Changes in ultracentrifugally separated plasma lipoprotein subfractions in patients with polygenic hypercholesterolemia, familial combined hyperlipoproteinemia, and familial hypercholesterolemia after treatment with atorvastatin

Koichiro Honma, Yasuhiko Homma, Tadashi Yoshida, Hideki Ozawa, Yutaka Shiina, Shu Wakino, Koichi Hayashi, Hiroshi Itoh, Shingo Hori

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Abstract

Background Plasma levels of low-density lipoproteins (LDLs) are decreased through stimulation of their hepatic uptake by statins via an LDL receptor. However, it is unclear whether statins equally stimulate the hepatic uptake of all LDL subfractions. Objective We compared the effects of atorvastatin on 3 LDL subfractions, and their associations with LDL-receptor activities, in Japanese patients with polygenic hypercholesterolemia (PHC), familial combined hyperlipoproteinemia (FCHL), and familial hypercholesterolemia (FH). Materials and methods Atorvastatin was administered to patients with PHC (n = 11), FCHL (n = 16), and FH (n = 13). We measured plasma levels of lipids, remnant-like particle cholesterol, apoproteins, and cholesterol in lipoprotein fractions. Sequential ultracentrifugation was performed to subfractionate the plasma lipoproteins, and lymphocyte LDL-receptor activities were estimated using flow cytometry. Results The average daily dosage of atorvastatin was 10, 27, and 40 mg in patients with PHC, FCHL, and FH, respectively; after 12 months of atorvastatin treatment, LDL cholesterol (LDL-C) plasma levels decreased by 44%, 50%, and 53%, respectively (all, P <.0001). Atorvastatin reduced low-density LDL-C plasma levels in patients with PHC (48% reduction), FCHL (53%), and FH (46%) (all, P <.0001). Plasma levels of medium-density and high-density LDL-C were also significantly reduced in the 3 patient groups (all, P ≤.0147). LDL-receptor activity was negatively correlated with baseline levels of medium-density LDL-C and with the decreases in plasma md-LDL-C levels. Conclusion Atorvastatin decreased the levels of the 3 LDL fractions. The md-LDL decrease appeared to be mainly because of stimulation of LDL-receptor activity.

Original languageEnglish
Pages (from-to)210-216
Number of pages7
JournalJournal of Clinical Lipidology
Volume9
Issue number2
DOIs
Publication statusPublished - 2015 Mar 1

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Hyperlipoproteinemia Type II
Hypercholesterolemia
LDL Lipoproteins
Lipoproteins
LDL Receptors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Therapeutics
Atorvastatin Calcium
Apoproteins
Liver
Ultracentrifugation
HDL Lipoproteins
LDL Cholesterol
Flow Cytometry
Lymphocytes
Lipids

Keywords

  • Atorvastatin
  • Familial combined hyperlipoproteinemia
  • Familial hypercholesterolemia
  • Hypercholesterolemia
  • LDL-receptor activity
  • Lipoprotein subfractions
  • Polygenic hypercholesterolemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Nutrition and Dietetics

Cite this

@article{7b4645c8f6444628bfd5a1f63846e849,
title = "Changes in ultracentrifugally separated plasma lipoprotein subfractions in patients with polygenic hypercholesterolemia, familial combined hyperlipoproteinemia, and familial hypercholesterolemia after treatment with atorvastatin",
abstract = "Background Plasma levels of low-density lipoproteins (LDLs) are decreased through stimulation of their hepatic uptake by statins via an LDL receptor. However, it is unclear whether statins equally stimulate the hepatic uptake of all LDL subfractions. Objective We compared the effects of atorvastatin on 3 LDL subfractions, and their associations with LDL-receptor activities, in Japanese patients with polygenic hypercholesterolemia (PHC), familial combined hyperlipoproteinemia (FCHL), and familial hypercholesterolemia (FH). Materials and methods Atorvastatin was administered to patients with PHC (n = 11), FCHL (n = 16), and FH (n = 13). We measured plasma levels of lipids, remnant-like particle cholesterol, apoproteins, and cholesterol in lipoprotein fractions. Sequential ultracentrifugation was performed to subfractionate the plasma lipoproteins, and lymphocyte LDL-receptor activities were estimated using flow cytometry. Results The average daily dosage of atorvastatin was 10, 27, and 40 mg in patients with PHC, FCHL, and FH, respectively; after 12 months of atorvastatin treatment, LDL cholesterol (LDL-C) plasma levels decreased by 44{\%}, 50{\%}, and 53{\%}, respectively (all, P <.0001). Atorvastatin reduced low-density LDL-C plasma levels in patients with PHC (48{\%} reduction), FCHL (53{\%}), and FH (46{\%}) (all, P <.0001). Plasma levels of medium-density and high-density LDL-C were also significantly reduced in the 3 patient groups (all, P ≤.0147). LDL-receptor activity was negatively correlated with baseline levels of medium-density LDL-C and with the decreases in plasma md-LDL-C levels. Conclusion Atorvastatin decreased the levels of the 3 LDL fractions. The md-LDL decrease appeared to be mainly because of stimulation of LDL-receptor activity.",
keywords = "Atorvastatin, Familial combined hyperlipoproteinemia, Familial hypercholesterolemia, Hypercholesterolemia, LDL-receptor activity, Lipoprotein subfractions, Polygenic hypercholesterolemia",
author = "Koichiro Honma and Yasuhiko Homma and Tadashi Yoshida and Hideki Ozawa and Yutaka Shiina and Shu Wakino and Koichi Hayashi and Hiroshi Itoh and Shingo Hori",
year = "2015",
month = "3",
day = "1",
doi = "10.1016/j.jacl.2014.12.007",
language = "English",
volume = "9",
pages = "210--216",
journal = "Journal of Clinical Lipidology",
issn = "1933-2874",
publisher = "Elsevier BV",
number = "2",

