Center for Cardiovascular Disease Prevention, Divisions of Preventive and Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Am Coll Cardiol. 2012 Apr 24;59(17):1521-8. doi: 10.1016/j.jacc.2011.12.035.
OBJECTIVES: The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), trigylcerides, or lipid ratios, and how they compare with on-treatment LDL-C. BACKGROUND: Guidelines focus on LDL-C as the primary target of therapy, yet residual risk for cardiovascular disease (CVD) among statin-treated individuals remains high and not fully explained. METHODS: Participants in the randomized placebo-controlled JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial were adults without diabetes or CVD, with baseline LDL-C levels <130 mg/dl, high-sensitivity C-reactive protein levels ≥2 mg/l, and triglyceride concentrations <500 mg/dl. Individuals allocated to receive rosuvastatin 20 mg daily with baseline and on-treatment lipids and lipoproteins were examined in relation to the primary endpoint of incident CVD (nonfatal myocardial infarction or stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death). RESULTS: Using separate multivariate Cox models, statistically significant associations of a similar magnitude with residual risk of CVD were found for on-treatment LDL-C, non-HDL-C, apolipoprotein B, total cholesterol/HDL-C, LDL-C/HDL-C, and apolipoprotein B/A-I. The respective adjusted standardized hazard ratios (95% confidence intervals) for each of these measures were 1.31 (1.09 to 1.56), 1.25 (1.04 to 1.50), 1.27 (1.06 to 1.53), 1.22 (1.03 to 1.44), 1.29 (1.09 to 1.52), and 1.27 (1.09 to 1.49). The overall residual risk and the risk associated with these measures decreased among participants achieving on-treatment LDL-C ≤70 mg/dl, on-treatment non-HDL-C ≤100 mg/dl, or on-treatment apolipoprotein B ≤80 mg/dl. In contrast, on-treatment triglycerides showed no association with CVD. CONCLUSIONS: In this primary prevention trial of nondiabetic individuals with low LDL-C and elevated high-sensitivity C-reactive protein, on-treatment LDL-C was as valuable as non-HDL-C, apolipoprotein B, or ratios in predicting residual risk. (JUPITER-Crestor 20mg Versus Placebo in Prevention of Cardiovascular [CV] Events; NCT00239681).
目的：本研究旨在确定对于 LDL-C 水平降低的原发性预防个体，高强度他汀治疗后残余风险是否与治疗中的载脂蛋白 B、非高密度脂蛋白胆固醇（non-HDL-C）、三酰甘油或脂质比值有关，以及它们与治疗中的 LDL-C 相比如何。
背景：指南主要关注 LDL-C 作为治疗的主要目标，但接受他汀类药物治疗的个体的心血管疾病（CVD）残余风险仍然很高，且无法完全解释。
方法：随机安慰剂对照 JUPITER（他汀类药物在预防中的应用的合理性：评价瑞舒伐他汀的干预试验）试验中的参与者为无糖尿病或 CVD、基线 LDL-C 水平<130mg/dl、高敏 C 反应蛋白水平≥2mg/l、三酰甘油浓度<500mg/dl 的成年人。接受每天 20mg 瑞舒伐他汀治疗的个体，以及基线和治疗中的脂质和脂蛋白，与 CVD 的主要终点（非致死性心肌梗死或中风、不稳定型心绞痛住院、动脉血运重建或心血管死亡）有关。
结果：使用单独的多变量 Cox 模型，发现治疗中的 LDL-C、非 HDL-C、载脂蛋白 B、总胆固醇/HDL-C、LDL-C/HDL-C 和载脂蛋白 B/A-I 与 CVD 残余风险具有相似的统计学意义。这些指标的相应调整后标准化风险比（95%置信区间）分别为 1.31（1.09 至 1.56）、1.25（1.04 至 1.50）、1.27（1.06 至 1.53）、1.22（1.03 至 1.44）、1.29（1.09 至 1.52）和 1.27（1.09 至 1.49）。在达到治疗 LDL-C≤70mg/dl、治疗非 HDL-C≤100mg/dl 或治疗载脂蛋白 B≤80mg/dl 的参与者中，总体残余风险和与这些指标相关的风险降低。相比之下，治疗中的三酰甘油与 CVD 无关联。
结论：在这项针对 LDL-C 水平低且高敏 C 反应蛋白升高的非糖尿病个体的一级预防试验中，治疗中的 LDL-C 与非 HDL-C、载脂蛋白 B 或比值一样，可用于预测残余风险。（JUPITER-Crestor 20mg 与安慰剂在预防心血管 [CV] 事件中的比较；NCT00239681）。
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