Miller B D, Alderman E L, Haskell W L, Fair J M, Krauss R M
Life Sciences Division, E.O. Lawrence Berkeley National Laboratory, University of California 94720, USA.
Circulation. 1996 Nov 1;94(9):2146-53. doi: 10.1161/01.cir.94.9.2146.
LDL particles differ in size and density. Individuals with LDL profiles that peak in relatively small, dense particles have been reported to be at increased risk of coronary artery disease. We hypothesized that response to coronary disease therapy in such individuals might differ from response in individuals whose profiles peak in larger, more buoyant LDL. We examined this hypothesis in the Stanford Coronary Risk Intervention Project, an angiographic trial that compared multifactorial risk-reduction intervention with the usual care of physicians.
For 213 men, a bimodal frequency distribution of peak LDL density (g/mL) determined by analytical ultracentrifugation was used to classify baseline LDL profiles as "buoyant mode" (density < or = 1.0378) or "dense mode" (density > 1.0378). Coronary disease progression after 4 years was assessed by rates of change (mm/y, negative when arteries narrow) of minimum artery diameter. Rates for buoyant-mode subjects were -0.038 +/- 0.007 (mean +/- SEM) in usual care (n = 65) and -0.039 +/- 0.010 in intervention (n = 56; P = .6). Rates for dense-mode subjects were -0.054 +/- 0.012 in usual care (n = 51) and -0.008 +/- 0.009 in intervention (n = 41, P = .007). Lipid changes did not account for this difference in angiographic response.
Different types of LDL profile may predict different-responses to specific therapies, perhaps because metabolic processes determine both LDL profiles and responses to therapies.
低密度脂蛋白（LDL）颗粒在大小和密度上存在差异。据报道，LDL谱在相对小而致密的颗粒中达到峰值的个体患冠状动脉疾病的风险增加。我们假设，这类个体对冠心病治疗的反应可能与LDL谱在较大、更具浮力的LDL中达到峰值的个体不同。我们在斯坦福冠状动脉风险干预项目中检验了这一假设，该项目是一项血管造影试验，比较了多因素风险降低干预与医生常规治疗。
对于213名男性，通过分析超速离心法测定的LDL峰值密度（g/mL）的双峰频率分布用于将基线LDL谱分类为“浮力模式”（密度≤1.0378）或“致密模式”（密度>1.0378）。4年后的冠状动脉疾病进展通过最小动脉直径的变化率（mm/年，动脉变窄时为负值）进行评估。在常规治疗中，浮力模式受试者的变化率为-0.038±0.007（平均值±标准误）（n = 65），在干预组中为-0.039±0.010（n = 56；P = 0.6）。在常规治疗中，致密模式受试者的变化率为-0.054±0.012（n = 51），在干预组中为-0.008±0.009（n = 41，P = 0.007）。脂质变化并不能解释血管造影反应的这种差异。
不同类型的LDL谱可能预测对特定治疗的不同反应，这可能是因为代谢过程既决定了LDL谱，也决定了对治疗的反应。
