Role of Novel Biomarkers Associated With In-stent Restenosis After Percutaneous Coronary Intervention

November 20, 2023 updated by: Elhussein Ahmed Mohamed, Assiut University

Risk Factors and Novel Biomarkers Associated With In-stent Restenosis After Percutaneous Coronary Intervention

To study the relation between ISR and neutrophil-to-lymphocyte ratio (NLR), novel biomarkers (high-sensitivity CRP (hs-CRP), bone morphogenetic protein-2 (BMP-2) and other risk factors (age, sex, smoking, hypertension, diabetes, obesity, chronic kidney disease (CKD; creatinine clearance).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Coronary artery disease (CAD) is the most common cardiovascular disease and remains a major global public health problem [1]. Due to the benefits of a shorter procedure time and reduced invasiveness, percutaneous coronary intervention (PCI) has become the predominant choice for coronary revascularization in patients with both stable and unstable CAD. However, in-stent restenosis (ISR) remains the leading problem after PCI, especially in patients with type 2 diabetes mellitus (T2DM) [2,3]. Diabetes mellitus is also regarded as one of the most powerful clinical predictors of ISR after drug-eluting stent (DES) implantation, which was also the case during the BMS era[4,5]. Although interventional approaches and pharmacological therapies have improved in recent years [6], ISR remains a problem; therefore, it is still important and useful to identify biomarkers that can predict ISR.

Bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor (TGF) superfamily, plays a significant role in both physiological and pathological vascular processes [7,8]. Recent studies have found that BMP-2 signalling is also associated with vascular disease, including atherosclerosis, vascular inflammation, vascular calcification and plaque instability [9,10]. Although diabetes has a well-known association with an increased risk for cardiovascular disease, the associated pathogenesis is not completely understood. In vitro studies have shown that high glucose concentrations are associated with increased expression of BMP-2 [11]. Plasma BMP-2 concentrations positively correlated with plaque burden and plaque calcification, which also positively correlated with plasma HbA1c. These findings suggest that BMP-2 may have a role in hyperglycaemia-induced calcification [12]. Endothelial dysfunction caused by stent implantation induces inflammation, which may also stimulate SMC proliferation [13-14]. Previous studies have revealed that chronic inflammation and fibrin deposition frequently persist for approximately 3 months after DES implantation, following the replacement of type III collagen by type I collagen and vascular smooth muscle cell (VSMC) proliferation [15]. Although the timing of intimal SMC proliferation is not clear, the migration of cells from within the plaque to the expanding neointima is the dominant factor that leads to ISR [15, 16]. BMP-2 is highly expressed in human vessels, and VSMCs are a significant source of BMP-2 [17,18]. In addition, several studies have indicated that BMP-2 promotes the migration of VSMCs by inducing the SMC phenotype towards a synthetic state and is closely associated with inflammation [8,19].Several studies have reported the clinical impact of hs-CRP levels in the chronic phase on clinical outcomes in CAD patients who underwent PCI. Hsieh et al. reported that higher hs-CRP levels (>3.0 mg/L) at 9-month follow-up angiography after PCI were associated with higher incidence of overall mortality and future clinical cardiovascular outcomes, including restenosis [20]. These findings indicate that hs-CRP could offer a useful biomarker for predicting the risk of adverse cardiovascular events or mortality in CAD patients after PCI.

These results are supported by the fact that inflammation underlies many of the processes contributing to atherogenesis and plaque destabilization. It has been indicated that hs-CRP may contribute to the development of arteriosclerosis in the presence of modified low-density lipoprotein (LDL) such as oxidized LDL [21].

This suggests that the type of stent is only one factor to consider when searching for additional promoters of ISR. The present study aimed to detect the clinical, biological, imagistic and procedural factors associated with ISR.

What is the meaning of ISR?ISR was defined as the narrowing of the lumen diameter of the target vessel ≥50%, including the coronary arteries in the stent and the ≤5 mm area adjacent to the stent [8]

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Salah Eldin Sayed Atta Mohammed, Professor
  • Phone Number: 01091318801
  • Email: salah_atta@aun.edu.eg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Patients with previously implanted 3rd generation DES (Sirolimus, Biolimus, Everolimus, Zotarolimus), whatever the duration since implantation or the setting of implantation or the number of implanted stents, and who are presenting to our institute along the coming two years for CA±PCI because of recurrent chest pain with suspicious of ISR or other newly developed lesions.

Description

Inclusion Criteria:

  • Patients with previously implanted 3rd generation DES (Sirolimus, Biolimus, Everolimus, Zotarolimus), whatever the duration since implantation or the setting of implantation or the number of implanted stents, and who are presenting to our institute along the coming two years for CA±PCI because of recurrent chest pain with suspicious of ISR or other newly developed lesions.

Exclusion Criteria:

  • • Previous CABG

    • ACS within the last 2ms before the index CA for those undergoing assessment of hs-CRP & BMP-2
    • Heart failure with reduced EF<40%
    • Severe liver or kidney disease
    • Autoimmune, inflammatory, or malignant diseases
    • Non-available previous PCI CD & report

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Role of novel biomarkers (high-sensitivity CRP (hs-CRP), bone morphogenetic protein-2 (BMP-2) associated with in-stent restenosis after percutaneous coronary intervention
Time Frame: Baseline
Analysis of high-sensitivity CRP (hs-CRP), bone morphogenetic protein-2 (BMP-2) and incidence of ISR after percutaneous coronary intervention
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2024

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

February 1, 2025

Study Registration Dates

First Submitted

November 20, 2023

First Submitted That Met QC Criteria

November 20, 2023

First Posted (Actual)

November 28, 2023

Study Record Updates

Last Update Posted (Actual)

November 28, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • novel biomarkers and ISR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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