血清和肽素在急性心肌梗死临床诊断和预后评估中的价值

doi:10.3969/j.issn.1673-8640.2025.09.004

摘要/Abstract

摘要：

目的探讨血清和肽素在急性心肌梗死（AMI）早期诊断和预后评估中的价值。方法选取2023年1月—2024年1月湖南中医药大学第一附属医院AMI患者102例（AMI组）、非AMI患者55例（对照组）。收集所有研究对象的临床资料，并检测血清和肽素、肌酸激酶MB同工酶（CK-MB）、心肌肌钙蛋白（cTn）I、肌红蛋白（MYO）和血脂水平。采用受试者工作特征（ROC）曲线评价各项指标诊断AMI的效能和预测6个月内发生主要心血管不良事件（MACE）的效能。采用Spearman相关分析评估AMI患者和肽素与CK-MB、cTnI、MYO的相关性。采用Cox比例风险回归分析评估各项指标与AMI患者发生MACE的关系。结果 AMI组血清和肽素、CK-MB 、MYO和cTnI水平均高于对照组（P<0.001）。血清和肽素与cTnI、MYO水平呈正相关（r值分别为0.578、0.624，P<0.001），与CK-MB无相关性（r=0.158，p=0.113）。血清和肽素单项检测诊断AMI的曲线下面积（AUC）为0.896，判断AMI患者6个月内发生MACE的AUC为0.810；和肽素+cTnI、CK-MB+MYO+cTnI、和肽素+cTnI+CK-MB+MYO诊断AMI的AUC分别为0.960、0.975、0.986，判断AMI患者6个月内发生MACE的AUC分别为0.961、0.958、0.949。和肽素、MYO、cTnI是AMI患者6个月内发生MACE的危险因素[风险比（HR）值分别为1.005、1.004、1.070，95%可信区间（CI）分别为1.001~1.008、1.000~1.008、1.015~1.128]。结论血清和肽素诊断AMI和预测患者6个月内发生MACE具有较高的效能，或可作为AMI早期诊断和预后评估的生物标志物。

关键词: 和肽素, 心肌肌钙蛋白I, 急性心肌梗死, 主要心血管不良事件

Abstract:

Objective To investigate the role of serum copeptin in the early diagnosis and prognosis assessment of acute myocardial infarction （AMI）. Methods A total of 102 AMI patients（AMI group）and 55 non-AMI patients（control group）from the First Affiliated Hospital of Hunan University of Chinese Medicine from January 2023 to January 2024 were enrolled. The clinical data were collected，and serum copeptin，creatine kinase MB isoenzyme（CK-MB），cardiac troponin（cTn）I，myoglobin（MYO） and blood lipid levels were determined. Receiver operating characteristic（ROC）curve was used to evaluate the efficacy of each index in diagnosing AMI and predicting major adverse cardiovascular events（MACE）within 6 months. Spearman correlation analysis was used to assess the correlation between serum copeptin and CK-MB，cTnI and MYO in AMI patients. Cox proportional hazard regression analysis was used to evaluate the relationship between each indicator and the occurrence of MACE in AMI patients. Results The levels of serum copeptin，CK-MB，MYO and cTnI in AMI group were higher than those in control group（P<0.001）. Serum copeptin was positively correlated with cTnI and MYO levels（r values were 0.578 and 0.624，respectively，P<0.001），but not with CK-MB（r=0.158，p=0.113）. The area under curve（AUC）of serum copeptin for diagnosing AMI was 0.896，and that for predicting MACE within 6 months in AMI patients was 0.810. The AUC of copeptin+cTnI，CK-MB+MYO+cTnI and the combined determination of the 4 indicators for diagnosing AMI were 0.960，0.975 and 0.986，respectively，and those for predicting MACE within 6 months in AMI patients were 0.961，0.958 and 0.949，respectively. Serum copeptin，MYO and cTnI were risk factors for MACE within 6 months in AMI patients [hazard ratios（HR）were 1.005，1.004 and 1.070，95% confidence intervals（CI）were 1.001-1.008，1.000-1.008 and 1.015-1.128，respectively]. Conclusions Serum copeptin has high efficacy in the diagnosis of AMI and the prediction of MACE within 6 months，and it may be used as a biomarker for the early diagnosis and prognosis assessment of AMI.

