The relationship between cholesteryl ester transfer protein levels and risk factor profile in patients with familial hypercholesterolemia.
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.


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.


CONCLUSIONS
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.
de Grooth
Greetje J
GJ
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Smilde
Tineke J
TJ
Van Wissen
Sanne
S
Klerkx
Anke H E M
AH
Zwinderman
Aeilko H
AH
Fruchart
Jean-Charles
JC
Kastelein
John J P
JJ
Stalenhoef
Anton F H
AF
Kuivenhoven
Jan Albert
JA
D000284:Administration, Oral; D000704:Analysis of Variance; D001161:Arteriosclerosis / Q000473:pathology* / Q000517:prevention & control; D000069059:Atorvastatin; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D016014:Linear Models; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D011758:Pyrroles / Q000008:administration & dosage*; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D019821:Simvastatin / Q000008:administration & dosage*; D016896:Treatment Outcome; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D006538:Heptanoic Acids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin