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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #297557
Title: Effects of atorvastatin on human c reactive protein metabolism

Author
item THONGTANG, NUNTAKORN - Bangkok Metropolitan Administration Medical College
item DIFFENDERFER, MARGARET - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item OOI, ESTHER M - University Of Western Australia
item ASZTALOS, BELA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item DOLNIKOWSKI, GREGORY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SCHAEFER, ERNST - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/9/2012
Publication Date: 2/1/2013
Citation: Thongtang, N., Diffenderfer, M.R., Ooi, E.M., Asztalos, B.F., Dolnikowski, G.G., Lamon-Fava, S., Schaefer, E.J. 2013. Effects of atorvastatin on human c reactive protein metabolism. Atherosclerosis. 226:466-470.

Interpretive Summary: Statins are commonly prescribed medications to lower blood cholesterol and the risk of heart disease. In addition to these effects, statins have also been shown to lower plasma levels of C-reactive protein (CRP), an indicator of whole-body inflammation. CRP levels are elevated in subjects at risk of heart disease. We conducted a study to assess the mechanism by which statins lower CRP levels. The rate of CRP production and clearance from plasma was measured in 8 subjects at the end of an 8-week treatment phase with 80 mg/day atorvastatin, and at the end of an 8week phase without atorvastatin (Placebo). Our data indicate that atorvastatin reduced plasma CRP levels by 28%, accompanied by a 40% increase in plasma CRP clearance and no change in CRP production.

Technical Abstract: Statins are known to reduce plasma C-reactive protein (CRP) concentrations. Our goals were to define the mechanisms by which CRP was reduced by maximal dose atorvastatin. Eight subjects with combined hyperlipidemia (5 men and 3 postmenopausal women) were enrolled in a randomized, placebo-controlled double-blind, cross over study. Subjects underwent a 15-hour primed-constant infusion with deuterated leucine after 8 weeks of placebo and 80 mg/day of atorvastatin. CRP was isolated from lipoprotein deficient plasma, density fraction greater than 1.21 g/ml by affinity chromatography. Isotope enrichment was determined by gas chromatography/mass spectrometry. Kinetic parameters were determined using compartmental modeling. Paired t test and Wilcoxon signed ranks test were used to compare differences between placebo and atorvastatin. Compared with placebo, atorvastatin decreased median CRP pool size (PS) by 28.4% (13.31 +/- 3.78 vs 10.26 +/- 3.93 mg; p=0.16), associated with a median CRP fractional catabolic rate (FCR) increase of 39.9% (0.34 +/- 0.06 vs 0.50 +/- 0.11 pools/day; p=0.09), with no significant effect on median CRP production rate (PR) (0.050 +/- 0.01 vs 0.049 +/- 0.01 mg/kg/day; p=0.78). Our data indicate that maximal doses of atorvastatin lower plasma CRP levels by substantially decreasing the median CRP plasma residence time from 2.94 days to 2.0 days, with no significant effect on the median CRP production rate.