Skip to main content
  • Plasma Myeloperoxidase in Acute Brain Ischemia and High-grade Carotid Stenosis

    Final Number:
    687

    Authors:
    David Orion MD; Yvonne Schwammenthal; von Landenberg Peter; Rakefet Tsabari; Joave Chapman; Elad I. Levy MD, FACS, FAHA, FAANS; David Tanne

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2014 Annual Meeting

    Introduction: Myeloperoxidase (MPO) is an important oxidative enzyme participating in different stages of cardiovascular disease and predicts prognosis. Little is known about its role in acute cerebrovascular events and carotid plaque vulnerability.

    Methods: Plasma MPO levels were assessed in patients presenting with acute brain ischemia within 36 hours of symptom onset (n=144, mean age 64.7± 11.6years, 67% men), and in patients with moderate-severe carotid stenosis undergoing angiography for carotid artery stenting (n=51, mean age 66.3?8.4 years, 75% men). Patients presenting with acute brain ischemia were assessed serially for stroke severity (NIH stroke scale; NIHSS), and disability [modified Rankin Scale (mRS).

    Results: Plasma MPO concentrations (ng/ml) were associated with interleukin-6 (r=0.38, p<0.0001.), gender [median (interquartile range)] of 68.6 (49.8-107.0) vs. 59.7 (42.7-85.5) in women vs. men,[p=0.02]. MPO levels did not differ significantly between patients with acute brain ischemia (66.7, 46.4-97.3), patients with carotid stenosis (54.2, 41.7-80.8)[p=0.1]). Among patients with acute brain ischemia, MPO concentrations were associated non-lacunar subtype (bottom, middle and top tertiles of 37.5%, 71.7%, 71.7% respectively, p=0.001), with stroke severity (baseline NIHSS score>10) bottom, middle and top tertiles 6.3%, vs. 41.7% and 31.3%, respectively; p<0.006) as well as with stroke severity at day 1-2, day 4-5, and at discharge (p <0.05 for all), less with disability at discharge [mRS=2 of 41.7% vs. 60.4% and 58.7% for bottom, middle and top tertiles, respectively; p=0.096). MPO concentrations did not differ between patients with symptomatic (n=23) median 50.1 (41.7-107) vs. asymptomatic carotid stenosis (n=28) 54.6 (41.9-70.3), nor by stenosis severity.

    Conclusions: Among patients with acute brain ischemia, plasma MPO concentrations were associated with stroke severity and non-lacunar subtype, but not with long term functional disability. MPO concentrations did not differ significantly between the groups: acute brain ischemia patients, patients with carotid stenosis, nor between symptomatic and asymptomatic carotid plaque.

    Patient Care: Inflammtory blood markers may help segregating stroke patients with worse prognosis for different treatemnts.

    Learning Objectives: plasma MPO concentrations were associated with stroke severity

