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Abstract: 585 LIPIDOMICS CAN BE USED IN PERSONALIZING CHOLESTEROL SYNTHESIS AND ABSORPTION INHIBITOR TREATMENTS
Workshop IV-2 - Pharmacology and Novel Therapies: Inhibition of Cholesterol Synthesis and/or Cholesterol Absorption Abstract: 585 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
LIPIDOMICS CAN BE USED IN PERSONALIZING CHOLESTEROL SYNTHESIS AND ABSORPTION INHIBITOR TREATMENTS R Laaksonen1, I Gouni-Berthold3, H Gylling1, H Berthold, A Verma, K Tarasov, R Hurme, K Ekroos 1
Zora Biosciences Oy, Espoo; 2University of Cologne, Cologne; 3University of Kuopio, Kuopio; 4 University of Bonn, Bonn Objectives: We characterized the individual lipidomic profiles of patients treated with ezetimibe, simvastatin, and their combination to evaluate in detail their effects on the lipid metabolism. Methods: State-of-the-art mass spectrometry based lipidomics was used. Plasma samples were from a randomized trial including 72 patients on ezetimibe (10 mg/day), simvastatin (40 mg/day) or their combination (10 + 40 mg/day). Results: Lipidomics revealed the presence of different responder types in the ezetimibe group, despite a homogenous LDL-C lowering effect. This analysis revealed five subjects with increased CE, PC, PC-O, LPC and SM concentrations while they were on ezetimibe treatment. This effect was not related to the fatty acid composition of these lipids Plant sterols and cholesterol precursor concentrations were measured to assess the effect on cholesterol absorption and synthesis. Striking individual differences were observed in all groups. Only half of the subjects on ezetimibe responded as expected. In 5 patients increased cholesterol absorption was recorded. Moreover, one third of the subjects in the simvastatin group had unexpectedly elevated plasma markers for cholesterol. Finally all possible combinations of cholesterol synthesis and absorption markers were recorded in the combination treatment group. Conclusions: Lipidomics allows more detailed efficacy assessment than LDL-C measurement alone. Optimization of the dosage ratio between cholesterol synthesis and absorption inhibitors could improve the treatment. Funding: The Finnish Funding Agency for Technology and Innovation.
LIPIDOMICS CAN BE USED IN PERSONALIZING CHOLESTEROL SYNTHESIS AND ABSORPTION INHIBITOR TREATMENTS R Laaksonen1, I Gouni-Berthold3, H Gylling1, H Berthold, A Verma, K Tarasov, R Hurme, K Ekroos 1
Zora Biosciences Oy, Espoo; 2University of Cologne, Cologne; 3University of Kuopio, Kuopio; 4 University of Bonn, Bonn Objectives: We characterized the individual lipidomic profiles of patients treated with ezetimibe, simvastatin, and their combination to evaluate in detail their effects on the lipid metabolism. Methods: State-of-the-art mass spectrometry based lipidomics was used. Plasma samples were from a randomized trial including 72 patients on ezetimibe (10 mg/day), simvastatin (40 mg/day) or their combination (10 + 40 mg/day). Results: Lipidomics revealed the presence of different responder types in the ezetimibe group, despite a homogenous LDL-C lowering effect. This analysis revealed five subjects with increased CE, PC, PC-O, LPC and SM concentrations while they were on ezetimibe treatment. This effect was not related to the fatty acid composition of these lipids Plant sterols and cholesterol precursor concentrations were measured to assess the effect on cholesterol absorption and synthesis. Striking individual differences were observed in all groups. Only half of the subjects on ezetimibe responded as expected. In 5 patients increased cholesterol absorption was recorded. Moreover, one third of the subjects in the simvastatin group had unexpectedly elevated plasma markers for cholesterol. Finally all possible combinations of cholesterol synthesis and absorption markers were recorded in the combination treatment group. Conclusions: Lipidomics allows more detailed efficacy assessment than LDL-C measurement alone. Optimization of the dosage ratio between cholesterol synthesis and absorption inhibitors could improve the treatment. Funding: The Finnish Funding Agency for Technology and Innovation.