on October 19, 2007
Published online before print October 19, 2007, doi: 10.1161/ATVBAHA.107.151688
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Submitted on April 24, 2007
Accepted on October 2, 2007
Inhibition of CETP by Torcetrapib Attenuates the Atherogenicity of Postprandial TG-Rich Lipoproteins in Type IIB Hyperlipidemia
Maryse Guerin *;
From INSERM U551 (M.G., W.L.E.G., E.D., Z.J., M.J.C.), Paris, France; Université Pierre et Marie Curie–Paris6 (M.G., W.L.E.G., E.D., Z.J., M.J.C.), UMR S551, Paris, France; and Pfizer Global Research and Development (T.N., T.T., C.L.S.), New London, Conn.
* To whom correspondence should be addressed. E-mail: mguerin{at}chups.jussieu.fr.
Objective—The purpose of this study was evaluate the impact of Torcetrapib on atherogenic TG-rich lipoprotein subfractions in the postprandial phase in Type IIB hyperlipidemia.
Methods and 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.
Key words: CETP • Torcetrapib • high-density lipoprotein • postprandial hypertriglyceridemia