Identification of CETP as a Marker of Atherosclerosis
Identification of CETP as a Marker of Atherosclerosis
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.
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