All Children’s Research Institute, All Children’s Hospital–Johns Hopkins Medicine, St Petersburg, FL, USA.
Haematologica. 2013 May;98(5):802-7. doi: 10.3324/haematol.2012.073833. Epub 2013 Jan 24.
Lipoprotein (a) is a risk factor for adult cardiovascular events, in which the apolipoprotein (a) component is thought to promote atherogenesis and impair fibrinolysis. We investigated whether elevated plasma lipoprotein (a) concentration and small predominant apolipoprotein (a) isoform size (number of kringle-4 domains) are risk factors for childhood arterial ischemic stroke and correlate with plasma fibrinolytic function. Patients who had had an arterial ischemic stroke in childhood (29 days - <21 years at onset; n=43) and healthy controls (n=127) were recruited for plasma sampling and laboratory determinations. Cases were followed for recurrence in a prospective cohort study. The median lipoprotein (a) concentration did not differ between groups [cases: median 18.0 nmol/L (7.5 mg/dL) and observed range 0.9-259 nmol/L (0.38-108.0 mg/dL), controls: 20.4 nmol/L (8.5 mg/dL) and 0.2-282 nmol/L (0.08-117.5 mg/dL); P=0.62]. While odds of incident stroke were not significantly increased, risks of recurrent arterial ischemic stroke were each more than ten-times increased for lipoprotein(a) >90(th) percentile of race-specific reference values and apolipoprotein (a) <10(th) percentiles [odds ratio=14.0 (95% confidence interval: 1.0-184), P=0.05 and odds ratio=12.8 (1.61-101), P=0.02]. Statistically significant but weak correlations were observed between euglobulin lysis time and both lipoprotein (a) level (r=0.18, P=0.03) and apolipoprotein (a) size (r= -0.26, P=0.002). In conclusion, elevated lipoprotein (a) and small apolipoprotein (a) potently increase the risk of recurrent arterial ischemic stroke in children, with a mechanism only partially attributable to impaired fibrinolysis. Collaborative studies are warranted to investigate these findings further and, more broadly, to establish key risk factors for incident and recurrent arterial ischemic stroke in children.
脂蛋白 (a) 是成人心血管事件的危险因素，其中载脂蛋白 (a) 成分被认为可促进动脉粥样硬化形成并损害纤维蛋白溶解。我们研究了血浆脂蛋白 (a) 浓度升高和小的主要载脂蛋白 (a) 同工型大小（克氏环 4 结构域的数量）是否为儿童动脉缺血性脑卒中的危险因素，并与血浆纤维蛋白溶解功能相关。我们招募了患有儿童期动脉缺血性脑卒中（发病时 29 天至 <21 岁；n=43）和健康对照者（n=127）进行血浆取样和实验室检测。在一项前瞻性队列研究中对病例进行复发随访。病例组和对照组的脂蛋白 (a) 浓度中位数无差异[病例组：中位数 18.0 nmol/L（7.5 mg/dL），观察范围 0.9-259 nmol/L（0.38-108.0 mg/dL），对照组：20.4 nmol/L（8.5 mg/dL），0.2-282 nmol/L（0.08-117.5 mg/dL）；P=0.62]。虽然事件性脑卒中的发病风险没有显著增加，但脂蛋白(a)>种族特异性参考值第 90 百分位数和载脂蛋白(a)<第 10 百分位数的患者发生复发性动脉缺血性脑卒中的风险增加了十倍以上[比值比=14.0（95%置信区间：1.0-184），P=0.05 和比值比=12.8（1.61-101），P=0.02]。我们观察到 euglobulin 溶解时间与脂蛋白 (a) 水平（r=0.18，P=0.03）和载脂蛋白 (a) 大小（r=-0.26，P=0.002）之间存在显著但较弱的相关性。总之，升高的脂蛋白 (a) 和小的载脂蛋白 (a) 可显著增加儿童复发性动脉缺血性脑卒中的风险，其机制部分归因于纤维蛋白溶解受损。需要进行协作研究以进一步研究这些发现，并更广泛地确定儿童事件性和复发性动脉缺血性脑卒中的关键危险因素。
