Disease Characteristics of IR-CAD: a Case-control Study

Disease Characteristics of Inflammation-associated Rapidly-progressive Coronary Artery Disease (IR-CAD): a Case-control Study

The present case-control study is designed to investigate the disease characteristics of IR-CAD by comparing the demographics, clinical features, lab results, imaging findings, and prior treatment between 20 patients with IR-CAD and 10 patients with AS-CAD.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Inflammation; Coronary Artery Disease Progression; Coronary Artery Stenosis; Coronary Artery Restenosis; Inflammatory Disease; Inflammation Vascular
• Intervention / Treatment: Diagnostic test: Protocol-defined Examinations

Detailed Description

A special type of coronary artery disease (CAD) has been identified in the investigators' clinical practice, which has completely different clinical features from those of typical atherosclerotic coronary artery disease (AS-CAD). The patients often have sterile inflammatory diseases and/or clinical evidence of inflammation, whose CAD progresses rapidly, recurs frequently, and responds poorly to intensified secondary prevention of AS-CAD, especially after percutaneous coronary intervention (PCI). The investigators name this special type of CAD with inflammation-associated rapidly-progressive coronary artery disease (IR-CAD). Currently, the overall disease characteristics of IR-CAD remain unknown.

The present case-control study is designed to investigate the disease characteristics of IR-CAD by comparing the demographics, clinical features, lab results, imaging findings, and prior treatment between 20 patients with IR-CAD and 10 patients with AS-CAD.

The first 20 patients who were enrolled in the IR-CAD cohort study, which included patients who met the inclusion/exclusion criteria for IR-CAD and received comprehensive treatment, will be enrolled in the case group of the present IR-CAD case-control study. Patients were diagnosed as IR-CAD if they have 1) evidence of rapidly progressive (occurred within 6 months or occurred on immunosuppressive therapy within 12 months of the last coronary revascularization) myocardial ischemia (typical symptoms and non-invasive evidence) despite standard treatment for secondary prevention of AS-CAD; 2) angiographic evidence of new coronary lesions (de novo stenosis or restenosis) considered to be relevant to myocardial ischemia; 3) evidence of inflammation (positive inflammation markers or established diagnosis of inflammatory diseases or use of immunosuppressive therapy). The comprehensive treatment for IR-CAD included: 1) intensified secondary prevention of AS-CAD; 2) immunosuppressive therapy; 3) coronary revascularization; 4) supportive therapies.

Patients who fulfill the inclusion/exclusion criteria for AS-CAD defined by the protocol of the present case-control study will be enrolled in the control group of the present case-control study. Patients will be diagnoses as AS-CAD if they 1) are ≥ 45 but < 65 years of age; 2) are receiving standard treatment for secondary prevention of AS-CAD after the last PCI which was performed 12±6 months ago; 3) do not have evidence of rapidly progressive (occurred within 6 months or occurred on immunosuppressive therapy within 12 months of the last PCI) myocardial ischemia (typical symptoms and non-invasive evidence); 4) do not have angiographic evidence of new coronary lesions (de novo stenosis or restenosis) considered to be relevant to myocardial ischemia.

Patients in the IR-CAD cohort study underwent examinations after they met the inclusion/exclusion criteria for IR-CAD based on a protocol specifically designed for the clinical management of IR-CAD patients. The results of the above examinations will be used as the examination results of the case group of the present IR-CAD case-control study. While patients in the control group of the present case-control study will undergo similar examinations after enrollment according to the protocol of the present case-control study.

The information regarding the baseline characteristics and the examination results, 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).

