Effect of extended-release niacin on high-density lipoprotein (HDL) functionality, lipoprotein metabolism, and mediators of vascular inflammation in statin-treated patients

Rahul Yadav, Yifen Liu, See Kwok, Salam Hama, Michael France, Ruth Eatough, Phil Pemberton, Jonathan Schofield, Tarza J. Siahmansur, Rayaz Malik, Basil A. Ammori, Basil Issa, Naveed Younis, Rachelle Donn, Adam Stevens, Paul Durrington, Handrean Soran

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background-The aim of this study was to explore the influence of extended-release niacin/laropiprant (ERN/LRP) versus placebo on high-density lipoprotein (HDL) antioxidant function, cholesterol efflux, apolipoprotein B100 (apoB)-containing lipoproteins, and mediators of vascular inflammation associated with 15% increase in high-density lipoprotein cholesterol (HDL-C). Study patients had persistent dyslipidemia despite receiving high-dose statin treatment. Methods and Results-In a randomized double-blind, placebo-controlled, crossover trial, we compared the effect of ERN/LRP with placebo in 27 statin-treated dyslipidemic patients who had not achieved National Cholesterol Education Program-ATP III targets for low-density lipoprotein cholesterol (LDL-C). We measured fasting lipid profile, apolipoproteins, cholesteryl ester transfer protein (CETP) activity, paraoxonase 1 (PON1) activity, small dense LDL apoB (sdLDL-apoB), oxidized LDL (oxLDL), glycated apoB (glycapoB), lipoprotein phospholipase A2 (Lp-PLA2), lysophosphatidyl choline (lyso-PC), macrophage chemoattractant protein (MCP1), serum amyloid A (SAA) and myeloperoxidase (MPO). We also examined the capacity of HDL to protect LDL from in vitro oxidation and the percentage cholesterol efflux mediated by apoB depleted serum. ERN/LRP was associated with an 18% increase in HDL-C levels compared to placebo (1.55 versus 1.31 mmol/L, P<0.0001). There were significant reductions in total cholesterol, triglycerides, LDL cholesterol, total serum apoB, lipoprotein (a), CETP activity, oxLDL, Lp-PLA2, lyso-PC, MCP1, and SAA, but no significant changes in glyc-apoB or sdLDL-apoB concentration. There was a modest increase in cholesterol efflux function of HDL (19.5%, P=0.045), but no change in the antioxidant capacity of HDL in vitro or PON1 activity. Conclusions-ERN/LRP reduces LDL-associated mediators of vascular inflammation, but has varied effects on HDL functionality and LDL quality, which may counter its HDL-C-raising effect.

Original languageEnglish
Article numbere001508
JournalJournal of the American Heart Association
Volume4
Issue number9
DOIs
Publication statusPublished - 1 Sep 2015
Externally publishedYes

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Inflammation Mediators
Apolipoproteins
Niacin
HDL Lipoproteins
Lipoproteins
Blood Vessels
Cholesterol
Placebos
Cholesterol Ester Transfer Proteins
Aryldialkylphosphatase
Serum Amyloid A Protein
Phospholipases A2
Choline
LDL Cholesterol
Antioxidants
Lipoprotein(a)
Chemotactic Factors
Apolipoproteins B
Dyslipidemias

Keywords

  • Cholesterol efflux
  • Extended-release niacin
  • HDL functionality
  • Inflammation
  • Laropiprant
  • LDL quality
  • Oxidation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effect of extended-release niacin on high-density lipoprotein (HDL) functionality, lipoprotein metabolism, and mediators of vascular inflammation in statin-treated patients. / Yadav, Rahul; Liu, Yifen; Kwok, See; Hama, Salam; France, Michael; Eatough, Ruth; Pemberton, Phil; Schofield, Jonathan; Siahmansur, Tarza J.; Malik, Rayaz; Ammori, Basil A.; Issa, Basil; Younis, Naveed; Donn, Rachelle; Stevens, Adam; Durrington, Paul; Soran, Handrean.

In: Journal of the American Heart Association, Vol. 4, No. 9, e001508, 01.09.2015.

