Abstract
Background: Cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids
between lipoproteins. The role of CETP in atherogenesis is controversial. To better
understand the relationships between plasma CETP levels, lipoproteins and atherosclerosis,
we assessed these parameters in patients with an enhanced risk for atherosclerosis.
Methods and results: We investigated 281 patients with familial hypercholesterolemia (FH) in which the
effects of two statins were compared in a 2-year, randomized, double-blinded study.
Patients were stratified in quartiles according to their CETP baseline levels. In
addition to correlations with decreased high-density lipoprotein cholesterol (HDL-c),
increased low-density lipoprotein cholesterol (LDL-c) and enhanced triglyceride levels,
higher CETP levels were also associated with reduced HDL particle size, and smaller
and denser LDL. Statins reduced plasma CETP levels and atherogenic lipoproteins. Nevertheless,
baseline CETP concentration was positively associated with IMT after 2 years of therapy.
Conclusion: This study provides evidence that CETP levels are associated with a more atherogenic
lipid profile and increased progression of atherosclerosis. Statin treatment improved
the lipoprotein profile in FH patients, but to a lesser extent in those with high
CETP levels. These findings might imply that statin treatment does not entirely counteract
the lipoprotein abnormalities associated with high CETP levels.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Plasma cholesteryl ester transfer protein.J. Lipid Res. 1993; 34: 1255-1274
- Hugh Sinclair Lecture: the regulation and remodelling of HDL by plasma factors.Atheroscler. Suppl. 2002; 3: 39-47
- Atherogenic role of elevated CE transfer from HDL to VLDL(1) and dense LDL in type 2 diabetes: impact of the degree of triglyceridemia.Arterioscler. Thromb. Vasc. Biol. 2001; 21: 282-288
- Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation.N. Engl. J. Med. 1990; 323: 1234-1238
- Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins.Nature. 1989; 342: 448-451
- Low high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report.Circulation. 2001; 103: 2213-2218
- A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits.Nature. 2000; 406: 203-207
- Effect of antisense oligonucleotides against cholesteryl ester transfer protein on the development of atherosclerosis in cholesterol-fed rabbits.J. Biol. Chem. 1998; 273: 5033-5036
- Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose–response study.Circulation. 2002; 105: 2159-2165
- The plasma lecithins: cholesterol acyltransferase reaction.J. Lipid Res. 1968; 9: 155-167
- Severe atherosclerosis in transgenic mice expressing simian cholesteryl ester transfer protein.Nature. 1993; 364: 73-75
- Cholesteryl ester transfer protein corrects dysfunctional high density lipoproteins and reduces aortic atherosclerosis in lecithin cholesterol acyltransferase transgenic mice.J. Biol. Chem. 1999; 274: 36912-36920
- Genetic cholesteryl ester transfer protein deficiency is extremely frequent in the Omagari area of Japan. Marked hyperalphalipoproteinemia caused by CETP gene mutation is not associated with longevity.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1053-1059
- Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia.Atherosclerosis. 1985; 58: 175-186
- Increased coronary heart disease in Japanese–American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels.J. Clin. Invest. 1996; 97: 2917-2923
- Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial.Lancet. 2001; 357: 577-581
- Value of HDL cholesterol, apolipoprotein A-I, lipoprotein A-I, and lipoprotein A-I/A-II in prediction of coronary heart disease: the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction.Arterioscler. Thromb. Vasc. Biol. 2002; 22: 1155-1161
- Immunonephelometric assay of human apolipoprotein AI.Clin. Chem. 1980; 26: 1205-1208
- Sequential estrogen–progestin replacement therapy in healthy postmenopausal women: effects on cholesterol efflux capacity and key proteins regulating high-density lipoprotein levels.Metabolism. 2002; 51: 1410-1417
- Measurement of lipoprotein subclass profiles by nuclear magnetic resonance spectroscopy.Clin. Lab. 2002; 48: 171-180
- Reproducibility of ultrasonographic measurements of different carotid and femoral artery segments in healthy subjects and in patients with increased intima-media thickness.Clin. Sci. (Lond.). 1997; 93: 317-324
- Plasma concentrations of cholesteryl ester transfer protein in hyperlipoproteinemia. Relation to cholesteryl ester transfer protein activity and other lipoprotein variables.Arterioscler. Thromb. 1991; 11: 797-804
- Opposite effects on serum cholesteryl ester transfer protein levels between long-term treatments with pravastatin and probucol in patients with primary hypercholesterolemia and xanthoma.Atherosclerosis. 1999; 145: 405-413
- Interconversion between apolipoprotein A-I-containing lipoproteins of pre-beta and alpha electrophoretic mobilities.J. Lipid Res. 1992; 33: 1807-1816
- Evidence that cholesteryl ester transfer protein-mediated reductions in reconstituted high density lipoprotein size involve particle fusion.J. Biol. Chem. 1997; 272: 3953-3960
- Remodelling of high density lipoproteins by plasma factors.Atherosclerosis. 1999; 145: 227-238
- Relation of lipoprotein subclasses as measured by proton nuclear magnetic resonance spectroscopy to coronary artery disease.Arterioscler. Thromb. Vasc. Biol. 1998; 18: 1046-1053
- HDL and plasma phospholipids in coronary artery disease.Arterioscler. Thromb. 1994; 14: 1146-1150
- Clinical characteristics of double heterozygotes with familial hypercholesterolemia and cholesteryl ester transfer protein deficiency.Atherosclerosis. 1997; 132: 229-236
- Low density lipoprotein (LDL) binding affinity for the LDL receptor in hyperlipoproteinemia.Atherosclerosis. 1999; 147: 77-86
- Plasma lipoproteins and progression of coronary artery disease evaluated by angiography and clinical events.Circulation. 1993; 88: 2762-2770
Article info
Publication history
Accepted:
November 13,
2003
Received in revised form:
November 5,
2003
Received:
May 29,
2003
Identification
Copyright
© 2004 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.