Eligible patients will be enrolled in the case group and the control group with a 2:1 ratio. The primary endpoint of the present case-control study is elevated erythrocyte sedimentation rate (ESR), which is defined as ESR > 15 mm for male, or ESR > 20 mm for female. In case of normal ESR, prior use of immunosuppressive therapy or prior diagnosis of autoimmune diseases before enrollment is regarded as the equivalent to elevated ESR. Based on currently available data from the IR-CAD cohort study, the rate of elevated ESR in the case group (IR-CAD patients) is 88.9% (8/9). The investigators hypothesize that the rate of elevated ESR in the control group (AS-CAD patients) is 20%. In consequence, 20 patients in the case group and 10 patients in the control group would be required to test the difference of the rate of the primary endpoint between the two groups at a significance level of 0.05 (α = 0.05) with a power of 90% (β = 0.10) and a drop-out rate of 20%.

Continuous variables will be presented as mean ± standard deviation (SD) or median (interquartile range [IQR]) and compared with two-sample t-test or Wilcoxon rank sum test, as appropriate. Categorical data will be demonstrated as n (%) and compared using Chi-square test or Fisher's exact test, as appropriate.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Zhenyu Liu, M.D.; Phone Number: +861069155068; Email: Pumch_lzy@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The first 20 patients who were enrolled in the IR-CAD cohort study, which included patients who met the inclusion/exclusion criteria for IR-CAD and received comprehensive treatment, will be enrolled in the case group of the present IR-CAD case-control study.

Patients who fulfill the inclusion/exclusion criteria for AS-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 (IR-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 coronary artery bypass graft [CABG]).
4. Receiving standard treatment for secondary prevention of AS-CAD after the last coronary revascularization.

5. Hospitalization due to rapidly-progressive myocardial ischemia:

   • Typical symptoms of angina (Canadian Cardiovascular Society [CCS] III-IV) and non-invasive evidence of myocardial ischemia; and
   • Occurred within 6 months or occurred on immunosuppressive therapy within 12 months of the last coronary revascularization.
6. Angiographic evidence of new coronary lesions (de novo stenosis or restenosis) considered to be relevant to myocardial ischemia.

7. Evidence of inflammation:

   • At least one of the indexes indicating active inflammation has ever been elevated (ESR, high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, tumor necrosis factor [TNF]-α, ferritin, et al); or
   • Established diagnosis of systemic autoimmune disease or systemic vasculitis; or
   • Receiving immunosuppressive therapy.

Control group (AS-CAD patients):

1. ≥ 45 and < 65 years of age (based on the age distribution of the patients currently enrolled in the IR-CAD cohort study), male or female.
2. Negative results of urine or blood pregnancy test for females with childbearing potential (not post-menopausal or surgically sterile).
3. Currently, 12±6 months after the last PCI.
4. Receiving standard treatment for secondary prevention of AS-CAD after the last PCI.
5. Coronary angiography and/or optical coherence tomography (OCT) performed during the present hospitalization.

6. No evidence of rapidly-progressive myocardial ischemia, which is defined as follows:

   • Typical symptoms of angina (Canadian Cardiovascular Society [CCS] III-IV) and non-invasive evidence of myocardial ischemia; and
   • Occurred within 6 months or occurred on immunosuppressive therapy within 12 months of the last PCI.
7. No angiographic evidence of new coronary lesions (de novo stenosis or restenosis) considered to be relevant to myocardial ischemia.

Exclusion Criteria:

Case group (IR-CAD patients):

1. Coronary restenosis due to mechanical factors (stent under-expansion, stent mal-apposition, stent rupture, et al).
2. Other moderate to severe heart diseases (congenital heart disease, valvular heart disease, myocarditis, cardiomyopathy, pericardial diseases, pulmonary hypertension, heart failure, arrhythmia, et al).
3. Active acute or chronic infection (human immunodeficiency virus [HIV], tuberculosis, 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. Contraindications for or intolerance to treatment for secondary prevention of AS-CAD, contrast agents, glucocorticoids, immunosuppressive agents.
8. In pregnancy or breast-feeding, or with intention to be pregnant during the study period.
9. Risk of non-compliance (history of drug addiction or alcohol abuse, et al).
10. Previous enrollment in this study.
11. Participation in another study within 30 days.
12. Involvement in the planning and conduct of this study (applying to investigators, contract research organization staffs, study site staffs, et al).
13. Any condition, which in the opinion of the investigators, would make it unsuitable for the patient to participate in this study.

