脑梗死出血转化危险因素的前瞻性研究
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摘要
背景及目的
脑梗死出血转化(hemorrhagic transformation, HT)是指急性缺血性脑卒中后短时间内出现的继发脑出血现象。依据不同的分型原则,脑梗死出血转化有不同的分型标准：目前应用最广泛的分型是欧洲急性卒中协作研究根据脑CT表现将HT分为出血性脑梗死(hemorrhagic infarction, HI)和脑实质出血(parenchymal hemorrhage, PH),HT和PH又分别分两个亚型：沿梗死边缘小点状出血的HI1型；梗死区内片状无占位效应出血的HI2型；有血肿形成,占位效应轻,小于梗死面积30%为PH1型；血肿超过梗死面积30%,有明显占位效应以及远离梗死区的出血为PH2型。HT多发生在急性脑梗死后1～2周内,其发生机制包括血管再通、血管壁缺血性损伤、侧枝循环建立及血脑屏障破坏等。脑梗死后影像学检查中HT的出现率为6%～43%不等,而尸解发现其发生率可高达71%。由于HT的发生率较高,可能导致预后不良,从而加深医患矛盾。基于此,近年来国内外学者从临床、神经影像、生化指标等方面对其发病机制、可能的影响因素和预测因素进行了研究,但由于研究采用的标准不同,人群不同、研究方法不同,所得结论不完全一致,不利于对其进行有效的防治。本试验通过前瞻性登记急性脑梗死患者,观察急性脑梗死出血转化的发生情况及可能的危险因素,为有效预防和采取合适的医疗措施提供依据。
材料与方法
1.研究对象
前瞻性纳入从2011年3月至2012年3月,在郑州大学第一附属医院住院的发病1周内的急性脑梗死患者。纳入标准：①符合第四次全国脑血管病学术会议制定的脑梗死诊断标准；②从发病至就诊时间小于1周；③发病2周复查头颅CT或MRI。排除标准：①本次发病前出现任何原因导致的神经功能缺损；②发病2周内未复查头颅CT或MRI。③伴有严重的肝、肾疾病及恶性肿瘤患者。
2.研究方法
2.1纳入患者详细资料：年龄、性别、发病至就诊时间间隔、既往史(高血压病史、糖尿病史、高脂血症、房颤史、心肌梗塞病史、冠心病史、心瓣膜病史、既往卒中史、吸烟史、饮酒史)、入院首次血压、意识水平、神经功能缺损程度、空腹血糖、血常规、凝血指标、血小板计数、血脂(甘油三酯、胆固醇、高密度脂蛋白、低密度脂蛋白)、心电图表现、头颅CT及MRI、MRA表现、颈部血管彩超表现、心脏彩超表现、脑梗死病因(TOAST)分型。
2.2根据欧洲卒中协作组(The European Cooperative Acute Stroke Study, ECASS)标准将纳入患者分为脑梗死出血转化(hemorrhagic transformation, HT)组和非脑梗死出血转化组。HT组又分为出血性梗死(HI)和血肿型出血转化(PH)组。3.统计学处理
使用SPSS for Windows19.0软件包对相关资料进行统计分析。
3.1脑梗死出血转化的发生率及TOAST亚型出血转化发生率的比较
3.2脑梗死出血转化危险因素的单因素分析
对可能影响梗死后出血的危险因素进行单因素分析,计量资料采用方差分析,计数资料采用卡方检验或Fisher精确检验,P＜0.1为有统计学意义
3.3脑梗死出血转化危险因素的多因素分析以梗死后出血(HT)为因变量,以单因素分析有统计学差异的指标为自变量,进行Logistic回归分析,P<0.05为有统计学意义
3.4不同亚型脑梗死出血转化危险因素的多因素分析分别以出血性梗死(HI)和血肿型出血转化(PH)为因变量,以可能的危险因素为自变量进行Logistic回归分析,P<0.05为有统计学意义。
结果
最终共纳入865例研究对象,非脑梗死出血转化组810人,脑梗死出血转化组55例,其中出血性梗死47例,血肿型出血转化8例。
1.一般资料
2.脑梗死出血转化(HT)发病率及不同TOAST分型发病率
本研究中,脑梗死出血转化发生率为6.4%。不同TOAST病因分型脑梗死出血转化发病率大动脉粥样硬化梗死型出血转化发生率最高,为16.6%(29/175),其次为心源性栓塞出血转化发生率为9.5%(10/105),小动脉梗死型出血转化发生率3.6%(12/334),不明原因梗死出血转化发生率1.7%(4/229),各型发病率比较差异有统计学意义(x2=32.80,P＜0.05)。
3.脑梗死出血转化危险因素单因素分析
HT组与非HT组在性别、高血压史、糖尿病史、吸烟史、饮酒史、入院时间、入院高血压、首次舒张压、胆固醇、甘油三脂、高密度脂蛋白、低密度脂蛋白无差别无统计学意义(P＞0.1),在年龄、入院首次收缩压、卒中严重程度、意识状态、房颤、空腹血糖、血小板计数、梗死面积上差别具有统计学意义(P＜0.1)
4.脑梗死出血转化及其亚型危险因素多因素分析
4.1脑梗死出血转化危险因素多因素分析
