Current Cardiology Reports

, 11:12 | Cite as

Inflammatory markers and stroke

  • Mitchell S. V. Elkind


Basic and animal research implicate inflammatory mechanisms in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Inflammatory biomarkers, particularly high-sensitivity C-reactive protein and lipoproteinassociated phospholipase A2, have been identified as potential predictors of stroke risk and prognosis. Infections may also precipitate stroke. Medications, especially hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), reduce inflammatory marker levels independently of lipid effects, and the ability of statins to reduce coronary events and stroke correlates with their effect on inflammatory biomarkers. Vaccination against influenza may also reduce stroke risk. Determining whether reduction of biomarkers reduces risk of recurrent stroke, however, requires further study before inflammatory markers become a routine part of the evaluation of stroke patients.


Ischemic Stroke Stroke Patient Stroke Risk Carotid Plaque Cardiovascular Health Study 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References and Recommended Reading

  1. 1.
    Ross R: Atherosclerosis—an inflammatory disease. N Engl J Med 1999, 340:115–126.PubMedCrossRefGoogle Scholar
  2. 2.
    Libby P, Theroux P: Pathophysiology of coronary artery disease. Circulation 2005, 111:3481–3488.PubMedCrossRefGoogle Scholar
  3. 3.
    Frostegard J, Ulfgren AK, Nyberg P, et al.: Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis 1999, 145:33–43.PubMedCrossRefGoogle Scholar
  4. 4.
    Elkind MS, Cheng J, Boden-Albala B, et al.: Elevated white blood cell count and carotid plaque thickness: the Northern Manhattan Stroke Study. Stroke 2001, 32:842–849.PubMedGoogle Scholar
  5. 5.
    Elkind MS, Sciacca R, Boden-Albala B, et al.: Relative elevation in leukocyte count predicts first cerebral infarction. Neurology 2005, 64:2121–2125.PubMedCrossRefGoogle Scholar
  6. 6.
    Sen S, Hinderliter A, Sen PK, et al.: Association of leukocyte count with progression of aortic atheroma in stroke/transient ischemic attack patients. Stroke 2007, 38:2900–2905.PubMedCrossRefGoogle Scholar
  7. 7.
    Grau AJ, Boddy AW, Dukovic DA, et al.: Leukocyte count as an independent predictor of recurrent ischemic events. Stroke 2004, 35:1147–1152.PubMedCrossRefGoogle Scholar
  8. 8.
    Lange LA, Carlson CS, Hindorff LA, et al.: Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events. JAMA 2006, 296:2703–2711.PubMedCrossRefGoogle Scholar
  9. 9.
    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
  10. 10.
    Ridker PM, Hennekens CH, Buring JE, Rifai N: C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000, 342:836–843.PubMedCrossRefGoogle Scholar
  11. 11.
    Curb JD, Abbott RD, Rodriguez BL, et al.: C-reactive protein and the future risk of thromboembolic stroke in healthy men. Circulation 2003, 107:2016–2020.PubMedCrossRefGoogle Scholar
  12. 12.
    Cao JJ, Thach C, Manolio TA, et al.: C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study. Circulation 2003, 108:166–170.PubMedCrossRefGoogle Scholar
  13. 13.
    Verma S, Szmitko PE, Yeh ET: C-reactive protein. Structure affects function. Circulation 2004, 109:1914–1917.PubMedCrossRefGoogle Scholar
  14. 14.
    Pearson TA, Mensah GA, Alexander RW, et al.: 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.PubMedCrossRefGoogle Scholar
  15. 15.
    Ridker PM, Buring JE, Rifai N, Cook NR: Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA 2007, 297:611–619.PubMedCrossRefGoogle Scholar
  16. 16.