Control group (AS-CAD patients):

The same as those for the case group (IR-CAD patients).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case Group; IR-CAD patients (from the IR-CAD cohort study)	Diagnostic test: Protocol-defined Examinations; 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, Birmingham Vasculitis Activity Score (BVAS-3), 6-minute walk test, 1-minute squat test, vascular ultrasound, fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT), coronary angiography, optical coherence tomography (OCT), tests for exploratory biomarkers.
Control Group; AS-CAD patients	Diagnostic test: Protocol-defined Examinations; 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, Birmingham Vasculitis Activity Score (BVAS-3), 6-minute walk test, 1-minute squat test, vascular ultrasound, fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT), coronary angiography, optical coherence tomography (OCT), tests for exploratory biomarkers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elevated erythrocyte sedimentation rate (ESR)	Percentage of patients with elevated ESR (> 15 mm for male or > 20 mm for female). In case of normal ESR, prior use of immunosuppressive therapy or prior diagnosis of autoimmune diseases before enrollment is regarded as the equivalent to elevated ESR.	From the last coronary revascularization up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age	Age in years.	On the day of enrollment.
Female sex	Percentage of patients with female sex.	On the day of enrollment.
Yellow race	Percentage of patients with yellow race.	On the day of enrollment.
Acute coronary syndrome (ACS)	Percentage of patients admitted due to ACS for the index hospitalization.	On the day of enrollment.
Chronic coronary syndrome (CCS).	Percentage of patients admitted due to CCS for the index hospitalization.	On the day of enrollment.
Hypertension	Percentage of patients with prior history of hypertension.	On the day of enrollment.
Dyslipidemia	Percentage of patients with prior history of dyslipidemia.	On the day of enrollment.
Diabetes	Percentage of patients with prior history of diabetes.	On the day of enrollment.
Smoking	Percentage of patients with prior history of smoking.	On the day of enrollment.
Old myocardial infarction (OMI)	Percentage of patients with prior history of OMI.	On the day of enrollment.
Percutaneous coronary intervention (PCI)	Percentage of patients with prior history of PCI.	On the day of enrollment.
Coronary artery bypass graft (CABG)	Percentage of patients with prior history of CABG.	On the day of enrollment.
Number of prior coronary revascularization	Number of prior coronary revascularization	On the day of enrollment.
Blood pressure	Measurement of blood pressure.	On the day of enrollment.
Heart rate	Measurement of heart rate.	On the day of enrollment.
Body weight	Measurement of body weight.	On the day of enrollment.
Height	Measurement of height.	On the day of enrollment.
Body mass index (BMI)	BMI = Body weight [kg] / (Height [m])^2	On the day of enrollment.
Antithrombotic agents	Percentage of patients on antithrombotic agents.	On the day of enrollment.
β-blockers	Percentage of patients on β-blockers.	On the day of enrollment.
Blood pressure-lowering agents	Percentage of patients on blood pressure-lowering agents.	On the day of enrollment.
Lipid-lowering agents	Percentage of patients on lipid-lowering agents.	On the day of enrollment.
Hypoglycemic agents	Percentage of patients on hypoglycemic agents.	On the day of enrollment.
Glucocorticoids	Percentage of patients on glucocorticoids.	On the day of enrollment.
Immunosuppressive agents	Percentage of patients on immunosuppressive agents.	On the day of enrollment.
Other immunosuppressive therapy	Percentage of patients on other immunosuppressive therapy.	On the day of enrollment.
Major adverse cardiovascular events (MACE)	Percentage of patients with death, or Q wave myocardial infarction, or unplanned myocardial ischemia-driven coronary revascularization (PCI or CABG), or unplanned myocardial ischemia-driven hospitalization.	From the last coronary revascularization up to the day of enrollment.
Target vessel related major adverse cardiovascular events (TV-MACE)	Percentage of patients with cardiovascular death, or target vessel related Q wave myocardial infarction, or target vessel related unplanned myocardial ischemia-driven coronary revascularization (PCI or CABG), or target vessel related unplanned myocardial ischemia-driven hospitalization.	From the last coronary revascularization up to the day of enrollment.
Hemoglobin	Test result of hemoglobin.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Red blood cell	Test result of red blood cell count.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