多因素logistic回归分析显示：中度神经功能缺损(RR=3.23,95%CI1.31-7.99)、重度神经功能缺损(RR=9.00,95%CI2.17-37.31)、嗜睡状态(RR=5.024,95%CI,2.17-12.62)、房颤(OR=3.62,95%CI1.11-12.82)、入院高血糖(OR=2.016,95%CI1.01-4.03)、血小板低于200×109/L(OR=2.403,95%CI1.09-5.28)为脑梗死出血转化的独立危险因素。
4.2脑梗死出血转化亚型危险因素多因素分析
4.2.1HI型出血转化危险因素的多因素分析
多因素logistic回归分析显示：中度神经功能缺损(RR=3.89,95%CI1.52-9.93)、重度神经功能缺损(RR=6.58,95%CI1.50-28.94)、嗜睡状态(RR=4.24,95%C,1.75-10.27)、入院高血糖(OR=2.36,95%CI1.14-4.89)、血小板低于200×109/L(OR=2.40,95%CI1.04-5.53)为HI型脑梗死出血转化的独立危险因素。
4.2.2PH型出血转化危险因素的多因素分析
以PH型出血转化为因变量(无=0,有=1),以可能的危险因素为自变量,行多因素logistic回归分析显示：重度神经功能缺损(RR=24.81,95%CI3.50-175.66)、房颤(OR=16.021,95%CI2.4-106.96)为PH型脑梗死出血转化的独立危险因素结论1.大动脉型粥样硬化型脑梗死及心源性脑栓塞引起出血转化风险较小动脉梗死型高。2.中、重度神经功能缺损、嗜睡状态、房颤、入院高血糖、血小板低于200×109/L为脑梗死出血转化的独立危险因素。
Background and Objective
Hemorrhagic transformation (HT) is frequently seen in acute ischemic stroke patients, which can lead to the clinical symptom deterioration and cause conflicts in the treatment of the stroke. To prevent this phenomenon from happening, careful study of risk factors for HT in acute ischemic stroke patients and choosing proper treatment for these patients is necessary. Patients in different conditions carry different risks for HT. Most researches studied risk factors for HT retrospectively, using single factor analysis. It seems that they may not able to show the real risk for HT. The aim of this study was to study the risk factors for HT after acute ischemic stroke prospectively and help make a better choice for the thrombolytic therapy.
Materials and Methods
1. Research objective
Patients treated by the First affiliated hospital of Zhengzhou University within7days of with symptom of acute cerebral infarction onset between March2011and March2012were prospectively registered. Inclusion criteria:1) Meeting the diagnostic criteria of cerebral infarction in the fourth National Cerebrovascular Disease Conference.2) Time from symptoms onset to admission less than one week.3) Having a CT or MRI check for a second time within two weeks from symptoms onset. Exclusion criteria:1) Patients with any neurological deficits before this accident.2) Patients not having a CT or MRI check for a second time within two weeks from symptoms onset.3) Patients with severe liver or kidney disease, or malignant neoplasm.
