Current Cardiovascular Risk Reports

, Volume 1, Issue 1, pp 80–88 | Cite as

Blood biologic markers of stroke: Improved management, reduced cost?



Identifying blood biomarkers may be of particular value in neurologic disorders such as stroke because of the difficulty in directly studying the brain and its blood vessels. Markers of brain injury, inflammation, excitotoxicity, and oxidative damage have been evaluated for their value in stroke diagnosis, treatment, and management, but none has proved to be sensitive or specific enough for routine clinical use. However, new cellular and molecular profiling approaches using the peripheral blood offer the potential for identifying panels of genes and proteins by increasing specificity while maintaining sensitivity. Furthermore, the first biomarker for predicting stroke risk associated with atherosclerosis (lipoprotein-associated phospholipase A2) was recently approved by the United States Food and Drug Administration. The ultimate aim for stroke biomarkers is to develop rapid, easy to use, widely available, and inexpensive diagnostic tests that can be used in the clinic and in clinical trials.


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References and Recommended Reading

  1. 1.
    Hill MD: Diagnostic biomarkers for stroke: a stroke neurologist’s perspective. Clin Chem 2005, 51:2001–2002.PubMedCrossRefGoogle Scholar
  2. 2.
    Goldstein LB, Simel DL: Is this patient having a stroke? JAMA 2005, 293:2391–2402.PubMedCrossRefGoogle Scholar
  3. 3.
    Norris JW, Hachinski VC: Misdiagnosis of stroke. Lancet 1982, 1:328–331.PubMedCrossRefGoogle Scholar
  4. 4.
    Hand PJ, Kwan J, Lindley RI, et al.: Distinguishing between stroke and mimic at the bedside. The Brain Attack Study. Stroke 2006, 37:769–775.PubMedCrossRefGoogle Scholar
  5. 5.
    Kidwell CS, Chalela JA, Saver JL, et al.: Comparison of MRI and CT for detection of acute intracerebral hemorrhage. JAMA 2004, 292:1823–1830.PubMedCrossRefGoogle Scholar
  6. 6.
    Baird AE, Dambrosia J, Janket S, et al.: A three-item scale for the early prediction of stroke recovery. Lancet 2001, 357:2095–2099.PubMedCrossRefGoogle Scholar
  7. 7.
    Mayer SA, Brun NC, Begtrup K, et al.: Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2005, 352:777–785.PubMedCrossRefGoogle Scholar
  8. 8.
    Lees KR, Zivin JA, Ashwood T, et al.: NXY-059 for acute ischemic stroke. N Engl J Med 2006, 354:588–600.PubMedCrossRefGoogle Scholar
  9. 9.
    Hsieh KM, Blumenthal HT: Serum lactic dehydrogenase levels in various disease states. Proc Soc Exp Biol Med 1956, 91:626–630.PubMedGoogle Scholar
  10. 10.
    Biomarkers Definitions Working Group: Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001, 69:89–95.CrossRefGoogle Scholar
  11. 11.
    Griffiths HR, Moller L, Bartosz G, et al.: Biomarkers. Mol Aspects Med 2002, 23:101–208.PubMedCrossRefGoogle Scholar
  12. 12.
    Echt DS, Liebson PR, Mitchell LB, et al.: Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991, 324:781–788.PubMedCrossRefGoogle Scholar
  13. 13.
    Mitka M: Biomarkers for coronary heart disease: predictive value or background noise? JAMA 2004, 292:2824–2845.PubMedCrossRefGoogle Scholar
  14. 14.
    Brotman DJ, Walker E, Lauer MS, O’Brien RG: In search of fewer independent risk factors. Arch Intern Med 2005, 165:138–145.PubMedCrossRefGoogle Scholar
  15. 15.
