Improvement of endothelial dysfunction is mediated through reduction of remnant lipoprotein after statin therapy in patients with coronary artery disease
Improvement of endothelial dysfunction is mediated through reduction of remnant lipoprotein after statin therapy in patients with coronary artery disease
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DOI：
10.1016/j.jjcc.2019.08.006
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发表时间：
2020-03-01
影响因子：
2.5
通讯作者：
Kugiyama, Kiyotaka
中科院分区：
文献类型：
--
作者：
Nakamura, Takamitsu;Uematsu, Manabu;Kugiyama, Kiyotaka
背景：残留脂蛋白血症伴高水平的低密度脂蛋白胆固醇(LDL-C)是内皮功能障碍的高危因素。他汀类药物是治疗这种混合性高脂血症的一线降脂药物。然而，残余脂蛋白的减少是否在他汀类药物治疗后血管内皮功能障碍的改善和低密度脂蛋白胆固醇水平的降低之间的关系尚不确定。方法：本研究对122例冠状动脉疾病(CAD)患者进行了检测，其中FMD为100 mg/dL，残余脂蛋白颗粒胆固醇(RLPC)为5 mg/dL。在他汀类药物治疗前和治疗69个月后测定血脂谱和FMD。研究低密度脂蛋白水平的变化及其与FMD变化的关系。结果：他汀类药物治疗后69例(56.5%)患者的FMD改善。与FMD未改善组相比，FMD改善组的低密度脂蛋白-C、甘油三酯(TG)、RLP-C、RLP-C/TG和C-反应蛋白(CRP)水平的百分比变化较低，而高密度脂蛋白-C的百分比变化较高。FMD变化与低密度脂蛋白(r=-0.18，p=0.03)、糖化脂蛋白(r=-0.39，p<0.001)、糖化脂蛋白/甘油三酯(r=-0.34，p<0.001)、C反应蛋白(r=-0.27，p<0.01)呈显著负相关。中介分析显示，低密度脂蛋白-C降低与FMD改善之间的关系是通过降低RLP-C(34.5%)、RLP-C/TG(24.4%)和CRP(24.9%)水平来调节的。结论：残余脂蛋白血症的改善可能是他汀类药物治疗后冠心病患者内皮功能障碍改善与低密度脂蛋白降低关系的重要中介因素。(C)2019年由爱思唯尔有限公司代表日本心脏病学院出版。
Background: Remnant lipoproteinemia with high levels of low-density lipoprotein cholesterol (LDL-C) is a high risk for endothelial dysfunction. Statins are the first-line lipid-lowering drugs for this combined hyperlipidemia. However, it remains undetermined whether reduction of remnant lipoprotein mediates the relationship between improvement in endothelial dysfunction and reduction of LDL-C level after statin treatment.Methods: A total of 122 coronary artery disease (CAD) patients with impaired flow-mediated dilation (FMD; 100 mg/dL), and remnant-like lipoprotein particle cholesterol (RLPC) (>= 5 mg/dL) were examined in this study. The lipid profiles and FMD were measured before and after 69 months of statin treatment. The association between changes in LDL-C levels and its relationship with changes in FMD was investigated. Furthermore, mediation analysis was performed to assess the changes in RLP-C level as a mediator of the relationship between the reduction in LDL-C level and improvement of FMD.Results: Treatment with statins improved FMD in 69 (56.5%) patients. Patients with improved FMD showed lower percent changes of LDL-C, triglyceride (TG), RLP-C, RLP-C/TG, and C-reactive protein (CRP) levels, and higher percent change of HDL-C level, compared to patients who did not show improved FMD. The percent changes in FMD levels had a significant inverse correlation with the percent changes in LDLC, (r = -0.18, p = 0.03), RLP-C (r = -0.39, p < 0.001), RLP-C/TG (r = -0.34, p < 0.001), and CRP (r = -0.27, p< 0.01). Mediation analysis showed that the relationship between reduction in LDL-C and improvement of FMD was mediated by reduction of RLP-C (34.5%), RLP-C/TG (24.4%), and CRP (24.9%) levels.Conclusion: Improvement of remnant lipoproteinemia may be an important mediator for the relationship between improvement of endothelial dysfunction and LDL-lowering after statin treatment in patients with CAD. (C) 2019 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.