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Clinical Trial
. 2017 May;83(5):1002-1010.
doi: 10.1111/bcp.13198. Epub 2017 Jan 18.

Extended-release Niacin Increases Anti-Apolipoprotein A-I Antibodies That Block the Antioxidant Effect of High-Density Lipoprotein-Cholesterol: The EXPLORE Clinical Trial

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Free PMC article
Clinical Trial

Extended-release Niacin Increases Anti-Apolipoprotein A-I Antibodies That Block the Antioxidant Effect of High-Density Lipoprotein-Cholesterol: The EXPLORE Clinical Trial

Joana R Batuca et al. Br J Clin Pharmacol. .
Free PMC article

Abstract

Aims: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: antibodies; antioxidant; apoliproteins; high-density lipoprotein; immune system.

Figures

Figure 1
Figure 1
Study flow diagram
Figure 2
Figure 2
Correlation between anti‐apolipoprotein A‐I antibodies titres and target parameters at baseline and end of treatment in ERN group. Spearman's correlation between IgG anti‐apolipoprotein A‐I (aApoA‐I) and IgG anti‐high density lipoprotein (aHDL) antibodies at (A) baseline and (B) the end of treatment, HDL2 levels at (C) baseline and (D) the end of treatment and paraoxonase 1 (PON1) activity at (E) baseline and (F) end of treatment

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