2型糖尿病患者PCSK9、ET-1水平与并发动脉粥样硬化性心血管病的相关性

Association of levels of PCSK9 and ET-1 with concurrent atherosclerotic cardiovascular disease in patients with type 2 diabetes mellitus

摘要

目的：分析2型糖尿病（T2DM）前蛋白转化酶枯草溶菌素9（PCSK9）、内皮素-1（ET-1）水平与并发动脉粥样硬化性心血管病（ASCVD）的关联性。方法：选取2020年6月—2022年5月200例首次确诊为T2DM患者和46例健康人群（对照组），随访至2025年1月，根据是否并发ASCVD将T2DM患者分为ASCVD组和非ASCVD组，其中ASCVD组又根据是否发生急性ASCVD（如急性脑梗死、急性冠脉综合征等）分为急性组和非急性组，比较四组血清PCSK9和ET-1水平，分析其与生化指标、超声指标之间的相关性，通过二元Logistic回归分析T2DM患者并发ASCVD的危险因素，应用受试者工作特征（ROC）曲线评估预测价值。结果：四组PCSK9、ET-1水平，与对照组比较，非ASCVD组、非急性组、急性组依次升高（P<0.05）。PCSK9、ET-1与总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、颈动脉内膜中层厚度（CIMT）均呈正相关（P<0.05），与高密度脂蛋白胆固醇（HDL-C）、踝肱指数（ABI）呈负相关（P<0.05），与胰岛素抵抗指数（HOMA-IR）无明显相关性（P>0.05）。以是否发生ASCVD为状态变量，多因素Logistic回归分析显示，男性[OR(95%CI)：2.68(1.45~4.98)]、年龄[OR(95%CI)：1.15(1.04~1.26)]、PCSK9[OR(95%CI)：2.27(1.14~4.50)]、ET-1[OR(95%CI)：3.09(1.25~7.62)]是T2DM患者并发ASCVD独立危险因素。血清PCSK9、ET-1联合诊断的曲线下面积（AUC）为0.865（95%CI：0.809~0.909，P<0.05），灵敏度为80.77%，特异性为78.69%，两者联合诊断的AUC高于PCSK9、ET-1单独诊断的AUC（Z=2.67、3.56，P<0.05）。结论：PCSK9、ET-1与T2DM患者并发ASCVD密切相关，以上两者联合诊断ASCVD的价值较高。

Abstract

Objective: To analyze the association between levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and endothelin-1 (ET-1) and concurrent atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes mellitus (T2DM). Methods: From June 2020 to May 2022, 200 patients with firstly-diagnosed T2DM and 46 healthy people (control group) were selected and followed up to January 2025. According to whether they were complicated with ASCVD, T2DM patients were divided into ASCVD group and non-ASCVD group. The patients in ASCVD group were further classified into acute group and non-acute group according to whether acute ASCVD (such as acute cerebral infarction and acute coronary syndrome) occurred. The levels of serum PCSK9 and ET-1 were compared among the four groups, and the correlation with biochemical and ultrasound indexes was analyzed. The risk factors of ASCVD in T2DM patients were explored by binary Logistic regression analysis, and the predictive value was evaluated by receiver operating characteristic (ROC) curve. Results: The levels of PCSK9 and ET-1 in non-ASCVD group, non-acute group and acute group were increased in turn compared with those in control group (P<0.05). PCSK9 and ET-1 were positively correlated with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c) and carotid intima-media thickness (CIMT) (P<0.05), and were negatively associated with high-density lipoprotein cholesterol (HDL-C) and ankle-brachial index (ABI) (P<0.05), and were not significantly correlated with insulin resistance index (HOMA-IR) (P>0.05). Taking presence or absence of ASCVD occurrence as the state variable, multivariate Logistic regression analysis suggested that male (OR(95%CI)=2.68(1.45-4.98)), age (OR(95%CI)=1.15(1.04-1.26)), PCSK9 (OR(95%CI)=2.27(1.14-4.50)), and ET-1 (OR(95%CI)=3.09(1.25-7.62)) were independent risk factors of ASCVD in T2DM patients. The area under the curve (AUC), sensitivity, and specificity of serum PCSK9 combined with ET-1 were 0.865 (95%CI: 0.809-0.909, P<0.05), 80.77%, and 78.69%, respectively. TheAUC of combined diagnosis was higher than that of PCSK9 and ET-1 alone (Z=2.67 and 3.56, respectively, both P<0.05). Conclusion: PCSK9 and ET-1 are closely related to ASCVD in patients with T2DM, and the value of combined diagnosis on ASCVD is higher.

关键词

蛋白转化酶枯草溶菌素9 / 内皮素-1 / 2型糖尿病 / 动脉粥样硬化性心血管病

Key words

Protein Convertase Subtilisin/Kexin Type 9 / Endothelin-1 / Type 2 Diabetes Mellitus / Atherosclerotic Cardiovascular Disease

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基金资助

湖北省中医药管理局中医药科研项目(GZY-KJS-2025-006)