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Short-Term Effects of Extended-Release Niacin With and Without the Addition of Laropiprant on Endothelial Function in Individuals With Low HDL-C: A Randomized, Controlled Crossover Trial

Abstract Background Reduced plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with vulnerability to oxidative stress and propensity to endothelial dysfunction. Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong an... Full description

Journal Title: Clinical therapeutics 2014, Vol.36 (6), p.961-966
Main Author: Nasser Figueiredo, Valeria, PhD
Other Authors: Vendrame, Felipe , Colontoni, Bruno A., MD , Quinaglia, Thiago, MD, PhD , Roberto Matos-Souza, Jose, MD, PhD , Azevedo Moura, Filipe, MD , Coelho, Otavio R., MD, PhD , de Faria, Eliana C., MD, PhD , Sposito, Andrei C., MD, PhD
Format: Electronic Article Electronic Article
Language: English
Subjects:
HDL
Quelle: Alma/SFX Local Collection
Publisher: Bridgewater, NJ: EM Inc USA
ID: ISSN: 0149-2918
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title: Short-Term Effects of Extended-Release Niacin With and Without the Addition of Laropiprant on Endothelial Function in Individuals With Low HDL-C: A Randomized, Controlled Crossover Trial
format: Article
creator:
  • Nasser Figueiredo, Valeria, PhD
  • Vendrame, Felipe
  • Colontoni, Bruno A., MD
  • Quinaglia, Thiago, MD, PhD
  • Roberto Matos-Souza, Jose, MD, PhD
  • Azevedo Moura, Filipe, MD
  • Coelho, Otavio R., MD, PhD
  • de Faria, Eliana C., MD, PhD
  • Sposito, Andrei C., MD, PhD
subjects:
  • Aged
  • Apolipoproteins
  • Biological and medical sciences
  • Cholesterol
  • Cholesterol, HDL - blood
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Disease
  • Double-Blind Method
  • Dyslipidemias - drug therapy
  • endothelial function
  • Endothelium
  • Endothelium, Vascular - drug effects
  • Female
  • Glucose
  • HDL
  • Humans
  • Hypolipidemic Agents - therapeutic use
  • Indoles - therapeutic use
  • Internal Medicine
  • laropiprant
  • Lipoproteins
  • Male
  • Medical Education
  • Medical sciences
  • Middle Aged
  • Niacin
  • Niacin - administration & dosage
  • Niacin - pharmacology
  • Pharmacology. Drug treatments
  • Plasma
  • Proteins
  • Studies
  • Triglycerides
  • Vasodilation - drug effects
  • Vasodilator Agents - administration & dosage
  • Vasodilator Agents - pharmacology
  • Veins & arteries
  • Vitamin B
ispartof: Clinical therapeutics, 2014, Vol.36 (6), p.961-966
description: Abstract Background Reduced plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with vulnerability to oxidative stress and propensity to endothelial dysfunction. Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong anti-inflammatory and antioxidative effects, as well as induces immediate production of prostaglandin D2, leading to endothelial vasodilation. Objective This study investigated the short-term effects of extended-release niacin (ERN) administered with or without the prostaglandin D2 receptor antagonist laropiprant on endothelial function in patients with low HDL-C. Methods Asymptomatic men and women aged between 20 and 60 years who had plasma HDL-C levels
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0149-2918
fulltext: fulltext
issn:
  • 0149-2918
  • 1879-114X
url: Link


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titleShort-Term Effects of Extended-Release Niacin With and Without the Addition of Laropiprant on Endothelial Function in Individuals With Low HDL-C: A Randomized, Controlled Crossover Trial
sourceAlma/SFX Local Collection
creatorNasser Figueiredo, Valeria, PhD ; Vendrame, Felipe ; Colontoni, Bruno A., MD ; Quinaglia, Thiago, MD, PhD ; Roberto Matos-Souza, Jose, MD, PhD ; Azevedo Moura, Filipe, MD ; Coelho, Otavio R., MD, PhD ; de Faria, Eliana C., MD, PhD ; Sposito, Andrei C., MD, PhD
creatorcontribNasser Figueiredo, Valeria, PhD ; Vendrame, Felipe ; Colontoni, Bruno A., MD ; Quinaglia, Thiago, MD, PhD ; Roberto Matos-Souza, Jose, MD, PhD ; Azevedo Moura, Filipe, MD ; Coelho, Otavio R., MD, PhD ; de Faria, Eliana C., MD, PhD ; Sposito, Andrei C., MD, PhD
descriptionAbstract Background Reduced plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with vulnerability to oxidative stress and propensity to endothelial dysfunction. Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong anti-inflammatory and antioxidative effects, as well as induces immediate production of prostaglandin D2, leading to endothelial vasodilation. Objective This study investigated the short-term effects of extended-release niacin (ERN) administered with or without the prostaglandin D2 receptor antagonist laropiprant on endothelial function in patients with low HDL-C. Methods Asymptomatic men and women aged between 20 and 60 years who had plasma HDL-C levels <40 mg/dL were treated with ERN monotherapy 1 g/d or ERN/laropiprant 1 g/20 mg (ERN/LRP) in a crossover study design. The sequence of treatments was decided by simple randomization. Plasma samples and flow-mediated dilation (FMD) of the brachial artery were obtained at baseline, day 7 of treatment period 1, day 7 of washout, and day 7 of treatment period 2. Results Eighteen patients were enrolled (mean [SD] age, 42 [17] years; 11 men). Triglyceride levels decreased by 4% and 3%, and HDL size decreased by 5.8% and 6.2%, with ERN and ERN/LRP, respectively (both, P < 0.05). There were no changes in HDL-C levels or in cholesteryl esterase transfer protein activity with either treatment. The median increases in FMD were 4.5% and 4.1% with ERN and ERN/LRP, which receded after washout. On intergroup analysis, there were no differences with respect to variation in plasma HDL-C, triglycerides, C-reactive protein, direct bilirubin, or FMD. Conclusions In these patients, the addition of laropiprant did not influence the effects of niacin on endothelial function. Based on these findings, short-term niacin treatment might improve endothelial function in patients with low HDL-C levels. ClinicalTrials.gov identifier: NCT01942291.