    References: References 1. Weston RM, Jones NM, Jarrott B, Callaway JK. Inflammatory cell infiltration after endothelin-1-induced cerebral ischemia: Histochemical and myeloperoxidase correlation with temporal changes in brain injury. J Cereb Blood Flow Metab. 2007;27:100-114 2. Nicholls SJ, Hazen SL. Myeloperoxidase and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2005;25:1102-1111 3. Tsimikas S. Oxidative biomarkers in the diagnosis and prognosis of cardiovascular disease. Am J Cardiol. 2006;98:S9-S17 4. Rausch PG, Pryzwansky KB, Spitznagel JK. Immunocytochemical identification of azurophilic and specific granule markers in the giant granules of chediak-higashi neutrophils. N Engl J Med. 1978;298:693-698 5. Klebanoff SJ. Myeloperoxidase: Friend and foe. J Leukoc Biol. 2005;77:598-625 6. Vita JA, Brennan ML, Gokce N, Mann SA, Goormastic M, Shishehbor MH, Penn MS, Keaney JF, Jr., Hazen SL. Serum myeloperoxidase levels independently predict endothelial dysfunction in humans. Circulation. 2004;110:1134-1139 7. Zhang C, Yang J, Jennings LK. Leukocyte-derived myeloperoxidase amplifies high-glucose--induced endothelial dysfunction through interaction with high-glucose--stimulated, vascular non--leukocyte-derived reactive oxygen species. Diabetes. 2004;53:2950-2959 8. Bergt C, Pennathur S, Fu X, Byun J, O'Brien K, McDonald TO, Singh P, Anantharamaiah GM, Chait A, Brunzell J, Geary RL, Oram JF, Heinecke JW. The myeloperoxidase product hypochlorous acid oxidizes hdl in the human artery wall and impairs abca1-dependent cholesterol transport. Proc Natl Acad Sci U S A. 2004;101:13032-13037 9. Zheng L, Nukuna B, Brennan ML, Sun M, Goormastic M, Settle M, Schmitt D, Fu X, Thomson L, Fox PL, Ischiropoulos H, Smith JD, Kinter M, Hazen SL. Apolipoprotein a-i is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease. J Clin Invest. 2004;114:529-541 10. Zheng L, Settle M, Brubaker G, Schmitt D, Hazen SL, Smith JD, Kinter M. Localization of nitration and chlorination sites on apolipoprotein a-i catalyzed by myeloperoxidase in human atheroma and associated oxidative impairment in abca1-dependent cholesterol efflux from macrophages. J Biol Chem. 2005;280:38-47 11. Kutter D, Devaquet P, Vanderstocken G, Paulus JM, Marchal V, Gothot A. Consequences of total and subtotal myeloperoxidase deficiency: Risk or benefit? Acta Haematol. 2000;104:10-15 12. Nikpoor B, Turecki G, Fournier C, Theroux P, Rouleau GA. A functional myeloperoxidase polymorphic variant is associated with coronary artery disease in french-canadians. Am Heart J. 2001;142:336-339 13. Pecoits-Filho R, Stenvinkel P, Marchlewska A, Heimburger O, Barany P, Hoff CM, Holmes CJ, Suliman M, Lindholm B, Schalling M, Nordfors L. A functional variant of the myeloperoxidase gene is associated with cardiovascular disease in end-stage renal disease patients. Kidney Int Suppl. 2003:S172-176 14. Asselbergs FW, Reynolds WF, Cohen-Tervaert JW, Jessurun GA, Tio RA. Myeloperoxidase polymorphism related to cardiovascular events in coronary artery disease. Am J Med. 2004;116:429-430 15. Zhang R, Brennan ML, Fu X, Aviles RJ, Pearce GL, Penn MS, Topol EJ, Sprecher DL, Hazen SL. Association between myeloperoxidase levels and risk of coronary artery disease. Jama. 2001;286:2136-2142 16. Brevetti G, Schiano V, Laurenzano E, Giugliano G, Petretta M, Scopacasa F, Chiariello M. Myeloperoxidase, but not c-reactive protein, predicts cardiovascular risk in peripheral arterial disease. Eur Heart J. 2008;29:224-230 17. Brennan ML, Penn MS, Van Lente F, Nambi V, Shishehbor MH, Aviles RJ, Goormastic M, Pepoy ML, McErlean ES, Topol EJ, Nissen SE, Hazen SL. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med. 2003;349:1595-1604 18. Baldus S, Heeschen C, Meinertz T, Zeiher AM, Eiserich JP, Munzel T, Simoons ML, Hamm CW. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003;108:1440-1445 19. Tang WH, Brennan ML, Philip K, Tong W, Mann S, Van Lente F, Hazen SL. Plasma myeloperoxidase levels in patients with chronic heart failure. Am J Cardiol. 