Atherosclerosis 236 (2014) 144e149
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
The association baseline NIH Stroke Scale score with ABO bloodsubtypes in young patients with acute ischemic stroke Ning Yang c, 1, Bin Zhang a, b, 1, 2, Longchang Xie a, b, Jianrui Yin a, b, Yihua He a, b, Xinguang Yang a, b, Cong Gao a, b, *, 2 a
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neuroscience and the Second Affiliated Hospital of GuangZhou Medical University, 250# Changgang East Road, GuangZhou, 510260 Guangdong Province, China Department of Neurology, the Second Affiliated Hospital of GuangZhou Medical University, 250# Changgang East Road, GuangZhou, 510260 Guangdong Province, China c Department of Neurology, the Fifth Affiliated Hospital of GuangZhou Medical University, 621# Harbour Road, GuangZhou, 510700 Guangdong Province, China b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 11 February 2014 Received in revised form 26 April 2014 Accepted 18 June 2014 Available online 11 July 2014
Objectives: The presence of the A and B blood group antigens has been associated with risk of arterial thrombosis. The aim of the current study was to design a new simpler form of National Institutes of Health Stroke Scale (NIHSS) for use on admission, and assess the association of blood groups with NIHSS score in young stroke patients. Methods: We conducted this study in 1311 young Chinese adults with acute ischemic cerebral stroke. The outcome measures included a composite favorable outcome (defined as a modified Rankin Scale (mRS) of 0 or 2) and poor outcome (defined as a modified Rankin Scale score of 3 or 6) at discharge; a minor strokes (NIHSS scores 0e5) and severe strokes (NIHSS scores 6). Logistic regression analyses were used to determine the association between ABO blood groups and stroke severity. Results: Regression analysis confirmed in relative to patients with AB subtype, Oxfordshire community stroke project classification (OCSP) subtype and serum white blood cell (WBC) were the major predictors for stroke severity. Meanwhile, diabetes, serum triglyceride and uric acid levels were determined as independent indicators of stroke severity in A, B and O blood subtype respectively. The optimal cutoff score of the baseline NIHSS was 5 for patients with non-O subtype, the optimal cutoff score of the baseline NIHSS was 7 for patients with blood O subtype. Conclusions: Our analysis provide compelling information regarding the ABO blood groups differences in predictors of stroke severity and the different validity of NIHSS scores in predicting prognosis at discharge between O subtype and non-O subtype. © 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Blood groups NIHSS Young Ischemic stroke
1. Introduction The presence of the A and B blood group antigens, expressed on red blood cells and other cells and molecules within the body, has been associated with risk of arterial thrombosis. Most studies indicate an increased risk of thrombosis associated with
* Corresponding author. Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neuroscience and the Second Affiliated Hospital of GuangZhou Medical University, 250# Changgang East Road, GuangZhou, 510260 Guangdong Province, China. Tel./ fax: þ86 020 3415 3276. E-mail addresses: [email protected], [email protected] (C. Gao). 1 Ning Yang and Bin Zhang are co-first author. 2 Bin Zhang and Cong Gao contributed equally. http://dx.doi.org/10.1016/j.atherosclerosis.2014.06.019 0021-9150/© 2014 Elsevier Ireland Ltd. All rights reserved.
the non-O blood group, for example, the non-O phenotype (i.e. A, B or AB) is associated with myocardial infarction (MI) and coronary artery disease (CAD) [1]. However, it is argument for the association ABO blood group system with ischemic stroke. Early studies reported a lack of association between ABO and stroke [2,3], and some recent analysis also found ABO phenotype or genotype does not have a major impact in the pathophysiology of ischemic stroke or any of the ischemic stroke subtypes [4]. Especially, Wang et al. had demonstrated ABO blood antigens define human cerebral endothelial diversity that participate in almost all cerebrovascular pathological processes. They proposed that human ABO antigens are selectively expressed in endothelial cells and show a discontinuous pattern in blood type A individuals [5].