    Greenland P, O’Malley PG: When is a new prediction marker useful? A consideration of lipoprotein-associated phospholipase A2 and C-reactive protein for stroke risk. Arch Intern Med 2005, 165:2454–2456.PubMedCrossRefGoogle Scholar
  16. 16.
    Margolis KL, Manson JE, Greenland P, et al.: Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women’s Health Initiative Observational Study. Arch Intern Med 2005, 165:500–508.PubMedCrossRefGoogle Scholar
  17. 17.
    Elkind MS, Sciacca RR, Boden-Albala B, et al.: Relative elevation in baseline leukocyte count predicts first cerebral infarction. Neurology 2005, 64:2121–2125.PubMedCrossRefGoogle Scholar
  18. 18.
    Dubo H, Park DC, Pennington RJ, et al.: Serum-creatinekinase in cases of stroke, head injury, and meningitis. Lancet 1967, 2:743–748.PubMedCrossRefGoogle Scholar
  19. 19.
    Kaste M, Somer H, Kontinnen A: Brain-type creatine kinase iso-enzyme. Arch Neurol 1977, 34:142–144.PubMedGoogle Scholar
  20. 20.
    Bell RD, Rosenberg RN, Ting R, et al.: Creatine kinase BB isoenzyme levels by radio-immuno-assay in patients with neurological disease. Ann Neurol 1978, 3:52–59.PubMedCrossRefGoogle Scholar
  21. 21.
    Norris JW, Hachinski VC, Myers MG, et al.: Serum cardiac enzymes in stroke. Stroke 1979, 10:548–553.PubMedGoogle Scholar
  22. 22.
    Persson L, Hardemark HG, Gustafsson J, et al.: S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system. Stroke 1987, 18:911–918.PubMedGoogle Scholar
  23. 23.
    Fassbender K, Schmidt R, Schreiner A, et al.: Leakage of brain-originated proteins in peripheral blood: temporal profile and diagnostic value in early ischemic stroke. J Neurol Sci 1997, 148:101–105.PubMedCrossRefGoogle Scholar
  24. 24.
    Sharp FR, Lu A, Tang Y, Millhorn DE: Multiple molecular penumbras after focal cerebral ischemia. J Cereb Blood Flow Metab 2000, 20:1011–1032.PubMedCrossRefGoogle Scholar
  25. 25.
    Onteniente B, Rasika S, Benchoua A, Guegan C: Molecular pathways in cerebral ischemia: cues to novel therapeutic strategies. Mol Neurobiol 2003, 27:33–72.PubMedCrossRefGoogle Scholar
  26. 26.
    Weinstein PR, Hong S, Sharp FR: Molecular identification of the ischemic penumbra. Stroke 2004, 35(Suppl 1):2666–2670.PubMedCrossRefGoogle Scholar
  27. 27.
    Castillo J, Rodriguez I: Biochemical changes and inflammatory response as markers for brain ischaemia: molecular markers of diagnostic utility and prognosis in human clinical practice. Cerebrovasc Dis 2004, 17(Suppl):17–18.CrossRefGoogle Scholar
  28. 28.
    Cherubini A, Ruggiero C, Polidori MC, Mecocci P: Potential markers of oxidative stress in stroke. Free Radic Biol Med 2005, 39:841–852.PubMedCrossRefGoogle Scholar
  29. 29.
    Vila N, Castillo J, Davalos A, Chamorro A: Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke 2000, 31:2325–2329.PubMedGoogle Scholar
  30. 30.
    Castellanos M, Leira R, Serena J, et al.: Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke 2003, 34:40–46.PubMedCrossRefGoogle Scholar
  31. 31.
    Ransohoff DF: Developing molecular markers for cancer. Science 2003, 299:1679–1680.PubMedCrossRefGoogle Scholar
  32. 32.
    Calvano SE, Xiao W, Richards DR, et al.: A network-based analysis of systemic inflammation in humans. Nature 2005, 437:1032–1037.PubMedCrossRefGoogle Scholar
  33. 33.
    Sebastiani P, Ramoni MF, Nolan V, et al: Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia. Nat Genet 2005, 37:435–440.PubMedCrossRefGoogle Scholar
  34. 34.
