Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER Trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin).
Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER Trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin).
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DOI：
10.1161/circulationaha.113.004406
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发表时间：
2014-02-11
期刊：
影响因子：
37.8
通讯作者：
Mora S
中科院分区：
文献类型：
--
作者：
Khera AV;Everett BM;Caulfield MP;Hantash FM;Wohlgemuth J;Ridker PM;Mora S
脂蛋白（a）[Lp（a）]是一种LDL样颗粒，在很大程度上不依赖于已知的危险因素，并可预测心血管疾病（CVD）。他汀类药物可能抵消与Lp（a）升高相关的风险，但尚不清楚Lp（a）是否是强效他汀类药物治疗后低LDL胆固醇背景下剩余风险的决定因素。在随机分配至瑞舒伐他汀20 mg/天或安慰剂组之前和之后，评估了9，612例多种族JUPITER试验参与者的基线和治疗中Lp（a）浓度，报告了白人的结局（N= 7，746）。Lp（a）浓度（nmol/L）在黑人中最高（中位数[第25 - 75百分位数] 60 [34-100]），然后是亚洲人（38 [18-60]），西班牙人（24 [11-46]）和白人（23 [10-50]）; p<0.001。虽然瑞舒伐他汀和安慰剂组Lp（a）的中位变化为零，但瑞舒伐他汀导致总体Lp（a）分布出现较小但具有统计学显著性的正向偏移（p<0.0001）。基线Lp（a）浓度与心血管事件相关：Ln[Lp（a）]每增加1个标准差校正的风险比（HR）为1.18（95%CI 1.03 - 1.34; p=0.02）。同样，他汀类药物Lp（a）浓度与CVD的剩余风险相关：校正HR 1.27（95%CI 1.01 - 1.59; p=0.04），与LDL胆固醇和其他因素无关。在基线Lp（a）≥中位数（HR 0.62，0.43-0.90）和Lp（a）<中位数（HR 0.46，0.30-0.72）的受试者中，瑞舒伐他汀显著降低了CVD事件，无相互作用的证据。当分析包括非白人时，获得了类似的结果。在接受强效他汀类药物治疗的白色JUPITER参与者中，Lp（a）是剩余风险的重要决定因素。在高或低Lp（a）的受试者中，瑞舒伐他汀的相对风险降低幅度相似。
Lipoprotein(a) [Lp(a)] is an LDL-like particle largely independent of known risk factors and predictive of cardiovascular disease (CVD). Statins may offset the risk associated with elevated Lp(a), but it is unknown if Lp(a) is a determinant of residual risk in the setting of low LDL-cholesterol after potent statin therapy. Baseline and on-treatment Lp(a) concentrations were assessed in 9,612 multiethnic JUPITER trial participants before and after random allocation to rosuvastatin 20 mg/day or placebo, with outcomes reported for whites (N=7,746). Lp(a) concentrations (nmol/L) were highest in blacks (median [25th–75th percentile] 60 [34–100]), then Asians (38 [18–60]), hispanics (24 [11–46]), and whites (23 [10–50]); p<0.001. While the median change in Lp(a) with rosuvastatin and placebo was zero, rosuvastatin nonetheless resulted in a small but statistically significant positive shift in the overall Lp(a) distribution (p<0.0001). Baseline Lp(a) concentrations were associated with incident CVD: adjusted hazard ratio (HR) per 1-SD increment in Ln[Lp(a)] 1.18 (95%CI 1.03 – 1.34; p=0.02). Similarly, on-statin Lp(a) concentrations were associated with residual risk of CVD: adjusted HR 1.27 (95%CI 1.01 – 1.59; p=0.04), which was independent of LDL-cholesterol and other factors. Rosuvastatin significantly reduced incident CVD among participants with baseline Lp(a)≥median (HR 0.62, 0.43–0.90) and Lp(a)<median (HR 0.46, 0.30–0.72), with no evidence of interaction. Similar results were obtained when analyses included non-whites. Among white JUPITER participants treated with potent statin therapy, Lp(a) was a significant determinant of residual risk. The magnitude of relative risk reduction with rosuvastatin was similar among participants with high or low Lp(a).