This study is a single-center, prospective cohort study. The study is designed to identify novel circulating biomarkers for early prediction of high-risk coronary plaques. Patients diagnosed with chronic coronary syndrome (CCS) or non-ST-segment elevation acute coronary syndrome (NSTE-ACS), with marginal lesions or obstructive lesions in major coronary arteries detected by noninvasive coronary CT angiography (CCTA) or invasive coronary angiography (ICA), will be consecutively enrolled. Optical coherence tomography (OCT), with or without other intracoronary imaging modalities such as intravascular ultrasound (IVUS) and near infrared spectroscopy (NIRS), will be performed. Liquid chromatography-mass spectrometry (LC-MS/MS), bioinformatic analysis, and machine learning methods will be performed to characterize plasma proteomic profiles. The cohort will be followed-up every 3 months for 2 years. The association of novel biomarkers with the occurrence of major adverse cardiovascular events (MACEs) will be examined.

This study is a single-center, prospective cohort study. The study is designed to identify novel circulating biomarkers for early prediction of high-risk plaques. Patients diagnosed with chronic coronary syndrome (CCS) or non-ST-segment elevation acute coronary syndrome (NSTE-ACS), with marginal lesions (diameter stenosis [DS] between 40%-69%) or obstructive lesions (DS ≥70% or CT-FFR/FFR <0.8) in major coronary arteries detected by noninvasive coronary CT angiography (CCTA) or invasive coronary angiography (ICA), will be consecutively enrolled. Optical coherence tomography (OCT), with or without other intracoronary imaging modalities including intravascular ultrasound (IVUS) and near infrared spectroscopy (NIRS), will be performed to precisely measure plaque burden and other geometric parameters.

Under the guidance of OCT, these plaques will be classified into different types (intimal xanthoma, early and late fibroatheroma, thin-cap fibroatheroma [TCFA], plaque rupture [PR], plaque erosion [PE], calcified nodules, healed lesions). If IVUS is additionally performed, total atheroma volume (TAV), percent atheroma volume (PAV), and remodeling index will be calculated. If NIRS is additionally performed, lipid core burden index (LCBI) will be calculated. Integrated analysis will also be performed to investigate the relationship between plaque characteristics obtained from different imaging modalities.

Afterwards, liquid chromatography-mass spectrometry (LC-MS/MS), bioinformatic analysis, and machine learning methods will be performed to characterize plasma proteomic profiles in patients with different types of coronary atherosclerotic plaques. Differentially expressed proteins will be analyzed to identify novel biomarkers for high-risk plaques.

The cohort will be followed-up every 3 months for 2 years. The association of novel biomarkers with the occurrence of major adverse cardiovascular events (MACEs) will be examined.

Inclusion Criteria:

• Age ≥ 18 years
• Patients with CCS or NSTE-ACS
• Receive CCTA scan or ICA, with marginal lesions (DS between 40%-69%) or obstructive lesions (DS ≥70% or CT-FFR/FFR <0.8) in major coronary arteries
• Receive invasive coronary angiography and OCT, with or without other intracoronary imaging techniques such as IVUS and NIRS

Exclusion Criteria:

• Receive percutaneous coronary intervention (PCI) within 6 months
• Prior history of myocardial infarction or heart failure
• Prior history of coronary artery bypass graft (CABG)
• Abnormal liver function (serum alanine aminotransferase [ALT] level exceeding 3 times the upper limit of normal) or abnormal kidney function (eGFR ≤30%)
• Familial hypercholesterolemia
• Estimated survival ≤ 1 year
• Malignant tumor
• Pregnant or lactation, or have the intention to give birth within one year
• Poor compliance, unable to follow-up

Patients diagnosed with chronic coronary syndrome (CCS) or non-ST-segment elevation acute coronary syndrome (NSTE-ACS), with marginal lesions (diameter stenosis [DS] between 40%-69%) or obstructive lesions (DS ≥70% or CT-FFR/FFR <0.8) in major coronary arteries detected by noninvasive coronary CT angiography (CCTA) or invasive coronary angiography (ICA), will be consecutively enrolled.