White blood cell	Test result of white blood cell count.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Platelet	Test result of platelet count	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Alanine aminotransferase (ALT)	Test result of ALT.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Aspartate aminotransferase (AST)	Test result of AST.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Gamma-glutamyl transferase (GGT)	Test result of GGT.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Alkaline phosphatase (ALP)	Test result of ALP.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Lactate dehydrogenase (LDH)	Test result of LDH.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Total bilirubin (T-Bil)	Test result of T-Bil.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Direct bilirubin (D-Bil)	Test result of D-Bil.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Albumin	Test result of Albumin	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Creatinine	Test result of creatinine.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Blood urea nitrogen (BUN)	Test result of BUN.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Triiodothyronine (T3)	Test result of T3.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Thyroxine (T4)	Test result of T4.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Free triiodothyronine (FT3)	Test result of FT3.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Free thyroxine (FT4)	Test result of FT4.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Thyroid-stimulating hormone (TSH)	Test result of TSH.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Total cholesterol (TC)	Test result of TC.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Low-density lipoprotein cholesterol (LDL-C)	Test result of LDL-C.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
High-density lipoprotein cholesterol (HDL-C)	Test result of HDL-C.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Triglyceride (TG)	Test result of TG.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Apolipoprotein A (ApoA)	Test result of ApoA.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Apolipoprotein B (ApoB)	Test result of ApoB.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Lipoprotein (a) (Lp[a])	Test result of Lp(a).	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Fasting blood glucose (FBG)	Test result of FBG.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Hemoglobin A1c (HbA1c).	Test result of HbA1c.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Cardiac troponin I (cTnI)	Test result of cTnI.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Creatine kinase-myocardial band (CK-MB)	Test result of CK-MB.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Creatine kinase (CK)	Test result of CK.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
B-type natriuretic peptide (BNP)	Test result of BNP.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
N-terminal pro-B-type natriuretic peptide (NT-proBNP).	Test result of NT-proBNP.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Lupus anticoagulant	Test result of lupus anticoagulant.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Antiphospholipid antibody	Test result of antiphospholipid antibody.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Anti-phosphatidylserine antibody	Test result of anti-phosphatidylserine antibody.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Anti-prothrombin antibody	Test result of anti-prothrombin antibody.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Protein S	Test result of Protein S.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Protein C	Test result of Protein C.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Activated protein C resistance (APC-R)	Test result of APC-R.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Anti-thrombin III	Test result of anti-thrombin III.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Maximum platelet aggregation (MPA)	Test result of MPA.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Anti-nuclear antibody (ANA)	Test result of ANA.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Anti-neutrophil cytoplasmic antibody (ANCA)	Test result of ANCA.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Anti-endothelial cell antibody (AECA)	Test result of AECA.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Rheumatoid factor (RF)	Test result of RF.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Anti-cyclic citrullinated peptide (Anti-CCP)	Test result of Anti-CCP.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Immunoglobulin	Test result of immunoglobulin.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Complement	Test result of complement.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Erythrocyte sedimentation rate (ESR)	Test result of ESR.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
High-sensitivity C-reactive protein (hs-CRP)	Test result of hs-CRP.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Interleukin (IL)-6	Test result of IL-6.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Tumor necrosis factor (TNF)-α.	Test result of TNF-α.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Pathological Q waves	Percentage of patients with pathological Q wave.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Dynamic ST-T changes	Percentage of patients with dynamic ST-T changes.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Segmental wall motion abnormality	Percentage of patients with segmental wall motion abnormality.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Left atrial diameter (LAD)	Measurement of LAD.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Left ventricular end-systolic diameter (LVESD)	Measurement of LVESD.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Left ventricular end-diastolic diameter (LVEDD)	Measurement of LVEDD.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Left ventricular ejection fraction (LVEF)	Measurement of LVEF.