Abstract
目的
探讨血清髓过氧化物酶（myeloperoxidase, MPO）和血脂水平与急性冠脉综合征（acute coronary syndrome, ACS）患者冠状动脉病变程度、心血管不良事件（major adverse cardiovascular event, MACE）之间的关系。
方法
选取2023年5月–2025年1月延边大学附属医院收治的216例ACS患者为研究对象，依据疾病类型分为不稳定型心绞痛（UAP组，n=69）、ST段抬高型心肌梗死（STEMI组，n=101）、非ST段抬高型心肌梗死（NSTEMI组，n=46），另选择94例其他疾病患者作为对照组（n=94），对比四组的血清MPO及血脂水平，并分析其与ACS患者冠状动脉病变程度的关系，依据是否发生MACE将ACS患者分为MACE组、非MACE组，对比其血清MPO及血脂水平，绘制受试者工作特征（receiver operating characteristic, ROC）曲线分析血清MPO及血脂水平对MACE的预测价值。
结果
四组患者的总胆固醇（cholesterol, CHO）、高密度脂蛋白胆固醇（high density lipoprotein cholesterol, HDL-C）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol, LDL-C）、MPO水平存在统计学差异（P<0.05），其中STEMI组的CHO水平〔（4.70±1.30） mmol/L〕最高，而NSTEMI组HDL-C〔（0.92±0.32） mmol/L〕最低，NSTEMI组LDL-C、MPO水平〔（3.04±1.38） mmol/L、（175.90±14.59） ng/mL〕最高（P<0.05）；随ACS患者冠脉病变程度增加，其LDL-C及MPO水平增加（P<0.05），冠脉轻度、中度、重度病变者LDL-C水平分别为（2.51±0.91）、（3.08±1.37）、（2.78±0.92） mmol/L，MPO水平分别为（109.65±16.02）、（180.79±22.47）、（150.89±21.32） ng/mL；ACS患者Gensini评分与MPO呈正相关（r=0.148，P<0.05）；血清MPO与CHO、LDL-C呈正相关（r=0.277、0.356，P<0.05），与HDL-C呈负相关（r=－0.186，P<0.05）；MACE组HDL-C水平〔（0.49±0.21） mmol/L〕低于非MACE组〔（1.04±0.29） mmol/L〕，而CHO〔（6.20±1.27） mmol/L〕、LDL-C〔（5.23±0.70） mmol/L〕、血清MPO水平〔（400.52±84.41） ng/mL〕高于非MACE组〔（4.35±1.21） mmol/L、（2.66±0.94） mmol/L、（133.67±87.31） ng/mL〕（P<0.05）；CHO、HDL-C、LDL-C与血清MPO联合预测ACS患者发生MACE事件的曲线下面积为0.893（95%CI： 0.850～0.936），高于各指标单独预测结果〔曲线下面积分别为0.703（95%CI： 0.634～0.773）、0.788（95%CI： 0.729～0.847）、0.800（95%CI： 0.736～0.864）、0.805（95%CI： 0.747～0.862）〕。
结论
MPO、血脂与ACS患者及其冠脉病变程度、MACE密切相关，其联合对于MACE有较高预测价值，值得在临床推广实践。
Keywords: 髓过氧化物酶, 血脂, 急性冠脉综合征, 冠状动脉病变程度, 心血管不良事件
Abstract
Objective
This study aims to investigate the relationship of serum myeloperoxidase (MPO) and blood lipid levels with the severity of coronary artery lesions and major adverse cardiovascular event (MACE) in patients with acute coronary syndrome (ACS).
Methods
From May 2023 to January 2025, 216 ACS patients admitted to Yanbian University Hospital were enrolled as the study subjects. According to the disease types, they were divided into unstable angina pectoris (UAP group, n = 69), ST elevation myocardial infarction (STEMI group, n = 101), and non-ST elevation myocardial infarction (NSTEMI group, n = 46) groups. Additionally, 94 patients with other diseases were selected as controls (control group, n = 94). The serum MPO and blood lipid levels of the four groups were compared, and their relationships with the severity of coronary artery lesions in ACS patients were analyzed. ACS patients were further divided into MACE and non-MACE groups based on whether MACE occurred, and their serum MPO and blood lipid levels were compared. The receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of serum MPO and blood lipid levels for MACE.
