Lead, Cadmium,Arsenic, and cardiovascular risk in children

描述（由申请人提供）：本项目的主要目的是检验儿童接触金属会影响其心血管风险并可能使其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，表明接触铅、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。主要假设：1)暴露于铅、镉或砷与儿童血压水平呈正相关；2)暴露于铅、镉或砷与儿童炎症和内皮功能障碍的血清学标志物（c -反应蛋白[CRP]、白细胞介素-6 [IL-6]、细胞间粘附分子-1 [ICAM-1]和肿瘤坏死因子α [tnf - α]）呈正相关；3)接触镉或砷与儿童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市区的儿童进行一项接触铅、镉或砷与心血管危险标志物之间关系的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6 - 7岁儿童。我们预计将招募512名（85%）原始研究参与者，他们将在2009年为本研究进行实地工作时年龄在14 - 15岁。这一人群为评估金属对心血管的影响提供了一个独特的机会，这是一个庞大且特征明确的儿童群体，他们的铅暴露已被研究过。在本研究中，我们将获得两次间隔两个月的金属暴露测量（全血铅和尿中镉和砷），并评估它们与心血管危险标志物的关系。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）和心率变异性。其他终点也将被评估，包括肾近端小管损伤标志物、心脏代谢异常（胰岛素抵抗和脂质水平）和神经毒性终点。意义：托雷森的儿童暴露于美洲最大的铅冶炼厂——墨斯佩科尔斯冶炼厂——产生的粉尘中铅、镉和砷。虽然这一人群的平均金属接触量很高，但接触范围与美国和其他西方国家儿童的接触范围重叠。因此，目前的人口是一种有效的方法，可以获得关于人口水平上各种金属接触的影响的信息。从Torresn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：该项目的主要目的是检验儿童接触金属会影响其心血管风险并可能使其日后易患心血管疾病的假设。我们建议对居住在墨西哥托雷森大都市区的儿童进行一项关于暴露于铅、镉或砷与心血管危险标志物之间关系的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。这项研究获得的信息将与美国和国外数百万长期暴露于铅、镉和砷环境中的儿童有关。

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.