Albers John J, Slee April, Fleg Jerome L, O'Brien Kevin D, Marcovina Santica M
University of Washington, Northwest Lipid Metabolism and Diabetes Research Laboratories, 401 Queen Anne Ave N, Seattle, WA 98109, USA.
AIM-HIGH Coordinating Center, Axio Research, 2601 Fourth Ave, Ste 200, Seattle, WA 98121, USA.
Atherosclerosis. 2016 Aug;251:454-459. doi: 10.1016/j.atherosclerosis.2016.06.019. Epub 2016 Jun 11.
Previous results of the AIM-HIGH trial showed that baseline levels of the conventional lipid parameters were not predictive of future cardiovascular (CV) outcomes. The aims of this secondary analysis were to examine the levels of cholesterol in high density lipoprotein (HDL) subclasses (HDL2-C and HDL3-C), small dense low density lipoprotein (sdLDL-C), and LDL triglyceride (LDL-TG) at baseline, as well as the relationship between these levels and CV outcomes.
Individuals with CV disease and low baseline HDL-C levels were randomized to simvastatin plus placebo or simvastatin plus extended release niacin (ERN), 1500 to 2000 mg/day, with ezetimibe added as needed in both groups to maintain an on-treatment LDL-C in the range of 40-80 mg/dL. The primary composite endpoint was death from coronary disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebrovascular revascularization. HDL-C, HDL3-C, sdLDL-C and LDL-TG were measured at baseline by detergent-based homogeneous assays. HDL2-C was computed by the difference between HDL-C and HDL3-C. Analyses were performed on 3094 study participants who were already on statin therapy prior to enrollment in the trial. Independent contributions of lipoprotein fractions to CV events were determined by Cox proportional hazards modeling.
Baseline HDL3-C was protective against CV events (HR: 0.84, p = 0.043) while HDL-C, HDL2-C, sdLDL-C and LDL-TG were not event-related (HR: 0.96, p = 0.369; HR: 1.07, p = 0.373; HR: 1.05, p = 0.492; HR: 1.03, p = 0.554, respectively).
The results of this secondary analysis of the AIM-HIGH Study indicate that levels of HDL3-C, but not other lipoprotein fractions, are predictive of CV events, suggesting that the HDL3 subclass may be primarily responsible for the inverse association of HDL-C and CV disease.
AIM-HIGH试验之前的结果显示，传统血脂参数的基线水平并不能预测未来心血管（CV）事件。这项二次分析的目的是检测高密度脂蛋白（HDL）亚类（HDL2-C和HDL3-C）、小而密低密度脂蛋白（sdLDL-C）以及低密度脂蛋白甘油三酯（LDL-TG）的基线水平，以及这些水平与心血管事件之间的关系。
患有心血管疾病且HDL-C基线水平较低的个体被随机分为辛伐他汀加安慰剂组或辛伐他汀加缓释烟酸（ERN）组（1500至2000毫克/天），两组均根据需要添加依泽替米贝，以使治疗期间的低密度脂蛋白胆固醇（LDL-C）维持在40-80毫克/分升范围内。主要复合终点为冠心病死亡、非致命性心肌梗死、缺血性中风、因急性冠状动脉综合征住院或症状驱动的冠状动脉或脑血管血运重建。HDL-C、HDL3-C、sdLDL-C和LDL-TG在基线时通过基于去污剂的均相测定法进行测量。HDL2-C通过HDL-C与HDL3-C的差值计算得出。对3094名在试验入组前已接受他汀类药物治疗的研究参与者进行了分析。通过Cox比例风险模型确定脂蛋白组分对心血管事件的独立影响。
基线HDL3-C对心血管事件具有保护作用（风险比：0.84，p = 0.043），而HDL-C、HDL2-C、sdLDL-C和LDL-TG与事件无关（风险比分别为：0.96，p = 0.369；1.07，p = 0.373；1.05，p = 0.492；1.03，p = 0.554）。
AIM-HIGH研究的这项二次分析结果表明，HDL3-C水平而非其他脂蛋白组分可预测心血管事件，这表明HDL3亚类可能是HDL-C与心血管疾病负相关的主要原因。
