van der Steeg Wim A, Holme Ingar, Boekholdt S Matthijs, Larsen Mogens Lytken, Lindahl Christina, Stroes Erik S G, Tikkanen Matti J, Wareham Nicholas J, Faergeman Ole, Olsson Anders G, Pedersen Terje R, Khaw Kay-Tee, Kastelein John J P
Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
J Am Coll Cardiol. 2008 Feb 12;51(6):634-42. doi: 10.1016/j.jacc.2007.09.060.
This study was designed to assess the relationship of high-density-lipoprotein cholesterol (HDL-C), HDL particle size, and apolipoprotein A-I (apoA-I) with the occurrence of coronary artery disease (CAD), with a focus on the effect of very high values of these parameters.
High plasma levels of HDL-C and apoA-I are inversely related to the risk of CAD. However, recent data suggest that this relationship does not hold true for very high HDL-C levels, particularly when a preponderance of large HDL particles is observed.
We conducted a post-hoc analysis of 2 prospective studies: the IDEAL (Incremental Decrease in End Points through Aggressive Lipid Lowering; n = 8,888) trial comparing the efficacy of high-dose to usual-dose statin treatment for the secondary prevention of cardiovascular events, and the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk case-control study, including apparently healthy individuals who did (cases, n = 858) or did not (control patients, n = 1,491) develop CAD during follow-up. In IDEAL, only HDL-C and apoA-I were available; in EPIC-Norfolk, nuclear magnetic resonance spectroscopy-determined HDL particle sizes were also available.
In the IDEAL study, higher HDL-C proved a significant major cardiac event risk factor following adjustment for age, gender, smoking, apoA-I, and apoB. A similar association was observed for HDL particle size in EPIC-Norfolk. Increased risk estimates were particularly present in the high ends of the distributions. In contrast, apoA-I remained negatively associated across the major part of its distribution in both studies.
When apoA-I and apoB are kept constant, HDL-C and HDL particle size may confer risk at very high values. This does not hold true for very high levels of apoA-I at fixed levels of HDL-C and apoB. These findings may have important consequences for assessment and treatment of CAD risk.
本研究旨在评估高密度脂蛋白胆固醇（HDL-C）、HDL颗粒大小和载脂蛋白A-I（apoA-I）与冠状动脉疾病（CAD）发生之间的关系，重点关注这些参数极高值的影响。
血浆中HDL-C和apoA-I水平升高与CAD风险呈负相关。然而，最近的数据表明，对于极高的HDL-C水平，这种关系并不成立，尤其是当观察到大量大HDL颗粒时。
我们对两项前瞻性研究进行了事后分析：IDEAL（通过积极降脂降低终点事件；n = 8888）试验，比较高剂量与常规剂量他汀类药物治疗对心血管事件二级预防的疗效，以及EPIC（欧洲癌症与营养前瞻性调查）-诺福克病例对照研究，包括在随访期间发生（病例，n = 858）或未发生（对照患者，n = 1491）CAD的明显健康个体。在IDEAL研究中，仅可获得HDL-C和apoA-I；在EPIC-诺福克研究中，还可获得通过核磁共振光谱法测定的HDL颗粒大小。
在IDEAL研究中，在对年龄、性别、吸烟、apoA-I和apoB进行调整后，较高的HDL-C被证明是主要心脏事件的显著危险因素。在EPIC-诺福克研究中，HDL颗粒大小也观察到类似的关联。风险估计增加尤其出现在分布的高端。相比之下，在两项研究中，apoA-I在其分布的主要部分仍保持负相关。
当apoA-I和apoB保持恒定时，HDL-C和HDL颗粒大小在极高值时可能会带来风险。在HDL-C和apoB固定水平下，极高水平的apoA-I则并非如此。这些发现可能对CAD风险的评估和治疗具有重要意义。