    Woodward M, Lowe GD, Campbell DJ, et al.: Associations of inflammatory and hemostatic variables with the risk of recurrent stroke. Stroke 2005, 36:2143–2147.PubMedCrossRefGoogle Scholar
  17. 17.
    Welsh P, Lowe GD, Chalmers J, et al.: Associations of proinflammatory cytokines with the risk of recurrent stroke. Stroke 2008, 39:2226–2230.PubMedCrossRefGoogle Scholar
  18. 18.
    Arenillas JF, Alvarez-Sabín J, Molina CA, et al.: Progression of symptomatic intracranial large artery atherosclerosis is associated with a proinflammatory state and impaired fibrinolysis. Stroke 2008, 39:1456–1463.PubMedCrossRefGoogle Scholar
  19. 19.
    Montaner J, Fernandez-Cadenas I, Molina CA, et al.: Poststroke C-reactive protein is a powerful prognostic tool among candidates for thrombolysis. Stroke 2006, 37:1205–1210.PubMedCrossRefGoogle Scholar
  20. 20.
    Cho AH, Kim JS, Jeon SB, et al.: Mechanism of multiple infarcts in multiple cerebral circulations on diffusionweighted imaging. J Neurol 2007, 254:924–930.PubMedCrossRefGoogle Scholar
  21. 21.
    Oei HH, van der Meer IM, Hofman A, et al.: Lipoproteinassociated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study. Circulation 2005, 111:570–575.PubMedCrossRefGoogle Scholar
  22. 22.
    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
  23. 23.
    Elkind MS, Tai W, Coates K, et al.: Lipoprotein-associated phospholipase A2, C-reactive protein, and outcome after ischemic stroke. Arch Intern Med 2006, 166:2073–2080.PubMedCrossRefGoogle Scholar
  24. 24.
    Elkind MS, Tai W, Coates K, et al.: Lipoprotein-associated phospholipase A2 activity and risk of recurrent stroke. Cerebrovasc Dis 2008 (in press).Google Scholar
  25. 25.
    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
  26. 26.
    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
  27. 27.
    Schumacher H, Kaiser E, Schnabel PA, et al.: Immunophenotypic characterisation of carotid plaque: increased amount of inflammatory cells as an independent predictor for ischaemic symptoms. Eur J Vasc Endovasc Surg 2001, 21:494–501.PubMedCrossRefGoogle Scholar
  28. 28.
    Ding S, Zhang M, Zhao Y, et al.: The role of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke. Am J Med Sci 2008, 336:27–31.PubMedCrossRefGoogle Scholar
  29. 29.
    Prabhakaran S, Rundek T, Ramas R, et al.: Carotid plaque surface irregularity predicts ischemic stroke: the Northern Manhattan Study. Stroke 2006, 37 2696–2701.PubMedCrossRefGoogle Scholar
  30. 30.
    Corrado E, Rizzo M, Tantillo R, et al.: Markers of inflammation and infection influence the outcome of patients with baseline asymptomatic carotid lesions: a 5-year follow-up study. Stroke 2006, 37:482–486.PubMedCrossRefGoogle Scholar
  31. 31.
    Schillinger M, Exner M, Mlekusch W, et al.: Inflammation and Carotid Artery—Risk for Atherosclerosis Study (ICARAS). Circulation 2005, 111:2203–2209.PubMedCrossRefGoogle Scholar
  32. 32.
    Gröchel K, Ernemann U, Larsen J, et al.: Preprocedural C-reactive protein levels predict stroke and death in patients undergoing carotid stenting. AJNR Am J Neuroradiol 2007, 28:1743–1746.CrossRefGoogle Scholar
  33. 33.
    Krupinski J, Turu MM, Font MA, et al.: Blood-borne tissue factor activity predicts major cerebrovascular events in patients undergoing carotid endarterectomy: results from a 1-year follow-up study. Cerebrovasc Dis 2008, 25:32–39.PubMedCrossRefGoogle Scholar
  34. 34.
    Weiss CR, Arai AE, Bui MN, et al.: Arterial wall MRI characteristics are associated with elevated serum markers of inflammation in humans. J Magn Reson Imaging 2001, 14:698–704.PubMedCrossRefGoogle Scholar
  35. 35.
    Corti R, Fuster V, Fayad ZA, et al.: Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging. J Am Coll Cardiol 2005, 46:106–112.PubMedCrossRefGoogle Scholar