Research output: Contribution to journalArticle

Yadav, R, Liu, Y, Kwok, S, Hama, S, France, M, Eatough, R, Pemberton, P, Schofield, J, Siahmansur, TJ, Malik, R, Ammori, BA, Issa, B, Younis, N, Donn, R, Stevens, A, Durrington, P & Soran, H 2015, 'Effect of extended-release niacin on high-density lipoprotein (HDL) functionality, lipoprotein metabolism, and mediators of vascular inflammation in statin-treated patients', Journal of the American Heart Association, vol. 4, no. 9, e001508. https://doi.org/10.1161/JAHA.114.001508
Yadav, Rahul ; Liu, Yifen ; Kwok, See ; Hama, Salam ; France, Michael ; Eatough, Ruth ; Pemberton, Phil ; Schofield, Jonathan ; Siahmansur, Tarza J. ; Malik, Rayaz ; Ammori, Basil A. ; Issa, Basil ; Younis, Naveed ; Donn, Rachelle ; Stevens, Adam ; Durrington, Paul ; Soran, Handrean. / Effect of extended-release niacin on high-density lipoprotein (HDL) functionality, lipoprotein metabolism, and mediators of vascular inflammation in statin-treated patients. In: Journal of the American Heart Association. 2015 ; Vol. 4, No. 9.
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abstract = "Background-The aim of this study was to explore the influence of extended-release niacin/laropiprant (ERN/LRP) versus placebo on high-density lipoprotein (HDL) antioxidant function, cholesterol efflux, apolipoprotein B100 (apoB)-containing lipoproteins, and mediators of vascular inflammation associated with 15{\%} increase in high-density lipoprotein cholesterol (HDL-C). Study patients had persistent dyslipidemia despite receiving high-dose statin treatment. Methods and Results-In a randomized double-blind, placebo-controlled, crossover trial, we compared the effect of ERN/LRP with placebo in 27 statin-treated dyslipidemic patients who had not achieved National Cholesterol Education Program-ATP III targets for low-density lipoprotein cholesterol (LDL-C). We measured fasting lipid profile, apolipoproteins, cholesteryl ester transfer protein (CETP) activity, paraoxonase 1 (PON1) activity, small dense LDL apoB (sdLDL-apoB), oxidized LDL (oxLDL), glycated apoB (glycapoB), lipoprotein phospholipase A2 (Lp-PLA2), lysophosphatidyl choline (lyso-PC), macrophage chemoattractant protein (MCP1), serum amyloid A (SAA) and myeloperoxidase (MPO). We also examined the capacity of HDL to protect LDL from in vitro oxidation and the percentage cholesterol efflux mediated by apoB depleted serum. ERN/LRP was associated with an 18{\%} increase in HDL-C levels compared to placebo (1.55 versus 1.31 mmol/L, P<0.0001). There were significant reductions in total cholesterol, triglycerides, LDL cholesterol, total serum apoB, lipoprotein (a), CETP activity, oxLDL, Lp-PLA2, lyso-PC, MCP1, and SAA, but no significant changes in glyc-apoB or sdLDL-apoB concentration. There was a modest increase in cholesterol efflux function of HDL (19.5{\%}, P=0.045), but no change in the antioxidant capacity of HDL in vitro or PON1 activity. Conclusions-ERN/LRP reduces LDL-associated mediators of vascular inflammation, but has varied effects on HDL functionality and LDL quality, which may counter its HDL-C-raising effect.",
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AU - Yadav, Rahul

AU - Liu, Yifen

AU - Kwok, See

AU - Hama, Salam

AU - France, Michael

AU - Eatough, Ruth

AU - Pemberton, Phil

AU - Schofield, Jonathan

AU - Siahmansur, Tarza J.

AU - Malik, Rayaz

AU - Ammori, Basil A.

AU - Issa, Basil

AU - Younis, Naveed

AU - Donn, Rachelle

AU - Stevens, Adam

AU - Durrington, Paul

AU - Soran, Handrean

PY - 2015/9/1

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N2 - Background-The aim of this study was to explore the influence of extended-release niacin/laropiprant (ERN/LRP) versus placebo on high-density lipoprotein (HDL) antioxidant function, cholesterol efflux, apolipoprotein B100 (apoB)-containing lipoproteins, and mediators of vascular inflammation associated with 15% increase in high-density lipoprotein cholesterol (HDL-C). Study patients had persistent dyslipidemia despite receiving high-dose statin treatment. Methods and Results-In a randomized double-blind, placebo-controlled, crossover trial, we compared the effect of ERN/LRP with placebo in 27 statin-treated dyslipidemic patients who had not achieved National Cholesterol Education Program-ATP III targets for low-density lipoprotein cholesterol (LDL-C). We measured fasting lipid profile, apolipoproteins, cholesteryl ester transfer protein (CETP) activity, paraoxonase 1 (PON1) activity, small dense LDL apoB (sdLDL-apoB), oxidized LDL (oxLDL), glycated apoB (glycapoB), lipoprotein phospholipase A2 (Lp-PLA2), lysophosphatidyl choline (lyso-PC), macrophage chemoattractant protein (MCP1), serum amyloid A (SAA) and myeloperoxidase (MPO). We also examined the capacity of HDL to protect LDL from in vitro oxidation and the percentage cholesterol efflux mediated by apoB depleted serum. ERN/LRP was associated with an 18% increase in HDL-C levels compared to placebo (1.55 versus 1.31 mmol/L, P<0.0001). There were significant reductions in total cholesterol, triglycerides, LDL cholesterol, total serum apoB, lipoprotein (a), CETP activity, oxLDL, Lp-PLA2, lyso-PC, MCP1, and SAA, but no significant changes in glyc-apoB or sdLDL-apoB concentration. There was a modest increase in cholesterol efflux function of HDL (19.5%, P=0.045), but no change in the antioxidant capacity of HDL in vitro or PON1 activity. Conclusions-ERN/LRP reduces LDL-associated mediators of vascular inflammation, but has varied effects on HDL functionality and LDL quality, which may counter its HDL-C-raising effect.

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KW - Cholesterol efflux

KW - Extended-release niacin

KW - HDL functionality

KW - Inflammation

KW - Laropiprant

KW - LDL quality

KW - Oxidation

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