Results
There were statistically significant differences in total cholesterol (CHO), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and MPO levels among the four groups (P < 0.05). The STEMI group had the highest CHO level, which was (4.70 ± 1.30) mmol/L. The NSTEMI group had the lowest HDL-C level, which was (0.92 ± 0.32) mmol/L. LDL-C and MPO levels in the NSTEMI group were the highest, which were (3.04 ± 1.38) mmol/L and (175.90 ± 14.59) ng/mL (P < 0.05). With the increase of coronary artery lesion severity in ACS patients, LDL-C and MPO levels showed an increasing trend (P < 0.05). LDL-C levels in patients with mild, moderate, and severe coronary artery lesions were (2.51 ± 0.91) mmol/L, (3.08 ± 1.37) mmol/L, and (2.78 ± 0.92) mmol/L, respectively. MPO levels were (109.65 ± 16.02) ng/mL, (180.79 ± 22.47) ng/mL, and (150.89 ± 21.32) ng/mL, respectively. The Gensini score of ACS patients was positively correlated with MPO (r = 0.148, P < 0.05). Serum MPO was positively correlated with CHO and LDL-C (r = 0.277 and 0.356, P < 0.05), and negatively correlated with HDL-C (r = －0.186, P < 0.05). The HDL-C level in the MACE group ([0.49 ± 0.21] mmol/L) was lower than that in the non-MACE group ([1.04 ± 0.29] mmol/L). The levels of CHO, LDL-C, and MPO ([6.20 ± 1.27] mmol/L, [5.23 ± 0.70] mmol/L, and [400.52 ± 84.41] ng/mL) were higher than those in the non-MACE group ([4.35 ± 1.21] mmol/L, [2.66 ± 0.94] mmol/L, and [133.67 ± 87.31] ng/mL) (P < 0.05). The area under the curve for the combined prediction of MACE in patients with ACS using CHO, HDL-C, LDL-C, and serum MPO was 0.893 (95% CI, 0.850-0.936), which was higher than that of each indicator (0.703 [95% CI, 0.634-0.773], 0.788 [95% CI, 0.729-0.847], 0.800 [95% CI, 0.736-0.864], and 0.805 [95% CI, 0.747-0.862]).
Conclusion
MPO and blood lipids are closely associated with the severity of coronary artery lesions and MACE in patients with ACS. Their combined use demonstrates high predictive value for MACE and is valuable for clinical application and promotion.
Keywords: Myeloperoxidase, Blood lipid, Acute coronary syndrome, Severity of coronary artery lesion, Major adverse cardiovascular event
急性冠脉综合征（acute coronary syndrome, ACS）是由于冠状动脉内粥样硬化斑块出现破裂，进而导致血管发生严重狭窄甚至完全闭塞，从而引发心肌缺血和（或）局部坏死的一组临床综合征，其是冠心病的严重临床表现，与炎症反应、动脉粥样硬化等密切相关，且可能是ACS早期最严重的始动因子，有诱发主要心血管不良事件（major adverse cardiovascular events, MACE）的风险[1]。ACS具有较高发病率、致残率及死亡率，且治疗费用也较高。其包括不稳定型心绞痛（unstable angina pectoris, UAP）、ST段抬高型心肌梗死（ST elevation myocardial infarction, STEMI）、非ST段抬高型心肌梗死（non-ST elevation myocardial infarction, NSTEMI），为冠心病的重要分型[2]。目前主要通过患者病史、临床表现及相关检测指标对ACS进行诊断分型[3]。随着对ACS研究的不断深入，发现一些敏感性细胞因子，如髓过氧化物酶（myeloperoxidase, MPO）、血脂、氨基末端B型脑钠肽（N-terminal probrain natriuretic peptide, NT-proBNP）等已成为研究热点。MPO为过氧化物酶家族中重要成员，能抵御真菌、细菌等病原菌入侵机体，是宿主先天性防御反应的一部分[4]，但目前其与ACS患者冠脉病变程度及MACE的关系研究仍较为匮乏。本文主要分析MPO、血脂水平与ACS患者冠状动脉病变程度及MACE的关系，旨在丰富ACS的诊疗内容。
