Relation of lipoprotein subclasses as measured by proton nuclear magnetic resonance spectroscopy to coronary artery disease

Relation of lipoprotein subclasses as measured by proton nuclear magnetic resonance spectroscopy to coronary artery disease
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DOI:
10.1161/01.atv.18.7.1046
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发表时间:
1998-07-01
影响因子:
8.7
通讯作者:
Walker, JA
Walker, JA
中科院分区:
医学1区
文献类型:
--
作者:
Freedman, DS;Otvos, JD;Walker, JA

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尽管每个主要脂蛋白组分都由不同的亚类组成,这些亚类在致动脉粥样硬化方面可能不同,但由于亚类测量方法的劳动密集性,这种异质性的重要性一直难以确定。我们最近开发了一种方法,使用质子核磁共振(NMR)光谱来同时定量极低密度(VLDL)、低密度(LDL)和高密度(I-IDL)脂蛋白亚类的水平;用该方法测定的亚类分布与梯度凝胶电泳法得出的亚类分布非常一致。目前对158名男性进行的这项研究的目的是检验在已知血脂和脂蛋白水平的情况下,核磁共振衍生的脂蛋白亚类水平是否可以改善动脉造影记录的冠状动脉疾病(CAD)的预测。我们发现,衡量冠心病严重程度的全球指标与大的极低密度脂蛋白和小的高密度脂蛋白颗粒水平呈正相关,与中等大小的高密度脂蛋白颗粒呈负相关;这些关联与年龄和标准血脂测量无关。例如,在类似的脂质和脂蛋白水平下,较小的高密度脂蛋白或较大的极低密度脂蛋白颗粒水平相对较高(高于中位数)的男性患广泛冠心病的可能性是其他男性的三到四倍;同时具有较大的极低密度脂蛋白和较小高密度脂蛋白的27名男性患广泛冠心病的可能性是低水平男性的15倍。相反,调整甘油三酯或高密度脂蛋白胆固醇的水平大大降低了小颗粒低密度脂蛋白与冠心病的关系。这些发现表明,大的极低密度脂蛋白和小的高密度脂蛋白颗粒可能在闭塞性疾病的发展中发挥重要作用,它们的测量--这是常规血脂测试所不可能的--可能导致更准确的风险评估。
Although each of the major lipoprotein fractions is composed of various subclasses that may differ in atherogenicity, the importance of this heterogeneity has been difficult to ascertain owing to the labor-intensive nature of subclass measurement methods. We have recently developed a procedure, using proton nuclear magnetic resonance (NMR) spectroscopy, to simultaneously quantify levels of subclasses of very low density (VLDL), low density (LDL), and high density (I-IDL) lipoproteins; subclass distributions determined with this method agree well with those derived by gradient gel electrophoresis. The objective of the current study of 158 men was to examine whether NMR-derived Lipoprotein subclass levels Improve the prediction of arteriographically documented coronary artery disease (CAD) when levels of Lipids and lipoproteins are known. We found that a global measure of CAD severity was positively associated with levels of large VLDL and small HDL particles and inversely associated with intermediate size HDL particles; these associations were independent of age and standard lipid measurements. At comparable lipid and lipoprotein levels, for example, men with relatively high (higher than the median) levels of either small HDL or large VLDL particles were three to four times more likely to have extensive CAD than were the other men; the 27 men with high levels of both large VLDL and small HDL were 15 times more likely to have extensive CAD than were men with low levels. In contrast, adjustment for levels of triglycerides or HDL cholesterol greatly reduced the relation of small LDL particles to CAD. These findings suggest that large VLDL and small HDL particles may play important roles in the development of occlusive disease and that their measurement: which is not possible with routine lipid testing, may lead to more accurate risk assessment.