Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia

Rgia A. Othman, Semone B. Myrie, David Mymin, Jean-Baptiste Roullet, Robert D. Steiner, Peter J H Jones

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background and aims Sitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported. Methods Sitosterolemia patients (n = 8) were taken off EZE for 14 weeks (OFF EZE) and placed on EZE (10 mg/d) for 14 weeks (ON EZE). Serum lipids were measured enzymatically and lipoprotein subclasses were assessed by polyacrylamide gel electrophoresis. Results EZE reduced (p < 0.05) total sterols (−12.5 ± 4.1%) and LDL-sterol (−22.7 ± 5.7%) and its sterol mass of large VLDL (−24.4 ± 4.5%), VLDL remnants (−21.1 ± 7.9%) and large IDL (−22.4 ± 7.2%) compared to OFF EZE. EZE did not affect large LDL subclasses or mean LDL particle size (273.8 ± 0.6 vs. 274.6 ± 0.3 Å). EZE increased HDL-sterol (25.5 ± 8.0%, p = 0.008) including intermediate (34 ± 14%, p = 0.02) and large (33 ± 16%, p = 0.06) HDL. EZE reduced non-HDL-sterol (−21.8± 5.0%), total sterols/HDL (−28.2 ± 5.5%) and TG/HDL (−27.4 ± 6.5%, all p < 0.01). Conclusions EZE improves VLDL and HDL subfraction distribution, thereby reducing the atherogenic lipid profile, thus providing potential clinical benefit in sitosterolemia beyond TC and PS reduction.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalAtherosclerosis
Volume260
DOIs
StatePublished - May 1 2017

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HDL Lipoproteins
Sterols
LDL Lipoproteins
VLDL Lipoproteins
Phytosterols
Lipoproteins
Cholesterol
IDL Lipoproteins
Sitosterolemia
Ezetimibe
Lipids
Particle Size
Polyacrylamide Gel Electrophoresis
Atherosclerosis
Triglycerides

Keywords

  • Ezetimibe
  • HDL subclasses
  • LDL cholesterol
  • LDL subclasses
  • Mean LDL particle size
  • Non-HDL cholesterol
  • Sitosterolemia
  • Sterols

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Othman, R. A., Myrie, S. B., Mymin, D., Roullet, J-B., Steiner, R. D., & Jones, P. J. H. (2017). Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia. Atherosclerosis, 260, 27-33. https://doi.org/10.1016/j.atherosclerosis.2017.03.015

Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia. / Othman, Rgia A.; Myrie, Semone B.; Mymin, David; Roullet, Jean-Baptiste; Steiner, Robert D.; Jones, Peter J H.

In: Atherosclerosis, Vol. 260, 01.05.2017, p. 27-33.

Research output: Contribution to journalArticle

Othman, RA, Myrie, SB, Mymin, D, Roullet, J-B, Steiner, RD & Jones, PJH 2017, 'Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia', Atherosclerosis, vol. 260, pp. 27-33. https://doi.org/10.1016/j.atherosclerosis.2017.03.015
Othman, Rgia A. ; Myrie, Semone B. ; Mymin, David ; Roullet, Jean-Baptiste ; Steiner, Robert D. ; Jones, Peter J H. / Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia. In: Atherosclerosis. 2017 ; Vol. 260. pp. 27-33.
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AU - Othman, Rgia A.

AU - Myrie, Semone B.

AU - Mymin, David

AU - Roullet, Jean-Baptiste

AU - Steiner, Robert D.

AU - Jones, Peter J H

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Background and aims Sitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported. Methods Sitosterolemia patients (n = 8) were taken off EZE for 14 weeks (OFF EZE) and placed on EZE (10 mg/d) for 14 weeks (ON EZE). Serum lipids were measured enzymatically and lipoprotein subclasses were assessed by polyacrylamide gel electrophoresis. Results EZE reduced (p < 0.05) total sterols (−12.5 ± 4.1%) and LDL-sterol (−22.7 ± 5.7%) and its sterol mass of large VLDL (−24.4 ± 4.5%), VLDL remnants (−21.1 ± 7.9%) and large IDL (−22.4 ± 7.2%) compared to OFF EZE. EZE did not affect large LDL subclasses or mean LDL particle size (273.8 ± 0.6 vs. 274.6 ± 0.3 Å). EZE increased HDL-sterol (25.5 ± 8.0%, p = 0.008) including intermediate (34 ± 14%, p = 0.02) and large (33 ± 16%, p = 0.06) HDL. EZE reduced non-HDL-sterol (−21.8± 5.0%), total sterols/HDL (−28.2 ± 5.5%) and TG/HDL (−27.4 ± 6.5%, all p < 0.01). Conclusions EZE improves VLDL and HDL subfraction distribution, thereby reducing the atherogenic lipid profile, thus providing potential clinical benefit in sitosterolemia beyond TC and PS reduction.

AB - Background and aims Sitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported. Methods Sitosterolemia patients (n = 8) were taken off EZE for 14 weeks (OFF EZE) and placed on EZE (10 mg/d) for 14 weeks (ON EZE). Serum lipids were measured enzymatically and lipoprotein subclasses were assessed by polyacrylamide gel electrophoresis. Results EZE reduced (p < 0.05) total sterols (−12.5 ± 4.1%) and LDL-sterol (−22.7 ± 5.7%) and its sterol mass of large VLDL (−24.4 ± 4.5%), VLDL remnants (−21.1 ± 7.9%) and large IDL (−22.4 ± 7.2%) compared to OFF EZE. EZE did not affect large LDL subclasses or mean LDL particle size (273.8 ± 0.6 vs. 274.6 ± 0.3 Å). EZE increased HDL-sterol (25.5 ± 8.0%, p = 0.008) including intermediate (34 ± 14%, p = 0.02) and large (33 ± 16%, p = 0.06) HDL. EZE reduced non-HDL-sterol (−21.8± 5.0%), total sterols/HDL (−28.2 ± 5.5%) and TG/HDL (−27.4 ± 6.5%, all p < 0.01). Conclusions EZE improves VLDL and HDL subfraction distribution, thereby reducing the atherogenic lipid profile, thus providing potential clinical benefit in sitosterolemia beyond TC and PS reduction.

KW - Ezetimibe

KW - HDL subclasses

KW - LDL cholesterol

KW - LDL subclasses

KW - Mean LDL particle size

KW - Non-HDL cholesterol

KW - Sitosterolemia

KW - Sterols

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