1. 资料与方法
1.1. 基线资料
以2023年5月–2025年1月期间延边大学附属医院收治的216例ACS患者作为研究对象，根据疾病类型的不同，将这些患者分为三组：不稳定型心绞痛（UAP组，共69患者）、ST段抬高型心肌梗死（STEMI组，共101例患者）、非ST段抬高型心肌梗死（NSTEMI组，共46例患者）。纳入标准：①符合《急性冠脉综合征急诊快速诊治指南(2019)》[5]中ACS的诊断标准，首次诊断为ACS，并经CT等影像学检查证实既往无冠心病手术史；②所有行冠状动脉造影者均符合经皮冠状动脉介入治疗（percutaneous coronary intervention, PCI）适应证，且冠脉造影发现至少1支主要血管（如左主干、左前降支、左回旋支）出现管腔狭窄≥50%。排除标准：①有严重肝肾功能障碍或存在甲亢、甲状腺功能减退等内分泌病变者；②因冠状动脉痉挛导致的急性心肌梗死或陈旧性心肌梗死；③慢性房颤、症状性心衰、主动脉夹层、肺栓塞；④合并恶性肿瘤或心肌炎、脑血管意外疾病、心脏瓣膜病变等引起的心肌标志物水平上升。另选择94例其他疾病患者作为对照组，包括心血管神经症33例、X综合征29例、冠状动脉心肌桥22例、冠状动脉粥样硬化症9例、缺血性心肌病1例。本研究已获延边大学附属医院医学伦理委员会审批。
1.2. 方法
1.2.1. 冠脉病变程度评估
入院后尽快开展冠状动脉造影检查，经德国西门子公司提供的DSA监测仪进行检查，对每一段血管予以投照，投照体位至少3个，经Seldinger技术对股动脉或桡动脉进行左前斜30°、右前斜45°及头脚轴位投影，由2名经验丰富的高年资医师予以冠状动脉造影定量分析。参照美国心脏协会（AHA）的标准对冠状动脉狭窄程度予以评估，采用Gensini评分[6]进行，对于每支冠状动脉病变狭窄程度的定量评定，首先以冠脉狭窄程度确定基本评分，即狭窄直径<25%时计1分；狭窄直径≥25%～<50%计2分；≥50%～<75%计4分；≥75%～<90%计8分；≥90%～<99%计为16分；≥99%～100%计为32分。随后依据不同的冠脉分支来确定对应的系数。对于每一个冠脉狭窄基本评分，将其与该病变部位的系数进行相乘操作。经过这样的计算，所得到的结果即为该病变血管的评分，而总评分是由各个病变血管的评分累加求和所得。病变程度分级：总评分<20分为轻度病变，20～43分为中度病变，>43分为重度病变[7]。本次最终判断为轻度163例、中度60例、重度87例。
1.2.2. 随访及MACE事件的判定
MACE涵盖了多种严重的心血管不良后果，主要包括复发心绞痛、急性心肌梗死、严重心律失常、心力衰竭以及死亡等情况。
1.2.3. 临床资料采集
对比四组临床资料，包括性别、年龄、体质量指数（body mass index, BMI）、收缩压、舒张压、心率、Gensini评分、血管病变数、吸烟史、饮酒史、高血压、糖尿病、糖代谢异常、脂质异常、心梗病史、PCI病史、既往脑血管病史、实验室指标〔肌红蛋白（myoglobin, MYO）、肌钙蛋白I（cardiac troponin I, cTnI）、NT-proBNP、白细胞计数、尿酸、肌酐、总胆固醇（cholesterol, CHO）、高密度脂蛋白胆固醇（high density lipoprotein cholesterol, HDL-C）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol, LDL-C）、三酰甘油（triglyceride, TG）、肌酸激酶同工酶（creatine kinase-MB, CK-MB）、超敏C反应蛋白（hypersensitive C-reactive protein, hs-CRP）、MPO〕。其中MPO测定方法[8]：在进行冠状动脉造影当日8:00，经真空EDTA抗凝管采集受试者空腹状态下的静脉血4 mL，静置2 h后在3500 r/min速率下离心10 min分离血清，经比色法测定血浆MPO水平，试剂盒购自上海康朗生物有限公司。
1.3. 统计学方法
以SPSS23.0软件对数据进行统计学分析，性别等各类计数资料以例数（%）表示，开展χ2检验、Fisher精确概率法分析，计量资料经Shapiro-Wilk正态性检验、Levene检验显示满足正态分布与方差齐性要求，以
表示，进行单因素方差分析及LSD-t检验或两独立样本间的t检验分析。相关性采用Pearson相关分析。绘制受试者工作特征（receiver operating characteristic, ROC）曲线分析各指标预测ACS患者发生MACE事件的价值。均采用双侧检验，α=0.05。
2. 结果
2.1. 四组临床资料及实验室指标比较
四组性别、年龄、Gensini评分、血管病变数、糖尿病、糖代谢异常、心梗病史、PCI病史及MYO、cTnI、NT-proBNP、白细胞计数、肌酐、CHO、HDL-C、LDL-C、CK-MB、hs-CRP、MPO差异有统计学意义（P<0.05），其中STEMI组CHO水平最高，而NSTEMI组HDL-C最低，NSTEMI组LDL-C、MPO水平最高（P<0.05）；两组其他资料比较差异无统计学意义（P>0.05）。见表1。
表 1. Comparison of clinical data and laboratory indices among the four groups.
