Serum Uric Acid and Outcome after Acute Ischemic Stroke: PREMIER StudyChiquete E.a · Ruiz-Sandoval J.L.b · Murillo-Bonilla L.M.c · Arauz A.d · Orozco-Valera D.R.b · Ochoa-Guzmán A.b · Villarreal-Careaga J.e · León-Jiménez C.f · Barinagarrementeria F.g · Ramos-Moreno A.h · Cantú-Brito C.a
aDepartment of Neurology and Psychiatry, Instituto Nacional de Ciencias Médicas y Nutrición ‘Salvador Zubirán', Mexico City, bDepartment of Neurology, Hospital Civil de Guadalajara ‘Fray Antonio Alcalde', Guadalajara, cDepartment of Neurology, Universidad Autónoma de Guadalajara, Zapopan, dStroke Clinic, Instituto Nacional de Neurología y Neurocirugía, Mexico City, eDepartment of Neurology, Hospital General de Culiacán, Culiacán, fDepartment of Neurology, Hospital Regional ‘Dr. Valentín Gómez Farías', ISSSTE, Zapopan, gDepartment of Neurology, Hospital Ángeles de Querétaro, Querétaro, hMedical Research Area, Sanofi-Aventis, Mexico City, Mexico
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Background: Current evidence shows that uric acid is a potent antioxidant whose serum concentration increases rapidly after acute ischemic stroke (AIS). Nevertheless, the re-lationship between serum uric acid (SUA) levels and AIS outcome remains debatable. We aimed to describe the prognostic significance of SUA in AIS. Methods: We studied 463 patients (52% men, mean age 68 years, 13% with glomerular filtration rate <60 ml/min at hospital arrival) with AIS pertaining to the multicenter registry PREMIER, who had SUA measurements at hospital presentation. Multivariate models were constructed to analyze the association of SUA with functional outcome as assessed by the modified Rankin scale (mRS) at 30-day, 3-, 6- and 12-month follow-up. A mRS 0-1 was regarded as a very good outcome. Results: Mean SUA concentration at hospital arrival was 6.1 ± 3.7 mg/dl (362.8 ± 220.0 μmol/l). Compared with cases with higher SUA levels at hospital admission, patients with ≤4.5 mg/dl (≤267.7 μmol/l; the lowest tertile of the sample) had more cases of a very good 30-day outcome (30.5 vs. 18.9%, respectively; p = 0.004). SUA was not associated with mortality or functional dependence (mRS >2) at 30 days, or with any outcome measure at 3, 6 or 12 months poststroke. After adjustment for age, gender, stroke type and severity (NIHSS <9), time since event onset, serum creatinine, hypertension, diabetes and smoking, a SUA ≤4.5 mg/dl (≤267.7 μmol/l) was positively associated with a very good short-term outcome (odds ratio: 1.76, 95% confidence interval: 1.05-2.95; negative predictive value: 81.1%), but not at 3, 6 or 12 months of follow-up. When NIHSS was entered in the multivariate model as a continuous variable, the independent association of SUA with outcome was lost. Compared with cases with higher levels, patients with SUA ≤4.5 mg/dl (≤267.7 μmol/l) were more frequently younger than 55 years, women, with mild strokes, with normal serum creatinine and fewer had hypertension. The time since event onset to hospital arrival was not significantly associated with AIS severity or SUA levels; nevertheless, a nonsignificant tendency was observed for patients with severe strokes and high SUA levels arriving in <24 h. Conclusions: A low SUA concentration is modestly associated with a very good short-term outcome. Our findings support the hypothesis that SUA is more a marker of the magnitude of the cerebral infarction than an independent predictor of stroke outcome.
© 2013 S. Karger AG, Basel
- Lehto S, Niskanen L, Rönnemaa T, Laakso M: Serum uric acid is a strong predictor of stroke in patients with non-insulin-dependent diabetes mellitus. Stroke 1998;29:635-639.
- Koton S, Howard SC, Warlow CP, Murphy MF, Rothwell PM: Serum urate predicts long-term risk of acute coronary events in women after a transient ischaemic attack and stroke. Cerebrovasc Dis 2008;26:517-524.
- Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G: Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417,734 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). J Intern Med 2009;266:558-570.
- Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA: Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum. 2009;61:885-892.
- Kawai T, Ohishi M, Takeya Y, Onishi M, Ito N, Yamamoto K, et al: Serum uric acid is an independent risk factor for cardiovascular disease and mortality in hypertensive patients. Hypertens Res 2012;35:1087-1092.
- Waring WS: Uric acid: an important antioxidant in acute ischaemic stroke. QJM 2002;95:691-693.
- Yang T, Chu CH, Bai CH, You SL, Chou YC, Chou WY, et al: Uric acid level as a risk marker for metabolic syndrome: a Chinese cohort study. Atherosclerosis 2012;220:525-531.
- Zhang Z, Bian L, Choi Y: Serum uric Acid: a marker of metabolic syndrome and subclinical atherosclerosis in Korean men. Angiology 2012;63:420-428.
- Chamorro A, Obach V, Cervera A, Revilla M, Deulofeu R, Aponte JH: Prognostic significance of uric acid serum concentration in patients with acute ischemic stroke. Stroke 2002;33:1048-1052.
- 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.
