JAMA：非高密度脂蛋白胆固醇浓度或与严重心血管事件风险相关

荷兰阿姆斯特丹市学术医学中心研究人员在3月28日出版的《美国医学会杂志》上发表的一项研究成果显示，在他汀类药物治疗的患者中，非高密度脂蛋白胆固醇（非-HDL-C）的浓度似乎与发生某种诸如心肌梗塞或中风等严重心血管事件的风险有关，而低密度脂蛋白胆固醇（LDL-C）和载脂蛋白B的浓度也与严重心血管事件的风险有关。

根据文章的背景资料：“他汀类药物治疗是对心血管疾病进行原发性和继发性预防的药理学治疗的基石。所有目前可得到的治疗方针指出，LDL-C浓度应该被用作启动及滴定降脂治疗的首要目标。然而，研究他汀类治疗功效的试验显示，他汀的心血管裨益可能会超越其对LDL-C浓度的影响。因此，LDL-C可能不是最好的预测心血管事件风险或对他汀类药物治疗的动脉保护效应进行定量的脂质参数。”人们提出用数种替代性脂质和载脂蛋白参数来作为LDL-C的替代品，其中最突出是载脂蛋白B和非HDL-C（即总胆固醇减去HDL）。

荷兰阿姆斯特丹市学术医学中心的S. Matthijs Boekholdt, M.D., Ph.D.及其同事开展了一项荟萃分析，旨在在接受他汀类治疗的病人中，对非-HDL-C 和apoB是否与未来心血管事件的风险有着比LDL-C更强的关联进行评估。该研究包括了来自随机控制性的他汀类试验中的个体患者的资料，这些试验确认了所有研究参与者在基线和治疗1年时随访的常规性脂质和载脂蛋白水平。研究人员发现了在1994年至2008年期间发表结果的8个试验符合纳入该荟萃分析的标准。这些试验包括了6，2154名患者的个人资料。

共有3，8153名研究的参与者被随机分入一个他汀治疗组并在他汀治疗期间具有一套完整的脂质和载脂蛋白浓度的数据。在随访期间，这些人中共有158人（0.4%）发生了致命性心肌梗塞，有1678人（4.4%）发生了非致命性心肌梗塞。有615名研究参与者（1.6%）发生了其它致命性的冠心病，有1029名研究参与者（2.7%）发生了致命性或非致命性中风。共有2806名参与者（7.4%）因为不稳定型心绞痛而住院。在5387名研究参与者中总共发生了6286起严重的心血管事件（事件发生率为14.1%）。

数据分析表明，在他汀类药物治疗的病人中，LDL-C水平、非-HDL-C水平和apoB水平，每一项都与严重心血管事件的风险有着强关联性，但非-HDL-C 比 LDL-C 和apoB有着更强的关联性。另外，非-HDL-C的变化比LDL-C和apoB的变化更能解释他汀类干预治疗的动脉保护功效。

文章的作者得出结论：“鉴于许多有关非-HDL-C 和 LDL-C的临床应用性论点是相同的这一事实，非-HDL-C可能是一个比LDL-C更恰当的他汀类治疗的目标。”（生物谷 bioon.com）

doi:10.1001/jama.2012.366
PMC:
PMID:

Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins

S. Matthijs Boekholdt, MD, PhD; Benoit J. Arsenault, PhD; Samia Mora, MD, MHS; Terje R. Pedersen, MD, PhD; John C. LaRosa, MD; Paul J. Nestel, MD; R. John Simes, MD; Paul Durrington, MD; Graham A. Hitman, MD; K. M. A. Welch, MB, ChB; David A. DeMicco, DPharm; Aeilko H. Zwinderman, PhD; Michael B. Clearfield, DO; John R. Downs, MD; Andrew M. Tonkin, MD; Helen M. Colhoun, MD; Antonio M. Gotto Jr, MD, DPhil; Paul M Ridker, MD, MPH; John J. P. Kastelein, MD, PhD

Context The associations of low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non–HDL-C), and apolipoprotein B (apoB) levels with the risk of cardiovascular events among patients treated with statin therapy have not been reliably documented. Objective To evaluate the relative strength of the associations of LDL-C, non–HDL-C, and apoB with cardiovascular risk among patients treated with statin therapy. Design Meta-analysis of individual patient data from randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Data Sources Relevant trials were identified by a literature search updated through December 31, 2011. Investigators were contacted and individual patient data were requested and obtained for 62 154 patients enrolled in 8 trials published between 1994 and 2008. Data Extraction Hazard ratios (HRs) and corresponding 95% CIs for risk of major cardiovascular events adjusted for established risk factors by 1-SD increase in LDL-C, non–HDL-C, and apoB. Results Among 38 153 patients allocated to statin therapy, 158 fatal myocardial infarctions, 1678 nonfatal myocardial infarctions, 615 fatal events from other coronary artery disease, 2806 hospitalizations for unstable angina, and 1029 fatal or nonfatal strokes occurred during follow-up. The adjusted HRs for major cardiovascular events per 1-SD increase were 1.13 (95% CI, 1.10-1.17) for LDL-C, 1.16 (95% CI, 1.12-1.19) for non–HDL-C, and 1.14 (95% CI, 1.11-1.18) for apoB. These HRs were significantly higher for non–HDL-C than LDL-C (P = .002) and apoB (P = .02). There was no significant difference between apoB and LDL-C (P = .21). Conclusion Among statin-treated patients, on-treatment levels of LDL-C, non–HDL-C, and apoB were each associated with risk of future major cardiovascular events, but the strength of this association was greater for non–HDL-C than for LDL-C and apoB.