N. Yang et al. / Atherosclerosis 236 (2014) 144e149
The NIH Stroke Scale (NIHSS) is a neurologic severity scale that is valid, reliable, and reproducible [6]; Baseline NIHSS scores on admission are associated with chronic functional outcome [7], hospital disposition after stroke [8], but there is no study regarding the association baseline NIHSS Score with ABO blood-subtypes in young patients with acute ischemic stroke. Against this background, we aimed to find the association NIHSS score with ABO blood-group in youth ischemic stroke, and to identify the different predictors of stroke severity among ABO blood-group. 2. Subjects and methods All patients were 18e50 years old and first-ever cerebral infarction during 2001e2013. Consecutive patients come from the Second Affiliated Hospital of Guangzhou Medicine University, Guangzhou, Chinese mainland. Our institution is the biggest hospital that covers an urban area of approximately 2,500,000 individuals, all Chinese. All patients experiencing a new focal or global neurological event were admitted within 48 h. Brain imaging (magnetic resonance imaging MRI) was performed routinely within 24e48 h after admission. We excluded those patients with cerebral infarction caused by subarachnoid hemorrhage, sinus venous thrombosis, or severe head trauma. Strokes were classified according to the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) system [9] and Oxfordshire community stroke project classification (OCSP) [32]. The TOAST classification is based on etiology, and denotes five subtypes of ischemic stroke: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) stroke of other determined etiology, and 5) stroke of undetermined etiology [9]. The Oxfordshire Community Stroke Project (OCSP) classification is a simple tool to categorize clinical stroke syndromes. The OCSP classification denotes total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), posterior circulation infarcts (POCI), or lacunar infarcts (LACI) [32]. The modified Rankin Scale (mRS) and NIHSS were available in 1311 patients. The mRS score at discharge in our study was classified as independent (score 0e2) or dependent/dead (score 3e6) [10], and the NIHSS score on admission was classified as minor strokes (NIHSS scores 0e5) versus severe strokes (NIHSS scores 6) [11]. At baseline, demographic data (age, sex), history of conventional vascular risk factors (hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, smoking habit, alcohol abuse) were obtained. Routine blood and biochemical tests, Electrocardiogram (ECG), and a baseline brain MRI scan were performed in all patients on admission, laboratory investigations for vascular risk factors, duplex sonography of the carotid and vertebral arteries, and a thorough cardiac investigation were all taken. All patients received treatment according to the current guidelines but none of them underwent thrombolysis or surgical treatment. In fact, because the time from stroke onset to coming in hospital for our patients basically are longer than 10 h (namely thrombolysis time), therefore, none of them underwent thrombolysis. Meanwhile, fearing the risks of surgery and expensive cost, although we strongly recommend appropriate surgical treatment for our patients, but none of them consent to surgery treatment including cerebral vascular stents. We received written informed patient consent to perform this study. All patients had given informed consent to participate in the study. Permission for the study was obtained by the local ethics committees. 3. Blood-type measurement One to two ml of blood sample for grouping was collected from patients and controls by a staff nurse. ABO blood group was
145
determined using ABO gel card test. The gel test was first released in Europe and then in USA [12]. The technology was developed by Lapierre et al. [13]. We used ID-Card gel forward grouping and IDCard gel reverse grouping, which were supplied by DiaMed. 4. Statistical analyses Data are presented as means ± standard deviations. For the outcome of ischemic stroke, the following demographic variables and vascular risk factors at study entry were compared between patients with and without severe outcome by univariate and multivariate analyses: sex, age at onset, hypertension, smoking and drinking, atrial fibrillation, diabetes mellitus, lipid disorder, TOAST and OCSP stroke classification, serum white blood cell, platelet, uric acid, glucose, and serum lipids levels. Demographic variables and vascular risk factors at study entry were compared between patients with/without severe stroke by the x2 test for binary and categorical data and the ManneWhitney U test for continuous variables among different blood-group system. Multivariate analysis was performed by multinomial and binary logistic regression analysis, which allows adjustment for confounding factors. All variables have an inclusion criterion of P < 0.10 that were at least weakly associated with stroke severity. To obtain the baseline NIHSS score as the cutoff point for discriminating between patients with a favorable outcome and those without, we constructed receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC) with 95% CIs. p < 0.05 was considered significant. The analyses were undertaken with the SPSS (version 13.1) software package. 5. Results Table 1 showed characteristics of ischemic stroke patients with baseline NIHSS