- Romanos E, Planas AM, Amaro S, Chamorro A: Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model of thromboembolic stroke. J Cereb Blood Flow Metab 2007;27:14-20.
- Hong JM, Bang OY, Chung CS, Joo IS, Gwag BJ, Ovbiagele B: Influence of recanalization on uric acid patterns in acute ischemic stroke. Cerebrovasc Dis 2010;29:431-439.
- Brouns R, Wauters A, Van De Vijver G, De Surgeloose D, Sheorajpanday R, De Deyn PP: Decrease in uric acid in acute ischemic stroke correlates with stroke severity, evolution and outcome. Clin Chem Lab Med 2010;48:383-390.
- Schretlen DJ, Inscore AB, Vannorsdall TD, Kraut M, Pearlson GD, Gordon B, et al: Serum uric acid and brain ischemia in normal elderly adults. Neurology 2007;69:1418-1423.
- Dawson J, Lees KR, Weir CJ, Quinn T, Ali M, Hennerici MG, et al: Baseline serum urate and 90-day functional outcomes following acute ischemic stroke. Cerebrovasc Dis 2009;28:202-203.
- Kanellis J, Johnson RJ: Editorial comment - Elevated uric acid and ischemic stroke: accumulating evidence that it is injurious and not neuroprotective. Stroke 2003;34:1956-1957.
- Miedema I, Uyttenboogaart M, Koch M, Kremer B, de Keyser J, Luijckx GJ: Lack of association between serum uric acid levels and outcome in acute ischemic stroke. J Neurol Sci 2012;319:51-55.
- Seet RC, Kasiman K, Gruber J, Tang SY, Wong MC, Chang HM, et al: Is uric acid protective or deleterious in acute ischemic stroke? A prospective cohort study. Atherosclerosis 2010;209:215-219.
- Dimitroula HV, Hatzitolios AI, Karvounis HI: The role of uric acid in stroke: the issue remains unresolved. Neurologist 2008;14:238-242.
- Weir CJ, Muir SW, Walters MR, Lees KR: Serum urate as an independent predictor of poor outcome and future vascular events after acute stroke. Stroke 2003;34:1951-1956.
- Karagiannis A, Mikhailidis DP, Tziomalos K, Sileli M, Savvatianos S, Kakafika A, et al: Serum uric acid as an independent predictor of early death after acute stroke. Circ J 2007;71:1120-1127.
- Higgins P, Ferguson LD, Walters MR: Xanthine oxidase inhibition for the treatment of stroke disease: a novel therapeutic approach. Expert Rev Cardiovasc Ther 2011;9:399-401.
- Amaro S, Soy D, Obach V, Cervera A, Planas AM, Chamorro A: A pilot study of dual treatment with recombinant tissue plasminogen activator and uric acid in acute ischemic stroke. Stroke 2007;38:2173-2175.
- Amaro S, Cánovas D, Castellanos M, Gállego J, Martí-Fèbregas J, Segura T, Chamorro A: The URICO-ICTUS study, a phase 3 study of combined treatment with uric acid and rtPA administered intravenously in acute ischaemic stroke patients within the first 4.5 h of onset of symptoms. Int J Stroke 2010;5:325-328.
- Logallo N, Naess H, Idicula TT, Brogger J, Waje-Andreassen U, Thomassen L: Serum uri acid: neuroprotection in thrombolysis. The Bergen NORSTROKE study. BMC Neurol 2011;11:114.
- Cantú-Brito C, Ruiz-Sandoval JL, Murillo-Bonilla LM, Chiquete E, León-Jiménez C, Arauz A, et al: Acute care and one-year outcome of Mexican patients with first-ever acute ischemic stroke: the PREMIER study. Rev Neurol 2010;51:641-649.
- Chiquete E, Cantú-Brito C, Villarreal-Careaga J, Murillo-Bonilla LM, Rangel-Guerra R, León-Jiménez C, et al: [Obesity paradox and functional recovery in first-ever acute ischemic stroke survivors: the PREMIER study]. Rev Neurol 2010;51:705-713.
- Cantú-Brito C, Ruiz-Sandoval JL, Murillo-Bonilla LM, Chiquete E, León-Jiménez C, Arauz A, et al: The first Mexican multicenter register on ischaemic stroke (the PREMIER study): demographics, risk factors and outcome. Int J Stroke 2011;6:93-94.
- Amaro S, Urra X, Gómez-Choco M, Obach V, Cervera A, Vargas M, et al: Uric acid levels are relevant in patients with stroke treated with thrombolysis. Stroke 2011;42(1 suppl):S28-S32.
- Zhang B, Gao C, Yang N, Zhang W, Song X, Yin J, et al: Is elevated SUA associated with a worse outcome in young Chinese patients with acute cerebral ischemic stroke? BMC Neurol 2010;10:82.
- Nardi K, Milia P: Letter by Nardi and Milia regarding article, ‘translational stroke research of the combination of thrombolysis and antioxidant therapy'. Stroke 2011;42:e547.
- Poss WB, Huecksteadt TP, Panus PC, Freeman BA, Hoidal JR: Regulation of xanthine dehydrogenase and xanthine oxidase activity by hypoxia. Am J Physiol 1996;270:L941-L946.
- George J, Struthers AD: Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. Vasc Health Risk Manag 2009;5:265-272.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.