Association of C-reactive protein and nitric oxide levels with the prognosis of acute ischemic stroke
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Keywords

Acute ischemic stroke
inflammation
C-reactive protein
nitric oxide
nitrites/nitrates (MeSH)

Abstract

Introduction: Inflammation and alterations in the bioavailability of nitric oxide (NO) have been involved in the pathophysiology of cerebrovascular disease.

Objective: The aim of the study was to determine the prognostic value of measuring NO metabolites and inflammatory markers in patients with acute ischemic stroke.

Materials and methods: A total of 158 patients with acute ischemic stroke were included in an observational cohort study. Between 48 and 72 hours post admission, a fasting blood sample was taken to determine the biochemical profile, inflammatory markers (CRP, IL1-?, IL6, TNF-?) and nitrites/nitrates plasma levels. The cohort's follow-up was conducted for two years to determine the occurrence of a new event (stroke, myocardial infarction, heart failure) or death of vascular origin. Comparisons between groups were made using the log-rank test. A Cox multivariate regression analysis permitted to determine factors independently associated with the outcome.

Result: The mean age was 70.5 ± 12.8 years. 39.2% of the subjects presented the outcome during the first 24 months of follow-up. CRP levels > 12 mg/L (HR 2.22, 95% CI 1.07-4.59) and a score > 13 on the NIHSS scale at admission (HR 2.81 95% CI 1.46-5.41) were significantly associated with an increased risk of a new event. The combination of CRP levels < 12 mg/L and nitrites/nitrates levels < 35.5 mmol/L was identified as a protective factor (HR 0.21, 95% CI 0.06-0.71).

Conclusion: This study demonstrates that the determination of CRP and NOx levels could be beneficial in clinical practice to stratify the risk of future events or death of vascular origin in acute ischemic stroke patients.

https://doi.org/10.22379/2422402221

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References

CASTILLO J, LEIRA R. Predictors of deteriorating cerebral infarct. Would its early treatment be useful? Cerebrovasc Dis. 2001;11(suppl. 1):40-8.

CASTELLANOS M, CASTILLO J, GARCÍA MM, LEIRA R, SERENA J, CHAMORRO A, ET AL. Inflammation-mediated damage in progressing lacunar infarctions. Stroke 2002;33:982-7.

SILVA FA, ZARRUK JG, SILVA S, BERNAL O, RUEDA-CLAUSEN C, PRADILLA G, ET AL. Estudio de correlación entre marcadores de inflamación y grosor íntima media carotídeo, en pacientes con ataque cerebrovascular isquémico. Acta Neurol Col. 2006;22:3-11.

MCCOLL BW, ALLAN SM, ROTHWELL NJ. Systemic inflammation and stroke: aetiology, pathology and targets for therapy. Biochem Soc Trans. 2007;35:1163-5.

DENES A, PINTEAUX E, ROTHWELL NJ, ALLAN SM. Interleukin-1 and stroke: biomarker, harbinger of damage, and therapeutic target. Cerebrovasc Dis. 2011;32:517-27.

LEIRA R, RODRÍGUEZ-YANEZ M, CASTELLANOS M, BLANCO M, NOMBELA F, SOBRINO T, ET AL. Hyperthermia is a surrogate marker of inflammation-mediated cause of brain damage in acute ischaemic stroke. J Intern Med. 2006;260:343-9.

MUIR KW, TYRRELL P, SATTAR N, WARBURTON E. Inflammation and ischemic stroke. Curr Opin Neurol. 2007;20:334-42.

ZARRUK JG, SILVA FA, CAMACHO PA, ARENAS W, RESTREPO J, BERNAL O, ET AL. Factors associated to mortality after 30 days, in a group of patients with cerebro-vascular ischemic disease. Acta Med Colomb. 2007;32:2-8.

SHANTIKUMAR S, GRANT PJ, CATTO AJ, BAMFORD JM, CARTER AM. Elevated C-reactive protein and long-term mortality after ischaemic stroke: relationship with markers of endothelial cell and platelet activation. Stroke 2009;40:977-9.

CORSO G, BOTTACCHI E, BRUSA A, BENEDETTO MD, GIARDINI G, LIA C, ET AL. Is there a prognostic role for C-reactive protein in ischemic stroke? Acta Neurol Scand. 2010;122:209-16.

CLAPP BR, HINGORANI AD, KHARBANDA RK, MOHAMED-ALI V, STEPHENS JW, VALLANCE P, ET AL. Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. Cardiovasc Res. 2004;64:172-8.

KADER A, FRAZZINI VI, SOLOMON RA, TRIFILETTI RR. Nitric oxide production during focal cerebral ischemia in rats. Stroke 1993;24:1709-16.

KUMURA E, KOSAKA H, SHIGA T, YOSHIMINE T, HAYAKAWA T. Elevation of plasma nitric oxide end products during focal cerebral ischemia and reperfusion in the rat. J Cereb Blood Flow Metab. 1993;14:487-91.

