title: Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients.
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.
  
  
  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 (glyc-apoB), 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.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01054508.
authors.affiliation: Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.) Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom (R.Y., S.K., M.F., R.E., J.S., H.S.).
authors.forename: Rahul
authors.initials: R
authors.lastname: Yadav
authors.affiliation: Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.).
authors.forename: Yifen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom (R.Y., S.K., M.F., R.E., J.S., H.S.).
authors.forename: See
authors.initials: S
authors.lastname: Kwok
authors.affiliation: Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.).
authors.forename: Salam
authors.initials: S
authors.lastname: Hama
authors.affiliation: Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.) Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom (R.Y., S.K., M.F., R.E., J.S., H.S.) The Institute of Inflammation & Repair at the University of Manchester, United Kingdom (M.F.).
authors.forename: Michael
authors.initials: M
authors.lastname: France
authors.affiliation: Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom (R.Y., S.K., M.F., R.E., J.S., H.S.).
authors.forename: Ruth
authors.initials: R
authors.lastname: Eatough
authors.affiliation: Department of Biochemistry, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom (P.P.).
authors.forename: Phil
authors.initials: P
authors.lastname: Pemberton
authors.affiliation: Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.) Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom (R.Y., S.K., M.F., R.E., J.S., H.S.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schofield
authors.affiliation: Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.).
authors.forename: Tarza J
authors.initials: TJ
authors.lastname: Siahmansur
authors.affiliation: Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.).
authors.forename: Rayaz
authors.initials: R
authors.lastname: Malik
authors.affiliation: Department of Surgery, Salford Royal NHS Foundation Trust, Salford, United Kingdom (B.A.A.).
authors.forename: Basil A
authors.initials: BA
authors.lastname: Ammori
authors.affiliation: Department of Diabetes and Endocrinology, University Hospital of South Manchester, United Kingdom (B.I., N.Y.).
authors.forename: Basil
authors.initials: B
authors.lastname: Issa
authors.affiliation: Department of Diabetes and Endocrinology, University Hospital of South Manchester, United Kingdom (B.I., N.Y.).
authors.forename: Naveed
authors.initials: N
authors.lastname: Younis
authors.affiliation: Complex Disease Genetics, Centre for Musculoskeletal Research, University of Manchester, United Kingdom (R.D.).
authors.forename: Rachelle
authors.initials: R
authors.lastname: Donn
authors.affiliation: Royal Manchester Children's Hospital, Manchester, United Kingdom (A.S.).
authors.forename: Adam
authors.initials: A
authors.lastname: Stevens
authors.affiliation: Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.).
authors.forename: Paul
authors.initials: P
authors.lastname: Durrington
authors.affiliation: Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.) Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom (R.Y., S.K., M.F., R.E., J.S., H.S.).
authors.forename: Handrean
authors.initials: H
authors.lastname: Soran
mesh_terms: D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004739:England; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; C518174:MK-0524; C099252:oxidized low density lipoprotein; D009525:Niacin
keywords: HDL functionality; LDL quality; cholesterol efflux; extended‐release niacin; inflammation; laropiprant; oxidation