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Birmingham Vasculitis Activity Score (BVAS)	Result of BVAS (version 3) assessment.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Walking distance in 6 minutes	Result of 6-minute walk test (6MWT).	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Number of squats in 1 minute	Result of 1-minute squatting test (1MST).	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Temporal artery stenosis	Percentage of patients with ≥ 50% diameter stenosis in either temporal artery on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Carotid artery stenosis	Percentage of patients with ≥ 50% diameter stenosis in either carotid artery on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Vertebral artery stenosis	Percentage of patients with ≥ 50% diameter stenosis in either vertebral artery on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Subclavian artery stenosis	Percentage of patients with ≥ 50% diameter stenosis in either subclavian artery on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Iliac artery stenosis	Percentage of patients with ≥ 50% diameter stenosis in either Iliac artery on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Upper extremity artery stenosis	Percentage of patients with ≥ 50% diameter stenosis in either upper extremity artery on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Lower extremity artery stenosis	Percentage of patients with ≥ 50% diameter stenosis in either lower extremity artery on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Abdominal aorta stenosis	Percentage of patients with ≥ 50% diameter stenosis in abdominal aorta on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Celiac trunk stenosis	Percentage of patients with ≥ 50% diameter stenosis in celiac trunk on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Superior mesenteric artery stenosis	Percentage of patients with ≥ 50% diameter stenosis in superior mesenteric artery on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Renal artery stenosis	Percentage of patients with ≥ 50% diameter stenosis in either renal artery on vascular ultrasound.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
SYNTAX score	Result of SYNTAX score assessment based on coronary angiogram.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Number of vessel segments with coronary lesions.	Number of vessel segments with ≥ 50% diameter stenosis on coronary angiogram.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Target lesion minimal lumen area (TL-MLA)	Measurement of the minimum lumen area of the target lesion on optical coherence tomography (OCT).	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Target lesion percent area stenosis (TL-%AS)	Measurement of percent area stenosis (% AS) of target lesion = { [ ( proximal RLA + distal RLA ) - (MLA × 2) ] / ( proximal RLA + distal RLA ) } × 100% in the cross-section with the MLA of the target lesion on optical coherence tomography (OCT). RLA = reference lumen area; MLA = minimum lumen area; % AS = percent area stenosis.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum standardized uptake value (SUVmax)	The mean of SUVmax of each major coronary artery on fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT).	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
RNA sequencing	Test result of RNA sequencing.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Proteomics	Test result of proteomics.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.
Metabolomics	Test result of metabolomics.	From the index hospital admission up to 2 weeks of enrollment, but before the initiation of comprehensive treatment for patients with IR-CAD.

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T, Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mahfoud F, Masip J, Muneretto C, Valgimigli M, Achenbach S, Bax JJ; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/eurheartj/ehz425. No abstract available. Erratum In: Eur Heart J. 2020 Nov 21;41(44):4242.
• Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Juni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM; ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021 Apr 7;42(14):1289-1367. doi: 10.1093/eurheartj/ehaa575. No abstract available. Erratum In: Eur Heart J. 2021 May 14;42(19):1908. Eur Heart J. 2021 May 14;42(19):1925. Eur Heart J. 2021 May 13;:
• Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimsky P; ESC Scientific Document Group. 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). Eur Heart J. 2018 Jan 7;39(2):119-177. doi: 10.1093/eurheartj/ehx393. No abstract available.
• Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, van den Brand M, Van Dyck N, Russell ME, Mohr FW, Serruys PW. The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention. 2005 Aug;1(2):219-27. No abstract available.
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Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: July 7, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 23, 2023

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Coronary Artery Disease; Coronary Revascularization; Progression, Disease; Characteristics Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease Attributes; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Disease Progression; Inflammation; Coronary Stenosis; Coronary Restenosis
• Other Study ID Numbers: K3819

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