Skip to main content
Erschienen in: Cardiovascular Drugs and Therapy 3/2017

28.07.2017 | ORIGINAL ARTICLE

Plasma Lipidome Analysis by Liquid Chromatography-High Resolution Mass Spectrometry and Ion Mobility of Hypertriglyceridemic Patients on Extended-Release Nicotinic Acid: a Pilot Study

verfasst von: Véronique Ferchaud-Roucher, Mikaël Croyal, Thomas Moyon, Yassine Zair, Michel Krempf, Khadija Ouguerram

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 3/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

Plasma high triacylglycerols and low HDL-C concentration are associated with increased cardiovascular events. Extended-release nicotinic acid (ERN) was shown to reduce plasma triacylglycerols and total cholesterol but also to markedly increase high-density lipoprotein-cholesterol (HDL-C). No data on the effect of ERN on different species of triacylglycerol, cholesteryl ester, and phospholipids are available. In this study, we applied a nontargeted lipidomic approach to investigate the plasma and lipoproteins lipids profile of hypertriglyceridemic patients treated with ERN or a placebo in order to identify new lipids markers associated with this treatment.

Methods

Eight hypertriglyceridemic patients enrolled in a crossover randomized trial with ERN for 8 weeks and treated with 2 g/day of ERN or a placebo. Ultra-performance liquid chromatography (UPLC) coupled to high-resolution mass spectrometry (HRMS) was used in mass spectrometry energy mode (HRMSE) combined with ion mobility spectrometry to characterize the plasma and very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) lipidome. The accuracy and precision of the method were validated on plasma samples.

Results

Compared to placebo, among 155 plasma lipids characterized using UPLC-ESI-HRMS, a multivariate analysis revealed a significant increase of lysophosphatidylcholine (LPC 20:5), a significant decrease of phosphatidylethanolamine (PE 16:0/22:3) and sphingomyelin (SM d18:1/22:0) and a decrease of triacylglycerol (TG 16:0/16:1/18:2) after ERN treatment. Analysis of these lipids in lipoproteins showed an increase of LPC (20:5) in HDL, a decrease of PE (16:0/22:3) in HDL and LDL, of SM (d18:1/22:0) in VLDL and LDL and of TG (16:0/16:1/18:2) in VLDL.

Conclusion

This lipidomic strategy characterized new specific lipid markers likely to be involved in the effect of ERN on cardiovascular risk opening a new strategy to analyze randomized controlled with this treatment.