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
The association baseline NIH Stroke Scale score with ABO bloodsubtypes in young patients with acute ischemic stroke Ning Yang c, 1, Bin Zhang a, b, 1, 2, Longchang Xie a, b, Jianrui Yin a, b, Yihua He a, b, Xinguang Yang a, b, Cong Gao a, b, *, 2 a
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neuroscience and the Second Affiliated Hospital of GuangZhou Medical University, 250# Changgang East Road, GuangZhou, 510260 Guangdong Province, China Department of Neurology, the Second Affiliated Hospital of GuangZhou Medical University, 250# Changgang East Road, GuangZhou, 510260 Guangdong Province, China c Department of Neurology, the Fifth Affiliated Hospital of GuangZhou Medical University, 621# Harbour Road, GuangZhou, 510700 Guangdong Province, China b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 11 February 2014 Received in revised form 26 April 2014 Accepted 18 June 2014 Available online 11 July 2014
Objectives: The presence of the A and B blood group antigens has been associated with risk of arterial thrombosis. The aim of the current study was to design a new simpler form of National Institutes of Health Stroke Scale (NIHSS) for use on admission, and assess the association of blood groups with NIHSS score in young stroke patients. Methods: We conducted this study in 1311 young Chinese adults with acute ischemic cerebral stroke. The outcome measures included a composite favorable outcome (defined as a modified Rankin Scale (mRS) of 0 or 2) and poor outcome (defined as a modified Rankin Scale score of 3 or 6) at discharge; a minor strokes (NIHSS scores 0e5) and severe strokes (NIHSS scores 6). Logistic regression analyses were used to determine the association between ABO blood groups and stroke severity. Results: Regression analysis confirmed in relative to patients with AB subtype, Oxfordshire community stroke project classification (OCSP) subtype and serum white blood cell (WBC) were the major predictors for stroke severity. Meanwhile, diabetes, serum triglyceride and uric acid levels were determined as independent indicators of stroke severity in A, B and O blood subtype respectively. The optimal cutoff score of the baseline NIHSS was 5 for patients with non-O subtype, the optimal cutoff score of the baseline NIHSS was 7 for patients with blood O subtype. Conclusions: Our analysis provide compelling information regarding the ABO blood groups differences in predictors of stroke severity and the different validity of NIHSS scores in predicting prognosis at discharge between O subtype and non-O subtype. © 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Blood groups NIHSS Young Ischemic stroke
1. Introduction The presence of the A and B blood group antigens, expressed on red blood cells and other cells and molecules within the body, has been associated with risk of arterial thrombosis. Most studies indicate an increased risk of thrombosis associated with
* Corresponding author. Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neuroscience and the Second Affiliated Hospital of GuangZhou Medical University, 250# Changgang East Road, GuangZhou, 510260 Guangdong Province, China. Tel./ fax: þ86 020 3415 3276. E-mail addresses: [email protected], [email protected] (C. Gao). 1 Ning Yang and Bin Zhang are co-first author. 2 Bin Zhang and Cong Gao contributed equally. http://dx.doi.org/10.1016/j.atherosclerosis.2014.06.019 0021-9150/© 2014 Elsevier Ireland Ltd. All rights reserved.
the non-O blood group, for example, the non-O phenotype (i.e. A, B or AB) is associated with myocardial infarction (MI) and coronary artery disease (CAD) [1]. However, it is argument for the association ABO blood group system with ischemic stroke. Early studies reported a lack of association between ABO and stroke [2,3], and some recent analysis also found ABO phenotype or genotype does not have a major impact in the pathophysiology of ischemic stroke or any of the ischemic stroke subtypes [4]. Especially, Wang et al. had demonstrated ABO blood antigens define human cerebral endothelial diversity that participate in almost all cerebrovascular pathological processes. They proposed that human ABO antigens are selectively expressed in endothelial cells and show a discontinuous pattern in blood type A individuals [5].
