title: Effect of extended-release niacin on serum lipids and on endothelial function in adults with sickle cell anemia and low high-density lipoprotein cholesterol levels.
abstract: Through bound apolipoprotein A-I (apoA-I), high-density lipoprotein cholesterol (HDL-C) activates endothelial nitric oxide synthase, inducing vasodilation. Because patients with sickle cell disease (SCD) have low apoA-I and endothelial dysfunction, we conducted a randomized, double-blinded, placebo-controlled trial to test whether extended-release niacin (niacin-ER) increases apoA-I-containing HDL-C and improves vascular function in SCD. Twenty-seven patients with SCD with levels of HDL-C <39 mg/dl or apoA-I <99 mg/dl were randomized to 12 weeks of niacin-ER, increased in 500-mg increments to a maximum of 1,500 mg/day, or placebo. The primary outcome was the absolute change in HDL-C level after 12 weeks, with endothelial function assessed before and at the end of treatment. Niacin-ER-treated patients trended to greater increase in HDL-C level compared with placebo treatment at 12 weeks (5.1 ± 7.7 vs 0.9 ± 3.8 mg/dl, 1-tailed p = 0.07), associated with significantly greater improvements in the ratios of low-density lipoprotein to HDL-C levels (1.24 vs 1.95, p = 0.003) and apolipoprotein B to apoA-I levels (0.46 vs 0.58, p = 0.03) compared with placebo-treated patients. No improvements were detected in 3 independent vascular physiology assays of endothelial function. Thus, the relatively small changes in HDL-C levels achieved by the dose of niacin-ER used in our study are not associated with improved vascular function in patients with SCD with initially low levels of apoA-I or HDL-C.
authors.affiliation: Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Bethesda, Maryland; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Scoffone
authors.forename: Megan
authors.initials: M
authors.lastname: Krajewski
authors.forename: Suzana
authors.initials: S
authors.lastname: Zorca
authors.forename: Candice
authors.initials: C
authors.lastname: Bereal-Williams
authors.forename: Patricia
authors.initials: P
authors.lastname: Littel
authors.forename: Catherine
authors.initials: C
authors.lastname: Seamon
authors.forename: Laurel
authors.initials: L
authors.lastname: Mendelsohn
authors.forename: Eleni
authors.initials: E
authors.lastname: Footman
authors.forename: Nadine
authors.initials: N
authors.lastname: Abi-Jaoudeh
authors.forename: Vandana
authors.initials: V
authors.lastname: Sachdev
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Machado
authors.forename: Michael
authors.initials: M
authors.lastname: Cuttica
authors.forename: Robert
authors.initials: R
authors.lastname: Shamburek
authors.forename: Richard O
authors.initials: RO
authors.lastname: Cannon
authors.forename: Alan
authors.initials: A
authors.lastname: Remaley
authors.forename: Caterina P
authors.initials: CP
authors.lastname: Minniti
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kato
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008076:Cholesterol, HDL / Q000097:blood* / Q000187:drug effects; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage*; D011446:Prospective Studies; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D008055:Lipids; D009525:Niacin
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