Nowak-Göttl U, Junker R, Hartmeier M, Koch H G, Münchow N, Assmann G, von Eckardstein A
Department of Pediatrics, Laboratory Medicine, Westfälische Wilhelms-Universität, Münster, Germany.
Circulation. 1999 Aug 17;100(7):743-8. doi: 10.1161/01.cir.100.7.743.
Serum levels of lipoprotein(a) [Lp(a)] are determined largely by genetic variation in the gene encoding for apolipoprotein(a) [apo(a)], the specific protein component of Lp(a) that is very homologous to plasminogen. High plasma levels of Lp(a) increase the risk for premature atherosclerotic vessel diseases. We investigated the little-characterized role of Lp(a) as a risk factor for venous thromboembolic diseases, alone and in conjunction with established thrombophilic risk factors of proteins regulating blood coagulation and fibrinolysis.
Serum levels of Lp(a) and lipids, protein C, protein S, and antithrombin, as well as the size of apo(a) isoforms and the presence of the factor V:Q(506) mutation, were determined in 186 consecutively admitted children from neonates to 18 years old with a history of venous thrombosis and in 186 age- and disease-matched control subjects. Children with a history of venous thrombosis had a significantly higher median Lp(a) level (19 versus 4.4 mg/dL) than control subjects. The risk for thromboembolic events in children with Lp(a) levels in the upper quartile, ie, >30 mg/dL, was 7.2 (95% CI, 3.7 to 14.5). The size of apo(a) isoforms was inversely related to Lp(a) levels and to the risk for thromboembolic events. Compared with the highest quartile of the apo(a) size distribution, the lowest quartile was associated with a risk of 8.2. In addition, multivariate statistical analysis gives evidence that the factor V:Q(506) mutation (OR/CI, 2.8/1.6 to 4.9), protein C (OR/CI, 6.5/2.1 to 19), and antithrombin deficiency (OR/CI, 10.4/1.2 to 90) were independent risk factors of childhood venous thrombosis. Coincidence of elevated Lp(a) with factor V:Q(506) mutation or deficiencies of protein C or antithrombin further increased the risk for thromboembolic events to 8.4.
Lp(a) >30 mg/dL is a risk factor for venous thromboembolism in childhood. Lp(a) measurements should be included in the screening of causal factors in children with venous thromboembolic events.
血清脂蛋白(a)[Lp(a)]水平很大程度上由载脂蛋白(a)[apo(a)]编码基因的遗传变异决定，apo(a)是Lp(a)的特定蛋白质成分，与纤溶酶原高度同源。血浆Lp(a)水平升高会增加早发性动脉粥样硬化血管疾病的风险。我们研究了Lp(a)作为静脉血栓栓塞性疾病危险因素的鲜为人知的作用，单独以及与调节血液凝固和纤维蛋白溶解的蛋白质的既定血栓形成危险因素共同作用时的情况。
测定了186例连续入院的有静脉血栓形成病史的新生儿至18岁儿童以及186例年龄和疾病匹配的对照受试者的血清Lp(a)和脂质、蛋白C、蛋白S和抗凝血酶水平，以及apo(a)异构体的大小和因子V:Q(506)突变的存在情况。有静脉血栓形成病史的儿童的Lp(a)中位数水平(19对4.4mg/dL)显著高于对照受试者。Lp(a)水平处于上四分位数即>30mg/dL的儿童发生血栓栓塞事件的风险为7.2(95%CI，3.7至14.5)。apo(a)异构体的大小与Lp(a)水平及血栓栓塞事件风险呈负相关。与apo(a)大小分布的最高四分位数相比，最低四分位数的风险为8.2。此外，多变量统计分析表明，因子V:Q(506)突变(OR/CI，2.8/1.6至4.9)、蛋白C(OR/CI，6.5/2.1至19)和抗凝血酶缺乏(OR/CI，10.4/1.2至90)是儿童静脉血栓形成的独立危险因素。Lp(a)升高与因子V:Q(506)突变或蛋白C或抗凝血酶缺乏同时存在会使血栓栓塞事件风险进一步增加至8.4。
Lp(a)>30mg/dL是儿童静脉血栓栓塞的危险因素。在对有静脉血栓栓塞事件的儿童进行病因筛查时应包括Lp(a)检测。