N. Yang et al. / Atherosclerosis 236 (2014) 144e149
The NIH Stroke Scale (NIHSS) is a neurologic severity scale that is valid, reliable, and reproducible [6]; Baseline NIHSS scores on admission are associated with chronic functional outcome [7], hospital disposition after stroke [8], but there is no study regarding the association baseline NIHSS Score with ABO blood-subtypes in young patients with acute ischemic stroke. Against this background, we aimed to find the association NIHSS score with ABO blood-group in youth ischemic stroke, and to identify the different predictors of stroke severity among ABO blood-group. 2. Subjects and methods All patients were 18e50 years old and first-ever cerebral infarction during 2001e2013. Consecutive patients come from the Second Affiliated Hospital of Guangzhou Medicine University, Guangzhou, Chinese mainland. Our institution is the biggest hospital that covers an urban area of approximately 2,500,000 individuals, all Chinese. All patients experiencing a new focal or global neurological event were admitted within 48 h. Brain imaging (magnetic resonance imaging MRI) was performed routinely within 24e48 h after admission. We excluded those patients with cerebral infarction caused by subarachnoid hemorrhage, sinus venous thrombosis, or severe head trauma. Strokes were classified according to the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) system [9] and Oxfordshire community stroke project classification (OCSP) [32]. The TOAST classification is based on etiology, and denotes five subtypes of ischemic stroke: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) stroke of other determined etiology, and 5) stroke of undetermined etiology [9]. The Oxfordshire Community Stroke Project (OCSP) classification is a simple tool to categorize clinical stroke syndromes. The OCSP classification denotes total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), posterior circulation infarcts (POCI), or lacunar infarcts (LACI) [32]. The modified Rankin Scale (mRS) and NIHSS were available in 1311 patients. The mRS score at discharge in our study was classified as independent (score 0e2) or dependent/dead (score 3e6) [10], and the NIHSS score on admission was classified as minor strokes (NIHSS scores 0e5) versus severe strokes (NIHSS scores 6) [11]. At baseline, demographic data (age, sex), history of conventional vascular risk factors (hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, smoking habit, alcohol abuse) were obtained. Routine blood and biochemical tests, Electrocardiogram (ECG), and a baseline brain MRI scan were performed in all patients on admission, laboratory investigations for vascular risk factors, duplex sonography of the carotid and vertebral arteries, and a thorough cardiac investigation were all taken. All patients received treatment according to the current guidelines but none of them underwent thrombolysis or surgical treatment. In fact, because the time from stroke onset to coming in hospital for our patients basically are longer than 10 h (namely thrombolysis time), therefore, none of them underwent thrombolysis. Meanwhile, fearing the risks of surgery and expensive cost, although we strongly recommend appropriate surgical treatment for our patients, but none of them consent to surgery treatment including cerebral vascular stents. We received written informed patient consent to perform this study. All patients had given informed consent to participate in the study. Permission for the study was obtained by the local ethics committees. 3. Blood-type measurement One to two ml of blood sample for grouping was collected from patients and controls by a staff nurse. ABO blood group was
145
determined using ABO gel card test. The gel test was first released in Europe and then in USA [12]. The technology was developed by Lapierre et al. [13]. We used ID-Card gel forward grouping and IDCard gel reverse grouping, which were supplied by DiaMed. 4. Statistical analyses Data are presented as means ± standard deviations. For the outcome of ischemic stroke, the following demographic variables and vascular risk factors at study entry were compared between patients with and without severe outcome by univariate and multivariate analyses: sex, age at onset, hypertension, smoking and drinking, atrial fibrillation, diabetes mellitus, lipid disorder, TOAST and OCSP stroke classification, serum white blood cell, platelet, uric acid, glucose, and serum lipids levels. Demographic variables and vascular risk factors at study entry were compared between patients with/without severe stroke by the x2 test for binary and categorical data and the ManneWhitney U test for continuous variables among different blood-group system. Multivariate analysis was performed by multinomial and binary logistic regression analysis, which allows adjustment for confounding factors. All variables have an inclusion criterion of P < 0.10 that were at least weakly associated with stroke severity. To obtain the baseline NIHSS score as the cutoff point for discriminating between patients with a favorable outcome and those without, we constructed receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC) with 95% CIs. p < 0.05 was considered significant. The analyses were undertaken with the SPSS (version 13.1) software package. 5. Results Table 1 showed characteristics of ischemic stroke patients with baseline NIHSS
