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

NCT ID: NCT06148441

Last Updated: 2023-11-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-01-01
• Study Completion Date: 2025-02-28

Brief Summary

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).

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]

Conditions

In-stent Restenosis

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: CROSS_SECTIONAL

Interventions

bone morphogenetic protein-2 (BMP-2)

novel biomarkers associated with in-stent restenosis after percutaneous coronary intervention

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

novel biomarkers (high-sensitivity CRP (hs-CRP)

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Elhussein Ahmed Mohamed

Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Elhussein Ahmed Mohamed, Doctor

Role: CONTACT

elhusseinahmed21@gmail.com

01006424580

Salah Eldin Sayed Atta Mohammed, Professor

Role: CONTACT

salah_atta@aun.edu.eg

01091318801

References

Assimes TL, Roberts R. Genetics: Implications for Prevention and Management of Coronary Artery Disease. J Am Coll Cardiol. 2016 Dec 27;68(25):2797-2818. doi: 10.1016/j.jacc.2016.10.039.

Reference Type: BACKGROUND

PMID: 28007143 (View on PubMed)

Mauri L, Silbaugh TS, Wolf RE, Zelevinsky K, Lovett A, Zhou Z, Resnic FS, Normand SL. Long-term clinical outcomes after drug-eluting and bare-metal stenting in Massachusetts. Circulation. 2008 Oct 28;118(18):1817-27. doi: 10.1161/CIRCULATIONAHA.108.781377. Epub 2008 Oct 13.

Reference Type: BACKGROUND

PMID: 18852368 (View on PubMed)

Kitoga M, Pasquet A, Preumont V, Kefer J, Hermans MP, Vanoverschelde JL, Buysschaert M. Coronary in-stent restenosis in diabetic patients after implantation of sirolimus or paclitaxel drug-eluting coronary stents. Diabetes Metab. 2008 Feb;34(1):62-7. doi: 10.1016/j.diabet.2007.09.002.

Reference Type: BACKGROUND

PMID: 18069029 (View on PubMed)

Csiszar A, Smith KE, Koller A, Kaley G, Edwards JG, Ungvari Z. Regulation of bone morphogenetic protein-2 expression in endothelial cells: role of nuclear factor-kappaB activation by tumor necrosis factor-alpha, H2O2, and high intravascular pressure. Circulation. 2005 May 10;111(18):2364-72. doi: 10.1161/01.CIR.0000164201.40634.1D. Epub 2005 Apr 25.

Reference Type: BACKGROUND

PMID: 15851600 (View on PubMed)

Other Identifiers

novel biomarkers and ISR

Identifier Type: -

Identifier Source: org_study_id