Effects of atorvastatin on human C-reactive protein metabolism

Objective: Statins are known to reduce plasma C-reactive protein (CRP) concentrations. Our goal was to define the mechanisms by which CRP was reduced by maximal dose atorvastatin. Methods: Eight subjects with combined hyperlipidemia (5 men and 3 postmenopausal women) were enrolled in a randomized, p...

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Main Authors: Nuntakorn Thongtang, Margaret R. Diffenderfer, Esther M.M. Ooi, Bela F. Asztalos, Gregory G. Dolnikowski, Stefania Lamon-Fava, Ernst J. Schaefer
Other Authors: Tufts University
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Published: 2018
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/32556
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spelling th-mahidol.325562018-10-19T12:33:45Z Effects of atorvastatin on human C-reactive protein metabolism Nuntakorn Thongtang Margaret R. Diffenderfer Esther M.M. Ooi Bela F. Asztalos Gregory G. Dolnikowski Stefania Lamon-Fava Ernst J. Schaefer Tufts University Mahidol University University of Western Australia Faculty of Medicine and Dentistry Medicine Objective: Statins are known to reduce plasma C-reactive protein (CRP) concentrations. Our goal was to define the mechanisms by which CRP was reduced by maximal dose atorvastatin. Methods: 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-h 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 > 1.21 g/ml) by affinity chromatography. Isotopic 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. Results: Compared with placebo, atorvastatin decreased median CRP pool size by 28.4% (13.31 ± 3.78 vs 10.26 ± 3.93 mg; p = 0.16), associated with a median CRP fractional catabolic rate 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 (0.050 ± 0.01 vs 0.049 ± 0.01 mg/kg/day; p = 0.78). Conclusion: 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. © 2012 Elsevier Ireland Ltd. 2018-10-19T05:33:45Z 2018-10-19T05:33:45Z 2013-02-01 Article Atherosclerosis. Vol.226, No.2 (2013), 466-470 10.1016/j.atherosclerosis.2012.11.012 18791484 00219150 2-s2.0-84872410105 https://repository.li.mahidol.ac.th/handle/123456789/32556 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84872410105&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Medicine
spellingShingle Medicine
Nuntakorn Thongtang
Margaret R. Diffenderfer
Esther M.M. Ooi
Bela F. Asztalos
Gregory G. Dolnikowski
Stefania Lamon-Fava
Ernst J. Schaefer
Effects of atorvastatin on human C-reactive protein metabolism
description Objective: Statins are known to reduce plasma C-reactive protein (CRP) concentrations. Our goal was to define the mechanisms by which CRP was reduced by maximal dose atorvastatin. Methods: 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-h 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 > 1.21 g/ml) by affinity chromatography. Isotopic 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. Results: Compared with placebo, atorvastatin decreased median CRP pool size by 28.4% (13.31 ± 3.78 vs 10.26 ± 3.93 mg; p = 0.16), associated with a median CRP fractional catabolic rate 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 (0.050 ± 0.01 vs 0.049 ± 0.01 mg/kg/day; p = 0.78). Conclusion: 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. © 2012 Elsevier Ireland Ltd.
author2 Tufts University
author_facet Tufts University
Nuntakorn Thongtang
Margaret R. Diffenderfer
Esther M.M. Ooi
Bela F. Asztalos
Gregory G. Dolnikowski
Stefania Lamon-Fava
Ernst J. Schaefer
format Article
author Nuntakorn Thongtang
Margaret R. Diffenderfer
Esther M.M. Ooi
Bela F. Asztalos
Gregory G. Dolnikowski
Stefania Lamon-Fava
Ernst J. Schaefer
author_sort Nuntakorn Thongtang
title Effects of atorvastatin on human C-reactive protein metabolism
title_short Effects of atorvastatin on human C-reactive protein metabolism
title_full Effects of atorvastatin on human C-reactive protein metabolism
title_fullStr Effects of atorvastatin on human C-reactive protein metabolism
title_full_unstemmed Effects of atorvastatin on human C-reactive protein metabolism
title_sort effects of atorvastatin on human c-reactive protein metabolism
publishDate 2018
url https://repository.li.mahidol.ac.th/handle/123456789/32556
_version_ 1763488129659961344