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中华脑血管病杂志(电子版)

中华脑血管病杂志(电子版) ›› 2023, Vol. 17 ›› Issue (02) : 94 -101. doi: 10.11817/j.issn.1673-9248.2023.02.003

临床研究

维生素D水平与接受静脉溶栓治疗的缺血性卒中患者预后的关系
俞刘珍雄1, 张康睿2, 杨若蕊1, 刘学春2, 王龙2, 吴竹青2, 吴君仓1,†()   
  1. 1. 230011　合肥，安徽医科大学附属合肥医院　合肥市第二人民医院神经内科；230022　合肥，安徽医科大学第五临床医学院
    2. 230022　合肥，安徽医科大学第五临床医学院
  • 收稿日期:2022-08-25 出版日期:2023-04-01
  • 通信作者: 吴君仓
  • 基金资助:
    合肥市自主创新政策“借转补”项目(J2019Y01); 合肥市第二人民医院2021年度青年科研基金项目(2021yqn07)

Association of vitamin D levels with prognosis in ischemic stroke patients receiving intravenous thrombolytic therapy

Zhenxiong Yu-Liu1, Kangrui Zhang2, Ruorui Yang1, Xuechun Liu2, Long Wang2, Zhuqing Wu2, Juncang Wu1,†()   

  1. 1. Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University, the Second People's Hospital of Hefei City, Hefei 230011, China; the Fifth Clinical School of Medicine, Anhui Medical University, Hefei 230022, China
    2. the Fifth Clinical School of Medicine, Anhui Medical University, Hefei 230022, China
  • Received:2022-08-25 Published:2023-04-01
  • Corresponding author: Juncang Wu
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引用本文：

俞刘珍雄, 张康睿, 杨若蕊, 刘学春, 王龙, 吴竹青, 吴君仓. 维生素D水平与接受静脉溶栓治疗的缺血性卒中患者预后的关系[J]. 中华脑血管病杂志(电子版), 2023, 17(02): 94-101.

Zhenxiong Yu-Liu, Kangrui Zhang, Ruorui Yang, Xuechun Liu, Long Wang, Zhuqing Wu, Juncang Wu. Association of vitamin D levels with prognosis in ischemic stroke patients receiving intravenous thrombolytic therapy[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2023, 17(02): 94-101.

目的

探讨血清25羟基维生素D[25（OH）D]水平与接受静脉溶栓（IVT）治疗的急性缺血性脑卒中（AIS）患者3个月临床转归之间的关系。

方法

收集2020年2月至2022年6月在合肥市第二人民医院连续接受IVT治疗的AIS患者的临床资料及实验室指标，根据溶栓后24 h内空腹血清25（OH）D水平是否＜20 ng/ml，将患者分为维生素D缺乏组和非维生素D缺乏组。根据发病后3个月的改良Rankin量表（mRS）评分，将mRS评分＜3分定义为转归良好，mRS评分≥3分定义为转归不良。应用多变量logistic回归分析确定3个月临床转归的独立影响因素，采用受试者工作特征（ROC）曲线分析25（OH）D水平对3个月临床转归不良的预测价值。

结果

共纳入177例接受IVT治疗的AIS患者，其中112例临床转归良好，65例转归不良。多变量logistic回归分析显示，接受IVT治疗的AIS患者25（OH）D水平与3个月时转归不良呈显著独立负相关（OR=0.83，95%CI：0.77~0.90，P＜0.001），且维生素D缺乏组患者发生转归不良的风险显著高于非维生素D缺乏组患者（OR=18.52，95%CI：6.29~54.53，P＜0.001）。ROC曲线分析显示，接受IVT治疗的患者25（OH）D水平预测3个月临床转归不良的曲线下面积（AUC）为0.737（95%CI：0.66~0.82，P＜0.001），最佳截断值为19.50，敏感度和特异度分别为58.5%和86.6%。

结论

在接受IVT治疗的AIS患者中，溶栓后24 h内空腹血清25（OH）D水平是3个月转归不良的保护因素，且25（OH）D水平对3个月时的临床转归不良有预测价值。

关键词: 缺血性脑卒中, 静脉溶栓, 25羟基维生素D, 临床转归
Objective

To investigate the relationship between serum 25-hydroxyvitamin D [25 (OH) D] levels and 3-month clinical outcomes in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis (IVT).

