Batuca Joana R, Amaral Marta C, Favas Catarina, Paula Filipe S, Ames Paul R J, Papoila Ana L, Delgado Alves José
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.
Br J Clin Pharmacol. 2017 May;83(5):1002-1010. doi: 10.1111/bcp.13198. Epub 2017 Jan 18.
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 (men) or ≤50 mg dl (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 , 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 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl , 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 , 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.
缓释烟酸（ERN）是提高高密度脂蛋白胆固醇（HDL-C）最有效的药物。我们之前已鉴定出抗HDL抗体，在此研究ERN是否会影响HDL的抗氧化能力，以及ERN是否与抗HDL抗体（aHDL）和载脂蛋白A-I抗体（aApoA-I）的产生有关。
21名年龄超过18岁、HDL-C男性≤40mg/dl或女性≤50mg/dl的患者被随机分配，在两个连续的12周期间每日接受ERN（n = 10）或安慰剂（n = 11）治疗，交叉治疗前有4周的洗脱期。主要结局是对氧磷酶-1（PON1）活性的变化，次要结局是aHDL和aApoA-I抗体的变化。临床试验唯一标识符：EudraCT 2006-006889-42。
ERN对PON1活性的影响不显著（系数估计值20.83U/l，95%置信区间[CI] -9.88至51.53；P = 0.184）。ERN与HDL-C水平升高有关（系数估计值5.21mg/dl，95%CI 1.16至9.25；P = 0.012）及其亚类HDL2（系数估计值2.46mg/dl，95%CI 0.57至4.34；P = 0.011）和HDL3（系数估计值2.73mg/dl，95%CI 0.47至4.98；P = 0.018）。ERN与aApoA-I抗体的产生显著相关（系数估计值0.25μg/ml，95%CI 0.09 - 0.40；P = 0.001）。基线时的aApoA-I滴度与PON活性降低相关。
ERN使HDL-C升高，但抗氧化能力并未相应提高，最终因aApoA-I抗体的出现而受阻。这些结果可能解释了为什么烟酸和其他降脂药物未能降低心血管风险。