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1EISSN: 1879-114X
2DOI: 10.1016/j.clinthera.2014.03.012
3PMID: 24768191
languageeng
publisherBridgewater, NJ: EM Inc USA
subjectAged ; Apolipoproteins ; Biological and medical sciences ; Cholesterol ; Cholesterol, HDL - blood ; Cross-Over Studies ; Delayed-Action Preparations ; Disease ; Double-Blind Method ; Dyslipidemias - drug therapy ; endothelial function ; Endothelium ; Endothelium, Vascular - drug effects ; Female ; Glucose ; HDL ; Humans ; Hypolipidemic Agents - therapeutic use ; Indoles - therapeutic use ; Internal Medicine ; laropiprant ; Lipoproteins ; Male ; Medical Education ; Medical sciences ; Middle Aged ; Niacin ; Niacin - administration & dosage ; Niacin - pharmacology ; Pharmacology. Drug treatments ; Plasma ; Proteins ; Studies ; Triglycerides ; Vasodilation - drug effects ; Vasodilator Agents - administration & dosage ; Vasodilator Agents - pharmacology ; Veins & arteries ; Vitamin B
ispartofClinical therapeutics, 2014, Vol.36 (6), p.961-966
rights
0Elsevier HS Journals, Inc.
12014 Elsevier HS Journals, Inc.
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5Copyright Elsevier Limited Jun 2014
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0Nasser Figueiredo, Valeria, PhD
1Vendrame, Felipe
2Colontoni, Bruno A., MD
3Quinaglia, Thiago, MD, PhD
4Roberto Matos-Souza, Jose, MD, PhD
5Azevedo Moura, Filipe, MD
6Coelho, Otavio R., MD, PhD
7de Faria, Eliana C., MD, PhD
8Sposito, Andrei C., MD, PhD
title
0Short-Term Effects of Extended-Release Niacin With and Without the Addition of Laropiprant on Endothelial Function in Individuals With Low HDL-C: A Randomized, Controlled Crossover Trial
1Clinical therapeutics
addtitleClin Ther
descriptionAbstract Background Reduced plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with vulnerability to oxidative stress and propensity to endothelial dysfunction. Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong anti-inflammatory and antioxidative effects, as well as induces immediate production of prostaglandin D2, leading to endothelial vasodilation. Objective This study investigated the short-term effects of extended-release niacin (ERN) administered with or without the prostaglandin D2 receptor antagonist laropiprant on endothelial function in patients with low HDL-C. Methods Asymptomatic men and women aged between 20 and 60 years who had plasma HDL-C levels <40 mg/dL were treated with ERN monotherapy 1 g/d or ERN/laropiprant 1 g/20 mg (ERN/LRP) in a crossover study design. The sequence of treatments was decided by simple randomization. Plasma samples and flow-mediated dilation (FMD) of the brachial artery were obtained at baseline, day 7 of treatment period 1, day 7 of washout, and day 7 of treatment period 2. Results Eighteen patients were enrolled (mean [SD] age, 42 [17] years; 11 men). Triglyceride levels decreased by 4% and 3%, and HDL size decreased by 5.8% and 6.2%, with ERN and ERN/LRP, respectively (both, P < 0.05). There were no changes in HDL-C levels or in cholesteryl esterase transfer protein activity with either treatment. The median increases in FMD were 4.5% and 4.1% with ERN and ERN/LRP, which receded after washout. On intergroup analysis, there were no differences with respect to variation in plasma HDL-C, triglycerides, C-reactive protein, direct bilirubin, or FMD. Conclusions In these patients, the addition of laropiprant did not influence the effects of niacin on endothelial function. Based on these findings, short-term niacin treatment might improve endothelial function in patients with low HDL-C levels. ClinicalTrials.gov identifier: NCT01942291.
