TY - JOUR
T1 - 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
AU - Scoffone, Heather M.
AU - Krajewski, Megan
AU - Zorca, Suzana
AU - Bereal-Williams, Candice
AU - Littel, Patricia
AU - Seamon, Catherine
AU - Mendelsohn, Laurel
AU - Footman, Eleni
AU - Abi-Jaoudeh, Nadine
AU - Sachdev, Vandana
AU - Machado, Roberto F.
AU - Cuttica, Michael
AU - Shamburek, Robert
AU - Cannon, Richard O.
AU - Remaley, Alan
AU - Minniti, Caterina P.
AU - Kato, Gregory J.
N1 - Funding Information:
The authors are grateful to the patients with sickle cell disease who enrolled on this study. They also thank additional clinical research staff who assisted in the recruitment and follow-up of these patients, including James Nichols, RN. The authors thank Mary K. Hall, CIP, and Stephanie Housel, MS, for protocol management. Dr. Scoffone acknowledges the support of the NIH Clinical Research Training Program and the Case Western Reserve University Clinical Research Scholars Program.
PY - 2013/11/1
Y1 - 2013/11/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.amjcard.2013.06.035
DO - 10.1016/j.amjcard.2013.06.035
M3 - Article
C2 - 24035168
AN - SCOPUS:84885953035
SN - 0002-9149
VL - 112
SP - 1499
EP - 1504
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 9
ER -