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Letter by Heo et al Regarding Article, “Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke”
To the Editor: We read with great interest the recent article by Llull et al1 based on the Efficacy Study of Combined Treatment with Uric Acid and rtPA in Acute Ischemic Stroke (URICO-ICTUS) trial.2 The authors report that uric acid (UA) treatment was effective in female patients who received recombinant tissue-type plasminogen activator by preventing infarct growth, which led to excellent outcome. The results support the hypotheses that the poorer outcome in female patients rather than male patients treated with recombinant tissue-type plasminogen activator can be explained by the low levels of UA and that the outcome may be improved by treating with UA. The UA level has been known to be associated with the risk of hypertension and cardiovascular disease in the chronic stage, whereas it is protective in the acute stage. However, these associations were different between men and women in previous reports.3,4 Therefore, this study helps to understand the complicated sexual differences on the effect of UA at each stage of ischemic stroke. In URICO-ICTUS trial, UA treatment was more effective in patients with mild to moderate severity (baseline National Institutes of Health Stroke Scale score, 15) with high serum UA levels had a good outcome.3 As your group previously reported, the baseline UA level must be considered to conclude that the total amount of UA (the sum of baseline body UA and administrated UA) determines the patient’s clinical outcome.5 However, there was no detailed description of baseline UA levels. Furthermore, the differences in UA levels from serial blood samples for each sex were not described. As the baseline UA level is an important factor affecting the clinical outcome, it should be entered into the multivariate analysis model. If the baseline UA level is not considered, then it
is difficult to determine whether the effect is because of a sexual difference or baseline UA level. In this study, the data were analyzed from only 43 patients (10.5%) with multimodal brain imaging and allantoin/UA ratios. The allantoin/UA ratio was greater in female patients. This finding may explain the difference of clinical outcome according to sex, but the cause of different responses to the allantoin/UA ratio in female patients is unexplainable. Thus, further experimental studies by a larger sample of patients with baseline UA level should be performed to confirm the different effect of UA treatment in both sexes.
Disclosures None.
Sung Hyuk Heo, MD, PhD Dae-Il Chang, MD, PhD Department of Neurology Kyung Hee University College of Medicine Seoul, Korea Bum Joon Kim, MD Department of Neurology Asan Medical Center University of Ulsan Seoul, Korea 1. Llull L, Laredo C, Renú A, Pérez B, Vila E, Obach V, et al. Uric acid therapy improves clinical outcome in women with acute ischemic stroke. Stroke. 2015;46:2162–2167. doi: 10.1161/STROKEAHA.115.009960. 2. Chamorro A, Amaro S, Castellanos M, Segura T, Arenillas J, MartíFábregas J, et al; URICO-ICTUS Investigators. Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial. Lancet Neurol. 2014;13:453–460. doi: 10.1016/S1474-4422(14)70054-7. 3. Lee SH, Heo SH, Kim JH, Lee D, Lee JS, Kim YS, et al. Effects of uric acid levels on outcome in severe ischemic stroke patients treated with intravenous recombinant tissue plasminogen activator. Eur Neurol. 2014;71:132–139. doi: 10.1159/000355020. 4. Heo SH, Lee SH. High levels of serum uric acid are associated with silent brain infarction. J Neurol Sci. 2010;297:6–10. doi: 10.1016/j. jns.2010.07.007. 5. 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. doi: 10.1161/ STROKEAHA.110.596528.