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2Biological and medical sciences
3Cholesterol
4Cholesterol, HDL - blood
5Cross-Over Studies
6Delayed-Action Preparations
7Disease
8Double-Blind Method
9Dyslipidemias - drug therapy
10endothelial function
11Endothelium
12Endothelium, Vascular - drug effects
13Female
14Glucose
15HDL
16Humans
17Hypolipidemic Agents - therapeutic use
18Indoles - therapeutic use
19Internal Medicine
20laropiprant
21Lipoproteins
22Male
23Medical Education
24Medical sciences
25Middle Aged
26Niacin
27Niacin - administration & dosage
28Niacin - pharmacology
29Pharmacology. Drug treatments
30Plasma
31Proteins
32Studies
33Triglycerides
34Vasodilation - drug effects
35Vasodilator Agents - administration & dosage
36Vasodilator Agents - pharmacology
37Veins & arteries
38Vitamin B
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titleShort-Term Effects of Extended-Release Niacin With and Without the Addition of Laropiprant on Endothelial Function in Individuals With Low HDL-C: A Randomized, Controlled Crossover Trial
authorNasser Figueiredo, Valeria, PhD ; Vendrame, Felipe ; Colontoni, Bruno A., MD ; Quinaglia, Thiago, MD, PhD ; Roberto Matos-Souza, Jose, MD, PhD ; Azevedo Moura, Filipe, MD ; Coelho, Otavio R., MD, PhD ; de Faria, Eliana C., MD, PhD ; Sposito, Andrei C., MD, PhD
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1Apolipoproteins
2Biological and medical sciences
3Cholesterol
4Cholesterol, HDL - blood
5Cross-Over Studies
6Delayed-Action Preparations
7Disease
8Double-Blind Method
9Dyslipidemias - drug therapy
10endothelial function
11Endothelium
12Endothelium, Vascular - drug effects
13Female
14Glucose
15HDL
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17Hypolipidemic Agents - therapeutic use
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22Male
23Medical Education
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31Proteins
32Studies
33Triglycerides
34Vasodilation - drug effects
35Vasodilator Agents - administration & dosage
36Vasodilator Agents - pharmacology
37Veins & arteries
38Vitamin B
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4Roberto Matos-Souza, Jose, MD, PhD
5Azevedo Moura, Filipe, MD
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atitleShort-Term Effects of Extended-Release Niacin With and Without the Addition of Laropiprant on Endothelial Function in Individuals With Low HDL-C: A Randomized, Controlled Crossover Trial
jtitleClinical therapeutics
addtitleClin Ther
date2014
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abstractAbstract Background Reduced plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with vulnerability to oxidative stress and propensity to endothelial dysfunction. Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong anti-inflammatory and antioxidative effects, as well as induces immediate production of prostaglandin D2, leading to endothelial vasodilation. Objective This study investigated the short-term effects of extended-release niacin (ERN) administered with or without the prostaglandin D2 receptor antagonist laropiprant on endothelial function in patients with low HDL-C. Methods Asymptomatic men and women aged between 20 and 60 years who had plasma HDL-C levels <40 mg/dL were treated with ERN monotherapy 1 g/d or ERN/laropiprant 1 g/20 mg (ERN/LRP) in a crossover study design. The sequence of treatments was decided by simple randomization. Plasma samples and flow-mediated dilation (FMD) of the brachial artery were obtained at baseline, day 7 of treatment period 1, day 7 of washout, and day 7 of treatment period 2. Results Eighteen patients were enrolled (mean [SD] age, 42 [17] years; 11 men). Triglyceride levels decreased by 4% and 3%, and HDL size decreased by 5.8% and 6.2%, with ERN and ERN/LRP, respectively (both, P < 0.05). There were no changes in HDL-C levels or in cholesteryl esterase transfer protein activity with either treatment. The median increases in FMD were 4.5% and 4.1% with ERN and ERN/LRP, which receded after washout. On intergroup analysis, there were no differences with respect to variation in plasma HDL-C, triglycerides, C-reactive protein, direct bilirubin, or FMD. Conclusions In these patients, the addition of laropiprant did not influence the effects of niacin on endothelial function. Based on these findings, short-term niacin treatment might improve endothelial function in patients with low HDL-C levels. ClinicalTrials.gov identifier: NCT01942291.
copBridgewater, NJ
pubEM Inc USA
pmid24768191
doi10.1016/j.clinthera.2014.03.012