Correlation Between Serum Markers of Unstable Plaque and Virtual Histology of Unstable Plaque Visualized by IVUS

This study has been completed.
Sponsor:
Information provided by:
Ziv Hospital
ClinicalTrials.gov Identifier:
NCT00466050
First received: April 25, 2007
Last updated: August 23, 2009
Last verified: April 2007
  Purpose

Thirty patients scheduled to coronary angiography and IVUS in according to their treating physician decision will be enrolled in the study. The coronary angiography and IVUS will be done on according to regular clinical standards.

As the study protocol, 40 cc of blood will be drawn from the patients after written informed consent.

The laboratory tests will be processed for the above mentioned serum markers of unstable plaque.

A multivariate correlation test will be done between the different serum markers and the plaque morphology by angiography and composition (virtual histology) by IVUS.


Condition
Acute Coronary Thrombose
Plaque Rupture
Acute Coronary Syndrome

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Correlation Between Serum Markers of Unstable Plaque and Virtual Histology of Unstable Plaque Visualized by IVUS

Further study details as provided by Ziv Hospital:

Estimated Enrollment: 30
Study Start Date: April 2007
Study Completion Date: May 2009
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

Serum markers of unstable plaque Myeloperoxidase is a lysosomal enzyme, requiring heme as a cofactor, released from neutrophilic granules, monocytes, and some subtypes of tissue macrophages.

Myeloperoxidase is also linked to oxidation of lipids in low-density lipoproteins (LDL), dysfunctional high density lipoproteins (HDL), and consumption of nitric oxide thereby rendering the normally anti-thrombotic endothelial surface thrombogenic via the expression of various pro-thrombotic and anti-fibrinolytic factor (19).

Myeloperoxidase plays a role in the degradation of the fibrous cap, making it both a marker of inflammation and one of plaque instability.

Interest in MPO intensified after a report by Brennan and colleagues (20) indicated that a single initial measurement of plasma myeloperoxidase independently predicts the early risk of myocardial infraction, as well as the risk of major adverse cardiac events in the ensuring 30-day and 6-month periods.

Two markers of recent interest relating to plaque vulnerability pregnancy-associated protein A(PAPP-A) and placenta growth factor (P1GF).

Pregnancy -associated protein A is a metalloproteinase, initially identified in the sera of pregnant women (21).

A large study has illustrated that decreases in IGF-1 appear to be cardio protective, yet some research shows that increases in PAPP-A, which should also increase the bioavailability of IGF-1, may be a relevant marker for the presence and extent of coronary atherosclerosis (22). It is believed that PAPP-A is released during plaque destabilization and appears to be a valuable indicator of unstable angina and acute MI in patients lacking other indicators of necrosis (23).

Placenta growth factor, is a member of the vascular endothelial growth factor family, which stimulates vascular smooth muscle growth, recruits macrophages into atherosclerotic lesion, up-regulates production of tumor necrosis factor- and monocyte chemotactic protein 1 by macrophages, and stimulates pathological angiogenesis (24). It appears to be an initiator of the inflammatory process.

In one study, elevated P1GF levels not only identified patients with acute chest pain who developed ACS, but also those patients with an increased risk of recurrent instability after hospital discharge (25).

Plasma elevation of CRP have been reported fraction, and are acute ischemia and myocardial in fraction, and are predictive of the risk of recurrent ischemia among hospitalization patients with unstable angina (26).

Matrix metalloproteinases. MMPs are a diverse family of powerful, zinc-containing enzymes expressed by macrophage- derived foam cells, SMCs and other vascular cells within atherosclerotic lesions (27) .It has been previously demonstrated that MMPs are responsible for remodeling of the ECM during all stages of atheromatous development and may directly contribute to fibrous cap weakening and plaque rupture within disease arteries (28).

CD40 ligand (CD40L) is an immunoregulatory transmembrane protein that belongs to the tumor necrosis factor (TNF) super family. It is expressed on the surface of many cells types, including leukocytes, ECs, SMSs, macrophages, and activated platelets (29). Ligand receptor binding on these cells triggers the expression and secretion of a variety of pro-inflammatory and procoagulant mediators, including CAMs, cytokines, chemokines, growth factors, MMPs, and TF (29). Recent data suggest that CD40L plays a central role in the inflammatory process that contributes to plaque destabilization in CAD (30), and elevation in soluble, biologically active CD40L (Scd40l) have been demonstrated in the serum of ACS patients (31).

Paraoxonase and atherogenic HDL The enzyme PON1 is known to be tightly bound with HDL in serum, and several studies suggest that it is this association that contributes to the protection conferred by HDL against LDL oxidation (33-36).

The aim of the study is to find a correlation between serum markers of unstable plaque and virtual histology of unstable plaque visualized by IVUS.

Patients and methods:

Thirty patients scheduled to coronary angiography and IVUS in according to their treating physician decision will be enrolled in the study. The coronary angiography and IVUS will be done on according to regular clinical standards.

As the study protocol, 40 cc of blood will be drawn from the patients after written informed consent.

The laboratory tests will be processed for the above mentioned serum markers of unstable plaque.

A multivariate correlation test will be done between the different serum markers and the plaque morphology by angiography and composition (virtual histology) by IVUS.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients scheduled to coronary angiography and IVUS

Criteria

Inclusion Criteria:

  • Both genders: males and females
  • Age - above 18 years
  • Patients scheduled to coronary angiography and IVUS
  • Written Informed Consent Form

Exclusion Criteria:

  • Pregnant or breast-feeding woman
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00466050

Locations
Israel
Heart Institute ,Ziv Medical Center
Safed, Israel, 13110
Sponsors and Collaborators
Ziv Hospital
Investigators
Principal Investigator: Osamah Hussein, MD Ziv Medical Center
Principal Investigator: Alon Marmor, Prof Ziv Medical Center
  More Information

Publications:

Responsible Party: Ziv Hospital
ClinicalTrials.gov Identifier: NCT00466050     History of Changes
Other Study ID Numbers: HP-7-234-S
Study First Received: April 25, 2007
Last Updated: August 23, 2009
Health Authority: Israel: Ministry of Health

Keywords provided by Ziv Hospital:
plaque rupture,
acute coronary thrombose,
coronary angiography,
IVUS

Additional relevant MeSH terms:
Acute Coronary Syndrome
Rupture
Angina Pectoris
Cardiovascular Diseases
Chest Pain
Heart Diseases
Myocardial Ischemia
Pain
Signs and Symptoms
Vascular Diseases
Wounds and Injuries

ClinicalTrials.gov processed this record on October 20, 2014