(Stroke. 2015;46:e241. DOI: 10.1161/STROKEAHA.115.011162.) © 2015 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.115.011162
Downloaded from http://stroke.ahajournals.org/ at University of Otago Library on November 25, 2015 e241
Letter by Heo et al Regarding Article, ''Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke'' Sung Hyuk Heo, Dae-Il Chang and Bum Joon Kim Stroke. 2015;46:e241; originally published online October 8, 2015; doi: 10.1161/STROKEAHA.115.011162 Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2015 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/46/11/e241
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/
Downloaded from http://stroke.ahajournals.org/ at University of Otago Library on November 25, 2015
Letter by Heo et al Regarding Article, “Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke”
To the Editor: We read with great interest the recent article by Llull et al1 based on the Efficacy Study of Combined Treatment with Uric Acid and rtPA in Acute Ischemic Stroke (URICO-ICTUS) trial.2 The authors report that uric acid (UA) treatment was effective in female patients who received recombinant tissue-type plasminogen activator by preventing infarct growth, which led to excellent outcome. The results support the hypotheses that the poorer outcome in female patients rather than male patients treated with recombinant tissue-type plasminogen activator can be explained by the low levels of UA and that the outcome may be improved by treating with UA. The UA level has been known to be associated with the risk of hypertension and cardiovascular disease in the chronic stage, whereas it is protective in the acute stage. However, these associations were different between men and women in previous reports.3,4 Therefore, this study helps to understand the complicated sexual differences on the effect of UA at each stage of ischemic stroke. In URICO-ICTUS trial, UA treatment was more effective in patients with mild to moderate severity (baseline National Institutes of Health Stroke Scale score, 15) with high serum UA levels had a good outcome.3 As your group previously reported, the baseline UA level must be considered to conclude that the total amount of UA (the sum of baseline body UA and administrated UA) determines the patient’s clinical outcome.5 However, there was no detailed description of baseline UA levels. Furthermore, the differences in UA levels from serial blood samples for each sex were not described. As the baseline UA level is an important factor affecting the clinical outcome, it should be entered into the multivariate analysis model. If the baseline UA level is not considered, then it
is difficult to determine whether the effect is because of a sexual difference or baseline UA level. In this study, the data were analyzed from only 43 patients (10.5%) with multimodal brain imaging and allantoin/UA ratios. The allantoin/UA ratio was greater in female patients. This finding may explain the difference of clinical outcome according to sex, but the cause of different responses to the allantoin/UA ratio in female patients is unexplainable. Thus, further experimental studies by a larger sample of patients with baseline UA level should be performed to confirm the different effect of UA treatment in both sexes.
Disclosures None.
Sung Hyuk Heo, MD, PhD Dae-Il Chang, MD, PhD Department of Neurology Kyung Hee University College of Medicine Seoul, Korea Bum Joon Kim, MD Department of Neurology Asan Medical Center University of Ulsan Seoul, Korea 1. Llull L, Laredo C, Renú A, Pérez B, Vila E, Obach V, et al. Uric acid therapy improves clinical outcome in women with acute ischemic stroke. Stroke. 2015;46:2162–2167. doi: 10.1161/STROKEAHA.115.009960. 2. Chamorro A, Amaro S, Castellanos M, Segura T, Arenillas J, MartíFábregas J, et al; URICO-ICTUS Investigators. Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial. Lancet Neurol. 2014;13:453–460. doi: 10.1016/S1474-4422(14)70054-7. 3. Lee SH, Heo SH, Kim JH, Lee D, Lee JS, Kim YS, et al. Effects of uric acid levels on outcome in severe ischemic stroke patients treated with intravenous recombinant tissue plasminogen activator. Eur Neurol. 2014;71:132–139. doi: 10.1159/000355020. 4. Heo SH, Lee SH. High levels of serum uric acid are associated with silent brain infarction. J Neurol Sci. 2010;297:6–10. doi: 10.1016/j. jns.2010.07.007. 5. 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. doi: 10.1161/ STROKEAHA.110.596528.
(Stroke. 2015;46:e241. DOI: 10.1161/STROKEAHA.115.011162.) © 2015 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.115.011162
Downloaded from http://stroke.ahajournals.org/ at University of Otago Library on November 25, 2015 e241
Letter by Heo et al Regarding Article, ''Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke'' Sung Hyuk Heo, Dae-Il Chang and Bum Joon Kim Stroke. 2015;46:e241; originally published online October 8, 2015; doi: 10.1161/STROKEAHA.115.011162 Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2015 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/46/11/e241
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/
Downloaded from http://stroke.ahajournals.org/ at University of Otago Library on November 25, 2015