}

TY - JOUR

T1 - Changes in ultracentrifugally separated plasma lipoprotein subfractions in patients with polygenic hypercholesterolemia, familial combined hyperlipoproteinemia, and familial hypercholesterolemia after treatment with atorvastatin

AU - Honma, Koichiro

AU - Homma, Yasuhiko

AU - Yoshida, Tadashi

AU - Ozawa, Hideki

AU - Shiina, Yutaka

AU - Wakino, Shu

AU - Hayashi, Koichi

AU - Itoh, Hiroshi

AU - Hori, Shingo

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Background Plasma levels of low-density lipoproteins (LDLs) are decreased through stimulation of their hepatic uptake by statins via an LDL receptor. However, it is unclear whether statins equally stimulate the hepatic uptake of all LDL subfractions. Objective We compared the effects of atorvastatin on 3 LDL subfractions, and their associations with LDL-receptor activities, in Japanese patients with polygenic hypercholesterolemia (PHC), familial combined hyperlipoproteinemia (FCHL), and familial hypercholesterolemia (FH). Materials and methods Atorvastatin was administered to patients with PHC (n = 11), FCHL (n = 16), and FH (n = 13). We measured plasma levels of lipids, remnant-like particle cholesterol, apoproteins, and cholesterol in lipoprotein fractions. Sequential ultracentrifugation was performed to subfractionate the plasma lipoproteins, and lymphocyte LDL-receptor activities were estimated using flow cytometry. Results The average daily dosage of atorvastatin was 10, 27, and 40 mg in patients with PHC, FCHL, and FH, respectively; after 12 months of atorvastatin treatment, LDL cholesterol (LDL-C) plasma levels decreased by 44%, 50%, and 53%, respectively (all, P <.0001). Atorvastatin reduced low-density LDL-C plasma levels in patients with PHC (48% reduction), FCHL (53%), and FH (46%) (all, P <.0001). Plasma levels of medium-density and high-density LDL-C were also significantly reduced in the 3 patient groups (all, P ≤.0147). LDL-receptor activity was negatively correlated with baseline levels of medium-density LDL-C and with the decreases in plasma md-LDL-C levels. Conclusion Atorvastatin decreased the levels of the 3 LDL fractions. The md-LDL decrease appeared to be mainly because of stimulation of LDL-receptor activity.

AB - Background Plasma levels of low-density lipoproteins (LDLs) are decreased through stimulation of their hepatic uptake by statins via an LDL receptor. However, it is unclear whether statins equally stimulate the hepatic uptake of all LDL subfractions. Objective We compared the effects of atorvastatin on 3 LDL subfractions, and their associations with LDL-receptor activities, in Japanese patients with polygenic hypercholesterolemia (PHC), familial combined hyperlipoproteinemia (FCHL), and familial hypercholesterolemia (FH). Materials and methods Atorvastatin was administered to patients with PHC (n = 11), FCHL (n = 16), and FH (n = 13). We measured plasma levels of lipids, remnant-like particle cholesterol, apoproteins, and cholesterol in lipoprotein fractions. Sequential ultracentrifugation was performed to subfractionate the plasma lipoproteins, and lymphocyte LDL-receptor activities were estimated using flow cytometry. Results The average daily dosage of atorvastatin was 10, 27, and 40 mg in patients with PHC, FCHL, and FH, respectively; after 12 months of atorvastatin treatment, LDL cholesterol (LDL-C) plasma levels decreased by 44%, 50%, and 53%, respectively (all, P <.0001). Atorvastatin reduced low-density LDL-C plasma levels in patients with PHC (48% reduction), FCHL (53%), and FH (46%) (all, P <.0001). Plasma levels of medium-density and high-density LDL-C were also significantly reduced in the 3 patient groups (all, P ≤.0147). LDL-receptor activity was negatively correlated with baseline levels of medium-density LDL-C and with the decreases in plasma md-LDL-C levels. Conclusion Atorvastatin decreased the levels of the 3 LDL fractions. The md-LDL decrease appeared to be mainly because of stimulation of LDL-receptor activity.

KW - Atorvastatin

KW - Familial combined hyperlipoproteinemia

KW - Familial hypercholesterolemia

KW - Hypercholesterolemia

KW - LDL-receptor activity

KW - Lipoprotein subfractions

KW - Polygenic hypercholesterolemia

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U2 - 10.1016/j.jacl.2014.12.007

DO - 10.1016/j.jacl.2014.12.007

M3 - Article

VL - 9

SP - 210

EP - 216

JO - Journal of Clinical Lipidology

JF - Journal of Clinical Lipidology

SN - 1933-2874

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ER -