillation patients", J Am Coll Cardiol, 57, pp.2496~2504 (2011)
  43. Motoki H, "Coagulation activity is increased in the left atria of patients with paroxysmal atrial fibrillation during the non-paroxysmal period. Comparison with chronic atrial fibrillation", Circ J, 73, pp.1403~1407 (2009)
  44. Kang DW, "Inflammatory and hemostatic biomarkers associated with early recurrent ischemic lesions in acute ischemic stroke", Stroke, 40, pp.1653~1658 (2009)
  45. Siironen J, "The Met allele of the BDNF Val66Met polymorphism predicts poor outcome among survivors of aneurysmal subarachnoid hemorrhage", Stroke, 38, pp.2858~2860 (2007)
  46. Cheeran B, "A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS", J Physiol, 586, pp.5717~5725 (2008)
  47. Halim SA, "Biomarkers in cardiovascular clinical trials: past, present, future", Clin Chem, 58, pp.45~53 (2012)
  48. Echt DS, "Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial", N Engl J Med, 324, pp.781~788 (1991)
  49. Lynch JR, "Novel diagnostic test for acute stroke", Stroke, 35, pp.57~63 (2004)
  50. Ridker PM, "Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men", N Engl J Med, 336, pp.973~979 (1997)
  51. Van Der Meer IM, "C-reactive protein predicts progression of atherosclerosis measured at various sites in the arterial tree: the Rotterdam study", Stroke, 33, pp.2750~2755 (2002)
  52. Hemingway H, "Evaluating the quality of research into a single prognostic biomarker: a systematic review and meta-analysis of 83 studies of C-reactive protein in stable coronary artery disease", PLoS Med, 7, pp.1000286~ (2010)
  53. Hankey GJ, "Potential new risk factors for ischemic stroke: what is their potential?", Stroke, 37, pp.2181~2188 (2006)
  54. O’Donnell MJ, "Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study", Lancet, 376, pp.112~123 (2010)
  55. Dichgans M, "Genetics of ischaemic stroke", Lancet Neurol, 6, pp.149~161 (2007)
  56. Meschia JF, "Advances in genetics 2010", Stroke, 42, pp.285~287 (2011)
  57. Lanktree MB, "Advances in genomic analysis of stroke: what have we learned and where are we headed?", Stroke, 41, pp.825~832 (2010)
  58. Ikram MA, "Genomewide association studies of stroke", N Engl J Med, 360, pp.1718~1728 (2009)
  59. Cocucci E, "Shedding microvesicles: artefacts no more", Trends Cell Biol, 19, pp.43~51 (2009)
  60. Kim SJ, "Circulating mesenchymal stem cells microparticles in patients with cerebrovascular disease", PLoS One, 7, pp.37036~ (2012)
  61. Leroyer AS, "Microparticles from ischemic muscle promotes postnatal vasculogenesis", Circulation, 119, pp.2808~2817 (2009)
  62. Nozaki T, "Significance of a multiple biomarkers strategy including endothelial dysfunction to improve risk stratification for cardiovascular events in patients at high risk for coronary heart disease", J Am Coll Cardiol, 54, pp.601~608 (2009)
  63. Calvet D, "Prevalence of asymptomatic coronary artery disease in ischemic stroke patients: the PRECORIS study", Circulation, 121, pp.1623~1629 (2010)
  64. Kim SJ, "Are stroke biomarkers seeing brain vessels in patients with ischemic stroke? A C-reactive protein and homocysteine study", Stroke, 42, pp.1464~1468 (2011)
  65. Castellanos M, "Serum cellular fibronectin and matrix metalloproteinase- 9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke: a multicenter confirmatory study", Stroke, 38, pp.1855~1859 (2007)
  66. Reynolds MA, "Early biomarkers of stroke", Clin Chem, 49, pp.1733~1739 (2003)
  67. Jauch EC, "Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study", Stroke, 37, pp.2508~2513 (2006)
  68. Montaner J, "Plasmatic level of neuroinflammatory markers predict the extent of diffusion-weighted image lesions in hyperacute stroke", J Cereb Blood Flow Metab, 23, pp.1403~1407 (2003)
  69. Iwamoto T, "Platelet activation in the cerebral circulation in different subtypes of ischemic stroke and Binswanger’s disease", Stroke, 26, pp.52~56 (1995)