Trial Registration

NCT01216956
Anhänge
Nur mit Berechtigung zugänglich
Literatur
3.
Zurück zum Zitat Bucher HC, Griffith LE, Guyatt GH. Systematic review on the risk and benefit of different cholesterol-lowering interventions. Arterioscler Thromb Vasc Biol. 1999;19:187–95.CrossRefPubMed Bucher HC, Griffith LE, Guyatt GH. Systematic review on the risk and benefit of different cholesterol-lowering interventions. Arterioscler Thromb Vasc Biol. 1999;19:187–95.CrossRefPubMed
4.
Zurück zum Zitat Alaswad K, Jr O'Keefe JH, Moe RM. Combination drug therapy for dyslipidemia. Curr Atheroscler Rep. 1999;1:44–9.CrossRefPubMed Alaswad K, Jr O'Keefe JH, Moe RM. Combination drug therapy for dyslipidemia. Curr Atheroscler Rep. 1999;1:44–9.CrossRefPubMed
5.
6.
Zurück zum Zitat Lam S, Shui G. Lipidomics as a principal tool for advancing research. J Genet Genomics. 2013;40:375–90.CrossRefPubMed Lam S, Shui G. Lipidomics as a principal tool for advancing research. J Genet Genomics. 2013;40:375–90.CrossRefPubMed
7.
8.
Zurück zum Zitat Dunn W, Broadhurst D, Begley P, et al. And the human serum metabolome (HUSERMET) consortium. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc. 2011;6:1060–83.CrossRefPubMed Dunn W, Broadhurst D, Begley P, et al. And the human serum metabolome (HUSERMET) consortium. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc. 2011;6:1060–83.CrossRefPubMed
9.
Zurück zum Zitat Zhou Q, Gao B, Zhang X, Xu Y, et al. Chemical profiling of triacylglycerols and diacylglycerols in cow milk fat by ultra-performance convergence chromatography combined with a quadrupole time-of-flight mass spectrometry. Food Chem. 2014;14:3199–204. Zhou Q, Gao B, Zhang X, Xu Y, et al. Chemical profiling of triacylglycerols and diacylglycerols in cow milk fat by ultra-performance convergence chromatography combined with a quadrupole time-of-flight mass spectrometry. Food Chem. 2014;14:3199–204.
10.
Zurück zum Zitat Roux A, Lison D, Junot C, et al. Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: a review. Clin Biochem. 2011;44:119–35.CrossRefPubMed Roux A, Lison D, Junot C, et al. Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: a review. Clin Biochem. 2011;44:119–35.CrossRefPubMed
11.
Zurück zum Zitat Gallart-Ayala H, Courant F, Severe S, et al. Versatile lipid profiling by liquid chromatography-high resolution mass spectrometry using all ion fragmentation and polarity switching. Preliminary application for serum samples phenotyping related to canine mammary cancer. Anal Chim Acta. 2013;79:675–83. Gallart-Ayala H, Courant F, Severe S, et al. Versatile lipid profiling by liquid chromatography-high resolution mass spectrometry using all ion fragmentation and polarity switching. Preliminary application for serum samples phenotyping related to canine mammary cancer. Anal Chim Acta. 2013;79:675–83.
12.
Zurück zum Zitat Sandra K, Pereira Ados S, Vanhoenacker G, et al. Comprehensive blood plasma lipidomics by liquid chromatography/quadrupole time-of-flight mass spectrometry. J Chromatogr A. 2010;1217:4087–99.CrossRefPubMed Sandra K, Pereira Ados S, Vanhoenacker G, et al. Comprehensive blood plasma lipidomics by liquid chromatography/quadrupole time-of-flight mass spectrometry. J Chromatogr A. 2010;1217:4087–99.CrossRefPubMed
13.
Zurück zum Zitat Plumb R, Johnson K, Rainville P, et al. UPLC/MSE; a new approach for generating molecular fragment information for biomarker structure elucidation. Rapid Commun Mass Spectrom. 2006;20:1989–94.CrossRefPubMed Plumb R, Johnson K, Rainville P, et al. UPLC/MSE; a new approach for generating molecular fragment information for biomarker structure elucidation. Rapid Commun Mass Spectrom. 2006;20:1989–94.CrossRefPubMed
14.