四组临床资料及实验室指标比较
| Item | Type | UAP group (n = 69) |
STEMI group (n = 101) |
NSTEMI group (n = 46) |
Control group (n = 94) |
χ2/F | P |
| UAP: unstable angina pectoris; STEMI: ST elevation myocardial infarction; NSTEMI: non-ST elevation myocardial infarction; BMI: body mass index; PCI: percutaneous coronary intervention; MYO: myoglobin; cTnI: cardiac troponin I; NT-proBNP: N-terminal pro-brain natriuretic peptide; CHO: cholesterol; HDL-C: high density lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol; TG: triglyceride; CK-MB: creatine kinase-MB; hs-CRP: hypersensitive C-reactive protein; MPO: myeloperoxidase; MACE: major adverse cardiovascular event. 1 mmHg=0.133 kPa. * P < 0.05, vs. UAP group; # P < 0.05, vs. STEMI group; △ P < 0.05, vs. NSTEMI group. | |||||||
| Sex/case (%) | Male | 54 (78.26) | 77 (76.24) | 30 (65.22) | 33 (35.11) | 45.726 | < 0.001 |
| Female | 15 (21.74) | 24 (23.76) | 16 (34.78) | 61 (64.89) | |||
| Age/yr. | － | 65.99 ± 8.02 | 60.33 ± 11.43* | 68.20 ± 9.22# | 60.73 ± 10.28*, △ | 10.029 | < 0.001 |
| BMI/(kg/m2) | － | 24.71 ± 3.40 | 25.17 ± 3.50 | 24.78 ± 3.58 | 25.25 ± 3.82 | 0.438 | 0.726 |
| Systolic blood pressure/mmHg | － | 137.64 ± 12.20 | 130.55 ± 21.46* | 134.07 ± 24.50*, # | 135.94 ± 15.17*, # | 2.379 | 0.070 |
| Diastolic blood pressure/mmHg | － | 86.03 ± 11.70 | 82.18 ± 13.00* | 81.98 ± 13.63* | 82.73 ± 8.94# | 1.813 | 0.145 |
| Heart rate/min－1 | － | 79.88 ± 13.08 | 81.03 ± 16.31 | 78.78 ± 16.57 | 76.81 ± 13.02 | 1.408 | 0.241 |
| Gensini score | － | 23.87 ± 2.56 | 47.56 ± 5.25* | 55.13 ± 5.91*, # | 0.34 ± 0.08*, #, △ | 3102.651 | < 0.001 |
| Number of vascular lesions/case (%) | 0 | 2 (2.90) | 0 (0) | 0 (0) | 93 (98.94) | 318.014 | < 0.001 |
| 1 | 34 (49.28) | 34 (33.66) | 7 (15.22) | 1 (1.06) | |||
| 2 | 16 (23.19) | 33 (32.67) | 20 (43.48) | 0 (0) | |||
| 3 | 17 (24.63) | 34 (33.67) | 19 (41.30) | 0 (0) | |||
| Smoking history/case (%) | Yes | 32 (46.38) | 44 (43.56) | 24 (52.17) | 29 (30.85) | 7.395 | 0.060 |
| No | 37 (53.62) | 57 (56.44) | 22 (47.83) | 65 (69.15) | |||
| Drinking history/case (%) | Yes | 23 (33.33) | 32 (31.68) | 15 (32.61) | 17 (18.09) | 6.711 | 0.082 |
| No | 46 (66.67) | 69 (68.32) | 31 (67.39) | 77 (81.91) | |||
| Hypertension/case (%) | Yes | 45 (65.22) | 52 (51.49) | 28 (60.87) | 43 (45.74) | 7.205 | 0.066 |
| No | 24 (34.78) | 49 (48.51) | 18 (39.13) | 51 (54.26) | |||
| Diabetes/case (%) | Yes | 21 (30.43) | 34 (33.66) | 12 (26.09) | 12 (12.77) | 12.464 | < 0.001 |
| No | 48 (69.57) | 67 (66.34) | 34 (73.91) | 82 (87.23) | |||
