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. 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.
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. 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 IIBpatients (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.
Authors: Margaret R Diffenderfer; Margaret E Brousseau; John S Millar; P Hugh R Barrett; Chorthip Nartsupha; Peter M Schaefer; Megan L Wolfe; Gregory G Dolnikowski; Daniel J Rader; Ernst J Schaefer Journal: J Lipid Res Date: 2012-04-02 Impact factor: 5.922
Authors: Natalie L Trevaskis; Claire L McEvoy; Michelle P McIntosh; Glenn A Edwards; Ravi M Shanker; William N Charman; Christopher J H Porter Journal: Pharm Res Date: 2010-03-11 Impact factor: 4.200
Authors: Ronald W Clark; David Cunningham; Yang Cong; Timothy A Subashi; George T Tkalcevic; David B Lloyd; James G Boyd; Boris A Chrunyk; George A Karam; Xiayang Qiu; Ing-Kae Wang; Omar L Francone Journal: J Lipid Res Date: 2009-10-21 Impact factor: 5.922
Authors: Thomas A Bell; Mark J Graham; Richard G Lee; Adam E Mullick; Wuxia Fu; Dan Norris; Rosanne M Crooke Journal: J Lipid Res Date: 2013-06-25 Impact factor: 5.922
Authors: Eliane S Parra; Aline Urban; Natalia B Panzoldo; Rui T Nakamura; Rogério Oliveira; Eliana C de Faria Journal: Lipids Health Dis Date: 2011-05-24 Impact factor: 3.876