ZHENG G, CHOPP M, ZALOGA C, POLLOCK JS, FÖRSTERMANN U. Cerebral endothelial nitric oxide synthase expression after focal cerebral ischemia in rats. Stroke 1993;24:2016-22.

SCHERBAKOV N, SANDEK A, MARTENS-LOBENHOFFER J, KUNG T, TURHAN G, LIMAN T, ET AL. Endothelial dysfunction of the peripheral vascular bed in the acute phase after ischemic stroke. Cerebrovasc Dis. 2012;33:37-46.

SANTOS-GARCÍA D, BLANCO M, SERENA J, RODRÍGUEZ-YÁÑEZ M, LEIRA R, CASTILLO J. Impaired brachial flow-mediated dilation is a predictor of a new-onset vascular event after stroke. Cerebrovasc Dis. 2011;32:155-62.

HUANG PH, CHEN JW, LU TM, YU-AN P, LIN SJ. Combined use of endothelial function assessed by brachial ultrasound and high-sensitive C-reactive protein in predicting cardiovascular events. Clin Cardiol. 2007;30:135-40.

BROTT T, ADAMS HP, OLINGER CP, MARLER JR, BARSAN WG, BILLER J, ET AL. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989;20:864-70.

LIBBY P. Inflammation in atherosclerosis. Nature 2002;420:868-74.

HANSSON GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685-95.

BAUTISTA LE, LÓPEZ-JARAMILLO P, VERA LM, CASAS JP, OTERO AP, GUARACAO AI. Is C-reactive protein and independent risk factor for essential hypertension? J Hypertens. 2001;19:857-61.

GARCÍA RG, CELEDÓN J, SIERRA J, ALARCÓN MA, LUENGAS C, SILVA F, ET AL. Raised C-reactive protein and impaired flow-mediated vasodilation precede the development of preeclampsia. Am J Hypertens. 2007;20:98-103.

LÓPEZ-JARAMILLO P, HERRERA E, GARCÍA RG, CAMACHO PA, CASTILLO VR. Inter-relationships between body mass index, C-reactive protein and blood pressure in a hispanic pediatric population. Am J Hypertens. 2008;21:527-32.

GUSSEKLOO J, SCHAAP MC, FROLICH M, BLAUW GJ, WESTENDORP RG. C-reactive protein is a strong but nonspecific risk factor of fatal stroke in elderly persons. Arterioscler Thromb Vasc Biol. 2000;20:1047-51.

REYNOLDS MA, KIRCHICK HJ, DAHLEN JR, ANDERBERG JM, MCPHERSON PH, NAKAMURA KK, ET AL. Early biomarkers of stroke. Clin Chem. 2003;49:1733-9.

SUWANWELA NC, CHUTINET A, PHANTHUMCHINDA K. Inflammatory markers and conventional atherosclerotic risk factors in acute ischemic stroke: comparative study between vascular disease subtypes. J Med Assoc Thai 2006;89:2021-7.

CORSO G, BOTTACCHI E, BRUSA A, LIA C, CORDERA S, GIARDINI G, ET AL. Blood C-reactive protein concentration with ABCD2 is a better prognostic tool tan ABCD2 alone. Cerebrovasc Dis. 2011;32:97-105.

ARENILLAS JF, ÁLVAREZ-SABIN J, MOLINA CA, CHACÓN P, MONTANER J, ROVIRA A, ET AL. C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease. Stroke 2003;34:2463-70.

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;33:2459-64.

YEH KH, TSAI TH, CHAI HT, LEU S, CHUNG SY, CHUA S, ET AL. Comparison of acute versus convalescent stage high-sensitivity C-Reactive protein level predicting clinical outcome after acute ischemic stroke and impact of erythropoietin. J Transl Med. 2012;10:6.

ALDERTON WK, COOPER CE, KNOWLES RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001;357:593,615.

MORO AM, CÁRDENAS A, HURTADO O, LEZA JC, LIZASOAIN I. Role of nitric oxide after brain ischemia. Cell Calcium 2004;36:265-75.

CASTILLO J, RAMÓN R, DÁVALOS A. Nitric oxide-related brain damage in acute ischemic stroke. Stroke 2000;31:852-7.

RASHID PA, WHITEHURST A, LAWSON N, BATH PM. Plasma nitric oxide (nitrate/nitrite) levels in acute stroke and their relationship with severity and outcome. J Stroke Cerebrovasc Dis. 2003;12:82-7.

TAFFI R, NANETTI L, MAZZANTI L, BARTOLINI M, VIGNINI A, RAFFAELLI F, ET AL. Plasma levels of nitric oxide and stroke outcome. J Neurol. 2008;255:94-8.

WANG J, BROWN MA, TAM SH, CHAN MC, WHITWORTH JA. Effects of diet on measurement of nitric oxide metabolites. Clin Exp Pharmacol Physiol. 1997;24:418-20.

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