| Abnormal glucose metabolism/case (%) | Yes | 22 (31.88) | 35 (34.65) | 12 (26.09) | 13 (13.83) | 12.240 | < 0.001 |
| No | 47 (68.12) | 66 (65.35) | 34 (73.91) | 81 (86.17) | |||
| Lipid abnormalities/case (%) | Yes | 33 (47.83) | 54 (53.47) | 27 (58.70) | 43 (45.74) | 2.637 | 0.451 |
| No | 36 (52.17) | 47 (46.53) | 19 (41.30) | 51 (54.26) | |||
| History of myocardial infarction/case (%) | Yes | 9 (13.04) | 7 (6.93) | 9 (19.57) | 1 (1.06) | 16.267 | < 0.001 |
| No | 60 (86.96) | 94 (93.07) | 37 (80.43) | 93 (98.94) | |||
| History of PCI/case (%) | Yes | 17 (24.64) | 10 (9.90) | 9 (19.57) | 2 (2.13) | 21.606 | < 0.001 |
| No | 52 (75.36) | 91 (90.10) | 37 (80.43) | 92 (97.87) | |||
| Previous history of cerebrovascular disease/case (%) |
Yes | 6 (8.70) | 7 (6.93) | 9 (19.57) | 6 (6.38) | 7.567 | 0.056 |
| No | 63 (91.30) | 94 (93.07) | 37 (80.43) | 88 (93.62) | |||
| Laboratory indices | |||||||
| MYO/(ng/mL) | － | 26.47 ± 2.95 | 307.45 ± 52.36* | 130.64 ± 14.72*, # | 26.55 ± 2.78#, △ | 1760.254 | < 0.001 |
| cTnI/(pg/mL) | － | 0.020 ± 0.010 | 14.12 ± 2.24* | 13.68 ± 1.70* | 0.007 ± 0.002#, △ | 2436.180 | < 0.001 |
| NT-proBNP/(pg/mL) | － | 93.96 ± 23.81 | 949.41 ± 152.56* | 1914.18 ± 218.30*, # | 72.16 ± 7.31#, △ | 3054.724 | < 0.001 |
| White blood cell count/(×109 L－1) | － | 6.97 ± 2.01 | 10.36 ± 3.23* | 8.80 ± 4.32*, # | 5.83 ± 1.50*, #, △ | 47.987 | < 0.001 |
| Uric acid/(μmol/L) | － | 320.80 ± 101.77 | 317.51 ± 87.72 | 362.91 ± 198.64 | 309.24 ± 90.61 | 2.398 | 0.068 |
| Creatinine/(μmol/L) | － | 72.28 ± 9.58 | 71.77 ± 8.10 | 79.91 ± 8.81*, # | 61.56 ± 6.79*, #, △ | 58.917 | < 0.001 |
| CHO/(mmol/L) | － | 4.01 ± 1.09 | 4.70 ± 1.30* | 4.47 ± 1.31 | 4.41 ± 1.04* | 4.747 | 0.003 |
| HDL-C/(mmol/L) | － | 1.04 ± 0.25 | 1.05 ± 0.33 | 0.92 ± 0.32 | 1.14 ± 0.29*, △ | 5.986 | < 0.001 |
| LDL-C/(mmol/L) | － | 2.34 ± 0.80 | 2.96 ± 1.01* | 3.04 ± 1.38 | 2.60 ± 0.84# | 7.539 | < 0.001 |
| TG/(mmol/L) | － | 1.79 ± 1.01 | 1.95 ± 0.22 | 1.75 ± 0.87 | 1.85 ± 0.21 | 0.267 | 0.849 |
| CK-MB/(IU/L) | － | 2.35 ± 0.49 | 42.84 ± 5.52* | 35.16 ± 3.69*, # | 2.44 ± 0.33#, △ | 3145.627 | < 0.001 |
| hs-CRP/(mg/L) | － | 12.59 ± 1.37 | 19.56 ± 2.60* | 12.70 ± 1.58# | 1.45 ± 0.17*, #, △ | 1799.136 | < 0.001 |
| MPO/(ng/mL) | － | 100.43 ± 12.38 | 163.56 ± 16.76* | 175.90 ± 14.59*, # | 83.94 ± 9.17#, △ | 853.760 | < 0.001 |
| Incidence of MACE/case (%) | 0 (0) | 3 (2.97) | 7 (15.22) | 0 (0) | 26.644 | < 0.001 | |
2.2. 不同冠脉病变程度患者血脂及血清MPO水平比较
随ACS患者冠脉病变程度增加，其LDL-C及MPO水平增加（P<0.05），而CHO、HDL-C、TG变化不明显（P>0.05）。见表2。
表 2. Comparison of blood lipids and serum MPO levels in patients with coronary artery lesions of varying serverities.
