title: Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.
abstract: Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I).
  
  
  
  Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1(men) or ≤50 mg dl-1(women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42.
  
  
  
  The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1, 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1, 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1, 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1, 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 μg ml-1, 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity.
  
  
  
  The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.
authors.affiliation: CEDOC, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.
authors.forename: Joana R
authors.initials: JR
authors.lastname: Batuca
authors.affiliation: CEDOC, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.|Department of Medicine IV / Immune-mediated Systemic Diseases Unit, Fernando Fonseca Hospital, Amadora, Portugal.
authors.forename: Marta C
authors.initials: MC
authors.lastname: Amaral
authors.affiliation: Department of Medicine IV / Immune-mediated Systemic Diseases Unit, Fernando Fonseca Hospital, Amadora, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Favas
authors.affiliation: CEDOC, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.|Department of Medicine IV / Immune-mediated Systemic Diseases Unit, Fernando Fonseca Hospital, Amadora, Portugal.
authors.forename: Filipe S
authors.initials: FS
authors.lastname: Paula
authors.affiliation: CEDOC, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.
authors.forename: Paul R J
authors.initials: PRJ
authors.lastname: Ames
authors.affiliation: CEAUL, NOVA Medical School | Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Papoila
authors.affiliation: CEDOC, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.|Department of Medicine IV / Immune-mediated Systemic Diseases Unit, Fernando Fonseca Hospital, Amadora, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Delgado Alves
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D000975:Antioxidants / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000276:immunology*; D008076:Cholesterol, HDL / Q000097:blood* / Q000276:immunology; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000906:Antibodies; D000975:Antioxidants; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D009525:Niacin
keywords: antibodies; antioxidant; apoliproteins; high-density lipoprotein; immune system