2006;98:796-799 20. Takizawa S, Aratani Y, Fukuyama N, Maeda N, Hirabayashi H, Koyama H, Shinohara Y, Nakazawa H. Deficiency of myeloperoxidase increases infarct volume and nitrotyrosine formation in mouse brain. J Cereb Blood Flow Metab. 2002;22:50-54 21. Beray-Berthat V, Croci N, Plotkine M, Margaill I. Polymorphonuclear neutrophils contribute to infarction and oxidative stress in the cortex but not in the striatum after ischemia-reperfusion in rats. Brain Res. 2003;987:32-38 22. Benjelloun N, Renolleau S, Represa A, Ben-Ari Y, Charriaut-Marlangue C. Inflammatory responses in the cerebral cortex after ischemia in the p7 neonatal rat. Stroke. 1999;30:1916-1923; discussion 1923-1914 23. Martin A, Rojas S, Chamorro A, Falcon C, Bargallo N, Planas AM. Why does acute hyperglycemia worsen the outcome of transient focal cerebral ischemia? Role of corticosteroids, inflammation, and protein o-glycosylation. Stroke. 2006;37:1288-1295 24. Maier CM, Hsieh L, Yu F, Bracci P, Chan PH. Matrix metalloproteinase-9 and myeloperoxidase expression: Quantitative analysis by antigen immunohistochemistry in a model of transient focal cerebral ischemia. Stroke. 2004;35:1169-1174 25. Matsuo Y, Onodera H, Shiga Y, Nakamura M, Ninomiya M, Kihara T, Kogure K. Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke. 1994;25:1469-1475 26. McMillen TS, Heinecke JW, LeBoeuf RC. Expression of human myeloperoxidase by macrophages promotes atherosclerosis in mice. Circulation. 2005;111:2798-2804 27. Brennan ML, Anderson MM, Shih DM, Qu XD, Wang X, Mehta AC, Lim LL, Shi W, Hazen SL, Jacob JS, Crowley JR, Heinecke JW, Lusis AJ. Increased atherosclerosis in myeloperoxidase-deficient mice. J Clin Invest. 2001;107:419-430 28. Falke P, Elneihoum AM, Ohlsson K. Leukocyte activation: Relation to cardiovascular mortality after cerebrovascular ischemia. Cerebrovasc Dis. 2000;10:97-101 29. Blake GJ, Ridker PM. Inflammatory bio-markers and cardiovascular risk prediction. J Intern Med. 2002;252:283-294 30. Chamorro A. Role of inflammation in stroke and atherothrombosis. Cerebrovasc Dis. 2004;17 Suppl 3:1-5 31. Re G, Azzimondi G, Lanzarini C, Bassein L, Vaona I, Guarnieri C. Plasma lipoperoxidative markers in ischaemic stroke suggest brain embolism. Eur J Emerg Med. 1997;4:5-9 32. Hoy A, Leininger-Muller B, Poirier O, Siest G, Gautier M, Elbaz A, Amarenco P, Visvikis S. Myeloperoxidase polymorphisms in brain infarction. Association with infarct size and functional outcome. Atherosclerosis. 2003;167:223-230 33. Exner M, Minar E, Mlekusch W, Sabeti S, Amighi J, Lalouschek W, Maurer G, Bieglmayer C, Kieweg H, Wagner O, Schillinger M. Myeloperoxidase predicts progression of carotid stenosis in states of low high-density lipoprotein cholesterol. J Am Coll Cardiol. 2006;47:2212-2218 34. 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 35. Herndon R. Handbook of neurologic rating scales. New York: Demos Vermande; 1997. 36. Duncan PW, Lai SM, Bode RK, Perera S, DeRosa J. Stroke impact scale-16: A brief assessment of physical function. Neurology. 2003;60:291-296 37. Breckwoldt MO, Chen JW, Stangenberg L, Aikawa E, Rodriguez E, Qiu S, Moskowitz MA, Weissleder R. Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci U S A. 2008;105:18584-18589 38. Hossmann KA. Pathophysiology and therapy of experimental stroke. Cell Mol Neurobiol. 2006;26:1057-1083 39. Saeed SA, Shad KF, Saleem T, Javed F, Khan MU. Some new prospects in the understanding of the molecular basis of the pathogenesis of stroke. Exp Brain Res. 2007;182:1-10 40. Weston RM, Jarrott B, Ishizuka Y, Callaway JK. Am-36 modulates the neutrophil inflammatory response and reduces breakdown of the blood brain barrier after endothelin-1 induced focal brain ischaemia. Br J Pharmacol. 2006;149:712-723

We use cookies to improve the performance of our site, to analyze the traffic to our site, and to personalize your experience of the site. You can control cookies through your browser settings. Please find more information on the cookies used on our site. Privacy Policy