title: Effects of Extended-Release Nicotinic Acid on Apolipoprotein (a) Kinetics in Hypertriglyceridemic Patients.
abstract: OBJECTIVE
  To determine the mechanisms by which extended-release nicotinic acid reduces circulating lipoprotein (a) concentrations in hypertriglyceridemic patients.
  
  
  RESULTS
  Eight nondiabetic, obese male subjects (aged 48±12 years; body mass index, 31.2±1.8 kg/m(2)) with hypertriglyceridemia (triglycerides, 226±78 mg/dL) were enrolled in an 8 week, double blind, placebo-controlled cross-over study. At the end of each treatment phase, fasted subjects received a 10 µmol/L per kg bolus injection of [5,5,5-(2)H3]-l-Leucine immediately followed by constant infusion of [5,5,5-(2)H3]-l-Leucine (10 µmol L(-1) kg(-1) h(-1)) for 14 hours, and blood samples were collected. A liquid chromatography-tandem mass spectrometry method was used to study apolipoprotein (a) (Apo(a)) kinetics. The fractional catabolic rate of Apo(a) was calculated with a single compartmental model using the apolipoprotein B100 (ApoB100) containing very low density lipoprotein tracer enrichment as a precursor pool. Extended-release nicotinic acid decreased plasma triglycerides (-46%; P=0.023), raised high-density lipoprotein cholesterol (+20%; P=0.008), and decreased Apo(a) plasma concentrations (-20%; P=0.008). Extended-release nicotinic acid also decreased ApoB100 (22%; P=0.008) and proprotein convertase subtilisin/kexin type 9 (PCSK9, -29%; P=0.008) plasma concentrations. Apo(a) fractional catabolic rate and production rates were decreased by 37% (0.58±0.28 versus 0.36±0.19 pool/d; P=0.008) and 50% (1.4±0.8 versus 0.7±0.4 nmol/kg per day; P=0.008), respectively.
  
  
  CONCLUSIONS
  Extended-release nicotinic acid treatment decreased Apo(a) plasma concentrations by 20%, production rates by 50%, and catabolism by 37%. ApoB100 and PCSK9 concentrations were also decreased by treatment, but no correlation was found with Apo(a) kinetic parameters.
authors.affiliation: From the CRNH, West Human Nutrition Research Center, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K., E.N.); UMR 1280 PhAN Laboratory, National Institute of Agronomic Research, INRA, CHU Hôtel Dieu, HNB1, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K.); University of Nantes and Medical School, Nantes, France (M.C., K.O., M.P., M.C., S.B.-C., G.L., M.K., E.N.); GlaxoSmithKline, Les Ulis, France (A.-C.d.G.); and Endocrinology and Nutrition Department, G and R Laennec Hospital, Bd Jacques Monod, Nantes, France (M.K., E.N.).
authors.forename: Mikaël
authors.initials: M
authors.lastname: Croyal
authors.affiliation: From the CRNH, West Human Nutrition Research Center, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K., E.N.); UMR 1280 PhAN Laboratory, National Institute of Agronomic Research, INRA, CHU Hôtel Dieu, HNB1, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K.); University of Nantes and Medical School, Nantes, France (M.C., K.O., M.P., M.C., S.B.-C., G.L., M.K., E.N.); GlaxoSmithKline, Les Ulis, France (A.-C.d.G.); and Endocrinology and Nutrition Department, G and R Laennec Hospital, Bd Jacques Monod, Nantes, France (M.K., E.N.).
authors.forename: Khadija
authors.initials: K
authors.lastname: Ouguerram
authors.affiliation: From the CRNH, West Human Nutrition Research Center, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K., E.N.); UMR 1280 PhAN Laboratory, National Institute of Agronomic Research, INRA, CHU Hôtel Dieu, HNB1, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K.); University of Nantes and Medical School, Nantes, France (M.C., K.O., M.P., M.C., S.B.-C., G.L., M.K., E.N.); GlaxoSmithKline, Les Ulis, France (A.-C.d.G.); and Endocrinology and Nutrition Department, G and R Laennec Hospital, Bd Jacques Monod, Nantes, France (M.K., E.N.).
authors.forename: Maxime
authors.initials: M
authors.lastname: Passard
authors.affiliation: From the CRNH, West Human Nutrition Research Center, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K., E.N.); UMR 1280 PhAN Laboratory, National Institute of Agronomic Research, INRA, CHU Hôtel Dieu, HNB1, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K.); University of Nantes and Medical School, Nantes, France (M.C., K.O., M.P., M.C., S.B.-C., G.L., M.K., E.N.); GlaxoSmithKline, Les Ulis, France (A.-C.d.G.); and Endocrinology and Nutrition Department, G and R Laennec Hospital, Bd Jacques Monod, Nantes, France (M.K., E.N.).
