Broj leukocita je pokazatelj nestabilnosti karotidnog plaka kod bolesnika sa akutnim infarktom mozga
Sažetak
Uvod/Cilj. Porast dokaza o inflamatornom karakteru ateroskleroze istakao je više parametara zapaljenja kao pokazatelje cerebrovaskularnog rizika. Cilj istraživanja bio je da se ispita povezanost parametara zapaljenja u serumu i ultrazvučnih (UZ) karakteristika strukture i veličine karotidnog plaka. Pretpostavili smo da je broj leukocita (Le) pokazatelj nestabilnosti karotidnog plaka i povećanog rizika od razvoja akutnog infarkta mozga. Metode. Broj Le i ostali serumski parametri zapaljenja [sedimentacija eritrocita u prvom (Se Er I) i drugom satu (Se Er II), visokosenzitivni C-reaktivni protein (hs-CRP) i fibrinogen] mereni su standardnim metodama. Svi ispitanici (n = 75) imali su kompletan klinički pregled i bili podeljeni u tri grupe (simptomatska, asimptomatska i kontrolna). Ultrazvučni (UZ) pregled ekstrakranijalnih karotidnih arterija rađen je u dupleks sistemu. Plakovi su klasifikovani u kategorije prema procentu stenoze (≥ 50%, < 50%) i prema ehomorfološkim karakteristikama (Gray-Weale klasifikacija). Kod ispitanika sa akutnim infarktom mozga ishemijska lezija je potvrđena kompjuterizovanom tomografijom. Rezultati. Prosečne vrednosti ispitivanih biohemijskih parametara u simptomatskoj grupi bile su: Se Er I 29,57 ± 29,87 cm, Se Er II 51,60 ± 36,87 cm, broj Le 10,10 ± 3,20 ´ 10-9 U/L, hs-CRP 8,15 ± 5,50 mg/L i fibrinogen 4,03 ± 0,70 g/L. Prosečne vrednosti svih ispitivanih biohemijskih parametara u simptomatskoj bile su značajno više nego u asimptomatskoj i kontrolnoj grupi: za Se Er I (p < 0.05) i Se Er II (p < 0,05); za broj Le (p < 0,001) za hsCRP (p < 0,001) i fibrinogen (p < 0,001). Zastupljenost I kategorije ehomorfoloških karakteristika u simptomatskoj grupi (66,7% ispitanika) bila je značajno viša nego u asimptomatskoj (40,0%; p < 0,05) i kontrolnoj (20,0%; p < 0,01) grupi. Univarijantna logistička regresiona analiza potvrdila je da su svi ispitivani parametri indikatori rizika od akutnog infarkta mozga. Multivarijantna logistička regresiona analiza potvrdila je statistički značajnu povezanost broja Le i rizika od akutnog infarkta mozga. Povećanje vrednosti za jednu mernu jedinicu povezano je sa porastom rizika za 3,22 puta (1,67–6,22). Zaključak. Broj Le povezan je sa fenomenom nestabilnosti karotidnog plaka i može biti koristan dodatni pokazatelj povećanog rizika od razvoja akutnog infarkta mozga.
Reference
Davignon J, Ganz P. Role of Endothelial Dysfunction in Athe-rosclerosis. Circulation 2004; 109(23 Suppl 1): 27−32.
Faxon DP, Fuster V, Libby P, Beckman JA, Hiatt WR, Thompson RW, et al. Atherosclerotic Vascular Disease Conference: Writing Group III: pathophysiology. Circulation 2004; 109(21): 2617−25.
Morgan AR, Rerkasem K, Gallagher PJ, Zhang B, Morris GE, Calder PC, et al. Differences in matrix metalloproteinase-1 and matrix metalloproteinase-12 transcript levels among carotid atherosclerotic plaques with different histopathological characteristics. Stroke 2004; 35(6): 1310−5.
Ministry of Health RS. National Guide. Belgrade: Ministry of Health of the Republic of Serbia 2004. (Serbian).
Grant EG, Benson CB, Moneta GL, Alexandrov AV, Baker JD, Bluth EI, et al. Carotid Artery Stenosis: Gray-Scale and Doppler US Diagnosis—Society of Radiologists in Ultra-sound Consensus Conference. Radiology 2003; 229(2): 340−6.
Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, et al. Mannheim Intima-Media Thickness Consen-sus (2004-2006-2011). Crebrovasc Dis 2012; 34(4): 290−6.
Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993; 24(1): 35−41.
