Lead, Cadmium,Arsenic, and cardiovascular risk in children

描述(由申请人提供)：本项目的主要目标是检验儿童暴露于金属会影响他们的心血管风险并可能使他们容易患心血管疾病的假设。它是基于我们和其他人越来越多的流行病学文献，表明暴露于铅、镉或砷会增加心血管风险。然而，大多数关于金属对心血管风险影响的研究都是在成年人中进行的，儿童对金属对心血管影响的易感性在很大程度上是未知的。基本假设：1)铅、镉或砷的暴露与儿童的血压水平呈正相关；2)铅、镉或砷的暴露与儿童炎症和内皮功能障碍的血清标志物(C-反应蛋白、白细胞介素6[IL-6]、细胞间黏附分子-1[ICAM-1]和肿瘤坏死因子α[TNF-α])正相关；以及3)暴露、镉或砷与儿童的心率变异性呈负相关。设计和背景：我们建议对居住在墨西哥托雷森大都市地区的儿童暴露于铅、镉或砷与心血管风险标记物之间的关系进行横断面流行病学研究。我们将联系2001年参加Torresn铅与神经认知功能研究的儿童，当时他们6-7岁。我们预计招募512名(85%)最初的研究参与者，他们在2009年为本研究进行实地工作时将年满14-15岁。这一人群提供了一个独特的机会来评估金属对心血管的影响，在一大群具有良好特征的儿童中，他们的铅暴露以前已经被研究过。在这项研究中，我们将获得两项相隔两个月的金属暴露测量(全血中的铅和尿中的镉和砷)，并评估它们与心血管危险标记物的关系。主要结果将是血压、炎症和内皮功能障碍的血清学标志物(CRP、IL-6、ICAM-1和TNF-α)以及心率变异性。还将评估其他终点，包括肾近端小管损伤、心脏代谢异常(胰岛素抵抗和血脂水平)以及神经毒性终点的标志物。意义：托雷森的儿童暴露于Met-Mex Peqoles冶炼厂产生的粉尘中的铅、镉和砷，该冶炼厂是美洲最大的铅冶炼厂。虽然这一人群的平均金属暴露水平很高，但暴露范围与美国和其他西方国家的儿童重叠。因此，目前的人口是在人口一级获得关于大范围金属暴露的影响的信息的有效途径。从托雷森儿童那里获得的信息不仅与当地居民有关，而且与美国和国外的许多儿童有关。公共卫生相关性：该项目的主要目标是检验儿童接触金属会影响他们的心血管风险，并可能使他们更容易患上后来的心血管疾病的假设。我们建议对居住在墨西哥托雷森大都市地区的儿童中铅、镉或砷暴露与心血管风险标记物之间的关系进行一项横断面流行病学研究。几乎所有关于金属对心血管风险影响的研究都是在成人中进行的，儿童对金属对心血管影响的易感性在很大程度上是未知的。这项研究中获得的信息将与美国和国外数百万长期暴露在环境中的铅、镉和砷的儿童有关。

DESCRIPTION (provided by applicant): The main objective of this project is to test the hypothesis that exposure to metals in children will affect their cardiovascular risk and may predispose them to cardiovascular disease. It is based upon a growing epidemiological literature, by us and others, indicating that exposure to lead, cadmium, or arsenic increases cardiovascular risk. However, most studies of the impact of metals on cardiovascular risk have been carried out in adults, and the susceptibility of children to the cardiovascular effects of metals is largely unknown. Primary hypotheses: 1) Exposures to lead, cadmium, or arsenic are positively associated with blood pressure levels in children; 2) Exposures to lead, cadmium, or arsenic, are positively associated with serological markers of inflammation and endothelial dysfunction (C-reactive protein [CRP], interleukin-6 [IL-6], intercellular adhesion molecule-1 [ICAM-1], and tumor necrosis factor alpha [TNF-alpha]) in children; and 3) Exposures, cadmium, or arsenic are inversely associated with heart rate variability in children. Design and setting: We propose to conduct a cross sectional epidemiological study of the association between exposure to lead, cadmium, or arsenic and markers of cardiovascular risk in children residing in the Torresn metropolitan area, Mexico. We will contact the children who participated in the Torresn Study of Lead and Neurocognitive Function in 2001, when they were 6 - 7 years old. We expect to recruit 512 (85%) of the original study participants, who will be 14 - 15 years old at the time of field work for the present study in 2009. This population offers a unique opportunity to evaluate the cardiovascular effects of metals in a large and well characterized group of children whose lead exposure has been previously studied. In the present study, we will obtain two measurements of metal exposure two months apart (lead in whole blood and cadmium and arsenic in urine) and evaluate their association with cardiovascular risk markers. The primary outcomes will be blood pressure, serological markers of inflammation and endothelial dysfunction (CRP, IL-6, ICAM-1, and TNF- alpha), and heart rate variability. Other endpoints will also be assessed, including markers of renal proximal tubular injury, cardiometabolic abnormalities (insulin resistance and lipid levels), and neurotoxic endpoints. Significance: Children in Torresn are exposed to lead, cadmium, and arsenic from dusts generated by the Met-Mex Peqoles smelter, the largest lead smelter operating in the Americas. While the average exposure to metals in this population is high, the range of exposure overlaps with that of children in US and in other Western countries. The current population thus represents an efficient way to obtain information on the impact of a wide range of metal exposure at the population level. The information obtained from children in Torresn will be relevant not only to local area residents, but to many children in the US and abroad. PUBLIC HEALTH RELEVANCE: The main objective of this project is to test the hypothesis that exposure to metals in children will affect their cardiovascular risk and may predispose them to later cardiovascular disease. We propose to conduct a cross- sectional epidemiological study of the association between exposure to lead, cadmium, or arsenic and markers of cardiovascular risk in children residing in the Torresn metropolitan area, Mexico. Almost all studies of the impact of metals on cardiovascular risk have been carried out in adults, and the susceptibility of children to the cardiovascular effects of metals is largely unknown. The information obtained in this study will be relevant to millions of children in the US and abroad who are chronically exposed to lead, cadmium, and arsenic in the environment.