Methods

The clinical data and laboratory indicators of AIS patients who received IVT consecutively from February 2020 to June 2022 in the Second People's Hospital of Hefei City were collected. According to whether the fasting serum 25 (OH) D level was less than 20 ng/ml within 24 hours after thrombolysis, the patients were divided into the vitamin D deficiency group and the non-vitamin D deficiency group. According to the modified Rankin scale (mRS) score at 3 months after disease onset, the mRS score <3 was defined as a good outcome, and the mRS score ≥3 was defined as a poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of 3-month clinical outcome. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of 25 (OH) D level on 3-month clinical outcome.

Results

A total of 177 AIS patients treated with IVT were enrolled, of which 112 patients had good clinical outcomes and 65 patients had poor clinical outcomes. Multivariate logistic regression analysis showed that 24 h 25 (OH) D level in AIS patients treated with IVT was negatively and independently correlated with poor outcomes at 3 months (OR=0.83, 95%CI=0.77-0.90，P＜0.001), and the risk of poor outcomes in patients with vitamin D deficiency was significantly higher than that in patients without vitamin D deficiency (OR=18.52, 95%CI=6.29-54.53, P＜0.001). ROC curve analysis showed that the area under the curve (AUC) of 25 (OH) D collected after IVT treatment predicted poor clinical outcome at 3 months was 0.737 (95%CI=0.66-0.82, P＜0.001), the optimal cut-off value was 19.50, and the sensitivity and specificity were 58.5% and 86.6%, respectively.

Conclusion

In AIS patients treated with IVT, 25 (OH) D level is a protective factor for poor clinical outcomes at 3 months, and 25 (OH) D level has predictive value for poor clinical outcome at 3 months.