不同冠脉病变程度患者血脂及血清MPO水平比较
| Severity of coronary artery lesions | n | CHO/(mmol/L) | HDL-C/(mmol/L) | LDL-C/(mmol/L) | TG/(mmol/L) | MPO/(ng/mL) |
| All abbreviations are explained in the note to Table 1. * P < 0.05, vs. mild group. | ||||||
| Mild | 69 | 4.17 ± 1.08 | 1.03 ± 0.28 | 2.51 ± 0.91 | 1.77 ± 1.19 | 109.65 ± 16.02 |
| Moderate | 60 | 4.66 ± 1.44 | 1.05 ± 0.35 | 3.08 ± 1.37* | 1.64 ± 1.01 | 180.79 ± 22.47* |
| Severe | 87 | 4.48 ± 1.26 | 0.99 ± 0.30* | 2.78 ± 0.92 | 2.07 ± 1.80 | 150.89 ± 21.32* |
| F | 2.499 | 0.798 | 4.741 | 1.784 | 204.623 | |
| P | 0.085 | 0.452 | 0.010 | 0.171 | < 0.001 | |
2.3. Pearson相关分析结果
ACS患者的Gensini评分同MPO存在正相关关系（P<0.05）；血清MPO与CHO、LDL-C呈正相关，与HDL-C呈负相关（P<0.05）。见表3。
表 3. Correlation of Gensini score with blood lipids and serum MPO levels in ACS patients (n = 216).
ACS患者Gensini评分与血脂、血清MPO水平相关性（n=216）
| Indicator | CHO | HDL-C | LDL-C | TG | MPO | |||||||||
| r | P | r | P | r | P | r | P | r | P | |||||
| All abbreviations are explained in the note to Table 1. | ||||||||||||||
| Gensini score | 0.094 | 0.170 | －0.064 | 0.351 | 0.100 | 0.144 | 0.082 | 0.230 | 0.148 | 0.030 | ||||
| MPO | 0.277 | < 0.001 | －0.186 | 0.006 | 0.356 | < 0.001 | 0.030 | 0.663 | － | － | ||||
2.4. MACE组与非MACE组血脂及血清MPO水平比较
MACE组HDL-C水平低于非MACE组，而CHO、LDL-C、血清MPO水平高于非MACE组（P<0.05）。见表4。
表 4. Comparison of blood lipids and serum MPO level between the MACE group and the non-MACE group.
MACE组与非MACE组血脂及血清MPO水平比较
| Group | n | CHO/(mmol/L) | HDL-C/(mmol/L) | LDL-C/(mmol/L) | TG/(mmol/L) | MPO/(ng/mL) |
| All abbreviations are explained in the note to Table 1. | ||||||
| MACE | 10 | 6.20 ± 1.27 | 0.49 ± 0.21 | 5.23 ± 0.70 | 1.63 ± 1.01 | 400.52 ± 84.41 |
| Non-MACE | 206 | 4.35 ± 1.21 | 1.04 ± 0.29 | 2.66 ± 0.94 | 1.87 ± 1.45 | 133.67 ± 87.31 |
| t | 4.721 | 5.948 | 8.517 | 0.524 | 8.17 | |
| P | < 0.001 | < 0.001 | < 0.001 | 0.729 | < 0.001 | |
2.5. 血脂及MPO水平预测MACE的ROC曲线
CHO、HDL-C、LDL-C联合MPO预测MACE事件的曲线下面积为0.893，高于各指标单独预测结果0.703、0.788、0.800、0.805。见图1、表5。
图 1.
ROC curves of blood lipids and MPO levels for predicting MACE
血脂及MPO水平预测MACE事件的ROC曲线
表 5. Value of blood lipids and MPO levels in predicting MACE.