Zurück zum Zitat Creskey M, Li C, Wang J, et al. Simultaneous quantification of the viral antigens hemagglutinin and neuraminidase in influenza vaccines by LC-MSE. Vaccine. 2012;30:4762–70.CrossRefPubMed Creskey M, Li C, Wang J, et al. Simultaneous quantification of the viral antigens hemagglutinin and neuraminidase in influenza vaccines by LC-MSE. Vaccine. 2012;30:4762–70.CrossRefPubMed
15.
Zurück zum Zitat Fasciotti M, Sanvido G, Santos V, et al. Separation of isomeric disaccharides by traveling wave ion mobility mass spectrometry using CO2 as drift gas. J Mass Spectrom. 2012;47:1643–7.CrossRefPubMed Fasciotti M, Sanvido G, Santos V, et al. Separation of isomeric disaccharides by traveling wave ion mobility mass spectrometry using CO2 as drift gas. J Mass Spectrom. 2012;47:1643–7.CrossRefPubMed
16.
Zurück zum Zitat Ahonen L, Fasciotti M, Gennäs G, et al. Separation of steroid isomers by ion mobility mass spectrometry. J Chromatogr A. 2013;1310:133–7.CrossRefPubMed Ahonen L, Fasciotti M, Gennäs G, et al. Separation of steroid isomers by ion mobility mass spectrometry. J Chromatogr A. 2013;1310:133–7.CrossRefPubMed
17.
Zurück zum Zitat Dear G, Munoz-Muriedas J, Beaumont C, et al. Sites of metabolic substitution: investigating metabolite structures utilising ion mobility and molecular modelling. Rapid Commun Mass Spectrom. 2010;24:3157–62.CrossRefPubMed Dear G, Munoz-Muriedas J, Beaumont C, et al. Sites of metabolic substitution: investigating metabolite structures utilising ion mobility and molecular modelling. Rapid Commun Mass Spectrom. 2010;24:3157–62.CrossRefPubMed
18.
Zurück zum Zitat Castro-Perez J, Roddy T, Nibbering N, et al. Localization of fatty acyl and double bond positions in phosphatidylcholines using a dual stage CID fragmentation coupled with ion mobility mass spectrometry. J Am Soc Mass Spectrom. 2011;22:1552–67.CrossRefPubMedPubMedCentral Castro-Perez J, Roddy T, Nibbering N, et al. Localization of fatty acyl and double bond positions in phosphatidylcholines using a dual stage CID fragmentation coupled with ion mobility mass spectrometry. J Am Soc Mass Spectrom. 2011;22:1552–67.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Verbeck G, Ruotolo B, Sawyer HA, et al. A fundamental introduction to ion mobility mass spectrometry applied to the analysis of biomolecules. J Biomol Tech. 2002;13:56–61.PubMedPubMedCentral Verbeck G, Ruotolo B, Sawyer HA, et al. A fundamental introduction to ion mobility mass spectrometry applied to the analysis of biomolecules. J Biomol Tech. 2002;13:56–61.PubMedPubMedCentral
20.
Zurück zum Zitat Kanu A, Dwivedi P, Tam M, Matz L, et al. Ion mobility-mass spectrometry. J Mass Spectrom. 2008;43:1–22.CrossRefPubMed Kanu A, Dwivedi P, Tam M, Matz L, et al. Ion mobility-mass spectrometry. J Mass Spectrom. 2008;43:1–22.CrossRefPubMed
21.
Zurück zum Zitat Blond E, Rieusset J, Alligier M, et al. Nicotinic acid affects on insulin sensitivity and hepatic lipid metabolism: an in vivo to in vitro study. “Niacin” study group. Horm Metab Res. 2014;46:390–6.CrossRefPubMed Blond E, Rieusset J, Alligier M, et al. Nicotinic acid affects on insulin sensitivity and hepatic lipid metabolism: an in vivo to in vitro study. “Niacin” study group. Horm Metab Res. 2014;46:390–6.CrossRefPubMed
22.
Zurück zum Zitat Havel RJ, Eder HA, Bragdon JH. Composition of ultracentrifugally separated lipoproteins in human serum. J Ctin Invest. 1955;34:1345–53.CrossRef Havel RJ, Eder HA, Bragdon JH. Composition of ultracentrifugally separated lipoproteins in human serum. J Ctin Invest. 1955;34:1345–53.CrossRef
23.
Zurück zum Zitat Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37:911–7.CrossRefPubMed Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37:911–7.CrossRefPubMed
24.
Zurück zum Zitat Murphy R, Axelsen P. Mass spectrometric analysis of long-chain lipids. Mass Spectrom Rev. 2011;30:579–99.CrossRefPubMed Murphy R, Axelsen P. Mass spectrometric analysis of long-chain lipids. Mass Spectrom Rev. 2011;30:579–99.CrossRefPubMed
25.