authors.forename: Véronique
authors.initials: V
authors.lastname: Ferchaud-Roucher
authors.affiliation: From the CRNH, West Human Nutrition Research Center, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K., E.N.); UMR 1280 PhAN Laboratory, National Institute of Agronomic Research, INRA, CHU Hôtel Dieu, HNB1, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K.); University of Nantes and Medical School, Nantes, France (M.C., K.O., M.P., M.C., S.B.-C., G.L., M.K., E.N.); GlaxoSmithKline, Les Ulis, France (A.-C.d.G.); and Endocrinology and Nutrition Department, G and R Laennec Hospital, Bd Jacques Monod, Nantes, France (M.K., E.N.).
authors.forename: Maud
authors.initials: M
authors.lastname: Chétiveaux
authors.affiliation: From the CRNH, West Human Nutrition Research Center, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K., E.N.); UMR 1280 PhAN Laboratory, National Institute of Agronomic Research, INRA, CHU Hôtel Dieu, HNB1, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K.); University of Nantes and Medical School, Nantes, France (M.C., K.O., M.P., M.C., S.B.-C., G.L., M.K., E.N.); GlaxoSmithKline, Les Ulis, France (A.-C.d.G.); and Endocrinology and Nutrition Department, G and R Laennec Hospital, Bd Jacques Monod, Nantes, France (M.K., E.N.).
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Billon-Crossouard
authors.affiliation: From the CRNH, West Human Nutrition Research Center, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K., E.N.); UMR 1280 PhAN Laboratory, National Institute of Agronomic Research, INRA, CHU Hôtel Dieu, HNB1, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K.); University of Nantes and Medical School, Nantes, France (M.C., K.O., M.P., M.C., S.B.-C., G.L., M.K., E.N.); GlaxoSmithKline, Les Ulis, France (A.-C.d.G.); and Endocrinology and Nutrition Department, G and R Laennec Hospital, Bd Jacques Monod, Nantes, France (M.K., E.N.).
authors.forename: Anne-Charlotte
authors.initials: AC
authors.lastname: de Gouville
authors.affiliation: From the CRNH, West Human Nutrition Research Center, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K., E.N.); UMR 1280 PhAN Laboratory, National Institute of Agronomic Research, INRA, CHU Hôtel Dieu, HNB1, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K.); University of Nantes and Medical School, Nantes, France (M.C., K.O., M.P., M.C., S.B.-C., G.L., M.K., E.N.); GlaxoSmithKline, Les Ulis, France (A.-C.d.G.); and Endocrinology and Nutrition Department, G and R Laennec Hospital, Bd Jacques Monod, Nantes, France (M.K., E.N.).
authors.forename: Gilles
authors.initials: G
authors.lastname: Lambert
authors.affiliation: From the CRNH, West Human Nutrition Research Center, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K., E.N.); UMR 1280 PhAN Laboratory, National Institute of Agronomic Research, INRA, CHU Hôtel Dieu, HNB1, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K.); University of Nantes and Medical School, Nantes, France (M.C., K.O., M.P., M.C., S.B.-C., G.L., M.K., E.N.); GlaxoSmithKline, Les Ulis, France (A.-C.d.G.); and Endocrinology and Nutrition Department, G and R Laennec Hospital, Bd Jacques Monod, Nantes, France (M.K., E.N.). michel.krempf@univ-nantes.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Krempf
authors.affiliation: From the CRNH, West Human Nutrition Research Center, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K., E.N.); UMR 1280 PhAN Laboratory, National Institute of Agronomic Research, INRA, CHU Hôtel Dieu, HNB1, Nantes, France (M.C., K.O., M.P., V.F.-R., S.B.-C., G.L., M.K.); University of Nantes and Medical School, Nantes, France (M.C., K.O., M.P., M.C., S.B.-C., G.L., M.K., E.N.); GlaxoSmithKline, Les Ulis, France (A.-C.d.G.); and Endocrinology and Nutrition Department, G and R Laennec Hospital, Bd Jacques Monod, Nantes, France (M.K., E.N.).
authors.forename: Estelle
authors.initials: E
authors.lastname: Nobécourt
mesh_terms: D053241:Apoprotein(a) / Q000097:blood*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D014280:Triglycerides; D009525:Niacin; D053241:Apoprotein(a)
keywords: apolipoprotein (a); hypertriglyceridemia; kinetics; lipoprotein (a); niacin