Inhibition of CETP by torcetrapib attenuates the atherogenicity of postprandial TG-rich lipoproteins in type IIB hyperlipidemia.
OBJECTIVE
The purpose of this study was to evaluate the impact of torcetrapib on atherogenic TG-rich lipoprotein subfractions in the postprandial phase in Type IIB hyperlipidemia.


RESULTS
The quantitative and qualitative features of the postprandial profile of TG-rich lipoproteins were determined at baseline, after treatment for 6 weeks with 10 mg/d atorvastatin, and subsequently with an atorvastatin/torcetrapib combination (10/60 mg/d) in Type IIB patients (n=18). After ingestion of a standardized mixed meal, TG-rich lipoprotein subfractions were evaluated over 8 hours after each experimental period. On a background of atorvastatin, torcetrapib significantly attenuated the incremental postprandial area under the curve (iAUC 0 to 8 hours) for VLDL-1 (-40%), and the AUC 0 to 8 hours for VLDL-2 (-53%), with minor effect on chylomicron iAUC (-24%); concomitantly, the CE/TG ratio in both VLDL-1 and VLDL-2 was significantly reduced (-27% to -42%). Such reduction was attributable to torcetrapib-mediated attenuation of postprandial CE transfer to Chylomicrons (-17%) and VLDL-1 (-33%). Marked reduction in postprandial VLDL-1 levels was associated with apoE enrichment.


CONCLUSIONS
On a background of atorvastatin, torcetrapib attenuated the quantitative and qualitative features of the atherogenic postprandial profile of chylomicrons, VLDL-1 and VLDL-2. Such changes reflect the sum of torcetrapib-mediated effects on TG-rich lipoprotein production, intravascular remodeling, and catabolism.
Guerin
Maryse
M
INSERM Unité 551, Hôpital de la Pitié, Pavillon Benjamin Delessert, 83, 75651 Paris Cedex 13, France. mguerin@chups.jussieu.fr
Le Goff
Wilfried
W
Duchene
Emilie
E
Julia
Zélie
Z
Nguyen
Tu
T
Thuren
Tom
T
Shear
Charles L
CL
Chapman
M John
MJ
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D053480:Cholesterol Ester Transfer Proteins / Q000187:drug effects; D002914:Chylomicrons / Q000187:drug effects; D004041:Dietary Fats / Q000378:metabolism; D004044:Dietary Proteins / Q000378:metabolism; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D008079:Lipoproteins, VLDL / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects*; D011758:Pyrroles / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology*
D000924:Anticholesteremic Agents; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D002914:Chylomicrons; D004041:Dietary Fats; D004044:Dietary Proteins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008079:Lipoproteins, VLDL; D011758:Pyrroles; D011804:Quinolines; C483909:torcetrapib; D000069059:Atorvastatin