Department of Nutrition, Harvard School of Public Health, Boston, MA (M.K.J., E.B.R., J.D.F., F.M.S.).
J Am Heart Assoc. 2012 Apr;1(2). doi: 10.1161/JAHA.111.000232. Epub 2012 Apr 24.
High-density lipoproteins (HDL) are structurally and metabolically heterogeneous and subclasses with differential effects on coronary heart disease (CHD) might exist. Apolipoprotein (apo) C-III, a small proinflammatory protein that resides on the surface of lipoproteins, enhances the atherogenicity of VLDL and LDL particles, but little is known about the role apoC-III on HDL. We investigated whether the presence or absence of apoC-III differentiates HDL into subtypes with nonprotective or protective associations with risk of future CHD.
High-density lipoprotein cholesterol (HDL-C) levels were measured in plasma separated according to apoC-III (by immunoaffinity chromatography) in two prospective case-control studies nested within the Nurses' Health and the Health Professionals Follow-Up Studies. Baseline was in 1990 and 1994, and 634 incident CHD cases were documented through 10 to 14 years of follow-up. The relative risk of CHD per each standard deviation of total HDL-C was 0.78 (95% confidence intervals, 0.63-0.96). The HDL-C subtypes were differentially associated with risk of CHD, HDL-C without apoC-III inversely and HDL-C with apoC-III directly (P=0.02 for a difference between the HDL types). The relative risk per standard deviation of HDL-C without apoC-III was 0.66 (0.53 to 0.93) and 1.18 (1.03 to 1.34) for HDL-C with apoC-III. HDL-C with apoC-III comprised ∼13% of the total HDL-C. Adjustment for triglycerides and apoB attenuated the risks; however, the two HDL-C subgroups remained differentially associated with risk of CHD (P=0.05).
Separating HDL-C according to apoC-III identified two types of HDL with opposing associations with risk of CHD. The proatherogenic effects of apoC-III, as a component of VLDL and LDL, may extend to HDL. (J Am Heart Assoc. 2012;1:jah3-e000232 doi: 10.1161/JAHA.111.000232.).
高密度脂蛋白（HDL）在结构和代谢上具有异质性，可能存在对冠心病（CHD）具有不同影响的亚类。载脂蛋白（apo）C-III 是一种位于脂蛋白表面的小炎症蛋白，可增强 VLDL 和 LDL 颗粒的动脉粥样硬化性，但对 HDL 上 apoC-III 的作用知之甚少。我们研究了 apoC-III 的存在或缺失是否将 HDL 分为与未来 CHD 风险无保护或保护相关的亚类。
在嵌套于护士健康和健康专业人员随访研究中的两项前瞻性病例对照研究中，根据 apoC-III（通过免疫亲和色谱法）分离血浆中的高密度脂蛋白胆固醇（HDL-C）水平。基线时间为 1990 年和 1994 年，通过 10 至 14 年的随访记录了 634 例新发 CHD 病例。每标准偏差总 HDL-C 的 CHD 相对风险为 0.78（95%置信区间，0.63-0.96）。HDL-C 亚型与 CHD 风险呈不同相关性，无 apoC-III 的 HDL-C 呈负相关，有 apoC-III 的 HDL-C 呈正相关（HDL 类型之间的差异 P=0.02）。无 apoC-III 的 HDL-C 每标准偏差的相对风险为 0.66（0.53 至 0.93），有 apoC-III 的 HDL-C 为 1.18（1.03 至 1.34）。有 apoC-III 的 HDL-C 约占总 HDL-C 的 13%。调整甘油三酯和 apoB 可降低风险；然而，两个 HDL-C 亚组与 CHD 风险仍呈不同相关性（P=0.05）。
根据 apoC-III 分离 HDL-C 可鉴定出两种具有相反 CHD 风险相关性的 HDL。apoC-III 作为 VLDL 和 LDL 的组成部分的动脉粥样硬化作用可能扩展到 HDL。
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