Clinical Relationship between Glycolysis，Iron Metabolism Indicators and Cardiovascular Status in Patients with Chronic Obstructive Pulmonary Disease-Coronary Artery Disease
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摘要:
目的 评估丙酮酸激酶M2（PKM2）、转铁蛋白饱和度（TSAT）对经皮冠状动脉介入治疗（PCI）后的慢性阻塞性肺病（COPD）-冠状动脉疾病（CAD）患者的主要心血管不良事件（MACE）预测价值，并分析二者与患者心功能状态的关系。 方法 本研究队列包括2020年1月至2022年5月期间涿州市医院94例诊断为COPD-CAD患者。通过超声心动图检查左心室舒张末期容积（LVEDV）、左心室收缩末期容积（LVESV）、左心室射血分数（LVEF）、二尖瓣流入速度（E）和早期舒张二尖瓣环速度（e’）。通过酶联免疫吸附测定试剂盒分析血浆PKM2、TSAT水平。对所有患者进行2年随访，研究终点定义为MACE。 结果 在随访期间，22例患者（23.4%）发生了MACE。与无MACE组比较，MACE组外周血PKM2水平增加（P < 0.05），TSAT水平降低（P < 0.05）。PKM2与左心室收缩末期容积、E/e’呈正相关（r = 0.204、0.209，均P < 0.05），与射血分数、TSAT呈负相关（r = -0.430、-0.641，均P < 0.001）。TSAT与左心室舒张末期容积、左心室收缩末期容积、E/e’呈负相关（r = -0.309、-0.470、-0.411，均P < 0.001），与射血分数呈正相关（r = 0.470，P < 0.001）。PKM2（Hr = 9.375，95%CI = 4.145～21.203）和TSAT（Hr = 0.753，95%CI = 0.645～0.878）是COPD-CAD患者MACE事件发生的独立影响因素（P < 0.05）。PKM2、TSAT预测MACE事件的AUC分别为0.835（95%CI = 0.729～0.940）、0.878（95%CI = 0.811～0.946），特异度分别为72.7%、90.9%，敏感度分别为87.5%、80.6%。 结论 在经PCI治疗的COPD-CAD患者中，PKM2、TSAT水平变化与患者MACE事件独立相关，并有助于预测MACE事件的发生。 Abstract:Objective To evaluate the predictive value of pyruvate kinase M2（PKM2） and transferrin saturation （TSAT） for major adverse cardiovascular events （MACE） in chronic obstructive pulmonary disease （COPD）- coronary artery disease （CAD） patients after percutaneous coronary intervention （PCI）, and to analyze the relationship between these indicators and patients' cardiac function status. Methods The study cohort included 94 COPD-CAD patients diagnosed in Zhuozhou Hospital from January 2020 to May 2022. Left ventricular end-diastolic volume （LVEDV）, left ventricular end-systolic volume （LVSV）, left ventricular ejection fraction （LVEF）, mitral valve inflow velocity （E） and early diastolic mitral annular velocity （e'） were assessed by echocardiography. Plasma PKM2 and TSAT levels were analyzed using enzyme-linked immunosorbent assay kit. All patients were followed up for 2 years. The study end point was defined as MACE. Results During follow-up, 22 patients （23.4%） experienced MACE. Compared with the non-MACE group, the MACE group showed increased peripheral blood PKM2 levels （P < 0.05） and decreased TSAT levels （P < 0.05）. PKM2 was positively correlated with left ventricular end-systolic volume and E/e' （r = 0.204 and 0.209, both P < 0.05）, and negatively correlated with ejection fraction and TSAT （r = -0.430 and -0.641, both P < 0.001）. TSAT was negatively correlated with left ventricular end-diastolic volume, left ventricular end-systolic volume and E/e' （r = -0.309, -0.470, -0.411, all P < 0.001）, and positively correlated with ejection fraction （r = 0.470, P < 0.001）. PKM2 （Hr = 9.375, 95%CI = 4.145～21.203） and TSAT （Hr = 0.753, 95%CI = 0.645～0.878） were independent influencing factors of MACE events in COPD-CAD patients （P < 0.05）. The AUC of PKM2 and TSAT in predicting MACE events were 0.835 （95%CI = 0.729～0.940） and 0.878 （95%CI = 0.811～0.946）, respectively, with specificity of 72.7% and 90.9%, and sensitivity of 87.5% and 80.6%, respectively. Conclusion In patients with COPD-CAD treated by PCI, the changes of PKM2 and TSAT levels are independently related to MACE events, and are helpful to predict the occurrence of MACE events. -
