Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low-Density Lipoprotein Cholesterol.
Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low-Density Lipoprotein Cholesterol.
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DOI：
10.1161/jaha.117.005549
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发表时间：
2017-07-21
影响因子：
5.4
通讯作者：
Mora S
中科院分区：
文献类型：
--
作者：
Lawler PR;Akinkuolie AO;Chu AY;Shah SH;Kraus WE;Craig D;Padmanabhan L;Glynn RJ;Ridker PM;Chasman DI;Mora S
人群中的LDL（低密度脂蛋白）胆固醇水平正在下降，越来越多的注意力集中在LDL胆固醇以外的动脉粥样硬化性心血管疾病风险的剩余脂质相关途径上。在低密度脂蛋白胆固醇（<130 mg/dL）的个体中，我们在2个人群中进行了与心血管疾病相关的循环致动脉粥样硬化脂蛋白的详细分析。我们对11984名JUPITER试验参与者（NCT 00239681）进行了质子核磁共振波谱分析，以定量LDL和VLDL（极低密度脂蛋白）颗粒亚类的浓度。调整后的考克斯模型根据治疗分配检查与脂蛋白测量相关的心血管疾病风险。安慰剂分配受试者的风险（校正风险比[95%CI]/SD增量）与总LDL颗粒（1.19 [1.02，1.38]）和总VLDL颗粒（1.21 [1.04，1.41]）以及载脂蛋白B、非高密度脂蛋白胆固醇和甘油三酯相关，但与LDL-c无关。瑞舒伐他汀可降低LDL测量值，但对甘油三酯和VLDL测量值的影响不同。最小VLDL颗粒亚类的他汀类药物水平与剩余风险增加68%/SD（校正风险比1.68 [1.28，2.22]）相关-该风险与VLDL胆固醇相关，而与甘油三酯或较大VLDL颗粒无关。有证据表明，通过纳入关键的VLDL指标，他汀类药物治疗期间的剩余风险预测可显著改善（Harrell C-指数0.780 vs 0.712; P<0.0001）。在一项由4721名接受心导管插入术（CATHGEN）的个体组成的独立前瞻性队列中，观察到脂蛋白相关风险的相似模式。当低密度脂蛋白胆固醇低时，致动脉粥样硬化脂蛋白颗粒浓度与心血管疾病风险相关。极低密度脂蛋白，特别是最小的残余亚类，可能代表未使用的风险预测和潜在的治疗干预，以减少残余风险的目标。 URL：http://www.clinicaltrials.gov。唯一标识符：NCT 00239681。
Levels of LDL (low‐density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid‐related pathways of atherosclerotic cardiovascular disease risk beyond LDL cholesterol. Among individuals with low (<130 mg/dL) LDL cholesterol, we undertook detailed profiling of circulating atherogenic lipoproteins in relation to incident cardiovascular disease in 2 populations. We performed proton nuclear magnetic resonance spectroscopy to quantify concentrations of LDL and VLDL (very low‐density lipoprotein) particle subclasses in 11 984 JUPITER trial participants (NCT00239681). Adjusted Cox models examined cardiovascular disease risk associated with lipoprotein measures according to treatment allocation. Risk (adjusted hazard ratio [95%CI] per SD increment) among placebo‐allocated participants was associated with total LDL particles (1.19 [1.02, 1.38]) and total VLDL particles (1.21 [1.04, 1.41]), as well as apolipoprotein B, non–high‐density lipoprotein cholesterol, and triglycerides, but not LDL‐c. Rosuvastatin reduced LDL measures but had variable effects on triglyceride and VLDL measures. On‐statin levels of the smallest VLDL particle subclass were associated with a 68% per‐SD (adjusted hazard ratio 1.68 [1.28, 2.22]) increase in residual risk—this risk was related to VLDL cholesterol and not triglyceride or larger VLDL particles. There was evidence that residual risk prediction during statin therapy could be significantly improved through the inclusion of key VLDL measures (Harrell C‐index 0.780 versus 0.712; P<0.0001). In an independent, prospective cohort of 4721 individuals referred for cardiac catheterization (CATHGEN), similar patterns of lipoprotein‐related risk were observed. Atherogenic lipoprotein particle concentrations were associated with cardiovascular disease risk when LDL cholesterol was low. VLDL lipoproteins, particularly the smallest remnant subclass, may represent unused targets for risk prediction and potential therapeutic intervention for reducing residual risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.