Zurück zum Zitat Stokke KJ, Norum KR. Determination of 1ecithin:cholesterol acyltransferase in human blood plasma. Scand J Lab Invest. 1971;27:21–7. Stokke KJ, Norum KR. Determination of 1ecithin:cholesterol acyltransferase in human blood plasma. Scand J Lab Invest. 1971;27:21–7.
26.
Zurück zum Zitat Castro-Perez JM, Kamphorst J, DeGroot J, Lafeber F, Goshawk J, Yu K, et al. Comprehensive LC−MSE lipidomic analysis using a shotgun approach and its application to biomarker detection and identification in osteoarthritis patients. J Proteome Res. 2010;9:2377–89.CrossRefPubMed Castro-Perez JM, Kamphorst J, DeGroot J, Lafeber F, Goshawk J, Yu K, et al. Comprehensive LC−MSE lipidomic analysis using a shotgun approach and its application to biomarker detection and identification in osteoarthritis patients. J Proteome Res. 2010;9:2377–89.CrossRefPubMed
27.
Zurück zum Zitat Storey JD. A direct approach to false discovery rates. J R Stat Soc Ser B Stat Methodol. 2002;64:479–98.CrossRef Storey JD. A direct approach to false discovery rates. J R Stat Soc Ser B Stat Methodol. 2002;64:479–98.CrossRef
28.
Zurück zum Zitat Damen C, Isaac G, Langridge J, et al. Enhanced lipid isomer separation in human plasma using reversed-phase UPLC with ion-mobility/high-resolution MS detection. J Lipid Res. 2014;55:1772–83.CrossRefPubMedPubMedCentral Damen C, Isaac G, Langridge J, et al. Enhanced lipid isomer separation in human plasma using reversed-phase UPLC with ion-mobility/high-resolution MS detection. J Lipid Res. 2014;55:1772–83.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Zelena E, Dunn W, Broadhurst D, et al. Development of a robust and repeatable UPLC-MS method for the long-term metabolomic study of human serum. Anal Chem. 2009;81:1357–64.CrossRefPubMed Zelena E, Dunn W, Broadhurst D, et al. Development of a robust and repeatable UPLC-MS method for the long-term metabolomic study of human serum. Anal Chem. 2009;81:1357–64.CrossRefPubMed
30.
Zurück zum Zitat Choi J, Kim T, Cho JY, et al. Development of lipidomic platform and phosphatidylcholine retention time index for lipid profiling of rosuvastatin treated human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;944:157–65.CrossRefPubMed Choi J, Kim T, Cho JY, et al. Development of lipidomic platform and phosphatidylcholine retention time index for lipid profiling of rosuvastatin treated human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;944:157–65.CrossRefPubMed
31.
Zurück zum Zitat Holland W, Summers SA. Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev. 2008;29:381–402.CrossRefPubMedPubMedCentral Holland W, Summers SA. Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev. 2008;29:381–402.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Jin FY, Kamanna VS, Kashyap ML. Niacin accelerates intracellular ApoB degradation by inhibiting triacylglycerol synthesis in human hepatoblastoma (HepG2) cells. Arterioscler Thromb Vasc Biol. 1999;19:1051–9.CrossRefPubMed Jin FY, Kamanna VS, Kashyap ML. Niacin accelerates intracellular ApoB degradation by inhibiting triacylglycerol synthesis in human hepatoblastoma (HepG2) cells. Arterioscler Thromb Vasc Biol. 1999;19:1051–9.CrossRefPubMed
33.
Zurück zum Zitat Ganji SH, Tavintharan S, Zhu D, Xing Y, Kamanna VS, Kashyap ML. Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells. J Lipid Res. 2004;45:1835–45.CrossRefPubMed Ganji SH, Tavintharan S, Zhu D, Xing Y, Kamanna VS, Kashyap ML. Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells. J Lipid Res. 2004;45:1835–45.CrossRefPubMed
34.
