缓释烟酸对他汀治疗患者高密度脂蛋白（HDL）功能、脂蛋白代谢及血管炎症介质的影响。

Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients.

作者信息

Yadav Rahul, Liu Yifen, Kwok See, Hama Salam, France Michael, Eatough Ruth, Pemberton Phil, Schofield Jonathan, Siahmansur Tarza J, Malik Rayaz, Ammori Basil A, Issa Basil, Younis Naveed, Donn Rachelle, Stevens Adam, Durrington Paul, Soran Handrean

机构信息

Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.) Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom (R.Y., S.K., M.F., R.E., J.S., H.S.).

Cardiovascular Research Group, Core Technologies Facility, University of Manchester, United Kingdom (R.Y., Y.L., S.H., M.F., J.S., T.J.S., R.M., P.D., H.S.).

出版信息

J Am Heart Assoc. 2015 Sep 15;4(9):e001508. doi: 10.1161/JAHA.114.001508.

DOI:10.1161/JAHA.114.001508

PMID:26374297

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4599486/

Abstract

BACKGROUND

The aim of this study was to explore the influence of extended-release niacin/laropiprant (ERN/LRP) versus placebo on high-density lipoprotein (HDL) antioxidant function, cholesterol efflux, apolipoprotein B100 (apoB)-containing lipoproteins, and mediators of vascular inflammation associated with 15% increase in high-density lipoprotein cholesterol (HDL-C). Study patients had persistent dyslipidemia despite receiving high-dose statin treatment.

METHODS AND RESULTS

In a randomized double-blind, placebo-controlled, crossover trial, we compared the effect of ERN/LRP with placebo in 27 statin-treated dyslipidemic patients who had not achieved National Cholesterol Education Program-ATP III targets for low-density lipoprotein cholesterol (LDL-C). We measured fasting lipid profile, apolipoproteins, cholesteryl ester transfer protein (CETP) activity, paraoxonase 1 (PON1) activity, small dense LDL apoB (sdLDL-apoB), oxidized LDL (oxLDL), glycated apoB (glyc-apoB), lipoprotein phospholipase A2 (Lp-PLA2), lysophosphatidyl choline (lyso-PC), macrophage chemoattractant protein (MCP1), serum amyloid A (SAA) and myeloperoxidase (MPO). We also examined the capacity of HDL to protect LDL from in vitro oxidation and the percentage cholesterol efflux mediated by apoB depleted serum. ERN/LRP was associated with an 18% increase in HDL-C levels compared to placebo (1.55 versus 1.31 mmol/L, P<0.0001). There were significant reductions in total cholesterol, triglycerides, LDL cholesterol, total serum apoB, lipoprotein (a), CETP activity, oxLDL, Lp-PLA2, lyso-PC, MCP1, and SAA, but no significant changes in glyc-apoB or sdLDL-apoB concentration. There was a modest increase in cholesterol efflux function of HDL (19.5%, P=0.045), but no change in the antioxidant capacity of HDL in vitro or PON1 activity.

CONCLUSIONS

ERN/LRP reduces LDL-associated mediators of vascular inflammation, but has varied effects on HDL functionality and LDL quality, which may counter its HDL-C-raising effect.

CLINICAL TRIAL REGISTRATION

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01054508.

摘要

背景

本研究旨在探讨缓释烟酸/拉罗匹仑（ERN/LRP）与安慰剂相比，对高密度脂蛋白（HDL）抗氧化功能、胆固醇流出、含载脂蛋白B100（apoB）的脂蛋白以及与高密度脂蛋白胆固醇（HDL-C）升高15%相关的血管炎症介质的影响。尽管接受了高剂量他汀类药物治疗，研究患者仍存在血脂异常。

方法与结果

在一项随机双盲、安慰剂对照、交叉试验中，我们比较了ERN/LRP与安慰剂对27例未达到国家胆固醇教育计划成人治疗组第三次报告（ATP III）低密度脂蛋白胆固醇（LDL-C）目标的他汀类药物治疗的血脂异常患者的影响。我们测量了空腹血脂谱、载脂蛋白、胆固醇酯转运蛋白（CETP）活性、对氧磷酶1（PON1）活性、小而密LDL apoB（sdLDL-apoB）、氧化LDL（oxLDL）、糖化apoB（glyc-apoB）、脂蛋白磷脂酶A2（Lp-PLA2）、溶血磷脂酰胆碱（lyso-PC）、巨噬细胞趋化蛋白（MCP1）、血清淀粉样蛋白A（SAA）和髓过氧化物酶（MPO）。我们还检测了HDL在体外保护LDL免受氧化的能力以及apoB耗尽血清介导的胆固醇流出百分比。与安慰剂相比，ERN/LRP使HDL-C水平升高了18%（1.55对1.31 mmol/L，P<0.0001）。总胆固醇、甘油三酯、LDL胆固醇、总血清apoB、脂蛋白（a）、CETP活性、oxLDL、Lp-PLA2、lyso-PC、MCP1和SAA均显著降低，但glyc-apoB或sdLDL-apoB浓度无显著变化。HDL的胆固醇流出功能有适度增加（19.5%，P=0.045），但HDL的体外抗氧化能力或PON1活性无变化。