Suk Danik Jacqueline, Rifai Nader, Buring Julie E, Ridker Paul M
Donald W. Reynolds Center for Cardiovascular Research and the Leducq Foundation Center for Vascular Research, Boston, Mass, USA.
JAMA. 2006 Sep 20;296(11):1363-70. doi: 10.1001/jama.296.11.1363.
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.
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.
Hazard ratios (HRs) for first-ever major cardiovascular events (nonfatal myocardial infarction, nonfatal cerebrovascular event, coronary revascularization, or cardiovascular deaths).
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) (> or =44.0 mg/dL) were 1.47 times more likely (95% CI, 1.21-1.79; P for trend <.001) to develop cardiovascular events than women in the lowest quintile (< or =3.4 mg/dL). This association, however, was due almost entirely to a threshold effect among those with the highest lipoprotein(a) levels. After adjusting for all of the variables listed above, the HR associated with lipoprotein(a) levels exceeding the 90th percentile (> or =65.5 mg/dL) was 1.66 (95% CI, 1.38-1.99); 95th percentile (> or =83 mg/dL), 1.87 (95% CI, 1.50-2.34); and 99th percentile (> or =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).
In this cohort of initially healthy women, extremely high levels of lipoprotein(a) (> or =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.
与纤溶酶原具有同源性的脂蛋白(a)是否为女性临床上有意义的心血管风险标志物存在争议。不同检测方法所测得的脂蛋白(a)水平之间的一致性也较差。
确定使用与载脂蛋白(a)异构体大小无关的检测方法测得的脂蛋白(a)水平与未来心血管事件发生率之间的关联。
设计、地点和参与者：对女性健康研究中27791名最初健康的女性进行前瞻性研究，这些女性于1992年11月至1995年7月入组，并随访10年。使用与载脂蛋白(a)异构体大小无关的检测方法在基线时采集的血样中测量脂蛋白(a)水平。
首次发生主要心血管事件（非致命性心肌梗死、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(HRs)。
在随访期间，有899例心血管事件发生。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反应蛋白和随机分组治疗组后，脂蛋白(a)水平处于最高五分位数(≥44.0mg/dL)的女性发生心血管事件的可能性是处于最低五分位数(≤3.4mg/dL)女性的1.47倍(95%CI，1.21 - 1.79；趋势P值<.001)。然而，这种关联几乎完全归因于脂蛋白(a)水平最高者中的阈值效应。在调整上述所有变量后，脂蛋白(a)水平超过第90百分位数(≥65.5mg/dL)的HR为1.66(95%CI，1.38 - 1.99)；第95百分位数(≥83mg/dL)，1.87(95%CI，1.50 - 2.34)；第99百分位数(≥130.7mg/dL)，1.99(95%CI，1.32 - 3.00)，在较低水平时几乎没有风险梯度。在低密度脂蛋白胆固醇(LDL-C)高于中位数水平的女性中，这种关联最强。在该亚组中，脂蛋白(a)水平超过第90百分位数的调整后HR为1.81(95%CI，1.48 - 2.23)；第95百分位数，1.93(95%CI，1.51 - 2.48)；第99百分位数，1.93(95%CI，1.21 - 3.05)(与LDL-C的交互作用P值 =.001)。
在这个最初健康的女性队列中，使用与载脂蛋白(a)异构体大小无关的检测方法测得的极高水平的脂蛋白(a)(≥第90百分位数)与心血管风险增加相关，尤其是在LDL-C水平较高的女性中。然而，观察到的阈值和交互作用效应不支持对女性进行心血管分层时常规检测脂蛋白(a)。