2. Method
Candidate variables were selected among baseline variables. Candidate variables were selected according to the prior systematic analysis of risk factors for HT. Candidate variables were age, sex, history of hypertension, history of diabetes, history of smoking, history of drinking, atrial fibrillation at baseline, systolic blood pressure at baseline, diastolic blood pressure at baseline, level of consciousness at baseline, neurological deficits at baseline, blood glucose at baseline, serum total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein at baseline, platelet count, Stroke etiology, ischemic changes on CT/MRI, time from symptom onset to treatment. Patients were divided into HT group and none HT group according to EC ASS criteria, and the HT group into HI (hemorrhagic infarction) and PH (parenchyma hemorrhage).
3. Statistical analysis
The data were analyzed using Software SPSS19.0.The risk for HT was investigated using single factors analysis and multiple logistic regression analysis. The difference was statistically significant as P＜0.1in the single factors analysis, and P＜0.05in the multiple logistic regression analysis, all the analysis were two-sided test.
Results
A total of consecutive865acute cerebral infarction patients were included, and55cases were diagnosed as HT, including47HT and8PH.
1. General characteristic
2. Rate of HT in the total and rate of HT by different TOAST type
The rate HT of total number of patients was6.4%, and16.6%for LAA (large artery atherosclerosis)9.5%for CE (cardioembolism),3.86%for SAA (Small artery atherosclerosis),1.75%for UND (Stroke of undermined cause)(x2=32.80, P＜0.05)
3. Single factors analysis
Single factors analysis showed Single factors analysis showed significant (P＜0.1) differences in the age, level of consciousness at baseline, neurological deficits at baseline, serum glucose at baseline, platelet count＜200×109/L, large infarction, atrial fibrillation at baseline, high systolic blood pressure at baseline.
4. Multiple logistic regression analysis for HT
Multiple logistic regression analysis showed that moderate neurological deficits (RR=3.23,95%CI1.31-7.99),severe neurological deficits(RR=9.00,95%CI2.17-37.31) atrial fibrillation (OR=3.62,95%CI1.11-12.82), high blood glucose on admission (OR=2.016,95%CI1.01-4.03)), blood platelet count lower than200×109/L(OR=2.403,95%CI1.09-5.28) were independent risk factors(P＜0.05) for HT.
5. Multiple logistic regression analysis for HI and PH
5.1Multiple logistic regression analysis showed that moderate neurological deficits (RR=3.89,95%CI1.52-9.93), severe neurological deficits (RR=6.58,95%CI1.50-28.94), high blood glucose on admission (OR=2.36,95%CI1.14-4.89), blood platelet count lower than200×109/L (OR=2.40,95%CI1.04-5.53) were independent risk factors (P＜0.05) for HI.
5.2Multiple logistic regression analysis showed that severe neurological deficits (RR=24.81,95%CI3.50-175.66) atrial fibrillation (OR=3.62,95%CI1.11-12.82) were independent risk factors (P<0.05) for PH.
Conclusions
1. Patients of LAA and CE carry a higher risk for HT.
2. Moderate and serious neurological deficits, moderate level of consciousness, atrial fibrillation, high blood glucose on admission and blood platelet count lower than200x109/L are independent risk factors for HT.
