Identification of CETP as a Marker of Atherosclerosis (CETP-ATHERO)

Relationship Between Endogenous CETP Activity and Atherosclerosis Distribution in Patients With High Cardiovascular Risk

The reverse cholesterol transport (RCT) pathway, which involves the centripetal movement of free cholesterol from peripheral tissues, including the vessel wall, to the liver represent the primary mechanism by which HDL protects against atherosclerosis and by which it may induce plaque regression. Recent data reveal that the capacity of HDL to efflux cholesterol from macrophages, a metric of HDL function reflecting the initial step of the RCT, is clinically relevant, displaying a strong inverse association with both carotid intima-media thickness and the severity of angiographic CAD; such observations were independent of HDL-C levels.

In human, the Cholesteryl Ester Transfer Protein (CETP), represents a key protein of the RCT pathway and mediates redistribution of neutral lipids between lipoproteins, has been identified as a potential therapeutic target against atherosclerosis. It is known that CETP activity correlates with HDL-C levels and represents a key modulator of the ability of whole plasma to mediate free cholesterol efflux from human macrophages.

Recent studies showed that 23% of endogenous plasma CETP activity variability is explained by plasma LDL-C (12.0%), HDL-C (6.4%) and TG (4.4%) whereas sex and BMI accounted together for only 0.7% of its variability. Scoring patients for cardiovascular risk on the basis of their plasma lipid levels (TC, TG, LDL-C and HDL-C), revealed that patients with high cardiovascular risk (score ≥3) displayed a mean endogenous plasma CETP activity above 34%. Therefore plasma CETP activity represents a potent indicator of cardiovascular risk in patients with metabolic disorders since it integrates major independent risk factors.

The objective of this study is to decipher the relationship between CETP, HDL efflux capacity and the development of atherosclerosis in humans in order to identify CETP as a potent biomarker of atherosclerosis distribution.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Other: cardiovascular risk factors

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Inserm Umrs1166

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent prior to initiation of the study
• Men and women aged 18 or more years
• Patients displaying at least one abnormal plasma lipid parameter and/or receiving a lipid-lowering therapy unchanged for at least 3 months.

Exclusion Criteria:

• Current significant renal disease, including: nephrotic syndrome; chronic renal failure and/or serum creatinine >1.7 x upper limit of the reference range (ULRR)
• Uncontrolled hypothyroidism defined as TSH >2 x ULRR
• Active hepatobiliary disease, including chronic hepatitis B or hepatitis C infection (confirmed by serology); or an aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >3.0 x ULRR
• Any prior history of malignancy or current cancer
• Current chronic or acute inflammatory syndrome defined as CRP>10 mg/l

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: patients with cardiovascular risk factors	Other: cardiovascular risk factors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Endogenous CETP activity	Day 1
carotid intima-media thickness	day 1
Coronary calcium score	Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
plasma efflux capacity from human macrophage	Day 1
HDL genetic variant	Day1

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Maryse Guerin, PhD, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2014
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: February 10, 2014
• First Submitted That Met QC Criteria: March 6, 2014
• First Posted (Estimate): March 7, 2014

Study Record Updates

• Last Update Posted (Actual): August 26, 2021
• Last Update Submitted That Met QC Criteria: August 25, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Atherosclerosis
• Other Study ID Numbers: C13-20; 2013-A00798-37 (Registry Identifier: IDRCB)