    Moore DF, Li H, Jeffries N, et al.: Using peripheral blood mononuclear cells to determine a gene expression profile of acute ischemic stroke: a pilot investigation. Circulation 2005, 111:212–221.PubMedCrossRefGoogle Scholar
  35. 35.
    Tang Y, Xu H, Du X, et al.: Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study. J Cereb Blood Flow Metab 2006, 26:1089–1102.PubMedCrossRefGoogle Scholar
  36. 36.
    Lynch JR, Blessing R, White WD, et al.: Novel diagnostic test for acute stroke. Stroke 2004, 35:57–63.PubMedCrossRefGoogle Scholar
  37. 37.
    Reynolds MA, Kirchick HJ, Dahlen JR, et al.: Early biomarkers of stroke. Clin Chem 2003, 49:1733–1739.PubMedCrossRefGoogle Scholar
  38. 38.
    Allard L, Burkhard PR, Lescuyer P, et al.: PARK7 and nucleoside diphosphate kinase A as plasma markers for the early diagnosis of stroke. Clin Chem 2005, 51:2043–2051.PubMedCrossRefGoogle Scholar
  39. 39.
    Allard L, Lescuyer P, Burgess J, et al.: ApoC-I and ApoC-III as potential plasmatic markers to distinguish between ischemic and hemorrhagic stroke. Proteomics 2004, 4:2242–2251.PubMedCrossRefGoogle Scholar
  40. 40.
    Simak J, Gelderman M, Yu H, et al.: Elevated circulating endothelial microparticles in acute stroke patients: a correlation with brain lesion volume and clinical outcome. Blood 2004, 104:954.Google Scholar
  41. 41.
    Nadar SK, Lip GY, Lee KW, Blann AD: Circulating endothelial cells in acute ischaemic stroke. Thromb Haemost 2005, 94:707–712.PubMedGoogle Scholar
  42. 42.
    Nadareishvili ZG, Li H, Wright V, et al.: Elevated proinflammatory CD4+CD28-lymphocytes and stroke recurrence and death. Neurology 2004, 63:1446–1451.PubMedGoogle Scholar
  43. 43.
    Garlichs CD, Kozina S, Fateh-Moghadam S, et al.: Upregulation of CD40-CD40 ligand (CD154) in patients with acute cerebral ischemia. Stroke 2003, 34:1412–1418.PubMedCrossRefGoogle Scholar
  44. 44.
    Paczkowska E, Larysz B, Rzeuski R, et al.: Human hematopoietic stem/progenitor-enriched CD34(+) cells are mobilized into peripheral blood during stress related to ischemic stroke or acute myocardial infarction. Eur J Haematol 2005, 75:461–467.PubMedCrossRefGoogle Scholar
  45. 45.
    Elkind M, Coates A, Tai W, Sacco RL: Lipoprotein-associated phospholipase A2 and C-reactive protein as predictors of stroke recurrence and death: The Northern Manhattan Stroke Study. Stroke 2006, 37:625–626.CrossRefGoogle Scholar
  46. 46.
    Libby P: Inflammation in atherosclerosis. Nature 2002, 420:868–874.PubMedCrossRefGoogle Scholar
  47. 47.
    Ballantyne CM, Hoogeveen RC, Bang H, et al.: Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Arch Intern Med 2005, 165:2479–2484.PubMedCrossRefGoogle Scholar
  48. 48.
    Di Napoli M, Schwaninger M, Cappelli R, et al.: Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke: a statement for health care professionals from the CRP Pooling Project members. Stroke 2005, 36:1316–1329.PubMedCrossRefGoogle Scholar
  49. 49.
    Smith SC Jr, Anderson JL, Cannon RO 3rd, et al.: CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: report from the clinical practice discussion group. Circulation 2004, 110:e550–e553.PubMedCrossRefGoogle Scholar
  50. 50.
    Ridker PM; JUPITER Study Group: Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: rationale and design of the JUPITER trial. Circulation 2003, 108:2292–2297.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Stroke Neuroscience UnitNINDS/NIHBethesdaUSA

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