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Papers In Press, published online ahead of print April 1, 2009
J. Lipid Res., doi:10.1194/jlr.P800042-JLR200

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Journal of Lipid Research, Vol. 50, 730-739, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers^*,

Thomas M. van Himbergen^1,*,, Nirupa R. Matthan, Nancy A. Resteghini^*,, Seiko Otokozawa^*, Masumi Ai^*, Evan A. Stein^**, Peter H. Jones and Ernst J. Schaefer^*,

^* Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA
Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA
Cardiovascular Research Laboratory, Friedman School of Nutrition Science and Policy at Tufts University and Tufts University School of Medicine, Boston, MA
^** Metabolic and Atherosclerosis Research Center, Cincinnati, OH
Department of Medicine, Baylor College of Medicine, Houston, TX

^* T.M. van Himbergen was supported by the Ruth L. Kirschstein National Research Service Award, training grant DK07651. S. Otokozawa and M. Ai were supported by research fellowships from Kyowa Medex Co, Tokyo Japan and Denka Seiken Co, Tokyo Japan, respectively. E.J. Schaefer was supported by grants R01 HL-60935, HL 74753 and PO50HL083813 from the National Institutes of Health and contract 53-3K-06 from the United Department of Agriculture Research Service. The original Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin (STELLAR) study was supported by contracts to Drs. Stein and Jones from the AstraZeneca Company, Wilmington, DE; however no research support for this investigation was received from AstraZeneca.

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of two tables.

Presented in part at the annual Scientific Sessions of the American Heart Association and the Young Investigator Scientific Sessions of the Council on Arteriosclerosis, Thrombosis, and Vascular Biology, November 2008.

Published, JLR Papers in Press, November 30, 2008.

¹ To whom correspondence should be addressed. e-mail: thomas.vanhimbergen{at}tufts.edu

We measured plasma markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) in order to compare the effects of maximal doses of rosuvastatin with atorvastatin and investigate the basis for the significant individual variation in lipid lowering response to statin therapy. Measurements were performed in participants (n = 135) at baseline and after 6 weeks on either rosuvastatin (40 mg/day) or atorvastatin (80 mg/day) therapy. Plasma sterols were measured using gas-liquid chromatography. Rosuvastatin and atorvastatin significantly (P < 0.001) altered plasma total cholesterol (C) levels by –40%, and the ratios of lathosterol/C by –64% and –68%, and campesterol/C by +52% and +72%, respectively, with significant differences (P < 0.001) between the treatment groups for the latter parameter. When using absolute values of these markers, subjects with the greatest reductions in both synthesis (lathosterol) and absorption (campesterol) had significantly greater reductions in total C than subjects in whom the converse was true (–46% versus –34%, P = 0.001), with similar effects for LDL-C. Rosuvastatin and atorvastatin decreased markers of cholesterol synthesis and increased markers of fractional cholesterol absorption, with rosuvastatin having significantly less effect on the latter parameter than atorvastatin. In addition, alterations in absolute values of plasma sterols correlated with the cholesterol lowering response.

Supplementary key words plasma sterols • lathosterol • campesterol • sitosterol • STELLAR study

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