Disease Characteristics of R-CAD

Disease Characteristics of Rapidly Progressive Coronary Artery Disease (R-CAD): A Case-control Study

The present case-control study is designed to investigate the disease characteristics of rapidly progressive coronary artery disease (R-CAD) by comparing the demographics, clinical features, lab results, imaging findings, and prior treatment between patients in the case group (approximately 34 patients with R-CAD) and those in the control group (approximately 18 patients with non-rapidly progressive coronary artery disease [NR-CAD]).

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Percutaneous Coronary Intervention; Coronary Stenosis; Coronary Restenosis; Coronary Artery Disease Progression; Coronary Stent Occlusion; Myocardial Revascularization
• Intervention / Treatment: Diagnostic test: Protocol-defined Examinations and Evaluations

Detailed Description

The majority of coronary artery disease (CAD) is atherosclerotic coronary artery disease (AS-CAD), the pathological basis of which is atherosclerosis. Secondary prevention, including healthy life style and medical treatment, effectively controls the progression of AS-CAD. Coronary revascularization, including percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) are the dominant treatment modalities to restore the patency and/or blood flow of the diseased coronary arteries.

A special type of CAD is identified in the investigators' clinical practice, which progresses rapidly and recurs frequently after PCI or CABG, and responds poorly to intensified secondary prevention for AS-CAD. The investigators name this special type of CAD with rapidly progressive coronary artery disease (R-CAD), which has significantly different clinical features from those of typical AS-CAD. The CAD without the above characteristics is named with non-rapidly progressive coronary artery disease (NR-CAD).

Currently, the disease characteristics of R-CAD remain unknown. It has been identified that a proportion of R-CAD patients demonstrate certain manifestations of inflammation, including positive inflammatory markers, or positive autoantibodies, or established diagnosis of chronic inflammatory diseases, or use of immunosuppressive therapy, whose R-CAD is named as inflammation-associated rapidly progressive coronary artery disease (IR-CAD). However, the rest of R-CAD patients demonstrate no manifestations of inflammation. Therefore, the present case-control study is designed to investigate the disease characteristics of the overall R-CAD patients by comparing the demographics, clinical features, lab results, imaging findings, and prior treatment between the case group (approximately 34 patients with R-CAD) and the control group (approximately 18 patients with NR-CAD).

Patients will be enrolled in the case group (R-CAD patients) of the present case-control study if they 1) have prior history of coronary revascularization (PCI or CABG); 2) received standard treatment for secondary prevention of AS-CAD after the latest coronary revascularization; 3) have evidence of rapidly progressive myocardial ischemia leading to hospitalization and/or coronary revascularization; 4) have angiographic evidence of rapidly progressive coronary lesions leading to myocardial ischemia.

Patients will be enrolled in the control group (NR-CAD patients) of the present case-control study if they 1) are 35 to 75 years old; 2) received standard treatment for secondary prevention of AS-CAD after the latest PCI which was performed 12±6 months ago; 3) do not have evidence of rapidly progressive myocardial ischemia leading to hospitalization and/or coronary revascularization; 4) do not have angiographic evidence of rapidly progressive coronary lesions leading to myocardial ischemia.

Once enrolled, patients in both groups will receive examinations and evaluations according to a clinical management protocol specifically designed for the clinical management of R-CAD patients. The information regarding the baseline characteristics and the results of examinations and evaluations, including demographics, clinical features, lab results, imaging findings, and prior treatment, will be collected and compared between the case group and the control group.

The primary endpoint is the rate of elevated erythrocyte sedimentation rate (ESR) or high-sensitivity C-reactive protein (hs-CRP).

• Study Type: Observational
• Enrollment (Estimated): 52

Contacts and Locations

• Study Contact: Name: Zhenyu Liu, M.D.; Phone Number: +861069155068; Email: Pumch_lzy@163.com
• Study Contact Backup: Name: Lihong Xu, B.N.; Phone Number: +861069155068; Email: xulihong1990@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who fulfill the inclusion/exclusion criteria for R-CAD defined by the protocol of the present case-control study will be enrolled in the case group of the present case-control study.

Patients who fulfill the inclusion/exclusion criteria for NR-CAD defined by the protocol of the present case-control study will be enrolled in the control group of the present case-control study.

Description

Inclusion Criteria:

Case Group (R-CAD patients):

1. 18 years of age or older, male or female.
2. Negative results of urine or blood pregnancy test for females with childbearing potential (not post-menopausal or surgically sterile).
3. Prior history of coronary revascularization (PCI or CABG).
4. Receiving standard treatment for secondary prevention of AS-CAD after the latest coronary revascularization.

5. Rapidly progressive myocardial ischemia leading to hospitalization and/or coronary revascularization:

   1. Typical symptoms of angina (Canadian Cardiovascular Society [CCS] classification III-IV) and non-invasive evidence of myocardial ischemia; and
   2. Occurred within 6 months of the latest ischemia-driven hospitalization and/or coronary revascularization.

6. Rapidly progressive coronary lesions leading to myocardial ischemia:

   1. Angiographic evidence of new-onset or worsened coronary de novo or restenotic lesions relevant to myocardial ischemia, and
   2. Occurred within 6 months of the latest ischemia-driven coronary angiography and/or revascularization.