表 1 无MACE事件和有MACE事件患者的基线特征[（$\bar x \pm s $），M（P25，P75），n（%）]
Table 1. Baseline characteristics of patients with and without MACE event [（$\bar x \pm s $），M（P25，P75），n（%）]
特征 无MACE组（n=72） MACE组（n=22） z/t/χ2 P 年龄（岁） 60.69 ± 11.23 62.59 ± 16.03 0.623 0.535 男性 45（62.5） 15 （68.2） 0.236 0.627 BMI （kg/m2） 25.34 ± 3.71 23.84 ± 3.47 1.682 0.096 收缩压 （mmHg） 157.21 ± 27.74 158.09 ± 32.65 0.125 0.901 心率 （bpm） 73.65 ± 17.69 79.45 ± 15.11 0.139 0.168 FEV1/FVC 52.62 ± 6.99 55.09 ± 7.38 1.427 0.157 FEV1 52.50 ± 20.18 54.47 ± 18.92 0.406 0.686 高血压 43（59.7） 14（63.6） 0.108 0.742 糖尿病 20（27.8） 7（31.8） 0.134 0.714 吸烟 44（61.1） 11（50） 0.857 0.355 饮酒 34 （47.2） 7 （31.8） 1.626 0.202 eGFR （mL/min/1.73 m2） 76.4 ± 22.6 85.2 ± 32.4 1.402 0.240 CAD数量 1.438 0.487 单支血管疾病 22（30.6） 6（27.3） 双血管疾病 33（45.8） 8（36.4） 三支血管疾病 17（23.6） 8（36.4） 患病部位 左主干血管 8（11.1） 1（4.5） 0.839 0.360 左前降支动脉 63（87.5） 19（86.4） 0.020 0.898 左旋动脉 31（43.1） 11（50） 0.329 0.566 右冠状动脉 45（62.5） 16（72.7） 0.774 0.379 hsCRP （mg/L） 20.3 （6.1，46.6） 23.1 （5.2，50.4） 0.591 0.556 CK-MB （ng/mL） 38.11（6.02，156.54） 64.00（6.20，273.10） 1.571 0.120 脑钠肽 （ng/L） 153（65，349） 251（170，631） 1.717 0.097 PKM2 （ng/mL） 0.26 ± 0.05 0.34 ± 0.06 6.227 <0.001* TSAT 18.04 ± 3.51 12.74 ±1.85 6.792 <0.001* 超声心动图检查结果 射血分数 58.17 ± 9.31 55.64 ± 9.76 1.104 0.273 左心室舒张末期容积（mL） 103.32 ± 25.68 112.59 ± 47.62 0.875 0.390 左心室收缩末期容积（mL） 43.49 ± 15.02 51.41 ± 31.95 1.126 0.272 E/e’ 13.48 ± 4.68 14.57 ± 4.68 0.909 0.366 *P < 0.05。 
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表 2 PKM2、TSAT与COPD-CAD患者超声心动图检查结果的相关性分析
Table 2. Correlation analysis of PKM2，TSAT and echocardiographic examination results of COPD-CAD patients
指标 PKM2 左心室舒张末期容积 左心室收缩末期容积 射血分数 E/e’ TSAT PKM2 r 1 0.010 0.204 −0.430 0.209 −0.641 P 0.927 0.049* <0.001* 0.045* <0.001* TSAT r −0.641 −0.309 −0.470 0.470 −0.411 1 P <0.001* 0.002* <0.001* <0.001* <0.001* *P < 0.05。
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表 3 Cox比例风险回归模型分析MACE事件的独立影响因素
Table 3. Cox proportional hazard regression model analyzes the independent influencing factors of MACE events
指标 B SE Wald χ2 P HR 95%CI 下限 上限 PKM2 14.310 4.753 9.063 0.003* 9.375 4.145 21.203 TSAT −0.284 0.079 13.068 0.000* 0.753 0.645 0.878 *P < 0.05。
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表 4 PKM2、TSAT预测COPD-CAD患者发生MACE事件的价值
Table 4. The value of PKM2 and TSAT in predicting MACE events in COPD-CAD patients
指标 AUC SE P 95%CI 最佳截断值 灵敏度（%） 特异度（%） 约登指数 PKM2 0.835 0.054 0.000* 0.729～0.940 0.31 72.7 87.5 0.602 TSAT 0.878 0.035 0.000* 0.811～0.946 15.09 90.9 80.6 0.715 *P < 0.05。
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