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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) ›› 2022, Vol. 16 ›› Issue (01) : 32 -37. doi: 10.11817/j.issn.1673-9248.2022.01.007

论著

炎性及代谢指标与脑小血管病认知障碍的相关性
祁林瑞1, 曾嵘1, 胡风云1,†()   
  1. 1. 030000　太原，山西医科大学第五临床医学院神经内科
  • 收稿日期:2021-10-25 出版日期:2022-02-01
  • 通信作者: 胡风云
  • 基金资助:
    吴阶平医学基金会临床科研专项资助基金项目(320.6750.16129); 山西省重点研发计划（指南）项目(201603D321060)

The correlation of inflammatory and metabolic markers with cognitive impairment in patients with cerebral small vascular disease

Linrui Qi1, Rong Zeng1, Fengyun Hu1,†()   

  1. 1. Department of Neurology, the Fifth Clinical Medical College of Shanxi Medical University, Taiyuan 030000, China
  • Received:2021-10-25 Published:2022-02-01
  • Corresponding author: Fengyun Hu
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祁林瑞, 曾嵘, 胡风云. 炎性及代谢指标与脑小血管病认知障碍的相关性[J]. 中华脑血管病杂志(电子版), 2022, 16(01): 32-37.

Linrui Qi, Rong Zeng, Fengyun Hu. The correlation of inflammatory and metabolic markers with cognitive impairment in patients with cerebral small vascular disease[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2022, 16(01): 32-37.

目的

探讨炎性及代谢指标与脑小血管病（CSVD）认知障碍的相关性并建立早期预测模型。

方法

选取2020年9月至2021年9月于山西医科大学第五临床医学院神经内科就诊的CSVD患者120例，根据蒙特利尔认知评估评分分为无认知障碍组45例和认知障碍组75例，对2组患者炎性指标[包括超敏C反应蛋白（hs-CRP）、脂蛋白磷脂酶A2（Lp-PLA2）、白细胞介素6（IL-6）、总胆红素（TBIL）]及代谢指标[包括同型半胱氨酸（Hcy）、胱抑素C（CysC）、糖化血红蛋白（GHb）、低密度脂蛋白（LDL-C）]进行单因素及Logistic多因素回归分析，并建立预测模型，分析各指标与CSVD患者认知障碍的相关性及诊断价值。

结果

认知障碍组患者血清Lp-PLA2、IL-6、Hcy、CysC表达水平高于无认知障碍组[（124.03±55.00）ng/ml vs（58.58±39.66）ng/ml；（2.26±0.89）pg/ml vs（1.10±0.48）pg/ml；（31.07±11.63）μmol/L vs（14.81±7.40）μmol/L，（1.04±0.34）ng/L vs（0.76±0.20）ng/L]，血清TBIL表达水平低于无认知障碍组[（15.45±3.74）μmol/L vs（18.97±4.68）μmol/L]，差异均具有统计学意义（t=6.965、8.075、8.403、5.121、-4.536，P均＜0.001）；将5项指标进行多因素Logistic回归分析显示，其中血清Lp-PLA2、IL-6、Hcy、CysC水平升高是CSVD患者发生认知障碍的独立危险因素（OR=1.017，P=0.029；OR=2.117，P=0.004；OR=1.155，P=0.003；OR=2.901，P=0.002）；绘制血清Lp-PLA2、IL-6、Hcy、CysC及4项指标联合诊断CSVD患者继发认知障碍的受试者操作特征曲线，其曲线下面积值分别为0.883、0.886、0.905、0.803、0.951。

结论

炎症指标Lp-PLA2、IL-6及代谢指标CysC、Hcy的表达与CSVD患者的认知障碍具有一定的相关性，对CSVD患者认知损伤的早期诊断具有提示作用，联合检测2组指标，有利于提早发现CSVD患者的认知功能损伤，及时进行临床干预治疗，避免进一步进展为血管性痴呆。

关键词: 脑小血管病, 认知障碍, 炎性指标, 代谢指标
Objective

To explore the correlation of inflammatory and metabolic markers with cognitive impairment in patients with cerebral small vascular disease (CSVD), and to establish an early prediction model.

Methods

120 cases of CSVD patients admitted to Department of Neurology in our hospital from September 2020 to September 2021 were included. According to Montreal cognitive assessment (MoCA) score, they were divided into Non-cognitive impairment (NCI) group of 45 cases and Cognitive impairment (CI) group of 75 cases. Inflammatory biomarkers of patients in the two groups were compared, including hypersensitive C-reactive protein (hs-CRP), lipoprotein phospholipase A2 (Lp-PLA2), interleukin 6 (IL-6), total bilirubin (TBIL), and metabolic biochemical indexes including homocysteine (Hcy), cystatin C (Cys-C), glycosylated hemoglobin (GHb), and low density lipoprotein cholesterin (LDL-C). Univariate and logistic multifactor regression analyses were conducted, and prediction models were established to analyze the correlation and diagnostic value of each index with cognitive impairment in CSVD patients.