Key words: Copeptin, Cardiac troponin I, Acute myocardial infarction, Major adverse cardiovascular event

中图分类号:

R446.1

许莹芊, 王金全, 彭欢子, 彭嘉琪, 何坤, 谢小兵. 血清和肽素在急性心肌梗死临床诊断和预后评估中的价值[J]. 检验医学, 2025, 40(9): 848-855.

XU Yingqian, WANG Jinquan, PENG Huanzi, PENG Jiaqi, HE Kun, XIE Xiaobing. Roles of serum copeptin in clinical diagnosis and prognosis evaluation of acute myocardial infarction[J]. Laboratory Medicine, 2025, 40(9): 848-855.

图/表 8

参考文献 32

[1]	GBD 2017 DALYs and HALE Collaborators. Global,regional,and national disability-adjusted life-years(DALYs)for 359 diseases and injuries and healthy life expectancy(HALE)for 195 countries and territories,1990-2017:a systematic analysis for the global burden of disease study 2017[J]. Lancet, 2018, 392(10159):1859-1922.
[2]	IBANEZ B, JAMES S, AGEWALL S, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation:the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology(ESC)[J]. Eur Heart J, 2018, 39(2):119-177.
[3]	THYGESEN K, ALPERT J S, JAFFE A S, et al. Fourth universal definition of myocardial infarction(2018)[J]. Circulation, 2018, 138(20):e618-e651.
[4]	THYGESEN K, MAIR J, KATUS H, et al. Recommendations for the use of cardiac troponin measurement in acute cardiac care[J]. Eur Heart J, 2010, 31(18):2197-2204. DOI PMID
[5]	GUAN X, LIANG T, FAN J, et al. The value of copeptin,myocardial fatty acid-binding protein and myocardial markers in the early diagnosis of acute myocardial infarction[J]. Am J Transl Res, 2022, 14(11):8002-8008.
[6]	毛杰, 卢晴晴, 李萍, 等. 和肽素在不同疾病中的临床应用进展[J]. 检验医学, 2022, 37(3):291-294. DOI
[7]	杨烽华, 庄少伟. 和肽素与心血管疾病的关系研究进展[J]. 临床误诊误治, 2024, 37(2):143-146.
[8]	HANCOCK E W, DEAL B J, MIRVIS D M, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram:partⅤ:electrocardiogram changes associated with cardiac chamber hypertrophy:a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee,Council on Clinical Cardiology;the American College of Cardiology Foundation;and the Heart Rhythm Society:endorsed by the International Society for Computerized Electrocardiology[J]. Circulation, 2009, 119(10):e251-e261.
[9]	BYRNE R A, ROSSELLO X, COUGHLAN J J, et al. 2023 ESC guidelines for the management of acute coronary syndromes[J]. Eur Heart J,2023, 44(38):3720-3826.
[10]	中华医学会心血管病学分会, 中华心血管病杂志编辑委员会. 急性心肌梗死合并心原性休克诊断和治疗中国专家共识(2021)[J]. 中华心血管病杂志, 2022, 50(3):231-242.
[11]	STRUCK J, MORGENTHALER N G, BERGMANN A. Copeptin,a stable peptide derived from the vasopressin precursor,is elevated in serum of sepsis patients[J]. Peptides, 2005, 26(12):2500-2504.
[12]	MORGENTHALER N G, STRUCK J, ALONSO C, et al. Assay for the measurement of copeptin,a stable peptide derived from the precursor of vasopressin[J]. Clin Chem, 2006, 52(1):112-119.
[13]	HOLWERDA D A. A glycopeptide from the posterior lobe of pig pituitariesⅠ. Isolation and characterization[J]. Eur J Biochem, 1972, 28(3):334-339.
[14]	KATAN M, MORGENTHALER N, WIDMER I, et al. Copeptin,a stable peptide derived from the vasopressin precursor,correlates with the individual stress level[J]. Neuro Endocrinol Lett, 2008, 29(3):341-346.
[15]	PIYANUTTAPULL S. Correlation of plasma copeptin levels and early diagnosis of acute myocardial infarction compared with troponin-T[J]. J Med Assoc Thai, 2013, 96(1):13-19. PMID
