强效他汀类药物治疗后首次心血管事件残余风险的高密度脂蛋白胆固醇：来自 JUPITER 试验的分析。

HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial.

机构信息

Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.

出版信息

Lancet. 2010 Jul 31;376(9738):333-9. doi: 10.1016/S0140-6736(10)60713-1. Epub 2010 Jul 23.

DOI:10.1016/S0140-6736(10)60713-1

PMID:20655105

Abstract

BACKGROUND

HDL-cholesterol concentrations are inversely associated with occurrence of cardiovascular events. We addressed, using the JUPITER trial cohort, whether this association remains when LDL-cholesterol concentrations are reduced to the very low ranges with high-dose statin treatment.

METHODS

Participants in the randomised placebo-controlled JUPITER trial were adults without diabetes or previous cardiovascular disease, and had baseline concentrations of LDL cholesterol of less than 3.37 mmol/L and high-sensitivity C-reactive protein of 2 mg/L or more. Participants were randomly allocated by a computer-generated sequence to receive rosuvastatin 20 mg per day or placebo, with participants and adjudicators masked to treatment assignment. In the present analysis, we divided the participants into quartiles of HDL-cholesterol or apolipoprotein A1 and sought evidence of association between these quartiles and the JUPITER primary endpoint of first non-fatal myocardial infarction or stroke, hospitalisation for unstable angina, arterial revascularisation, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT00239681.

FINDINGS

For 17,802 patients in the JUPITER trial, rosuvastatin 20 mg per day reduced the incidence of the primary endpoint by 44% (p<0.0001). In 8901 (50%) patients given placebo (who had a median on-treatment LDL-cholesterol concentration of 2.80 mmol/L [IQR 2.43-3.24]), HDL-cholesterol concentrations were inversely related to vascular risk both at baseline (top quartile vs bottom quartile hazard ratio [HR] 0.54, 95% CI 0.35-0.83, p=0.0039) and on-treatment (0.55, 0.35-0.87, p=0.0047). By contrast, among the 8900 (50%) patients given rosuvastatin 20 mg (who had a median on-treatment LDL-cholesterol concentration of 1.42 mmol/L [IQR 1.14-1.86]), no significant relationships were noted between quartiles of HDL-cholesterol concentration and vascular risk either at baseline (1.12, 0.62-2.03, p=0.82) or on-treatment (1.03, 0.57-1.87, p=0.97). Our analyses for apolipoprotein A1 showed an equivalent strong relation to frequency of primary outcomes in the placebo group but little association in the rosuvastatin group.

INTERPRETATION

Although measurement of HDL-cholesterol concentration is useful as part of initial cardiovascular risk assessment, HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol.

FUNDING

AstraZeneca.

摘要

背景

高密度脂蛋白胆固醇浓度与心血管事件的发生呈负相关。我们利用 JUPITER 试验队列研究，当使用高剂量他汀类药物治疗将 LDL 胆固醇浓度降低到极低范围时，这种相关性是否仍然存在。

方法

未患糖尿病或心血管疾病的成年人参加了随机安慰剂对照 JUPITER 试验，基线 LDL 胆固醇浓度低于 3.37mmol/L，高敏 C 反应蛋白浓度为 2mg/L 或更高。参与者通过计算机生成的序列随机分配接受每天 20mg 瑞舒伐他汀或安慰剂治疗，参与者和裁决者对治疗分配进行了盲法。在本分析中，我们将参与者按 HDL-胆固醇或载脂蛋白 A1 的四分位数进行分组，并寻求这些四分位数与 JUPITER 主要终点（首次非致命性心肌梗死或中风、不稳定型心绞痛住院、动脉血运重建或心血管死亡）之间的关联证据。该试验在 ClinicalTrials.gov 注册，编号为 NCT00239681。

结果

在 JUPITER 试验的 17802 名患者中，每天 20mg 瑞舒伐他汀可使主要终点的发生率降低 44%（p<0.0001）。在接受安慰剂治疗的 8901 名（50%）患者中（治疗后 LDL 胆固醇中位数为 2.80mmol/L [IQR 2.43-3.24]），HDL 胆固醇浓度在基线时（最高四分位与最低四分位的危险比[HR]为 0.54，95%CI 0.35-0.83，p=0.0039）和治疗时（0.55，0.35-0.87，p=0.0047）与血管风险呈负相关。相比之下，在接受 20mg 瑞舒伐他汀治疗的 8900 名（50%）患者中（治疗后 LDL 胆固醇中位数为 1.42mmol/L [IQR 1.14-1.86]），HDL 胆固醇浓度的四分位数与血管风险之间未观察到显著关系，无论是在基线时（1.12，0.62-2.03，p=0.82）还是在治疗时（1.03，0.57-1.87，p=0.97）。我们对载脂蛋白 A1 的分析表明，在安慰剂组中，它与主要结局的发生频率有很强的关联，但在瑞舒伐他汀组中几乎没有关联。