Control Group (NR-CAD patients):

1. 35 to 75 years old*, male or female. (* Based on the age distribution characteristics of patients who have been diagnosed as R-CAD.)
2. Negative results of urine or blood pregnancy test for females with childbearing potential (not post-menopausal or surgically sterile).
3. Currently, at 12±6 months after the latest PCI.
4. Receiving standard treatment for secondary prevention of AS-CAD after the latest PCI.
5. Coronary angiography and/or optical coherence tomography (OCT) performed during the index hospitalization.
6. No evidence of rapidly progressive myocardial ischemia and coronary lesions, i.e., not fulfilling items 5) and 6) of the inclusion criteria for R-CAD.

Exclusion Criteria:

1. Receiving immunosuppressive therapy within 6 months.
2. Coronary restenosis due to mechanical factors (stent under-expansion, stent mal-apposition, stent rupture, et al).
3. Other moderate to severe heart diseases (congenital heart disease, valvular heart disease, myocarditis, cardiomyopathy, pericardial diseases, pulmonary hypertension, heart failure, arrhythmia, et al).
4. Active malignancy (diagnosed within 12 months or with ongoing requirement for treatment).
5. Vital organ failure.
6. Life expectancy < 1 year.
7. In pregnancy or breast-feeding, or with intention to be pregnant during the study period.
8. Risk of non-compliance (history of drug addiction or alcohol abuse, et al).
9. Previous enrollment in this study.
10. Participation in another study within 30 days.
11. Involvement in the planning and conduct of this study (applying to investigators, contract research organization staffs, study site staffs, et al).
12. Any condition, which in the opinion of the investigators, would make it unsuitable for the patient to participate in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case Group; R-CAD patients	Diagnostic test: Protocol-defined Examinations and Evaluations; Lab tests (blood and urine and stool routine tests, hepatic and renal and thyroid function tests, tests for metabolic markers, tests for cardiac biomarkers, thrombosis-related tests, rheumatology tests, tests for inflammation markers), electrocardiography, echocardiography, 6-minute walk test, vascular ultrasound, coronary angiography, optical coherence tomography (OCT), fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPI-PET/CT), photon-counting detector coronary computed tomography angiography (PCD-CCTA), tests for exploratory biomarkers.
Control Group; NR-CAD patients	Diagnostic test: Protocol-defined Examinations and Evaluations; Lab tests (blood and urine and stool routine tests, hepatic and renal and thyroid function tests, tests for metabolic markers, tests for cardiac biomarkers, thrombosis-related tests, rheumatology tests, tests for inflammation markers), electrocardiography, echocardiography, 6-minute walk test, vascular ultrasound, coronary angiography, optical coherence tomography (OCT), fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPI-PET/CT), photon-counting detector coronary computed tomography angiography (PCD-CCTA), tests for exploratory biomarkers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elevated ESR or hs-CRP	Percentage of patients with elevated ESR (> 15 mm/h for male or > 20 mm/h for female) or hs-CRP (≥ 2 mg/L).	From 30 days before enrollment up to 14 days after enrollment, but before the initiation of immunosuppressive therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive autoantibodies	Percentage of patients with positive autoantibodies (anti-nuclear antibody [ANA], anti-neutrophil cytoplasmic antibody [ANCA], anti-endothelial cell antibody [AECA], lupus anticoagulant [LA], antiphospholipid antibody (APL) (anti-cardiolipin antibody [ACL], anti-beta2-glycoprotein 1 antibody [abeta2GP1]), anti-phosphatidylserine antibody [APSA], rheumatoid factor [RF], anti-cyclic citrullinated peptide antibody [anti-CCP], et al.).	From 30 days before enrollment up to 14 days after enrollment, but before the initiation of immunosuppressive therapy.
Established diagnosis of chronic inflammatory diseases	Percentage of patients with established diagnosis of chronic inflammatory diseases (chronic infectious disease, autoimmune disease, other chronic inflammatory diseases, et al.).	Up to 14 days after enrollment
Elevated ESR or hs-CRP, or positive autoantibodies	Percentage of patients with elevated ESR or hs-CRP, or positive autoantibodies.	From 30 days before enrollment up to 14 days after enrollment, but before the initiation of immunosuppressive therapy.
Elevated ESR or hs-CRP, or positive autoantibodies, or established diagnosis of chronic inflammatory diseases	Percentage of patients with elevated ESR or hs-CRP, or positive autoantibodies, or established diagnosis of chronic inflammatory diseases.	For elevated ESR or hs-CRP and positive autoantibodies: from 30 days before enrollment up to 14 days after enrollment, but before the initiation of immunosuppressive therapy; for established diagnosis of chronic inflammatory diseases: up to 14 days after

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum standardized uptake value (SUVmax)	SUVmax based on fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPI-PET/CT).	From 30 days before enrollment up to 14 days after enrollment, but before the initiation of immunosuppressive therapy.
Maximum target background ratio (TBRmax)	TBRmax based on fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPI-PET/CT).	From 30 days before enrollment up to 14 days after enrollment, but before the initiation of immunosuppressive therapy.
Fat attenuation index (FAI)	FAI based on photon-counting detector coronary computed tomography angiography (PCD-CCTA).	From 30 days before enrollment up to 14 days after enrollment, but before the initiation of immunosuppressive therapy.

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Zhenyu Liu, M.D., Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: November 16, 2025
• First Submitted That Met QC Criteria: November 16, 2025
• First Posted (Estimated): November 20, 2025

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Percutaneous Coronary Intervention; Disease Progression; Coronary Stenosis; Coronary Restenosis; Disease Attributes; Myocardial Revascularization
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Pathological Conditions, Signs and Symptoms; Disease Progression; Coronary Artery Disease; Disease Attributes; Coronary Stenosis; Coronary Restenosis; Diagnostic Techniques and Procedures; Diagnosis; Physical Examination
• Other Study ID Numbers: K9096

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No