  70. Matsui T, "Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part I: enhanced astrocytic synthesis of s-100beta in the periinfarct area precedes delayed infarct expansion", J Cereb Blood Flow Metab, 22, pp.711~722 (2002)
  71. Foerch C, "S100B as a surrogate marker for successful clot lysis in hyperacute middle cerebral artery occlusion", J Neurol Neurosurg Psychiatry, 74, pp.322~325 (2003)
  72. Conway DS, "Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation", Circulation, 107, pp.3141~3145 (2003)
  73. Rost NS, "Brain natriuretic peptide predicts functional outcome in ischemic stroke", Stroke, 43, pp.441~445 (2012)
  74. Tohgi H, "Activated coagulation", fibrinolysis system and platelet function in acute thrombotic stroke patients with increased C-reactive protein levels, 2000, pp.100, 373~379
  75. Yip HK, "Levels and value of platelet activity in patients with severe internal carotid artery stenosis", Neurology, 66, pp.804~808 (2006)
  76. Barseghian A, "Adiponectin and vulnerable atherosclerotic plaques", J Am Coll Cardiol, 57, pp.761~770 (2011)
  77. Kim SJ, "Biomarkers of asymptomatic carotid stenosis in patients undergoing coronary artery bypass grafting", Stroke, 42, pp.734~739 (2011)
  78. Zacho J, "Genetically elevated C-reactive protein and ischemic vascular disease", N Engl J Med, 359, pp.1897~1908 (2008)
  79. Tosetto A, "Association of plasma fibrinogen, C-reactive protein and G-455>A polymorphism with early atherosclerosis in the VITA Project cohort", Thromb Haemost, 105, pp.329~335 (2011)
  80. Yamada Y, "Genetic factors for ischemic and hemorrhagic stroke in Japanese individuals", Stroke, 39, pp.2211~2218 (2008)
  81. Dong C, "Genomewide linkage and peakwide association analyses of carotid plaque in Caribbean Hispanics", Stroke, 41, pp.2750~2756 (2010)
  82. Wang C, "Lipoprotein lipase Ser447Ter polymorphism associated with the risk of ischemic stroke: a meta-analysis", Thromb Res, 128, pp.107~112 (2011)
  83. Hamrefors V, "A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis", J Intern Med, 271, pp.271~281 (2012)
  84. Kuriyama N, "Evaluation of factors associated with elevated levels of platelet-derived microparticles in the acute phase of cerebral infarction", Clin Appl Thromb Hemost, 16, pp.26~32 (2010)
  85. Jung KH, "Circulating endothelial microparticles as a marker of cerebrovascular disease", Ann Neurol, 66, pp.191~199 (2009)
  86. Arenillas JF, "Progression of symptomatic intracranial large artery atherosclerosis is associated with a proinflammatory state and impaired fibrinolysis", Stroke, 39, pp.1456~1463 (2008)
  87. Takahashi W, "The role of high-sensitivity C-reactive protein in asymptomatic intra- and extracranial large artery diseases", Cerebrovasc Dis, 26, pp.549~555 (2008)
  88. Arenillas JF, "Angiogenesis in symptomatic intracranial atherosclerosis: predominance of the inhibitor endostatin is related to a greater extent and risk of recurrence", Stroke, 36, pp.92~97 (2005)
  89. Bang OY, "Adiponectin levels in patients with intracranial atherosclerosis", Neurology, 68, pp.1931~1937 (2007)
  90. Lopez-Cancio E, "Biological Signatures of Asymptomatic Extra- and Intracranial Atherosclerosis: The Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) Study", Stroke, 43, pp.2712~2719 (2012)
  91. Kim BS, "Elevated serum lipoprotein(a) as a potential predictor for combined intracranial and extracranial artery stenosis in patients with ischemic stroke", Atherosclerosis, 212, pp.682~688 (2010)
  92. Arenillas JF, "High lipoprotein (a), diabetes, and the extent of symptomatic intracranial atherosclerosis", Neurology, 63, pp.27~32 (2004)
  93. Bang OY, "Intracranial atherosclerotic stroke: specific focus on the metabolic syndrome and inflammation", Curr Atheroscler Rep, 8, pp.330~336 (2006)
