Clin Chem Lab Med. 2015 Jun;53(7):1119-25. doi: 10.1515/cclm-2014-1081.
BACKGROUND: Obesity and cardiovascular disease (CVD) often co-exist, but the pathophysiologic mechanisms that link the two are not fully understood. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the modification of lipids within atheromatous plaques. Recently, circulating Lp-PLA2 was found to be predictive of thromboembolic episodes in adults, independently of a variety of other potential risk factors, including markers of inflammation, renal function, and hemodynamic stress. However, the function of this lipase and its importance as a biomarker in childhood obesity is much less studied. The aim of the study was to study Lp-PLA2, a non-traditional risk factor of CVD, in obese children. METHODS: Sixty-seven lean [39 boys and 28 girls, mean body mass index (BMI) z-score -0.2±0.8] and 66 obese (32 boys and 34 girls, mean BMI z-score 4.4±1.2) age-matched (p=0.251) children, aged 6-12 years, were studied. BMI z-score was calculated based on the Greek BMI growth curves, and children were categorized as obese according to the Cole criteria. All children underwent physical examination and a fasting morning blood sample was obtained for glucose, insulin, lipid profile, and Lp-PLA2 assessment. Plasma concentrations of Lp-PLA2 were determined by a commercially available Lp-PLA2 enzyme-linked immunosorbent assay kit (PLAC Test), while other measurements were performed using standard methods. RESULTS: Plasma Lp-PLA2 levels were significantly higher in obese children (322.5±77.8 ng/mL) compared with normal-weight ones (278.0±64.4 ng/mL, p<0.001). Lp-PLA2 concentrations were significantly correlated with the BMI z-score (p=0.004). Receiver operating characteristic analysis on Lp-PLA2 values resulted in significant areas under the curve (AUC) for distinguishing between obese and normal-weight groups of children (AUC, 0.726; p<0.001). CONCLUSIONS: We found significantly higher Lp-PLA2 levels in obese children than lean controls. Interestingly, they all had levels >200 ng/mL, which are considered to correlate with atherosclerosis and a high thromboembolic risk in adults. The positive correlation of Lp-PLA2 with BMI suggests that Lp-PLA2 might be the link between obesity and increased cardiovascular risk, which can be elevated even at a very young age. Measurement of Lp-PLA2 in plasma could therefore represent a further biomarker for assessing increased CVD risk in obese children and adolescents.
背景:肥胖症和心血管疾病(CVD)常同时存在,但两者之间的病理生理机制尚不完全清楚。脂蛋白相关磷脂酶 A2(Lp-PLA2)参与动脉粥样斑块内脂质的修饰。最近,研究发现循环 Lp-PLA2 可独立于多种其他潜在危险因素(包括炎症标志物、肾功能和血流动力学应激标志物)预测成年患者的血栓栓塞事件。然而,这种脂肪酶的功能及其作为儿童肥胖症生物标志物的重要性研究较少。本研究旨在研究肥胖儿童的非传统 CVD 危险因素 Lp-PLA2。
方法:研究纳入了 67 名肥胖儿童(32 名男孩和 34 名女孩,平均 BMI z 评分 4.4±1.2)和 66 名瘦儿童(39 名男孩和 28 名女孩,平均 BMI z 评分-0.2±0.8),这些儿童年龄相匹配(p=0.251),年龄在 6-12 岁之间。BMI z 评分基于希腊 BMI 生长曲线计算,根据 Cole 标准将儿童归类为肥胖。所有儿童均接受体格检查,并于清晨空腹采集血样以检测血糖、胰岛素、血脂和 Lp-PLA2。通过商用 Lp-PLA2 酶联免疫吸附试验试剂盒(PLAC Test)测定血浆 Lp-PLA2 浓度,其他测量均采用标准方法。
结果:肥胖儿童(322.5±77.8 ng/mL)的血浆 Lp-PLA2 水平明显高于体重正常的儿童(278.0±64.4 ng/mL,p<0.001)。Lp-PLA2 浓度与 BMI z 评分显著相关(p=0.004)。Lp-PLA2 值的受试者工作特征曲线分析产生了区分肥胖组和体重正常组的显著曲线下面积(AUC)(AUC,0.726;p<0.001)。
结论:与瘦对照组相比,肥胖儿童的 Lp-PLA2 水平明显更高。有趣的是,他们的 Lp-PLA2 水平均>200 ng/mL,这与成人的动脉粥样硬化和高血栓栓塞风险相关。Lp-PLA2 与 BMI 的正相关表明,Lp-PLA2 可能是肥胖与心血管风险增加之间的联系,即使在非常年轻时,这种风险也可能升高。血浆 Lp-PLA2 的测量因此可能成为评估肥胖儿童和青少年 CVD 风险增加的另一种生物标志物。
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