Zurück zum Zitat Fabbrini E, Mohammed BS, Korenblat KM, Magkos F, McCrea J, Patterson BW, et al. Effect of fenofibrate and niacin on intrahepatic triglyceride content, very low-density lipoproteins kinetics, and insulin action in obese subjects with nonalcoholic fatty liver disease. J Clin Endocrinol Metab. 2010;95:2727–35.CrossRefPubMedPubMedCentral Fabbrini E, Mohammed BS, Korenblat KM, Magkos F, McCrea J, Patterson BW, et al. Effect of fenofibrate and niacin on intrahepatic triglyceride content, very low-density lipoproteins kinetics, and insulin action in obese subjects with nonalcoholic fatty liver disease. J Clin Endocrinol Metab. 2010;95:2727–35.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Le Bloc’h J, Leray V, Chetiveaux M, Freuchet B, Magot T, Krempf M, et al. Nicotinic acid decreases apolipoprotein B100-containing lipoprotein levels by reducing hepatic very low density lipoprotein secretion through a possible diacylglycerol acyltransferase 2 inhibition in obese dogs. J Pharmacol Exp Ther. 2010;34:583–9. Le Bloc’h J, Leray V, Chetiveaux M, Freuchet B, Magot T, Krempf M, et al. Nicotinic acid decreases apolipoprotein B100-containing lipoprotein levels by reducing hepatic very low density lipoprotein secretion through a possible diacylglycerol acyltransferase 2 inhibition in obese dogs. J Pharmacol Exp Ther. 2010;34:583–9.
36.
Zurück zum Zitat Camont L, Lhomme M, Rachid F, et al. Small, dense high-density lipoprotein-3 particles are enriched in negatively charged phospholipids: relevance to cellular cholesterol efflux, antioxidative, antithrombotic, anti-inflammatory, and anti-apoptotic functionalities. Atheroscler Thromb Vasc Biol. 2013;33:2715–23.CrossRef Camont L, Lhomme M, Rachid F, et al. Small, dense high-density lipoprotein-3 particles are enriched in negatively charged phospholipids: relevance to cellular cholesterol efflux, antioxidative, antithrombotic, anti-inflammatory, and anti-apoptotic functionalities. Atheroscler Thromb Vasc Biol. 2013;33:2715–23.CrossRef
37.
Zurück zum Zitat Rader D, Alexander E, Weibel G, et al. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis. J Lipid Res. 2009;50:S189–94.CrossRefPubMedPubMedCentral Rader D, Alexander E, Weibel G, et al. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis. J Lipid Res. 2009;50:S189–94.CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Hara S, Shike T, Takasu N, Mizui T. Lysophosphatidylcholine promotes cholesterol efflux from mouse macrophage foam cells. Arterioscler Thromb Vasc Biol. 1997;17:1258–66.CrossRefPubMed Hara S, Shike T, Takasu N, Mizui T. Lysophosphatidylcholine promotes cholesterol efflux from mouse macrophage foam cells. Arterioscler Thromb Vasc Biol. 1997;17:1258–66.CrossRefPubMed
39.
Zurück zum Zitat Zhang LH, Kamanna VS, Ganji SH, et al. Niacin increases HDL biogenesis by enhancing DR4-dependent transcription of ABCA1 and lipidation of apolipoprotein A-I in HepG2 cells. J Lipid Res. 2012;53:941–50.CrossRefPubMedPubMedCentral Zhang LH, Kamanna VS, Ganji SH, et al. Niacin increases HDL biogenesis by enhancing DR4-dependent transcription of ABCA1 and lipidation of apolipoprotein A-I in HepG2 cells. J Lipid Res. 2012;53:941–50.CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Masana L, Cabré A, Heras M, Amigó N, Correig X, Martínez-Hervás S, et al. Plana N2, Blanco-Vaca F. Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients. Atherosclerosis. 2015;238:213–9.CrossRefPubMed Masana L, Cabré A, Heras M, Amigó N, Correig X, Martínez-Hervás S, et al. Plana N2, Blanco-Vaca F. Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients. Atherosclerosis. 2015;238:213–9.CrossRefPubMed
41.
Zurück zum Zitat Kasumov T, Li L, Li M, Gulshan K, Kirwan JP, Liu X, Previs S, Willard B, Smith JD, McCullough A. Ceramide as a mediator of non-alcoholic Fatty liver disease and associated atherosclerosis. PLoS One 2015;20;10:e0126910. Kasumov T, Li L, Li M, Gulshan K, Kirwan JP, Liu X, Previs S, Willard B, Smith JD, McCullough A. Ceramide as a mediator of non-alcoholic Fatty liver disease and associated atherosclerosis. PLoS One 2015;20;10:e0126910.
42.