血脂及MPO水平预测MACE事件的价值
| Variables | Sensitivity/% | Specificity/% | Cut-off value | Area under the curve | 95% CI |
| All abbreviations are explained in the note to Table 1. | |||||
| CHO | 72.31 | 69.88 | 6.37 | 0.703 | 0.634-0.773 |
| HDL-C | 77.63 | 75.52 | 0.62 | 0.788 | 0.729-0.847 |
| LDL-C | 74.59 | 76.26 | 5.56 | 0.800 | 0.736-0.864 |
| MPO | 76.92 | 72.79 | 399.46 | 0.805 | 0.747-0.862 |
| Combination of the four | 83.12 | 79.65 | － | 0.893 | 0.850-0.936 |
3. 讨论
PCI是治疗ACS的重要手段，能及时开通闭塞血管，改善心肌血供，挽救濒死心肌。虽然多数ACS患者能从PCI中获益[9-10]，但因受到球囊扩张、支架植入等因素影响，易造成血管内皮受损、免疫系统激活，继而释放大量炎症因子，导致心肌损伤加重，诱发心绞痛再发、恶性心律失常、心肌梗死等一系列MACE，严重地影响患者预后[11]。MPO基因位于17号染色体，它编码的蛋白是一种四聚体糖基化蛋白，含两条重链和轻链，结构较为复杂，这种特殊的结构使得MPO在生物体内能够发挥特定功能，并作为炎症介质参与形成冠状动脉粥样硬化的炎症反应。MPO的结构特点决定了它能够与特定的分子相互作用，从而在冠心病发生发展中发挥作用。研究[12]发现，血清MPO与急诊PCI术后发生造影剂所致急性肾损伤者的预后有显著相关性，但关于MPO与ACS患者冠脉病变程度、MACE的关系报道甚少。
MPO是血红素过氧化物酶超家族亚铁血红素酶中的一员，主要存在于嗜中性粒细胞和单核细胞中，在炎症反应中发挥着重要作用。MPO通过中性粒细胞激活后被释放出来，参与形成冠状动脉粥样硬化的炎症反应等多种生理和病理过程。张海生等[13]报道，急性心肌梗死组、UAP组MPO高于对照组及稳定型心绞痛组，不同冠脉狭窄组的MPO水平无差异。本研究同样发现，NSTEMI组MPO水平最高，与上述研究及刘志远等[14]的结果一致。此外，与之不同的是本研究发现不同ACS患者的血脂水平也有显著差异，表现为NSTEMI组HDL-C最低，NSTEMI组LDL-C最高，表明MPO可能与ACS发生发展有关，尤其是NSTEMI患者的MPO及血脂水平异常最明显。ACS的致病机制包括氧化低密度脂蛋白，加强低密度脂蛋白的致病作用，促使粥样斑块的形成。而MPO是一种白细胞酶，为糖基化的四聚体血红素蛋白，由单核细胞、中性粒细胞及巨噬细胞所分泌。血管内MPO主要源自多形核嗜中性粒细胞。MPO不仅具备较强的生物活性，也可在特定环境中发生催化反应而产生过量氧化剂，当局部抗氧化剂防御反应被超过时，将产生氧化应激反应，且会对组织细胞产生氧化性损伤；同时，MPO的作用会加速动脉粥样硬化斑块的形成，且会对粥样斑块稳定性造成影响，增强氧化应激反应，继而导致ACS[15]。
在相关性方面，凌娟等[16]发现，稳定型心绞痛患者的血浆MPO水平与冠状动脉Gensini积分呈正相关，认为MPO水平升高可以反映冠状动脉侧支循环的形成不良。本次发现随ACS患者冠脉病变程度增加，其HDL-C呈下降趋势，而LDL-C及MPO水平上升，同时ACS患者Gensini评分与HDL-C呈负相关，与LDL-C、MPO呈正相关，血清MPO与CHO、LDL-C呈正相关，与HDL-C呈负相关，表明ACS患者的血脂水平、MPO与冠脉病变程度存在密切关系。炎症因子在动脉粥样硬化斑块形成过程中起着重要作用，而氧化应激诱导的炎症反应是动脉粥样硬化斑块形成的重要机制，而MPO主要存在于嗜中性粒细胞或单核细胞的嗜天青颗粒中，炎症反应时嗜中性粒细胞发生脱颗粒并释放MPO，其可导致冠状动脉粥样硬化病灶不稳定甚至破裂，使血管内皮下胶原组织暴露，随之发生血小板黏附聚集与血栓形成，引起冠状动脉阻塞，发生ACS并致严重心肌不可逆性缺血损伤[17-18]。