  94. Huang YC, "Hypoalbuminemia and not hyperhomocysteinemia as a risk factor for dementia in hemodialysis patients", J Ren Nutr, 18, pp.347~354 (2008)
  95. Yoo JH, "Relation of plasma homocyst(e) ine to cerebral infarction and cerebral atherosclerosis", Stroke, 29, pp.2478~2483 (1998)
  96. Jeon SB, "Biomarkers and location of atherosclerosis: matrix metalloproteinase- 2 may be related to intracranial atherosclerosis", Atherosclerosis, 223, pp.442~447 (2012)
  97. Yamada Y, "Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome", Int J Mol Med, 21, pp.801~808 (2008)
  98. Arenillas JF, "C-reactive protein gene C1444T polymorphism and risk of recurrent ischemic events in patients with symptomatic intracranial atherostenoses", Cerebrovasc Dis, 28, pp.95~102 (2009)
  99. Liu ZZ, "Polymorphism in the human C-reactive protein (CRP) gene, serum concentrations of CRP, and the difference between intracranial and extracranial atherosclerosis", Clin Chim Acta, 389, pp.40~44 (2008)
  100. Montaner J, "Etiologic diagnosis of ischemic stroke subtypes with plasma biomarkers", Stroke, 39, pp.2280~2287 (2008)
  101. Kataoka S, "Activation of thrombosis and fibrinolysis following brain infarction", J Neurol Sci, 181, pp.82~88 (2000)
  102. Ferro D, "Soluble CD40 ligand predicts ischemic stroke and myocardial infarction in patients with nonvalvular atrial fibrillation", Arterioscler Thromb Vasc Biol, 27, pp.2763~2768 (2007)
  103. Gretarsdottir S, "Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke", Ann Neurol, 64, pp.402~409 (2008)
  104. Lemmens R, "The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology", Stroke, 41, pp.1850~1857 (2010)
  105. Choudhury A, "Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy", Chest, 131, pp.809~815 (2007)
  106. Fornage M, "Biomarkers of inflammation and MRI-defined small vessel disease of the brain: The Cardiovascular Health Study", Stroke, 39, pp.1952~1959 (2008)
  107. Kubo M, "A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction", Nat Genet, 39, pp.212~217 (2007)
  108. Bevan S, "Genetic variation in members of the leukotriene biosynthesis pathway confer an increased risk of ischemic stroke: a replication study in two independent populations", Stroke, 39, pp.1109~1114 (2008)
  109. Gormley K, "Polymorphisms in genes of the endothelin system and cerebral small-vessel disease", Stroke, 36, pp.1656~1660 (2005)
  110. Lanfranconi S, "COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review", Stroke, 41, pp.513~518 (2010)
  111. Paternoster L, "Genetic determinants of white matter hyperintensities on brain scans: a systematic assessment of 19 candidate gene polymorphisms in 46 studies in 19,000 subjects", Stroke, 40, pp.2020~2026 (2009)
  112. Di Tullio MR, "Aortic atherosclerosis, hypercoagulability, and stroke the APRIS (Aortic Plaque and Risk of Ischemic Stroke) study", J Am Coll Cardiol, 52, pp.855~861 (2008)
  113. 방오영, "Ischemic Stroke and Cancer: Stroke Severely Impacts Cancer Patients, While Cancer Increases the Number of Strokes", Journal of Clinical Neurology, 7(2), pp.53~59 (2011), 대한신경과학회
  114. Seok JM, "Coagulopathy and embolic signal in cancer patients with ischemic stroke", Ann Neurol, 68, pp.213~219 (2010)
  115. Kim SG, "Ischemic stroke in cancer patients with and without conventional mechanisms: a multicenter study in Korea", Stroke, 41, pp.798~801 (2010)
  116. Kim SJ, "Clues to occult cancer in patients with ischemic stroke", PLoS One, 7, pp.44959~ (2012)
  117. Hron G, "Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer", Thromb Haemost, 97, pp.119~123 (2007)
  118. Fernandez-Cadenas I, "Role of the MMP9 gene in hemorrhagic transformations after tissue-type plasminogen activator treatment in stroke patients", Stroke, 43, pp.1398~1400 (2012)
  119. Lackner P, "Cellular microparticles as a marker for cerebral vasospasm in spontaneous subarachnoid hemorrhage", Stroke, 41, pp.2353~2357 (2010)

관련 논문AI추천

이 간행물의 다른 논문 (8건)