Zurück zum Zitat Dong J, Liu J, Lou B, Li Z, Ye X, Wu M, et al. Adenovirus-mediated overexpression of sphingomyelin synthases 1 and 2 increases the atherogenic potential in mice. J Lipid Res. 2006;47:1307–14.CrossRefPubMed Dong J, Liu J, Lou B, Li Z, Ye X, Wu M, et al. Adenovirus-mediated overexpression of sphingomyelin synthases 1 and 2 increases the atherogenic potential in mice. J Lipid Res. 2006;47:1307–14.CrossRefPubMed
43.
Zurück zum Zitat Schissel SL, Tweedie-Hardman J, Rapp JH, Graham G, Williams KJ, Tabas I. Rabbit aorta and human atherosclerotic lesions hydrolyze the sphingomyelin of retained low-density lipoprotein. Proposed role for arterial-wall sphingomyelinase in subendothelial retention and aggregation of atherogenic lipoproteins. J Clin Invest. 1996;98:1455–64.CrossRefPubMedPubMedCentral Schissel SL, Tweedie-Hardman J, Rapp JH, Graham G, Williams KJ, Tabas I. Rabbit aorta and human atherosclerotic lesions hydrolyze the sphingomyelin of retained low-density lipoprotein. Proposed role for arterial-wall sphingomyelinase in subendothelial retention and aggregation of atherogenic lipoproteins. J Clin Invest. 1996;98:1455–64.CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Xu XX, Tabas I. Sphingomyelinase enhances low density lipoprotein uptake and ability to induce cholesteryl ester accumulation in macrophages. J Biol Chem. 1991;25(266):24849–58. Xu XX, Tabas I. Sphingomyelinase enhances low density lipoprotein uptake and ability to induce cholesteryl ester accumulation in macrophages. J Biol Chem. 1991;25(266):24849–58.
46.
Zurück zum Zitat Investigators AIM-HIGH, Boden W, Probstfield J, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–67.CrossRef Investigators AIM-HIGH, Boden W, Probstfield J, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–67.CrossRef
47.
Zurück zum Zitat HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, Hopewell JC, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371:203–12.CrossRef HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, Hopewell JC, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371:203–12.CrossRef
48.
Zurück zum Zitat Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis. 2010;210:353–61.CrossRefPubMed Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis. 2010;210:353–61.CrossRefPubMed
49.
Zurück zum Zitat Elam M, Hunninghake D, Davis K, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. Arterial disease multiple intervention trial JAMA. 2000;284:1263–70.PubMed Elam M, Hunninghake D, Davis K, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. Arterial disease multiple intervention trial JAMA. 2000;284:1263–70.PubMed
50.
Zurück zum Zitat Meyers C, Kashyap ML. Pharmacologic elevation of high-density lipoproteins: recent insights on mechanism of action and atherosclerosis protection. Curr Opin Cardiol. 2004;19:366–73.CrossRefPubMed Meyers C, Kashyap ML. Pharmacologic elevation of high-density lipoproteins: recent insights on mechanism of action and atherosclerosis protection. Curr Opin Cardiol. 2004;19:366–73.CrossRefPubMed
51.
Zurück zum Zitat Ganji S, Zhang L, Kamanna V, et al. Effect of niacin on lipoproteins and atherosclerosis. Futur Lipidol. 2006;1:549–57.CrossRef Ganji S, Zhang L, Kamanna V, et al. Effect of niacin on lipoproteins and atherosclerosis. Futur Lipidol. 2006;1:549–57.CrossRef
Metadaten
Titel
Plasma Lipidome Analysis by Liquid Chromatography-High Resolution Mass Spectrometry and Ion Mobility of Hypertriglyceridemic Patients on Extended-Release Nicotinic Acid: a Pilot Study
verfasst von
Véronique Ferchaud-Roucher
Mikaël Croyal
Thomas Moyon
Yassine Zair
Michel Krempf
Khadija Ouguerram
Publikationsdatum
28.07.2017
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 3/2017
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-017-6737-y

Weitere Artikel der Ausgabe 3/2017

Cardiovascular Drugs and Therapy 3/2017 Zur Ausgabe

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.