[16]	KELLY D, SQUIRE I B, KHAN S Q, et al. C-terminal provasopressin(copeptin)is associated with left ventricular dysfunction,remodeling,and clinical heart failure in survivors of myocardial infarction[J]. J Card Fail, 2008, 14(9):739-745.
[17]	KELLER T, TZIKAS S, ZELLER T, et al. Copeptin improves early diagnosis of acute myocardial infarction[J]. J Am Coll Cardiol, 2010, 55(19):2096-2106. DOI PMID
[18]	GEGENHUBER A, STRUCK J, DIEPLINGER B, et al. Comparative evaluation of B-type natriuretic peptide,mid-regional pro-A-type natriuretic peptide,mid-regional pro-adrenomedullin,and copeptin to predict 1-year mortality in patients with acute destabilized heart failure[J]. J Card Fail, 2007, 13(1):42-49.
[19]	KHAN S Q, DHILLON O S, O'BRIEN R J, et al. C-terminal provasopressin(copeptin)as a novel and prognostic marker in acute myocardial infarction:leicester acute myocardial infarction peptide(LAMP)study[J]. Circulation, 2007, 115(16):2103-2110.
[20]	MORGENTHALER N G. Copeptin:a biomarker of cardiovascular and renal function[J]. Congest Heart Fail, 2010, 16(Suppl 1):S37-S44.
[21]	HAMM C W, BASSAND J P, AGEWALL S, et al. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation:the task force for the management of acute coronary syndromes(ACS)in patients presenting without persistent ST-segment elevation of the European Society of Cardiology(ESC)[J]. Eur Heart J, 2011, 32(23):2999-3054.
[22]	KUMAR A, CANNON C P. Acute coronary syndromes:diagnosis and management,partⅠ[J]. Mayo Clin Proc, 2009, 84(10):917-938.
[23]	MUELLER C. Biomarkers and acute coronary syndromes:an update[J]. Eur Heart J, 2014, 35(9):552-556.
[24]	GANDHI P U, JANUZZI J L Jr. Can copeptin emerge from the growing shadow of the troponins?[J]. Eur Heart J, 2015, 36(6):333-336. DOI PMID
[25]	GIANNITSIS E, CLIFFORD P, SLAGMAN A, et al. Multicentre cross-sectional observational registry to monitor the safety of early discharge after rule-out of acute myocardial infarction by copeptin and troponin:the Pro-Core registry[J]. BMJ Open, 2019, 9(7):e028311.
[26]	VARGAS K G, KASSEM M, MUELLER C, et al. Copeptin for the early rule-out of non-ST-elevation myocardial infarction[J]. Int J Cardiol, 2016, 223:797-804. DOI PMID
[27]	MAISEL A, MUELLER C, NEATH S X, et al. Copeptin helps in the early detection of patients with acute myocardial infarction:primary results of the CHOPIN trial(copeptin helps in the early detection of patients with acute myocardial infarction)[J]. J Am Coll Cardiol, 2013, 62(2):150-160.
[28]	SHIN H, JANG B H, LIM T H, et al. Diagnostic accuracy of adding copeptin to cardiac troponin for non-ST-elevation myocardial infarction:a systematic review and meta-analysis[J]. PLoS One, 2018, 13(7):e0200379.
[29]	JEONG J H, SEO Y H, AHN J Y, et al. Performance of copeptin for early diagnosis of acute myocardial infarction in an emergency department setting[J]. Ann Lab Med, 2020, 40(1):7-14. DOI PMID
[30]	MEUNE C, ZUILY S, WAHBI K, et al. Combination of copeptin and high-sensitivity cardiac troponin T assay in unstable angina and non-ST-segment elevation myocardial infarction:a pilot study[J]. Arch Cardiovasc Dis, 2011, 104(1):4-10.
[31]	汤希凡, 秦辛玲. 高敏心肌肌钙蛋白T检测在急性心肌梗死诊断中的应用[J]. 实用医学杂志, 2012, 28(5):828-829.
[32]	SAILER C O, REFARDT J, BLUM C A, et al. Validity of different copeptin assays in the differential diagnosis of the polyuria-polydipsia syndrome[J]. Sci Rep, 2021, 11(1):10104. DOI PMID