Results

The expression levels of serum LP-PLA2, IL-6, Hcy and Cys-C in CI group were significantly higher than those in NCI group [(124.03±55.00) ng/ml vs (58.58±39.66) ng/ml; (2.26±0.89) pg/ml vs (1.10±0.48) pg/ml; (31.07±11.63) μmol/L vs (14.81±7.40) μmol/L; (1.04±0.34) ng/L vs (0.76±0.20) ng/L], and the expression levels of serum TBIL were significantly lower than those in NCI group[ (15.45±3.74) μmol/L vs (18.97±4.68) μmol/L], the differences were statistically significant (t=6.965, 8.075, 8.403, 5.121,-4.536; all P＜0.001). Multivariate logistic regression analysis of the 5 indexes showed that the increased levels of serum Lp-PLA2, IL-6, Hcy and Cys-C were independent risk factors of cognitive dysfunction in CSVD patients (OR=1.017, P=0.029; OR=2.117, P=0.004; OR=1.155, P=0.003; OR=2.901, P=0.002). Receiver operating characteristic (ROC) curve of serum LP-PLA2, IL-6, Hcy, Cys-C and the combination of the four indexes for the diagnosis of secondary cognitive impairment in patients with CSVD was plotted, and the areas under the curve (AUC) values were 0.883, 0.886, 0.905, 0.803 and 0.951, respectively.

Conclusion

The expressions of inflammatory markers Lp-PLA2 and IL-6 and metabolic markers Cys-C and Hcy are correlated with the cognitive impairment of CSVD patients to a certain extent, suggesting the early diagnosis of cognitive impairment in CSVD patients. The combined detection of the two markers is helpful for the early detection of cognitive impairment in CSVD patients and clinical intervention to avoid further progression to vascular dementia.

Key words: Cerebral small vessel disease (CSVD), Cognitive impairment, Inflammatory markers, Metabolic markers
表1 2组脑小血管病患者基础临床资料比较
组别 例数 女性[例（%）] 年龄（年，
x¯
±s）		 受教育年限（年，
x¯
±s）		 高血压[例（%）] 吸烟史（超过15年）[例（%）] 饮酒史（超过5年）[例（%）]
认知障碍组 75 33（44.00） 62.38±8.04 5.25±3.11 46（61.33） 52（69.33） 15（20.00）
无认知障碍组 45 25（55.56） 64.19±8.23 5.29±3.47 20（44.44） 26（57.78） 11（24.44）
统计值 χ2=1.504 t=1.183 t=0.065 χ2=3.241 χ2=1.651 χ2=0.327
P值 0.220 0.239 0.958 0.072 0.199 0.567
表2 2组CSVD患者血清炎性及代谢指标表达水平比较（
xˉ
±s）
组别 例数 hs-CRP（ng/L） Lp-PLA2（ng/ml） IL-6（pg/ml） TBIL（μmol/L） GHb（%） Hcy（μmol/L） CysC（ng/L） LDL-C（mmol/L）
认知障碍组 75 1.058±0.50 124.03±55.00 2.26±0.89 15.45±3.74 5.7±1.2 31.07±11.63 1.04±0.34 2.99±0.55
无认知障碍组 45 1.118±0.58 58.58±39.66 1.10±0.48 18.97±4.68 5.5±1.1 14.81±7.40 0.76±0.20 3.09±0.71
t值 0.696 6.965 8.075 -4.536 0.911 8.403 5.121 0.864
P值 0.488 ＜0.001 ＜0.001 ＜0.001 0.364 ＜0.001 ＜0.001 0.390
表3 CSVD患者认知障碍的多因素分析
指标 B值 SE值 Wals值 P值 OR值 95%可信区间
Hcy 0.144 0.048 9.070 0.003 1.155 1.052~1.268
CysC 7.293 2.408 9.172 0.002 2.901 0.846~6.991
TBIL -0.070 0.096 0.531 0.466 0.973 0.772~1.126
IL-6 2.144 0.740 8.399 0.004 2.117 1.027~5.500
Lp-PLA2 0.017 0.008 4.747 0.029 1.017 1.002~1.032
图1 Hcy、CysC、IL-6、Lp-PLA2各单项指标及联合4项指标预测脑小血管病患者认知障碍的受试者操作特征曲线 注：Hcy为同型半胱氨酸；CysC为胱抑素C；IL-6为白细胞介素6；Lp-PLA2为脂蛋白磷脂酶A2
表4 CSVD患者血清中的Hcy、CysC、IL-6以及Lp-PLA2对认知障碍的诊断价值
指标 Cutoff值 敏感度（%） 特异度（%） Youden值 AUC值 95%可信区间
Hcy 16.600 96.0 75.6 0.716 0.905 0.846~0.965
CysC 0.755 89.3 57.8 0.471 0.803 0.719~0.886
IL-6 1.655 76.0 86.7 0.627 0.886 0.829~0.943
Lp-PLA2 81.900 77.3 88.9 0.662 0.883 0.817~0.949
联合检测 92.0 82.2 0.742 0.951 0.918~0.984
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