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Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy

BACKGROUND: This study was performed to compare the effects of three different lipid-lowering therapies (statins, ezetimibe, and colestimide) on lipoprotein lipase and endothelial lipase masses in pre-heparin plasma (pre-heparin LPL and EL mass, respectively) from patients with familial hypercholest...

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Autores principales: Tada, Hayato, Kobayashi, Junji, Kawashiri, Masa-aki, Miyashita, Kazuya, Nohara, Atsushi, Inazu, Akihiro, Nakajima, Katsuyuki, Mabuchi, Hiroshi, Yamagishi, Masakazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818918/
https://www.ncbi.nlm.nih.gov/pubmed/27039080
http://dx.doi.org/10.1186/s12944-016-0238-z
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author Tada, Hayato
Kobayashi, Junji
Kawashiri, Masa-aki
Miyashita, Kazuya
Nohara, Atsushi
Inazu, Akihiro
Nakajima, Katsuyuki
Mabuchi, Hiroshi
Yamagishi, Masakazu
author_facet Tada, Hayato
Kobayashi, Junji
Kawashiri, Masa-aki
Miyashita, Kazuya
Nohara, Atsushi
Inazu, Akihiro
Nakajima, Katsuyuki
Mabuchi, Hiroshi
Yamagishi, Masakazu
author_sort Tada, Hayato
collection PubMed
description BACKGROUND: This study was performed to compare the effects of three different lipid-lowering therapies (statins, ezetimibe, and colestimide) on lipoprotein lipase and endothelial lipase masses in pre-heparin plasma (pre-heparin LPL and EL mass, respectively) from patients with familial hypercholesterolemia (FH). FH is usually treated by coadministration of these three drugs. METHODS: The pre-heparin LPL and EL masses were measured in fresh frozen plasma drawn and stored at various time points during coadministration of the three drugs from patients with heterozygous FH harboring a single mutation in the LDL receptor (n = 16, mean age 63 years). The patients were randomly divided into two groups based on the timing when ezetimibe was added. RESULTS: Plasma LPL mass concentration was significantly reduced by rosuvastatin at 20 mg/day (median = 87.4 [IQR: 71.4–124.7] to 67.5 [IQR: 62.1–114.3] ng/ml, P < 0.05). In contrast, ezetimibe at 10 mg/day as well as colestimide at 3.62 g/day did not alter its level substantially (median = 67.5 [IQR: 62.1–114.3] to 70.2 [IQR: 58.3–106.2], and to 74.9 [IQR: 55.6–101.3] ng/ml, respectively) in the group starting with rosuvastatin followed by the addition of ezetimibe and colestimide. On the other hand, the magnitude in LPL mass reduction was lower in the group starting with ezetimibe at 10 mg/day before reaching the maximum dose of 20 mg/day of rosuvastatin. Plasma EL mass concentration was significantly increased by rosuvastatin at 20 mg/day (median = 278.8 [IQR: 186.7–288.7] to 297.0 [IQR: 266.2–300.2] ng/ml, P < 0.05), whereas other drugs did not significantly alter its level. CONCLUSION: The effects on changes of LPL and EL mass differed depending on the lipid-lowering therapy, which may impact the prevention of atherosclerosis differently. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12944-016-0238-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-48189182016-04-04 Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy Tada, Hayato Kobayashi, Junji Kawashiri, Masa-aki Miyashita, Kazuya Nohara, Atsushi Inazu, Akihiro Nakajima, Katsuyuki Mabuchi, Hiroshi Yamagishi, Masakazu Lipids Health Dis Research BACKGROUND: This study was performed to compare the effects of three different lipid-lowering therapies (statins, ezetimibe, and colestimide) on lipoprotein lipase and endothelial lipase masses in pre-heparin plasma (pre-heparin LPL and EL mass, respectively) from patients with familial hypercholesterolemia (FH). FH is usually treated by coadministration of these three drugs. METHODS: The pre-heparin LPL and EL masses were measured in fresh frozen plasma drawn and stored at various time points during coadministration of the three drugs from patients with heterozygous FH harboring a single mutation in the LDL receptor (n = 16, mean age 63 years). The patients were randomly divided into two groups based on the timing when ezetimibe was added. RESULTS: Plasma LPL mass concentration was significantly reduced by rosuvastatin at 20 mg/day (median = 87.4 [IQR: 71.4–124.7] to 67.5 [IQR: 62.1–114.3] ng/ml, P < 0.05). In contrast, ezetimibe at 10 mg/day as well as colestimide at 3.62 g/day did not alter its level substantially (median = 67.5 [IQR: 62.1–114.3] to 70.2 [IQR: 58.3–106.2], and to 74.9 [IQR: 55.6–101.3] ng/ml, respectively) in the group starting with rosuvastatin followed by the addition of ezetimibe and colestimide. On the other hand, the magnitude in LPL mass reduction was lower in the group starting with ezetimibe at 10 mg/day before reaching the maximum dose of 20 mg/day of rosuvastatin. Plasma EL mass concentration was significantly increased by rosuvastatin at 20 mg/day (median = 278.8 [IQR: 186.7–288.7] to 297.0 [IQR: 266.2–300.2] ng/ml, P < 0.05), whereas other drugs did not significantly alter its level. CONCLUSION: The effects on changes of LPL and EL mass differed depending on the lipid-lowering therapy, which may impact the prevention of atherosclerosis differently. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12944-016-0238-z) contains supplementary material, which is available to authorized users. BioMed Central 2016-04-02 /pmc/articles/PMC4818918/ /pubmed/27039080 http://dx.doi.org/10.1186/s12944-016-0238-z Text en © Tada et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Tada, Hayato
Kobayashi, Junji
Kawashiri, Masa-aki
Miyashita, Kazuya
Nohara, Atsushi
Inazu, Akihiro
Nakajima, Katsuyuki
Mabuchi, Hiroshi
Yamagishi, Masakazu
Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy
title Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy
title_full Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy
title_fullStr Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy
title_full_unstemmed Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy
title_short Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy
title_sort changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818918/
https://www.ncbi.nlm.nih.gov/pubmed/27039080
http://dx.doi.org/10.1186/s12944-016-0238-z
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