Ion mobility analysis of lipoprotein subfractions identifies three independent axes of cardiovascular risk.
Ion mobility analysis of lipoprotein subfractions identifies three independent axes of cardiovascular risk.
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脂蛋白亚构件的离子迁移率分析标识了三个独立的心血管风险轴。
DOI：
10.1161/atvbaha.109.190405
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Krauss RM
中科院分区：
文献类型：
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作者：
Musunuru K;Orho-Melander M;Caulfield MP;Li S;Salameh WA;Reitz RE;Berglund G;Hedblad B;Engström G;Williams PT;Kathiresan S;Melander O;Krauss RM
尽管流行病学研究表明低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平可预测心血管疾病（CVD）的发生，但在前瞻性队列研究中，将脂蛋白亚组分和亚组分复合指标与CVD风险相关的证据有限。我们在4,594名最初健康的男性和女性的前瞻性队列中测试了脂蛋白亚组分的组合是否独立预测CVD（马尔默饮食和癌症研究，平均随访12.2年，377起心血管事件）。血浆脂蛋白和脂蛋白亚组分测定基线与一种新的，高分辨率的离子迁移率技术。亚组分浓度的主成分分析（PCA）鉴定了三个主要的独立（即，零相关性）组分，一个代表LDL相关的风险，第二个代表HDL相关的保护，第三个代表降低的大HDL、增加的小/中LDL和增加的甘油三酯的模式。最后一种对应于先前描述的“致动脉粥样硬化脂蛋白表型”。与小/中LDL和大HDL组合相关的SNP提示了可能构成该表型的几个基因-CETP、LIPC、GALNT 2、MLXIPL、APOA 1/A5、LPL。PCA脂蛋白亚组分产生了三个独立的CVD风险的组成部分。遗传分析表明，这些成分代表了CVD发展的独立机制途径。
Whereas epidemiologic studies show that levels of low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) predict incident cardiovascular disease (CVD), there is limited evidence relating lipoprotein subfractions and composite measures of subfractions to risk for CVD in prospective cohort studies. We tested whether combinations of lipoprotein subfractions independently predict CVD in a prospective cohort of 4,594 initially healthy men and women (the Malmö Diet and Cancer Study, mean follow-up 12.2 years, 377 incident cardiovascular events). Plasma lipoproteins and lipoprotein subfractions were measured at baseline with a novel, high-resolution ion mobility technique. Principal component analysis (PCA) of subfraction concentrations identified three major independent (i.e., zero correlation) components of CVD risk, one representing LDL-associated risk, a second representing HDL-associated protection, and the third representing a pattern of decreased large HDL, increased small/medium LDL, and increased triglycerides. The last corresponds to the previously described “atherogenic lipoprotein phenotype.” Several genes that may underlie this phenotype—CETP, LIPC, GALNT2, MLXIPL, APOA1/A5, LPL—are suggested by SNPs associated with the combination of small/medium LDL and large HDL. PCA on lipoprotein subfractions yielded three independent components of CVD risk. Genetic analyses suggest these components represent independent mechanistic pathways for development of CVD.