Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Department of Biostatistics and Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Am J Kidney Dis. 2019 Jun;73(6):827-836. doi: 10.1053/j.ajkd.2018.11.010. Epub 2019 Jan 25.
RATIONALE & OBJECTIVE: A large residual risk for atherosclerotic cardiovascular disease (ASCVD) remains in the setting of chronic kidney disease (CKD) despite treatment with statins. We sought to evaluate the associations of lipid and apolipoprotein levels with risk for ASCVD in individuals with CKD. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: Adults aged 21 to 74 years with non-dialysis-dependent CKD at baseline enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in 7 clinical study centers in the United States. PREDICTOR: Baseline total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), HDL-C, and apolipoprotein AI (Apo-AI) values stratified into tertiles. OUTCOME: A composite ASCVD event of myocardial infarction or ischemic stroke. ANALYTIC APPROACH: Multivariable Cox proportional hazards regression to estimate the risk for ASCVD for each tertile of lipoprotein predictor. RESULTS: Among 3,811 CRIC participants (mean age, 57.7 years; 41.8% white), there were 451 ASCVD events during a median follow-up of 7.9 years. There was increased ASCVD risk among participants with VLDL-C levels in the highest tertile (HR, 1.28; 95% CI, 1.01-1.64), Apo-B levels in the middle tertile (HR, 1.30; 95% CI, 1.03-1.64), HDL-C levels in the middle and lowest tertiles (HRs of 1.40 [95% CI, 1.08-1.83] and 1.77 [95% CI, 1.35-2.33], respectively), and Apo-AI levels in the middle and lowest tertiles (HRs of 1.77 [95% CI, 1.02-1.74] and 1.77 [95% CI, 1.36-2.32], respectively). LDL-C level was not significantly associated with the ASCVD outcome in this population (HR, 1.00 [95% CI, 0.77-1.30] for the highest tertile). LIMITATIONS: Associations based on observational data do not permit inferences about causal associations. CONCLUSIONS: Higher VLDL-C and Apo-B levels, as well as lower HDL-C and Apo-AI levels, are associated with increased risk for ASCVD. These findings support future investigations into pharmacologic targeting of lipoproteins beyond LDL-C, such as triglyceride-rich lipoproteins, to reduce residual risk for ASCVD among individuals with CKD.
背景与目的：尽管使用他汀类药物治疗，但在慢性肾脏病（CKD）患者中，动脉粥样硬化性心血管疾病（ASCVD）的残余风险仍然很大。我们旨在评估脂质和载脂蛋白水平与 CKD 患者 ASCVD 风险之间的关系。
研究设计：前瞻性队列研究。
地点和参与者：在美国 7 个临床研究中心的慢性肾脏不全队列（CRIC）研究中，年龄在 21 至 74 岁之间、基线时无透析依赖性 CKD 的成年人。
预测因子：基线总胆固醇、非高密度脂蛋白胆固醇（非-HDL-C）、极低密度脂蛋白胆固醇（VLDL-C）、甘油三酯、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白 B（Apo-B）、高密度脂蛋白胆固醇（HDL-C）和载脂蛋白 AI（Apo-AI）值分为三分位。
结果：在 3811 名 CRIC 参与者（平均年龄 57.7 岁；41.8%为白人）中，中位随访 7.9 年后有 451 例 ASCVD 事件。VLDL-C 水平最高三分位的参与者 ASCVD 风险增加（HR，1.28；95%CI，1.01-1.64），Apo-B 水平处于中间三分位（HR，1.30；95%CI，1.03-1.64），HDL-C 水平处于中间和最低三分位（HRs 分别为 1.40[95%CI，1.08-1.83]和 1.77[95%CI，1.35-2.33]），Apo-AI 水平处于中间和最低三分位（HRs 分别为 1.77[95%CI，1.02-1.74]和 1.77[95%CI，1.36-2.32]）。在该人群中，LDL-C 水平与 ASCVD 结局无显著相关性（最高三分位的 HR，1.00[95%CI，0.77-1.30]）。
局限性：基于观察性数据的关联不允许推断因果关系。
结论：VLDL-C 和 Apo-B 水平升高，以及 HDL-C 和 Apo-AI 水平降低，与 ASCVD 风险增加相关。这些发现支持未来对脂蛋白进行药物靶向治疗的研究，例如靶向甘油三酯丰富的脂蛋白，以降低 CKD 患者的 ASCVD 残余风险。
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