脑梗死出血转化(hemorrhagic transformation, HT)是指急性缺血性脑卒中后短时间内出现的继发脑出血现象。依据不同的分型原则,脑梗死出血转化有不同的分型标准：目前应用最广泛的分型是欧洲急性卒中协作研究根据脑CT表现将HT分为出血性脑梗死(hemorrhagic infarction, HI)和脑实质出血(parenchymal hemorrhage, PH),HT和PH又分别分两个亚型：沿梗死边缘小点状出血的HI1型；梗死区内片状无占位效应出血的HI2型；有血肿形成,占位效应轻,小于梗死面积30%为PH1型；血肿超过梗死面积30%,有明显占位效应以及远离梗死区的出血为PH2型。HT多发生在急性脑梗死后1～2周内,其发生机制包括血管再通、血管壁缺血性损伤、侧枝循环建立及血脑屏障破坏等。脑梗死后影像学检查中HT的出现率为6%～43%不等,而尸解发现其发生率可高达71%。由于HT的发生率较高,可能导致预后不良,从而加深医患矛盾。基于此,近年来国内外学者从临床、神经影像、生化指标等方面对其发病机制、可能的影响因素和预测因素进行了研究,但由于研究采用的标准不同,人群不同、研究方法不同,所得结论不完全一致,不利于对其进行有效的防治。本试验通过前瞻性登记急性脑梗死患者,观察急性脑梗死出血转化的发生情况及可能的危险因素,为有效预防和采取合适的医疗措施提供依据。
材料与方法
1.研究对象
前瞻性纳入从2011年3月至2012年3月,在郑州大学第一附属医院住院的发病1周内的急性脑梗死患者。纳入标准：①符合第四次全国脑血管病学术会议制定的脑梗死诊断标准；②从发病至就诊时间小于1周；③发病2周复查头颅CT或MRI。排除标准：①本次发病前出现任何原因导致的神经功能缺损；②发病2周内未复查头颅CT或MRI。③伴有严重的肝、肾疾病及恶性肿瘤患者。
2.研究方法
2.1纳入患者详细资料：年龄、性别、发病至就诊时间间隔、既往史(高血压病史、糖尿病史、高脂血症、房颤史、心肌梗塞病史、冠心病史、心瓣膜病史、既往卒中史、吸烟史、饮酒史)、入院首次血压、意识水平、神经功能缺损程度、空腹血糖、血常规、凝血指标、血小板计数、血脂(甘油三酯、胆固醇、高密度脂蛋白、低密度脂蛋白)、心电图表现、头颅CT及MRI、MRA表现、颈部血管彩超表现、心脏彩超表现、脑梗死病因(TOAST)分型。
2.2根据欧洲卒中协作组(The European Cooperative Acute Stroke Study, ECASS)标准将纳入患者分为脑梗死出血转化(hemorrhagic transformation, HT)组和非脑梗死出血转化组。HT组又分为出血性梗死(HI)和血肿型出血转化(PH)组。3.统计学处理
使用SPSS for Windows19.0软件包对相关资料进行统计分析。
3.1脑梗死出血转化的发生率及TOAST亚型出血转化发生率的比较
3.2脑梗死出血转化危险因素的单因素分析
对可能影响梗死后出血的危险因素进行单因素分析,计量资料采用方差分析,计数资料采用卡方检验或Fisher精确检验,P＜0.1为有统计学意义
3.3脑梗死出血转化危险因素的多因素分析以梗死后出血(HT)为因变量,以单因素分析有统计学差异的指标为自变量,进行Logistic回归分析,P<0.05为有统计学意义
3.4不同亚型脑梗死出血转化危险因素的多因素分析分别以出血性梗死(HI)和血肿型出血转化(PH)为因变量,以可能的危险因素为自变量进行Logistic回归分析,P<0.05为有统计学意义。
结果
最终共纳入865例研究对象,非脑梗死出血转化组810人,脑梗死出血转化组55例,其中出血性梗死47例,血肿型出血转化8例。
1.一般资料
2.脑梗死出血转化(HT)发病率及不同TOAST分型发病率
本研究中,脑梗死出血转化发生率为6.4%。不同TOAST病因分型脑梗死出血转化发病率大动脉粥样硬化梗死型出血转化发生率最高,为16.6%(29/175),其次为心源性栓塞出血转化发生率为9.5%(10/105),小动脉梗死型出血转化发生率3.6%(12/334),不明原因梗死出血转化发生率1.7%(4/229),各型发病率比较差异有统计学意义(x2=32.80,P＜0.05)。
3.脑梗死出血转化危险因素单因素分析
HT组与非HT组在性别、高血压史、糖尿病史、吸烟史、饮酒史、入院时间、入院高血压、首次舒张压、胆固醇、甘油三脂、高密度脂蛋白、低密度脂蛋白无差别无统计学意义(P＞0.1),在年龄、入院首次收缩压、卒中严重程度、意识状态、房颤、空腹血糖、血小板计数、梗死面积上差别具有统计学意义(P＜0.1)
4.脑梗死出血转化及其亚型危险因素多因素分析
4.1脑梗死出血转化危险因素多因素分析
多因素logistic回归分析显示：中度神经功能缺损(RR=3.23,95%CI1.31-7.99)、重度神经功能缺损(RR=9.00,95%CI2.17-37.31)、嗜睡状态(RR=5.024,95%CI,2.17-12.62)、房颤(OR=3.62,95%CI1.11-12.82)、入院高血糖(OR=2.016,95%CI1.01-4.03)、血小板低于200×109/L(OR=2.403,95%CI1.09-5.28)为脑梗死出血转化的独立危险因素。
4.2脑梗死出血转化亚型危险因素多因素分析
4.2.1HI型出血转化危险因素的多因素分析
多因素logistic回归分析显示：中度神经功能缺损(RR=3.89,95%CI1.52-9.93)、重度神经功能缺损(RR=6.58,95%CI1.50-28.94)、嗜睡状态(RR=4.24,95%C,1.75-10.27)、入院高血糖(OR=2.36,95%CI1.14-4.89)、血小板低于200×109/L(OR=2.40,95%CI1.04-5.53)为HI型脑梗死出血转化的独立危险因素。
4.2.2PH型出血转化危险因素的多因素分析
