载脂蛋白 A-I 高密度脂蛋白胆固醇与心血管事件和死亡率的关系：AIM-HIGH 试验的事后分析。
Relations of GlycA and lipoprotein particle subspecies with cardiovascular events and mortality: A post hoc analysis of the AIM-HIGH trial.
机构信息
Laboratory Corporation of America(®) Holdings (LabCorp), Morrisville, NC, USA.
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
出版信息
J Clin Lipidol. 2018 Mar-Apr;12(2):348-355.e2. doi: 10.1016/j.jacl.2018.01.002. Epub 2018 Jan 12.
BACKGROUND
The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial showed no incremental benefit of extended-release niacin (ERN) therapy added to simvastatin in subjects with cardiovascular disease (CVD).
OBJECTIVES
To examine the effects of ERN treatment on lipoprotein particles and GlycA, a new marker of systemic inflammation, and their relations with incident CVD events including mortality.
METHODS
GlycA and very low-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particle subclasses were quantified by nuclear magnetic resonance spectroscopy using available stored baseline (n = 2754) and 1-year in-trial (n = 2581) samples. Associations with CVD events and all-cause mortality were assessed using multivariable Cox proportional hazards regression adjusted for age, sex, diabetes, treatment assignment, and lipoproteins.
RESULTS
Compared to placebo, ERN treatment lowered very low-density lipoprotein and LDL and increased HDL particle concentrations, increased LDL and HDL particle sizes (all P < .0001), but did not affect GlycA. Baseline and in-trial GlycA levels were associated with increased risk of CVD events: hazard ratio (HR) per SD increment, 1.17 (95% confidence interval [CI], 1.06-1.28) and 1.13 (1.02-1.26), respectively. However, none of the lipoprotein particle classes or subclasses was associated with incident CVD. By contrast, all-cause mortality was significantly associated with both GlycA (baseline HR: 1.46 [1.22-1.75]; in-trial HR: 1.41 [1.24-1.60]) and low levels of small HDL particles (baseline HR: 0.69 [0.56-0.86]; in-trial HR: 0.69 [0.56-0.86]).
CONCLUSIONS
This Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial post hoc substudy indicates that inflammation, as indexed by GlycA, is unaffected by ERN treatment but is significantly associated with the residual risk of CVD and death in patients treated to low levels of LDL cholesterol.
背景
载脂蛋白血栓形成干预代谢综合征伴低高密度脂蛋白/高三酰甘油及对全球健康结果试验显示，在伴有心血管疾病（CVD）的患者中，烟酸（ERN）的延长释放治疗联合辛伐他汀并没有带来额外获益。
目的
研究ERN 治疗对脂蛋白颗粒和 GlycA（一种新的全身炎症标志物）的影响，以及它们与 CVD 事件（包括死亡率）之间的关系。
方法
使用核磁共振光谱法，根据可利用的基线（n=2754）和 1 年试验内（n=2581）样本，对 GlycA 和极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）颗粒亚类进行定量。使用多变量 Cox 比例风险回归评估 CVD 事件和全因死亡率的相关性，调整因素包括年龄、性别、糖尿病、治疗分组和脂蛋白。
结果
与安慰剂相比，ERN 治疗降低了 VLDL 和 LDL 并增加了 HDL 颗粒浓度，增加了 LDL 和 HDL 颗粒大小（均 P<.0001），但不影响 GlycA。基线和试验内 GlycA 水平与 CVD 事件风险增加相关：每增加一个标准差的危险比（HR）分别为 1.17（95%置信区间 [CI]，1.06-1.28）和 1.13（1.02-1.26）。然而，脂蛋白颗粒类别或亚类均与 CVD 事件无关。相比之下，全因死亡率与 GlycA（基线 HR：1.46[1.22-1.75]；试验内 HR：1.41[1.24-1.60]）和小 HDL 颗粒水平（基线 HR：0.69[0.56-0.86]；试验内 HR：0.69[0.56-0.86]）显著相关。
结论
本载脂蛋白血栓形成干预代谢综合征伴低高密度脂蛋白/高三酰甘油及对全球健康结果试验的事后亚研究表明，炎症（以 GlycA 为指标）不受 ERN 治疗的影响，但与 LDL 胆固醇水平降低的患者的 CVD 风险和死亡的残余风险显著相关。
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