|Van Himbergen, Thomas -|
|Matthan, Nirupa -|
|Resteghini, Nancy -|
|Otokozawa, Seiko -|
|Stein, Evan -|
|Jones, Peter -|
|Schaefer, Ernst -|
Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 25, 2009
Publication Date: April 20, 2009
Citation: Van Himbergen, T.M., Matthan, N.R., Resteghini, N.A., Otokozawa, S., Jones, P., Schaefer, E. 2009. Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers. Journal of Lipid Research. 50:730-739. Interpretive Summary: On one hand, the total cholesterol content in the human body is the result of synthesis of cholesterol by the body itself. On the other hand, it is the result of absorption of cholesterol in one’s diet. The synthesis and absorption of cholesterol are linked to each other, meaning that if we inhibit cholesterol production by administering a statin (a lipid lowering drug), we would typically observe an increase in cholesterol absorption from the intestine. In our study, we compared the effects of two different classes of statins, i.e. rosuvastatin and atorvastatin, on markers of cholesterol synthesis and absorption. As expected, the synthesis of cholesterol was markedly reduced. We also noticed an increase in cholesterol absorption for both statins. However, the strongest increase in cholesterol absorption was seen in the group of people taking the atorvastatin.
Technical Abstract: 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=5135) 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.