Lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform size, and risk of future cardiovascular events among initially healthy women
Lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform size, and risk of future cardiovascular events among initially healthy women
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DOI：
10.1001/jama.296.11.1363
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发表时间：
2006-09-20
影响因子：
120.7
通讯作者：
Ridker, Paul M.
中科院分区：
文献类型：
--
作者：
Danik, Jacqueline Suk;Rifai, Nader;Ridker, Paul M.
背景 对于脂蛋白（a）（一种与纤溶酶原同源的脂蛋白）是否是女性中具有临床意义的心血管风险标志物存在争议。不同测定方法获得的脂蛋白(a)水平之间的一致性也较差。目的 确定脂蛋白(a)水平（采用独立于载脂蛋白(a)亚型大小的测定方法测量）与未来心血管事件发生率的关系。设计、设置和参与者对妇女健康研究中的27 791名最初健康的女性进行前瞻性研究，于1992年11月至1995年7月期间入组并随访10年。通过独立于载脂蛋白(a)亚型大小的测定，测量基线时获得的血液样本中的脂蛋白(a)水平。主要结果测量首次重大心血管事件（非致命性心肌梗塞、非致命性脑血管事件、冠状动脉血运重建或心血管死亡）的风险比(HR)。结果在随访期间，发生了899起心血管事件。在调整年龄、吸烟、血压、体重指数、总胆固醇、高密度脂蛋白胆固醇、糖尿病、激素使用、C反应蛋白和随机化治疗组后，脂蛋白(a)最高五分位的女性(>=44.0mg/dL)的可能性高出1.47倍(95%CI，1.21-1.79；趋势P=83mg/dL)，1.87( 95% CI，1.50-2.34）； 99% (>= 130.7 mg/dL) 为 1.99 (95% CI, 1.32-3.00)，较低水平几乎没有风险梯度。低密度脂蛋白胆固醇（LDL-C）高于中位水平的女性之间的相关性最强。在该亚组中，与脂蛋白(a)水平超过第90个百分位数相关的调整HR为1.81（95% CI，1.48-2.23）；第 95 个百分位数，1.93（95% CI，1.51-2.48）；和第 99 个百分位数，1.93（95% CI，1.21-3.05）（与 LDL-C 相互作用的 P 值=. 001）。 结论 在这组最初健康的女性中，采用独立于载脂蛋白（a）亚型大小的测定法测量，极高水平的脂蛋白（a）（>=第 90 个百分位数）与心血管风险增加相关，特别是在脂蛋白（a）水平较高的女性中。低密度脂蛋白胆固醇。然而，观察到的阈值和相互作用效应并不支持脂蛋白（a）的常规测量用于女性心血管分层。
Context Controversy exists as to whether lipoprotein( a), a lipoprotein with homology to plasminogen, is a clinically meaningful cardiovascular risk marker in women. There is also poor agreement among lipoprotein( a) levels obtained by different assays.Objective To determine the association of lipoprotein( a) levels, measured with an assay independent of apolipoprotein( a) isoform size, with the incidence of future cardiovascular events.Design, Setting, and Participants Prospective study of 27 791 initially healthy women in the Women's Health Study, enrolled between November 1992 and July 1995 and followed up for 10 years. Lipoprotein( a) level was measured in blood samples obtained at baseline with an assay independent of apolipoprotein( a) isoform size.Main Outcome Measure Hazard ratios (HRs) for first-ever major cardiovascular events (nonfatal myocardial infarction, nonfatal cerebrovascular event, coronary revascularization, or cardiovascular deaths).Results During follow-up, there were 899 incident cardiovascular events. After adjusting for age, smoking, blood pressure, body mass index, total cholesterol, high-density lipoprotein cholesterol, diabetes, hormone use, C-reactive protein, and randomization treatment groups, women in the highest quintile of lipoprotein( a) ( >= 44.0 mg/dL) were 1.47 times more likely (95% CI, 1.21- 1.79; P for trend = 83 mg/dL), 1.87 ( 95% CI, 1.50-2.34); and 99th percentile ( >= 130.7 mg/dL), 1.99 ( 95% CI, 1.32-3.00), with almost no risk gradient at lower levels. Associations were strongest among women with low-density lipoprotein cholesterol (LDL-C) above the median level. In this subgroup, the adjusted HR associated with lipoprotein( a) levels exceeding the 90th percentile was 1.81 ( 95% CI, 1.48-2.23); 95th percentile, 1.93 ( 95% CI, 1.51-2.48); and 99th percentile, 1.93 ( 95% CI, 1.21-3.05) ( P value for interaction with LDL-C=. 001).Conclusions In this cohort of initially healthy women, extremely high levels of lipoprotein( a) (>= 90th percentile), measured with an assay independent of apolipoprotein( a) isoform size, were associated with increased cardiovascular risk, particularly in women with high levels of LDL-C. However, the threshold and interaction effects observed do not support routine measurement of lipoprotein( a) for cardiovascular stratification in women.