以PH型出血转化为因变量(无=0,有=1),以可能的危险因素为自变量,行多因素logistic回归分析显示：重度神经功能缺损(RR=24.81,95%CI3.50-175.66)、房颤(OR=16.021,95%CI2.4-106.96)为PH型脑梗死出血转化的独立危险因素结论1.大动脉型粥样硬化型脑梗死及心源性脑栓塞引起出血转化风险较小动脉梗死型高。2.中、重度神经功能缺损、嗜睡状态、房颤、入院高血糖、血小板低于200×109/L为脑梗死出血转化的独立危险因素。
Background and Objective
Hemorrhagic transformation (HT) is frequently seen in acute ischemic stroke patients, which can lead to the clinical symptom deterioration and cause conflicts in the treatment of the stroke. To prevent this phenomenon from happening, careful study of risk factors for HT in acute ischemic stroke patients and choosing proper treatment for these patients is necessary. Patients in different conditions carry different risks for HT. Most researches studied risk factors for HT retrospectively, using single factor analysis. It seems that they may not able to show the real risk for HT. The aim of this study was to study the risk factors for HT after acute ischemic stroke prospectively and help make a better choice for the thrombolytic therapy.
Materials and Methods
1. Research objective
Patients treated by the First affiliated hospital of Zhengzhou University within7days of with symptom of acute cerebral infarction onset between March2011and March2012were prospectively registered. Inclusion criteria:1) Meeting the diagnostic criteria of cerebral infarction in the fourth National Cerebrovascular Disease Conference.2) Time from symptoms onset to admission less than one week.3) Having a CT or MRI check for a second time within two weeks from symptoms onset. Exclusion criteria:1) Patients with any neurological deficits before this accident.2) Patients not having a CT or MRI check for a second time within two weeks from symptoms onset.3) Patients with severe liver or kidney disease, or malignant neoplasm.
2. Method
Candidate variables were selected among baseline variables. Candidate variables were selected according to the prior systematic analysis of risk factors for HT. Candidate variables were age, sex, history of hypertension, history of diabetes, history of smoking, history of drinking, atrial fibrillation at baseline, systolic blood pressure at baseline, diastolic blood pressure at baseline, level of consciousness at baseline, neurological deficits at baseline, blood glucose at baseline, serum total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein at baseline, platelet count, Stroke etiology, ischemic changes on CT/MRI, time from symptom onset to treatment. Patients were divided into HT group and none HT group according to EC ASS criteria, and the HT group into HI (hemorrhagic infarction) and PH (parenchyma hemorrhage).
