作者：王林军1 ，岳建巍1 ，李建春1 ，冯菲1 ，李洪磊1 ，陈娣1 ，刘丽平1，2

单位：

1.730000甘肃省兰州市，兰州大学第一临床医学院　2.730000甘肃省兰州市，兰州大学 第一医院急诊重症医学科

Units：

1.The First Clinical Medical School of Lanzhou University, Lanzhou 730000, China 2.Department of Emergency Critical Care Medicine, the First Hospital of Lanzhou University, Lanzhou 730000, China

关键词：

肺动脉高压；危重症；肝素裂合酶；肝素酶；预后

Keywords：

Pulmonary arterial hypertension; Critical illness; Heparin lyase; Heparinase; Prognosis

CLC：

R 541.5

DOI：

10.12114/j.issn.1008-5971.2024.00.067

Funds：

甘肃省科技计划项目（20JR5RA355；22JR10KA009）；兰州市城关区科技计划项目（2020RCCX0030）；兰州市科 技局科技发展指导性计划项目（2019-ZD-37）；兰州大学第一医院院内基金项目（Ldyyyn2020-79）

摘要：

目的　探讨肝素酶与危重症相关肺动脉高压（CIR-PH）患者预后及病情严重程度的关系。方法　回 顾性选取2021年4月— 2022 年6月兰州大学第一医院重症医学科收治的 108例CIR-PH患者为研究对象，根据预后情况 将其分为死亡组（ n=28 ）和生存组（ n=80）。比较两组一般资料〔包括年龄、性别、 BMI、肺动脉高压（PH）临床 分类、肝素酶、NT-proBNP及急性生理学和慢性健康状况评价系统Ⅱ（APACHEⅡ）评分〕、右心导管检查结果〔包 括平均肺动脉压（mPAP）、肺毛细血管楔压（PCWP）、肺血管阻力（PVR）、平均右心房压（mRAP）和心排血量 （CO）〕及超声心动图检查结果〔包括右心室直径（RVD）、右心房直径（RAD）、肺动脉宽度（PAW）、肺动脉 流速（PAV）、肺动脉压（PAP）、三尖瓣反流速度（TRV）〕。CIR-PH患者预后的影响因素分析采用单因素、多因 素Cox比例风险回归分析，采用ROC曲线分析肝素酶、NT-proBNP对CIR-PH患者死亡的预测价值，肝素酶与CIR-PH 病情相关指标（NT-proBNP、APACHEⅡ评分、mPAP、PCWP、PVR、CO）的相关性分析采用Pearson相关分析。结 果　死亡组年龄、RVD、RAD大于生存组，肝素酶、NT-proBNP、APACHEⅡ评分、mPAP、PCWP、PVR、mRAP、 PAP高于生存组，CO低于生存组，TRV快于生存组（P＜0.05）。单因素Cox比例风险回归分析结果显示，年龄、肝素 酶、NT-proBNP、APACHEⅡ评分、mPAP、PCWP、PVR、mRAP、CO、RVD、RAD、PAP、TRV可能是CIR-PH患者 死亡的影响因素（P＜0.05）。多因素Cox比例风险回归分析结果显示，肝素酶、NT-proBNP、mPAP、mRAP是CIR-PH 患者死亡的独立影响因素（P＜0.05）。ROC曲线分析结果显示，肝素酶预测CIR-PH患者死亡的AUC为0.784〔95%CI （0.688～0.879）〕，最佳截断值为10.4 μg/L，灵敏度为0.500，特异度为0.875；NT-proBNP预测CIR-PH患者死亡的 AUC为0.761〔95%CI（0.662～0.860）〕，最佳截断值为3 775 ng/L，灵敏度为0.357，特异度为0.950。Pearson相关分 析结果显示，肝素酶与CIR-PH患者NT-proBNP（r=0.639）、APACHEⅡ评分（r=0.763）、mPAP（r=0.876）、PCWP （r=0.858）、PVR（r=0.846）呈正相关，与CO（r=－0.702）呈负相关（P＜0.001）。结论　肝素酶是CIR-PH患者死 亡的独立影响因素，其对CIR-PH患者死亡有一定预测价值，且其与CIR-PH患者病情严重程度密切相关。

Abstract：

Objective To investigate the relationship between heparanase and prognosis and disease severity in patients with critical illness-related pulmonary hypertension (CIR-PH) . Methods A total of 108 patients with CIR-PH admitted to Department of Emergency Critical Care Medicine, the First Hospital of Lanzhou University from April 2021 to June 2022 were retrospectively selected as the research objects. According to the prognosis, they were divided into death group (n=28) and survival group (n=80) . The general data [including age, gender, BMI, clinical classification of pulmonary hypertension (PH) , heparinase, NT-proBNP and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score] , right heart catheterization results [including mean pulmonary artery pressure (mPAP) , pulmonary capillary wedge pressure (PCWP) , pulmonary vascular resistance (PVR) , mean right atrial pressure (mRAP) , cardiac output (CO) ] and echocardiography results [including right ventricular diameter (RVD) , right atrial diameter (RAD) , pulmonary artery width (PAW) , pulmonary artery velocity (PAV) , pulmonary artery pressure (PAP) , tricuspid regurgitation velocit (TRV) ] were compared between the two groups. Univariate and multivariate Cox proportional hazard regression analysis were used to analyze the influencing factors of prognosis in CIR PH patients. ROC curve was used to analyze the predictive value of heparanase and NT-proBNP for death in patients with CIR Pearson correlation analysis was used to analyze the correlation between heparinase and CIR-PH disease-related indicators (NT-proBNP, APACHEⅡ score, mPAP, PCWP, PVR and CO) . Results The age, RVD and RAD in the death group were larger than those in the survival group, heparanase, NT-proBNP, APACHEⅡ score, mPAP, PCWP, PVR, mRAP and PAP were higher than those in the survival group, CO was lower than that in the survival group, and TRV was faster than that in the survival group (P < 0.05) . Univariate Cox proportional hazard regression analysis showed that age, heparinase, NT-proBNP, APACHEⅡ score, mPAP, PCWP, PVR, mRAP, CO, RVD, RAD, PAP, TRV may be the influencing factors of death in patients with CIR PH (P < 0.05) . Multivariate Cox proportional hazard regression analysis showed that heparinase, NT-proBNP, mPAP and mRAP were independent influencing factors of death in patients with CIR-PH (P < 0.05) . ROC curve analysis showed that the AUC of heparinase in predicting death in CIR-PH patients was 0.784 [95%CI (0.688-0.879) ] , the optimal cut-off value was 10.4 μg/L, the sensitivity was 0.500, and the specificity was 0.875; the AUC of NT-proBNP in predicting death in CIR-PH patients was 0.761 [95%CI (0.662-0.860) ] , the optimal cut-off value was 3 775 ng/L, the sensitivity was 0.357, and the specificity was 0.950. Pearson correlation analysis showed that heparinase was positively correlated with NT-proBNP (r=0.639) , APACHEⅡ score (r=0.763) , mPAP (r=0.876) , PCWP ( r=0.858) and PVR (r=0.846) , and negatively correlated with CO (r=－0.702) in CIR-PH patients (P < 0.001) . Conclusion Heparanase is an independent influencing factor of death in patients with CIR-PH, and it has certain predictive value for death in CIR-PH patients, and it is closely related to the disease severity of CIR-PH patients.

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