Clinical Value of Serum TIMP-3 in Predicting Death in Patients with Malignant Middle Cerebral Artery Infarction

doi:10.3969/j.issn.1673-5765.2023.06.009

Abstract

Abstract: Objective By observing the changes of serum tissue inhibitor of matrix metalloproteinase (TIMP) -3
levels in patients with severe malignant middle cerebral artery infarction (MMCAI), and to determine its predictive value for hospital death in patients with MMCAI.
Methods Sixty-eight patients with MMCAI admitted to Mingji Hospital Affiliated to Nanjing Medical University from February 2019 to January 2022 were selected, and the patients divided into survival group and death group according to 30-day in-hospital outcomes. Serum TIMP-1, TIMP-2, TIMP-3, and TIMP-4 levels on day 1, day 4 and day 8 of admission were detected by immunoassay. ROC was established to analyze the predictive value of 30-day death in patients with MMCAI, and multivariate logistic regression was used to analyze the risk factors of 30-day death in patients with MMCAI.
Results Among 68 patients with MMCAI, 34 died within 30 days. Compared with the survival group, the serum TIMP-1 level in the death group was significantly increased on day 1 of admission [100.86 (77.85-137.33) ng/mL vs. 70.15 (61.70-82.83) ng/mL, P=0.001], and the serum TIMP-3
level on day 1 [309.86 (210.03-614.72) ng/mL vs. 174.54 (120.90-347.75) ng/mL, P<0.001], day 4 [288.32 (167.45-371.38) ng/mL vs. 172.42 (99.06-232.47) ng/mL, P=0.003] and day 8 [297.91 (238.98-353.83) ng/mL vs. 118.26 (81.59-190.70) ng/mL, P<0.001] were significantly increased. ROC curve analysis results showed that the AUC of serum TIMP-3 concentration on day 1, day 4 and day 8 after admission in predicting 30-day death of patients with MMCAI were 0.751 (95%CI 0.636-0.866, P<0.001, the cut-off value was 179.33 ng/mL), 0.748 (95%CI 0.606-0.889, P<0.001, the cut-off value was 333.41 ng/mL) and 0.840 (95%CI 0.726-0.955, P<0.001, the
cut-off value was 266.56 ng/mL). Multiple Logistic regression analysis showed that after adjusting for platelet count, GCS and lactic acid, high expression of serum TIMP-3 level on day 1 of admission was still an independent risk factor for 30-day death in patients with MMCAI (OR 1.006, 95%CI 1.002-1.011, P=0.008). Survival analysis showed that patients with serum TIMP-3 level>257.93 ng/mL on day 1 of admission had higher 30-day mortality (P<0.001).
Conclusions The change of serum TIMP-3 level is a risk factor for nosocomial death of MMCAI patients, and the serum TIMP-3 level on the first day of admission can be used as a biomarker to predict the recent death of MMCAI patients.

Key words: Tissue inhibitor of matrix metalloproteinase; Ischemic stroke; Mortality; Prognosis

摘要： 目的观察重度恶性大脑中动脉梗死（malignant middle cerebral artery infarction，MMCAI）患者早期血清MMP组织抑制剂（tissue inhibitor of matrix metalloproteinase，TIMP）3水平变化，确定其对患者30 d死亡的预测价值。
方法前瞻性纳入南京医科大学附属明基医院神经内科2019年2月—2022年1月收治的MMCAI患者，根据30 d结局分为存活组和死亡组。采用免疫分析法检测患者入院第1天、第4天和第8天时血清TIMP-1、TIMP-2、TIMP-3、TIMP-4水平。ROC曲线分析TIMP对MMCAI患者30 d死亡的预测价值，多因素logistic回归分析患者30 d死亡的危险因素。
结果共入组MMCAI患者68例，其中30 d内全因死亡34例。与存活组相比，死亡组入院第1天血清TIMP-1水平[100.86（77.85～137.33）ng/mL vs. 70.15（61.70～82.83）ng/mL，P=0.001]，以及第1天[309.86（210.03～614.72）ng/mL vs. 174.54（120.90～347.75）ng/mL，P＜0.001]、第4天[288.32（167.45～371.38）ng/mL vs. 172.42（99.06～232.47）ng/mL，P=0.003]和第8天[297.91（238.98～353.83）ng/mL vs. 118.26（81.59～190.70）ng/mL，P＜0.001]的血清TIMP-3水平较存活组均显著升高。ROC曲线分析显示，入院第1天、第4天和第8天血清TIMP-3水平预测MMCAI患者30 d死亡的AUC分别为0.751（95%CI 0.636～0.866，P＜0.001，截断值为179.33 ng/mL）、0.748（95%CI 0.606～0.889，P＜0.001，截断值为333.41 ng/mL）、0.840（95%CI 0.726～0.955，P＜0.001，截断值为266.56 ng/mL）。多元logistic回归分析表明，在校正血小板计数、GCS评分和乳酸水平后，入院第1天血清TIMP-3水平升高仍是影响MMCAI患者30 d死亡的独立危险因素（OR 1.006，95%CI 1.002～1.011，P=0.008）。生存分析显示，入院第1天血清TIMP-3水平＞257.93 ng/mL的患者30 d死亡率更高（P＜0.001）。
结论血清TIMP-3水平变化是MMCAI患者30 d死亡的危险因素，入院第1天血清TIMP-3水平可作为预测MMCAI患者死亡的生物标志物。

关键词: 基质金属蛋白酶组织抑制剂; 缺血性卒中; 死亡率; 预后

ZHANG Yingfang, YE min, SHANG Yu, WU Mingfeng. Clinical Value of Serum TIMP-3 in Predicting Death in Patients with Malignant Middle Cerebral Artery Infarction[J]. Chinese Journal of Stroke, 2023, 18(06): 677-683.

张莺芳, 叶民, 尚羽, 吴明凤. 血清TIMP-3预测恶性大脑中动脉梗死患者死亡的临床价值研究[J]. 中国卒中杂志, 2023, 18(06): 677-683.

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