3. Statistical analysis
The data were analyzed using Software SPSS19.0.The risk for HT was investigated using single factors analysis and multiple logistic regression analysis. The difference was statistically significant as P＜0.1in the single factors analysis, and P＜0.05in the multiple logistic regression analysis, all the analysis were two-sided test.
Results
A total of consecutive865acute cerebral infarction patients were included, and55cases were diagnosed as HT, including47HT and8PH.
1. General characteristic
2. Rate of HT in the total and rate of HT by different TOAST type
The rate HT of total number of patients was6.4%, and16.6%for LAA (large artery atherosclerosis)9.5%for CE (cardioembolism),3.86%for SAA (Small artery atherosclerosis),1.75%for UND (Stroke of undermined cause)(x2=32.80, P＜0.05)
3. Single factors analysis
Single factors analysis showed Single factors analysis showed significant (P＜0.1) differences in the age, level of consciousness at baseline, neurological deficits at baseline, serum glucose at baseline, platelet count＜200×109/L, large infarction, atrial fibrillation at baseline, high systolic blood pressure at baseline.
4. Multiple logistic regression analysis for HT
Multiple logistic regression analysis showed that moderate neurological deficits (RR=3.23,95%CI1.31-7.99),severe neurological deficits(RR=9.00,95%CI2.17-37.31) atrial fibrillation (OR=3.62,95%CI1.11-12.82), high blood glucose on admission (OR=2.016,95%CI1.01-4.03)), blood platelet count lower than200×109/L(OR=2.403,95%CI1.09-5.28) were independent risk factors(P＜0.05) for HT.
5. Multiple logistic regression analysis for HI and PH
5.1Multiple logistic regression analysis showed that moderate neurological deficits (RR=3.89,95%CI1.52-9.93), severe neurological deficits (RR=6.58,95%CI1.50-28.94), high blood glucose on admission (OR=2.36,95%CI1.14-4.89), blood platelet count lower than200×109/L (OR=2.40,95%CI1.04-5.53) were independent risk factors (P＜0.05) for HI.
5.2Multiple logistic regression analysis showed that severe neurological deficits (RR=24.81,95%CI3.50-175.66) atrial fibrillation (OR=3.62,95%CI1.11-12.82) were independent risk factors (P<0.05) for PH.
Conclusions
1. Patients of LAA and CE carry a higher risk for HT.
2. Moderate and serious neurological deficits, moderate level of consciousness, atrial fibrillation, high blood glucose on admission and blood platelet count lower than200x109/L are independent risk factors for HT.
引文
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[49]McColl B W, Rothwell N J, Allan S MSystemic inflammation alters the kinetics of cerebrovascular tight junction disruption after experimental stroke in mice[J].J. Neurosci., 2008,28(38):9451-9462.
[50]Murata Y, Rosell A, Scannevin R H, et al.Extension of the thrombolytic time window with minocycline in experimental stroke[J].Stroke,2008,39(12):3372-3377.
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[3]Arnould M C, Grandin C B, Peeters A, et al.Comparison of ct and three mr sequences for detecting and categorizing early (48 hours) hemorrhagic transformation in hyperacute ischemic stroke[J].AJNR. Am. J. Neuroradiol.,2004,25(6):939-944.
[4]中华神经科学会.各类脑血管疾病诊断要点[J].中华神经科杂志,1996,29(6)：379
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[6]Lee T H, Hsu W C, Chen C J, et al.Etiologic study of young ischemic stroke in taiwan[J]. Stroke,2002,33(8):1950-1955.
[7]中国高血压防治指南修订委员会.2004年中国高血压防治指南_实用本[J].中华心血管病杂志,2004,32(12)：1060
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