Metabolomics Profiling of Coronary Heart Disease

Study Overview
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Brief Summary
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This study sought to assess the diagnostic and prognostic values of metabolomics in coronary artery disease(CAD).

Detailed Description
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The purpose of this study is to establish a powerful diagnostic and prognostic model based on metabolites in CAD patients.A total of 821 hospitalized patients with CAD and 200 healthy volunteers are enrolled.Specifically, 200 CAD patients from single-centre are regarded as discovery set, 300 CAD patients from multicentre are regarded as validation set. A third independent set including 321patitents is regarded as application set. Untargeted and targeted metabolomics analysis about serum and urine samples in all subjects will be performed using high-performance liquid chromatography coupled with mass spectrometry technology. Univariate and multivariate analysis methods are used to extract and analyze the differential mebabolites. By exploring the relationship between the differential mebabolites and clinical manifestions, a set of diagnostic biomarkers for CAD will be identified. By elucidating the correlation between the differential mebabolites and MACEs, a effective prognostic model will be established. Adverse events are defined as the combined endpoints of death or major adverse cardiovascular events(MACEs) in patients with CAD for at least 1 year follow-up after discharge. In brief, we aim to establish valuabe diagnostic and predictive models based on novel baseline metabolites in patients with CAD.

Official Title
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LC-MS Based Metabolomics Study of Coronary Heart Disease: Diagnostic and Prognostic Value of Metabolites

Conditions
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Biomarkers

Intervention / Treatment
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* Other: treatments according guidelines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Objective evidence of coronary heart disease risk factors Or angina pectoris symptoms Or ECG ischemic changes Or elevated myocardial enzymes, myocardial radionuclide scanning showing myocardial filling defect, coronary CT showing coronary stenosis ≥ 50% Exclusion Criteria: Older than 80 years and younger than 18 years old, Aortic dissection Pulmonary embolism Malignant tumor Autoimmune diseases Systemic systemic diseases Severe infectious diseases Trauma, surgery in the last three months Myocarditis, cardiomyopathy, pericarditis, severe congenital heart disease Syphilis Human immunodeficiency virus / acquired immunodeficiency syndrome Hepatitis B and hepatitis C

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Stable angina (SA)<br>Typical chronic exersive angina pectoris attacks, lasting several minutes to more than 10 minutes, 3-5 minutes in most cases, generally not more than 30 minutes. The pain disappeared after rest or taking nitrates, and the pain degree, frequency, duration, nature and inducing factors did not change in the last 1-3 months. | Other: treatments according guidelines<br>* different group intervened with different treatment following guidelines/consensuses accordingly<br>|
| Unstable angina (UA）<br>Including resting angina (attack at rest, the duration is usually >20 minutes), primary angina (usually the first symptoms within 1-2 months, very light physical activity can be induced, at least CCSIII level), worsening angina (angina gradually increases on the basis of relatively stable labor angina. More severe pain, longer or more frequent pain, at least grade I increase according to THE CCS classification, at least GRADE II CCSI). TNI was negative, routine electrocardiogram may have transient ST segment depression, T wave low flat or inverted. | Other: treatments according guidelines<br>* different group intervened with different treatment following guidelines/consensuses accordingly<br>|
| Acute non-ST-segment elevation myocardial infarction （NSTEMI）<br>Patients with elevated troponin accompanied by one or more of the following conditions: electrocardiogram showed new ST segment depression or T wave flatness or inversion; Persistent ischemic chest pain; Echocardiography showed abnormal segmental ventricular wall activity. Abnormal coronary angiography. | Other: treatments according guidelines<br>* different group intervened with different treatment following guidelines/consensuses accordingly<br>|
| Acute ST-segment elevation myocardial infarction （STEMI）<br>Troponin was elevated, and ECG showed ST segment arcuate back elevation, accompanied by one or more of the following conditions: persistent ischemic chest pain; Echocardiography showed segmental abnormal ventricular wall activity; Abnormal coronary angiography. | Other: treatments according guidelines<br>* different group intervened with different treatment following guidelines/consensuses accordingly<br>|
| normal coronary artery （NCA）<br>symptoms of chest pain and no stenosis in coronary arteries (such as myocardial bridging, reflux esophagitis, intercostals neuralgia, cervical spondylopathy, and unexplained chest pain) | Other: treatments according guidelines<br>* different group intervened with different treatment following guidelines/consensuses accordingly<br>|
| nonobstructive coronary atherosclerosis （NOCA）<br>stenosis < 50% in coronary arteries | Other: treatments according guidelines<br>* different group intervened with different treatment following guidelines/consensuses accordingly<br>|
| healthy volunteers<br>Healthy control subjects who had no significant systemic diseases (e.g. ischemic heart disease, hypertension,diabetes,cancer, pulmonary disease, or infectious diseases) were recruited from Physical Examination Center of Ningxia Medical University General Hospital | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | A composite of death from cardiovascular causes in patients with CAD | Follow-up is expected to end on December 30, 2022 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiovascular events | Hospitalization for recurrent severe angina pectoris, acute myocardial infarction, revascularization, malignant arrhythmia, new heart failure or acute attack of chronic heart failure, cardiac arrest and stroke. | Follow-up is expected to end on December 30, 2022 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metabolomics, biomarkers, liquid chromatography-mass spectrometry, coronary artery disease, serum, urine