Nasser Figueiredo Valeria, Vendrame Felipe, Colontoni Bruno A, Quinaglia Thiago, Roberto Matos-Souza Jose, Azevedo Moura Filipe, Coelho Otavio R, de Faria Eliana C, Sposito Andrei C
Division of Cardiology, State University of Campinas Medical School, São Paulo, Brazil.
Lipids Laboratory, State University of Campinas Medical School, São Paulo, Brazil.
Clin Ther. 2014 Jun 1;36(6):961-6. doi: 10.1016/j.clinthera.2014.03.012. Epub 2014 Apr 24.
Reduced plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with vulnerability to oxidative stress and propensity to endothelial dysfunction. Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong anti-inflammatory and antioxidative effects, as well as induces immediate production of prostaglandin D2, leading to endothelial vasodilation.
This study investigated the short-term effects of extended-release niacin (ERN) administered with or without the prostaglandin D2 receptor antagonist laropiprant on endothelial function in patients with low HDL-C.
Asymptomatic men and women aged between 20 and 60 years who had plasma HDL-C levels <40 mg/dL were treated with ERN monotherapy 1 g/d or ERN/laropiprant 1 g/20 mg (ERN/LRP) in a crossover study design. The sequence of treatments was decided by simple randomization. Plasma samples and flow-mediated dilation (FMD) of the brachial artery were obtained at baseline, day 7 of treatment period 1, day 7 of washout, and day 7 of treatment period 2.
Eighteen patients were enrolled (mean [SD] age, 42 [17] years; 11 men). Triglyceride levels decreased by 4% and 3%, and HDL size decreased by 5.8% and 6.2%, with ERN and ERN/LRP, respectively (both, P < 0.05). There were no changes in HDL-C levels or in cholesteryl esterase transfer protein activity with either treatment. The median increases in FMD were 4.5% and 4.1% with ERN and ERN/LRP, which receded after washout. On intergroup analysis, there were no differences with respect to variation in plasma HDL-C, triglycerides, C-reactive protein, direct bilirubin, or FMD.
In these patients, the addition of laropiprant did not influence the effects of niacin on endothelial function. Based on these findings, short-term niacin treatment might improve endothelial function in patients with low HDL-C levels. ClinicalTrials.gov identifier: NCT01942291.
血浆高密度脂蛋白胆固醇（HDL-C）浓度降低与氧化应激易感性和内皮功能障碍倾向相关。烟酸可直接激活白细胞中的GPR-109A和血红素加氧酶-1途径，发挥强大的抗炎和抗氧化作用，并诱导前列腺素D2立即生成，从而导致内皮血管舒张。
本研究调查了在有或无前列腺素D2受体拮抗剂拉罗匹坦的情况下，服用缓释烟酸（ERN）对低HDL-C患者内皮功能的短期影响。
在一项交叉研究设计中，对年龄在20至60岁之间、血浆HDL-C水平<40mg/dL的无症状男性和女性，采用每日1g的ERN单药治疗或1g/20mg的ERN/拉罗匹坦（ERN/LRP）治疗。治疗顺序通过简单随机化确定。在基线、治疗期1的第7天、洗脱期第7天和治疗期2的第7天采集血浆样本并检测肱动脉的血流介导的舒张功能（FMD）。
共纳入18例患者（平均[标准差]年龄，42[17]岁；11例男性）。ERN和ERN/LRP治疗后，甘油三酯水平分别降低了4%和3%，HDL大小分别降低了5.8%和6.2%（均P<0.05）。两种治疗方法对HDL-C水平或胆固醇酯转移蛋白活性均无影响。ERN和ERN/LRP治疗后FMD的中位数增加分别为4.5%和4.1%，洗脱后恢复至基线水平。组间分析显示，血浆HDL-C、甘油三酯、C反应蛋白、直接胆红素或FMD的变化无差异。
在这些患者中，添加拉罗匹坦不影响烟酸对内皮功能的作用。基于这些发现，短期烟酸治疗可能改善低HDL-C水平患者的内皮功能。ClinicalTrials.gov标识符：NCT01942291。