Special report from the National Institute of Neurological Disorders and Stroke. Classification of cerebrovascular diseas-es III. Stroke 1990; 21(4): 637−76.
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16(1): 31−41.
Ding S, Zhang M, Zhao Y, Chen W, Yao G, Zhang C, et al. The role of carotid plaque vulnerability and inflammation in the pa-thogenesis of acute ischemic stroke. Am J Med Sci 2008; 336(1): 27−31.
Faul F, Erdfelder E, Lang A, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007; 39(2): 175−91.
Uteyboogaart M, Schrijvers E, Vroomen P, Dekeyser J, Luijckx GJ. Routine Thrombolysis With Intravenous Tissue Plasminogen Activator in Acute Ischemic Stroke. Oxford J Med 2012; 36(5): 577−9.
Demarin V, Štikovac M, Thaller N. Blood-Vessel Doppler Ultra-sonography. Zagreb: Školska knjiga; 1990. (Croatian)
Gray-Weale AC, Graham JC, Burnett JR, Byrne K, Lusby RJ. Ca-rotid Artery Atheroma: Comparison of Preoperative B-mode Ultrasound Appearance With Carotid Endarterectomy Specimen Pathology. J Cardiovasc Surg 1988; 29(6): 676−81.
Chambless LE, Folsom AR, Davis V, Sharrett R, Heiss G, Sorlie P, et al. Risk factors for progression of common carotid atherosclerosis: the Atherosclerosis Risk in Communities Study, 1987-1998. Am J Epidemiol 2002; 155(1): 38−47.
Spagnoli LG, Mauriello A, Sangiorgi G, Fratoni S, Bonanno E, Schwartz RS, et al. Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. JAMA 2004; 292(15): 1845−52.
Mathiesen EB, Bønaa KH, Joakimsen O. Echolucent plaques are associated with high risk of ischemic cerebrovascular events in carotid stenosis: the tromsø study. Circulation 2001; 103(17): 2171−5.
AbuRahma AF, Wulu JT, Crotty B. Carotid plaque ultrasonic heterogeneity and severity of stenosis. Stroke 2002; 33(7): 1772−5.
Yoshida K, Narumi O, Chin M, Inoue K, Tabuchi T, Oda K, et al. Characterization of Carotid Atherosclerosis and Detection of Soft Plaque with Use of Black-Blood MR Imaging. Am J Neu-roradiol 2008; 29(5): 868−74.
Ohara T, Toyoda K, Otsubo R, Nagatsuka K, Kubota Y, Yasaka M, et al. Eccentric stenosis of the carotid artery associated with ipsilateral cerebrovascular events. Am J Neuroradiol 2008; 29(6): 1200−3.
Laskowitz DT, Kasner SE, Saver J, Remmel KS, Jauch EC. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study. Stroke 2009; 40(1): 77−85.
Packard RR, Libby P. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem 2008; 54(1): 24−38.
Mallika V, Goswami B, Rajappa M. Atherosclerosis pathophysi-ology and the role of novel risk factors: a clinicobiochemical perspective. Angiology 2007; 58(5): 513−22.
Yang W. High Red Blood Cell Distribution Width is Closely Associated With Risk of Carotid Artery Atherosclerosis in Pa-tients With Hypertension. Exp Clin Cardiol 2010; 15(3): 37−40.
Zaremba J, Skrobanski P, Losy J. Acute Ischaemic Increases the Erytrocyte Sedimentation Rate, Which Correlates With Early Brain Damage. Folia Morphol (Warsz) 2004; 63(4): 373−6.
Mauriello A, Sangiorgi G, Palmieri G, Virmani R, Holmes DR, Schwartz RS, et al. Hyperfibrinogenemia is associated with spe-cific histocytological composition and complications of athe-rosclerotic carotid plaques in patients affected by transient ischemic attacks. Circulation 2000; 101(7): 744−50.
Krupinski J, Tiru M, Font AM, Ahmed N, Sullivan M, Luque A, et al. Increased Tissue Factor, MMP-8 and D-dimer Expression in Diabetic Patients With Instable Advanced Carotid Atheros-clerosis. Vasc Health Risk Manag 2007; 3(4): 405−12.
Magyar MT, Szikszai Z, Balla J, Valikovics A, Kappelmayer J, Imre S, et al. Early-onset carotid atherosclerosis is associated with increased intima-media thickness and elevated serum levels of inflammatory markers. Stroke 2003; 34(1): 58−63.