组别	例数	性别		年龄/岁	吸烟史/[例（%）]	饮酒史/[例（%）]	糖尿病史/[例（%）]	呼吸系统疾病史/[例（%）]	BMI/（kg·m^-2）
组别	例数	男/例	女/例	年龄/岁	吸烟史/[例（%）]	饮酒史/[例（%）]	糖尿病史/[例（%）]	呼吸系统疾病史/[例（%）]	BMI/（kg·m^-2）
AMI组	102	62	40	62.24±10.77	30（29.4）	26（25.4）	22（21.6）	15（14.7）	23.01±2.82
对照组	55	36	19	65.22±7.89	13（23.6）	20（36.4）	12（24）	6（10.9）	22.44±2.67
统计值		0.322		-1.808	0.599	2.039	0.001	0.445	1.227
P值		0.564		0.073	0.439	0.153	0.971	0.505	0.222
组别	收缩压/kPa			舒张压/kPa		TG/（mmol·L^-1）	TC/（mmol·L^-1）	LDL-C/（mmo·L^-1）	HDL-C/（mmol·L^-1）
AMI组	16.63±0.70			9.18±1.29		1.55±1.05	5.23±0.43	3.1±0.71	1.29±0.19
对照组	16.44±0.86			9.04±1.32		1.41±0.75	5.24±0.49	2.9±0.84	1.3±0.19
统计值	1.523			0.636		0.883	-0.146	1.506	-0.451
P值	0.130			0.525		0.379	0.884	0.134	0.653

组别	例数	性别		年龄/岁	吸烟史/[例（%）]	饮酒史/[例（%）]	糖尿病史/[例（%）]	呼吸系统疾病史/[例（%）]	BMI/（kg·m^-2）
组别	例数	男/例	女/例	年龄/岁	吸烟史/[例（%）]	饮酒史/[例（%）]	糖尿病史/[例（%）]	呼吸系统疾病史/[例（%）]	BMI/（kg·m^-2）
AMI组	102	62	40	62.24±10.77	30（29.4）	26（25.4）	22（21.6）	15（14.7）	23.01±2.82
对照组	55	36	19	65.22±7.89	13（23.6）	20（36.4）	12（24）	6（10.9）	22.44±2.67
统计值		0.322		-1.808	0.599	2.039	0.001	0.445	1.227
P值		0.564		0.073	0.439	0.153	0.971	0.505	0.222
组别	收缩压/kPa			舒张压/kPa		TG/（mmol·L^-1）	TC/（mmol·L^-1）	LDL-C/（mmo·L^-1）	HDL-C/（mmol·L^-1）
AMI组	16.63±0.70			9.18±1.29		1.55±1.05	5.23±0.43	3.1±0.71	1.29±0.19
对照组	16.44±0.86			9.04±1.32		1.41±0.75	5.24±0.49	2.9±0.84	1.3±0.19
统计值	1.523			0.636		0.883	-0.146	1.506	-0.451
P值	0.130			0.525		0.379	0.884	0.134	0.653

组别	例数	和肽素/（pg·mL^-1）	CK-MB/（U·L^-1）	cTnI/（ng·mL^-1）	MYO/（μg·L^-1）
对照组	55	5.02（3.81，6.75）	5.01（2.38，10.50）	0.23（0.06，0.43）	36.10（22.00，50.20）
AMI组	102	12.47（8.18，25.94）	20.00（10.98，52.50）	2.16（0.78，5.75）	80.75（41.25，143.85）
Z值		-8.170	-7.647	-8.592	-6.656
P值		<0.001	<0.001	<0.001	<0.001

组别	例数	和肽素/（pg·mL^-1）	CK-MB/（U·L^-1）	cTnI/（ng·mL^-1）	MYO/（μg·L^-1）
对照组	55	5.02（3.81，6.75）	5.01（2.38，10.50）	0.23（0.06，0.43）	36.10（22.00，50.20）
AMI组	102	12.47（8.18，25.94）	20.00（10.98，52.50）	2.16（0.78，5.75）	80.75（41.25，143.85）
Z值		-8.170	-7.647	-8.592	-6.656
P值		<0.001	<0.001	<0.001	<0.001

指标	联合检测方程	AUC（95%CI^①）	最佳临界值	敏感性/%	特异性/%	约登指数
和肽素		0.896（0.849~0.943）	8.29 pg·mL^-1	73.0	92.7	0.672
和肽素+ cTnI	Logit（P）=-5.108+0.452×和肽素+3.759×cTnI	0.960（0.935~0.986）	0.698	84.3	98.2	0.825
CK-MB+MYO+cTnI	Logit（P）=-5.961+3.875×cTnI+0.217×CK-MB+0.034×MYO	0.975（0.955~0.994）	0.876	91.2	96.4	0.876
4项指标联合	Logit（P）=-9.079+0.530×和肽素+0.262×CK-MB+3.519×cTnI+0.011×MYO	0.986（0.971~1.000）	0.688	94.1	98.2	0.923