Key words: Ischemic stroke, Intravenous thrombolysis, 25 (OH) D, Clinical outcome
图1 研究对象纳入和排除流程图
表1 转归良好组与转归不良组临床资料和实验室指标比较
临床资料 转归良好（112例） 转归不良（65例） 统计值 P值
年龄[岁，M（QR）] 67.50（57.00，76.00） 74.00（64.00，81.00） Z=2.583 0.010
男[例（%）] 75（62.62） 34（48.00） χ2=3.735 0.053
入院时收缩压（mmHg，
x¯
±s）		 151.87±17.79 159.12±21.60 t=2.415 0.017
入院时舒张压（mmHg，
x¯
±s）		 85.08±13.86 85.26±12.07 t=0.088 0.930
BMI（kg/m2，
x¯
±s）		 24.36±3.44 24.22±4.03 t=0.256 0.799
血管危险因素[例（%）]
高血压 71（63.39） 49（75.38） χ2=2.709 0.100
既往脑梗死或TIA 31（27.68） 25（38.46） χ2=2.211 0.137
糖尿病 28（25.00） 25（38.46） χ2=3.553 0.059
冠心病 8（7.14） 21（32.31） χ2=19.012 ＜0.001
心房颤动 13（11.61） 18（27.69） χ2=7.366 0.007
吸烟 29（25.89） 15（23.08） χ2=0.175 0.676
梗死位置[例（%）] χ2=2.352 0.308
前循环 75（66.96） 50（76.92）
后循环 21（18.75） 7（10.77）
前循环+后循环 16（14.29） 8（12.31）
NIHSS评分[分，M（QR）]
溶栓前 5.00（3.00，9.00） 10.00（7.00，15.50） Z=5.957 ＜0.001
溶栓后14 d 2.00（1.00，3.00） 7.00（5.00，16.00） Z=9.271 ＜0.001
mRS评分[分，M（QR）]
溶栓前 3.00（2.00，4.00） 4.00（4.00，5.00） Z=6.097 ＜0.001
溶栓后14 d 1.00（1.00，2.00） 3.00（3.00，4.00） Z=9.873 ＜0.001
维生素D分组 χ2=39.825 ＜0.001
25（OH）D＜20 ng/ml 15（13.4） 38（58.5）
25（OH）D≥20 ng/ml 97（86.6） 27（41.5）
25（OH）D[ng/ml，M（QR）] 26.00（22.00，29.00） 19.00（17.00，24.00） Z=6.293 ＜0.001
血清钙水平（mmol/L，
x¯
±s）		 2.26±0.09 2.23±0.11 t=1.823 0.070
白细胞[×109/L，M（QR）] 7.48（5.99，9.05） 7.62（6.38，9.33） Z=1.243 0.214
NLR[M（QR）] 3.51（2.44，5.06） 4.15（2.70，8.42） Z=2.308 0.021
hs-CRP[mg/L，M（QR）] 2.83（1.04，4.99） 5.23（1.85，16.59） Z=2.833 0.005
空腹血糖[mmol/L，M（QR）] 5.88（4.91，7.33） 6.18（5.43，8.40） Z=1.872 0.061
糖化血红蛋[%，M（QR）] 5.90（5.50，6.90） 6.00（5.59，7.30） Z=1.270 0.205
LDL（mmol/L，
x¯
±s）		 2.97±1.05 2.77±0.80 t=1.325 0.187
Hcy[μmmol/L，M（QR）] 11.09（9.22，14.60） 13.94（10.17，16.90） Z=2.040 0.041
尿酸（μmmol/L，
x¯
±s）		 327.60±85.06 332.49±97.83 t=0.352 0.726
表2 3个月临床转归不良相关的单因素logistic回归分析
影响因素 B SE Wald χ2 OR 95%CI P值
年龄 0.02 0.01 3.89 1.03 1.00~1.05 0.049
男性 -0.61 0.32 3.70 0.54 0.29~1.01 0.055
入院时收缩压 0.02 0.01 5.52 1.02 1.00~1.04 0.019
入院时舒张压 0.00 0.01 0.01 1.00 0.98~1.03 0.930
BMI -0.01 0.04 0.07 0.99 0.91~1.08 0.797
高血压 0.57 0.35 2.68 1.77 0.89~3.50 0.102
既往脑梗死或TIA 0.49 0.33 2.20 1.63 0.85~3.13 0.138
糖尿病 0.63 0.34 3.51 1.88 0.97~3.62 0.061
冠心病 1.83 0.45 16.26 6.21 2.56~15.07 ＜0.001
心房颤动 1.07 0.41 6.99 2.92 1.32~6.45 0.008
吸烟 -0.15 0.37 0.17 0.86 0.42~1.76 0.676
溶栓前NIHSS评分 0.17 0.03 26.68 1.19 1.11~1.27 ＜0.001
溶栓前mRS评分 0.97 0.18 29.71 2.64 1.86~3.74 ＜0.001
25（OH）D <20 ng/ml 2.21 0.38 34.76 9.10 4.37~18.97 ＜0.001
25（OH）D水平 -0.15 0.03 20.65 0.86 0.81~0.92 ＜0.001
血清钙水平 -2.91 1.62 3.22 0.05 0.002~1.31 0.073
白细胞 0.10 0.06 3.03 1.11 0.99~1.24 0.082
NLR 0.09 0.04 5.48 1.09 1.01~1.18 0.019
hs-CRP 0.02 0.01 2.18 1.02 0.99~1.04 0.140
空腹血糖 0.08 0.06 1.96 1.08 0.97~1.20 0.162
糖化血红蛋白 0.08 0.10 0.59 1.08 0.89~1.31 0.441
LDL -0.23 0.18 1.73 0.80 0.56~1.12 0.189
Hcy 0.02 0.02 1.76 1.02 0.99~1.06 0.185
尿酸 0.001 0.002 0.13 1.001 0.997~1.004 0.724
表3 与3个月转归不良相关的多因素logistic回归分析
影响因素 B SE Wald χ2 OR 95% CI P值
模型一[25（OH）D水平]
年龄 -0.02 0.02 1.45 0.98 0.95~1.01 0.228
入院时收缩压 0.03 0.01 5.98 1.03 1.01~1.05 0.014
冠心病 1.80 0.74 5.85 6.02 1.41~25.77 0.016
心房颤动 -0.31 0.72 0.19 0.73 0.18~2.98 0.665
溶栓前NIHSS评分 0.08 0.07 1.48 1.09 0.95~1.25 0.224
溶栓前mRS评分 0.89 0.34 6.91 2.43 1.25~4.70 0.009
25（OH）D水平 -0.18 0.04 19.45 0.83 0.77~0.90 ＜0.001
NLR -0.00 0.05 0.002 1.00 0.91~1.10 0.961
模型二[25（OH）D分组]
年龄 -0.01 0.02 0.22 0.99 0.96~1.03 0.640
入院时收缩压 0.03 0.01 6.78 1.03 1.01~1.06 0.009
冠心病 1.83 0.74 6.16 6.21 1.47~26.28 0.013
心房颤动 -0.26 0.73 0.12 0.78 0.19~3.25 0.727
溶栓前NIHSS评分 0.05 0.07 0.43 1.05 0.91~1.20 0.514
溶栓前mRS评分 1.13 0.38 9.03 3.09 1.48~6.45 0.003
维生素D缺乏 2.92 0.55 28.04 18.52 6.29~54.53 ＜0.001
NLR -0.03 0.05 0.47 0.97 0.88~1.07 0.495
图2 维生素D缺乏组和非维生素D缺乏组在3个月时mRS评分的频数分布
图3 入院时25（OH）D水平预测接受IVT治疗的AIS患者3个月转归不良的受试者操作特征曲线
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