Paximadas SA, Pagoni SN, Pitsavos CE, Skoumas JN, Karagianni ET, Nikitopoulou PD, et al. The changes of fibrinogen and li-poprotein a levels after six months treatment with statins. Atherosclerosis Suppl 2001; 2(2): 99.
Sen S, Hinderliter A, Sen PK, Simmons J, LeGrys VA, Beck J, et al. Association of leukocyte count with progression of aortic atheroma in stroke/transient ischemic attack patients. Stroke 2007; 38(11): 2900−5.
Elkind MS, Sciacca R, Boden-Albala B, Homma S, di Tullio MR. Leukocyte count is associated with aortic arch plaque thick-ness. Stroke 2002; 33(11): 2587−92.
Temelkova-Kurktschiev T, Koehler C, Henkel E, Hanefeld M. Leuko-cyte count and fibrinogen are associated with carotid and femoral intima-media thickness in a risk population for diabetes. Cardiovasc Res 2002; 56(2): 277−83.
Libby P, Shi G. Mast cells as mediators and modulators of atherogenesis. Circulation 2007; 115(19): 2471−3.
Rost NS, Wolf PA, Kase CS, Kelly-Hayes M, Silbershatz H, Massaro JM, et al. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke 2001; 32(11): 2575−9.
Jander S, Sitzer M, Schumann R, Schroeter M, Siebler M, Steinmetz H, et al. Inflammation in High-Grade Carotid Stenosis : A Possible Role for Macrophages and T Cells in Plaque Destabilization. Stroke 1998; 29(8): 1625−30.
Hashimoto H, Kitagawa K, Hougaku H, Etani H, Hori M. Relationship between C-reactive protein and progression of early carotid atherosclerosis in hypertensive subjects. Stroke 2004; 35(7): 1625−30.
Wardlaw JM, Farrall A, Armitage PA, Carpenter T, Chappell F, Doubal F, et al. Changes in background blood-brain barrier integrity between lacunar and cortical ischemic stroke subtypes. Stroke 2008; 39(4): 1327−32.
Willeit J, Kiechl S, Oberhollenzer F, Rungger G, Egger G, Bonora E, et al. Distinct Risk Profiles of Early and Advanced Atheroscle-rosis : Prospective Results From the Bruneck Study. Atherosc-ler Thromb Vasc Biol 2000; 20(2): 529−37.
Hashimoto H, Kitagawa K, Hougaku H, Shimizu Y, Sakaguchi M, Nagai Y, et al. C-Reactive Protein Is an Independent Predictor of the Rate of Increase in Early Carotid Atherosclerosis. Circulation 2001; 104(1): 63−7.
Ceulemans A, Zgavc T, Kooijman R, Hachimi-Idrissi S, Sarre S, Mi-chotte Y. The dual role of the neuroinflammatory response after ischemic stroke: modulatory effects of hypothermia. J Neuroinflammation 2010; 7(1): 74.
Libby P, Ridker PM, Maseri A. Inflammation and atherosclero-sis. Circulation 2002; 105(9): 1135−43.
Silva D, Albuquerque L, Narvaes L, Goldani M, Pereira G. C-Reactive Protein and Clinical Instability in Carotid Artery Ob-structive Disease. J Vasc Bras 2007; 6(2): 1−7.
Everett BM, Ridker PM. Using inflammatory biomarkers to guide lipid therapy. Curr Cardiovasc Risk Reports 2008; 2(1): 29−34.
Bos MJ, Schipper CM, Koudstaal PJ, Witteman JC, Hofman A, Breteler MM. High Serum C-Reactive Protein Level Is Not an Inde-pendent Predictor for Stroke: The Rotterdam Study. Circula-tion 2006; 114(15): 1591−8.
Winbeck K, Poppert H, Etgen T, Conrad B, Sander D. Prognostic relevance of early serial C-reactive protein measurements after first ischemic stroke. Stroke 2002; 33(10): 2459−64.
Laterza O, Modur V, Crimmins D, Olander J, Landt Y, Lee JM. Identification of Novel Brain Biomarkers. Clin Chem 2006; 52(9): 1713−21.
Taylor A, Kent S, Flaherty P, Coyle L, Markwood T, Vernalis M. ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: A Randomized Trial Comparing the Effects of Atorvastatin and Pravastatin on Carotid Intima Medial Thickness. Circulation 2002; 106(16): 2055−60.
Kettani F, Dragomir A, Côté R, Roy L, Bérard A, Blais L, et al. Impact of a better adherence to antihypertensive agents on ce-rebrovascular disease for primary prevention. Stroke 2009; 40(1): 213−20.