  36. 36.
    van Dijk EJ, Prins ND, Vermeer SE, et al.: C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation 2005, 112:900–905.PubMedCrossRefGoogle Scholar
  37. 37.
    Fornage M, Chiang A, O’Meara ES, et al.: Biomarkers of inflammation and MRI-defined small vessel disease of the brain. The Cardiovascular Health Study. Stroke 2008, 39:1952–1959.PubMedCrossRefGoogle Scholar
  38. 38.
    Jefferson AL, Massaro JM, Wolf PA, et al.: Inflammatory biomarkers are associated with total brain volume: the Framingham Heart Study. Neurology 2007, 68:1032–1038.PubMedCrossRefGoogle Scholar
  39. 39.
    Revilla M, Obach V, Cervera A, et al.: A -174G/C polymorphism of the interleukin-6 gene in patients with lacunar infarction. Neurosci Lett 2002, 324:29–32.PubMedCrossRefGoogle Scholar
  40. 40.
    Castellanos M, Castillo J, Garcia MM, et al.: Inflammation-mediated damage in progressing lacunar infarctions: a potential therapeutic target. Stroke 2002, 33:982–987.PubMedCrossRefGoogle Scholar
  41. 41.
    Smeeth L, Thomas SL, Hall AJ, et al.: Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med 2004, 351:2611–2618.PubMedCrossRefGoogle Scholar
  42. 42.
    Grau AJ, Fischer B, Barth C, et al.: Influenza vaccination is associated with a reduced risk of stroke. Stroke 2005, 36:1501–1506.PubMedCrossRefGoogle Scholar
  43. 43.
    Nagel MA, Cohrs RJ, Mahalingam R, et al.: The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology 2008, 70:853–860.PubMedCrossRefGoogle Scholar
  44. 44.
    Davis MM, Taubert K, Benin AL, et al.: Influenza vaccination as secondary prevention for cardiovascular disease: a science advisory from the American Heart Association/ American College of Cardiology. Circulation 2006, 114:1549–1553.PubMedCrossRefGoogle Scholar
  45. 45.
    Zeller JA, Lenz A, Eschenfelder CC, et al.: Platelet-leukocyte interaction and platelet activation in acute stroke with and without preceding infection. Arterioscler Thromb Vasc Biol 2005, 25:1519–1523.PubMedCrossRefGoogle Scholar
  46. 46.
    Herzberg MC, Nobbs A, Tao L, et al.: Oral streptococci and cardiovascular disease: searching for the platelet aggregation-associated protein gene and mechanisms of Streptococcus sanguis-induced thrombosis. J Periodontol 2005, 76(11 Suppl):2101–2105.CrossRefGoogle Scholar
  47. 47.
    Elkind MS, Sciacca R, Boden-Albala B, et al.: Leukocyte count is associated with reduced endothelial reactivity. Atherosclerosis 2005, 181:329–338.PubMedCrossRefGoogle Scholar
  48. 48.
    Charakida M, Donald AE, Terese M, et al.: Endothelial dysfunction in childhood infection. Circulation 2005, 111:1660–1665.PubMedCrossRefGoogle Scholar
  49. 49.
    Pleiner J, Schaller G, Mittermayer F, et al.: Simvastatin prevents vascular hyporeactivity during inflammation. Circulation 2004, 110:3349–3354.PubMedCrossRefGoogle Scholar
  50. 50.
    Elkind MS: Implications of stroke prevention trials: treatment of global risk. Neurology 2005, 65:17–21.PubMedCrossRefGoogle Scholar
  51. 51.
    Ridker PM, Cannon CP, Morrow D, et al.: C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005, 352:20–28.PubMedCrossRefGoogle Scholar
  52. 52.
    Kinlay S, Schwartz GG, Olsson AG, et al.: Inflammation, statin therapy, and risk of stroke after an acute coronary syndrome in the MIRACL study. Arterioscler Thromb Vasc Biol 2008, 28:142–147.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2009

Authors and Affiliations

  1. 1.Department of NeurologyColumbia University, New York-Presbyterian HospitalNew YorkUSA

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