在与预后的关系上，武华荣等[19]报道，MACE组MPO水平高于无MACE组，MPO为STEMI患者预后不良的独立危险因素（β=0.006，P=0.047，OR=1.006，95%CI：1.000～1.012）。马学华等[20]发现，MPO可预测ACS患者的预后，能有效筛查其他心肌损伤标志物不高的ACS患者。本研究发现，MACE组HDL-C水平低于非MACE组，而LDL-C、血清MPO水平高于非MACE组，表明MPO及血脂水平可用于预测ACS患者的预后。MPO作为一种重要的促炎介质，可通过促进组织生成过氧化氢、次氯酸等活性氧，同时经介导粒细胞、单核细胞及巨噬细胞等免疫细胞的黏附与聚集过程，而在炎症反应启动、维持及调控中发挥多维度作用，与ACS患者MACE事件密切相关[21]。既往刘胜聪等[22]发现，在住院ACS患者中，STEMI患者血浆MPO水平高于NSTEMI患者，基线血浆MPO水平与患者院内或长期心血管事件均无相关性，作者解释该研究结果可能存在一定偏差，原因如下：首先受试者的血样采集是在首次住院期间进行MPO水平检测，绝大多数患者的血样本在入院7 d内采集，其中近50%的患者更是在入院24 h内完成采血，这一时间节点的集中性可能影响样本的代表性；其次，该研究的失访率近20%，这必然会导致一定程度的数据偏倚；此外诊断分组的各个亚组例数较少，样本量不足，也可能对统计结果产生影响。
武智晓等[23]发现，MPO也是PCI术后发生MACE的独立影响因素（OR=3.725，95%CI：1.533～9.052）；ROC发现外周血MPO预测STEMI患者PCI术后发生MACE的AUC为0.749（95%CI： 0.650～0.849）。吕帅等[24]报道，MPO预测MACE的曲线下面积为0.879，MPO与STEMI患者发生MACE呈正相关。本研究也发现，CHO、HDL-C、LDL-C联合MPO预测MACE事件的曲线下面积为0.893，高于各指标单独预测结果（0.703、0.788、0.800、0.805），与以上报道结果相近，表明血清MPO与血脂水平联合利于提高对ACS患者MACE的预测价值。原因在于MPO浓度上升会降低机体对NO的利用，高水平的MPO可能通过多种机制影响NO生物利用度，当MPO浓度升高导致NO利用降低时，可能会影响血管的正常功能，从而增加血栓形成的风险。此外，MPO浓度上升也会促进LDL氧化，催化中产生的次氯酸等强氧化剂也能够攻击LDL中的脂质和蛋白质成分，使其发生氧化修饰。修饰后的LDH具有更强的致动脉粥样硬化作用，进一步促进动脉粥样硬化斑块的形成。MPO也可通过影响血小板的功能，如促进血小板聚集和活化，增加血栓形成的风险[25]。最终，MPO通过这些途径实现对MACE事件的预测，这些优势可以弥补常规血脂预测MACE的低特异性，使综合诊断效能明显提高，因此可在临床推广应用。
综上所述，血清MPO及血脂水平与ACS患者的冠脉病变程度、MACE有密切关系，联合检测能够对ACS患者发生MACE进行准确预测，值得在临床推广实践。本研究也存在局限性，因其本质上属于观察性研究，研究结果会受到多种混杂因素的干扰，未考虑各种混杂因素的控制，因此本研究结果仅可作为探索性分析结论。
* * *
作者贡献声明 李宇龙负责论文构思、数据审编、正式分析、调查研究、研究方法、研究项目管理和软件，李香负责论文构思、数据审编、经费获取、调查研究、研究方法、提供资源、监督指导和审读与编辑写作。所有作者已经同意将文章提交给本刊，且对将要发表的版本进行最终定稿，并同意对工作的所有方面负责。
Author Contribution LI Yulong is responsible for conceptualization, data curation, formal analysis, investigation, methodology, project administration, and software. LI Xiang is responsible for conceptualization, data curation, funding acquisition, investigation, methodology, resources, supervision, and writing--review and editing. Both authors consented to the submission of the article to the Journal. Both authors approved the final version to be published and agreed to take responsibility for all aspects of the work.
利益冲突 所有作者均声明不存在利益冲突
Declaration of Conflicting Interests Both authors declare no competing interests.
Funding Statement
国家自然科学基金（No. 82060052）资助
Contributor Information
宇龙 李 (Yulong LI), Email: 18943302508@163.com.
香 李 (Xiang LI), Email: 15526770377@163.com.
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