Low-level Arsenic Exposure and Cardiovascular Disease in Multi-Ethnic Adults (MESA As)

多种族成年人的低水平砷暴露与心血管疾病 (MESA As)

• 批准号: 10170347
• 负责人: Ana Navas-Acien
• 金额: $ 61.55万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170347
• 关键词: Adult; African American; Age-Years; Air; Air Pollution; Area; Arsenic; Arteries; Asians; Bangladesh; Biological; Biological Markers; Blood Pressure; Blood Vessels; C-reactive protein; Carbon; Carcinogens; Cardiovascular Diseases; Cardiovascular system; Carotid Atherosclerotic Disease; Categories; Cell Adhesion Molecules; Chile; Chinese American; Chronic; Cities; Clinical; Cohort Studies; Coronary heart disease; Country; Cox Proportional Hazards Models; DNA Methylation; Data; Development; Diabetes Mellitus; Diet; Disease Outcome; Electrophysiology (science); Endothelium; Epidemiology; Epigenetic Process; Ethnic Origin; Ethnic group; Event; Exposure to; Fibrinogen; Food; General Population; Genes; Genetic; Geography; Gluten-free diet; Health; Heart; Hispanic Americans; Hispanics; Homocysteine; Hypertension; Incidence; Individual; Inflammation; Intake; Interleukin-2; Interleukin-6; International; Linear Models; Link; Measurement; Measures; Mediating; Mediation; Mediator of activation protein; Metabolism; Metals; Methods; Methyltransferase; Modeling; Modification; Multi-Ethnic Study of Atherosclerosis; Nutritional status; Outcome; Oxidative Stress; Participant; Pattern; Peer Review; Peripheral arterial disease; Pilot Projects; Plasma; Plasminogen Activator Inhibitor 1; Population; Population Study; Publications; Race; Research; Rice; Risk Assessment; Risk Factors; Role; Safety; Sampling; Seafood; Smoking; Smoking Status; Source; Spottings; Stroke; Subgroup; Testing; Thrombosis; Time; Tobacco smoke; Toxic effect; United States; United States Environmental Protection Agency; Urine; Water; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular effects; cardiovascular risk factor; carotid intima-media thickness; caucasian American; clinical risk; cohort; coronary artery calcification; disorder control; drinking water; environmental tobacco smoke; flexibility; follow-up; genetic variant; genome-wide; inflammatory marker; mortality; multi-ethnic; multi-racial; prospective; racial and ethnic; sex; sociodemographics; toxicant

PROJECT SUMMARY Epidemiologic and experimental evidence supports that exposure to moderate-to-high arsenic (As) is a cardiovascular disease (CVD) risk factor. Little is known, however, on the cardiovascular effects of low As exposure through diet, particularly rice. We aim to investigate the prospective association of As exposure and metabolism with clinical and subclinical CVD (Aim 1), as well as effect modification (Aim 2), and potential mediators (Aim 3) of these associations in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of White, Black, Hispanic, and Chinese-American adults 45-84 years of age from 6 US cities. In a pilot study in MESA (n=310), median (percentile 90) urine As not derived from seafood was 4.9 (11.7), 3.8 (11.3), 2.2 (8.5), 2.2 (6.1) µg/L for Chinese Americans, Hispanics, Blacks and Whites; higher rice intake was associated with higher urine As; and a candidate SNP in AS3MT (gene encoding As(III) methyltransferase), was non- significantly associated with urine As metabolism profile. In the proposed study, we will include 6,725 MESA participants free of CVD at baseline who have been followed for a mean of 12.1 years with up to 5 exams. Urine samples, cardiovascular risk factors, genetic and epigenetic data, early markers of CVD, and subclinical and clinical CVD outcomes are available. We will measure As species and total As and other metals in spot urine samples and estimate non seafood As using a previously validated method. We will evaluate all CVD, coronary heart disease and stroke mortality and incidence (as clinical outcomes) and carotid intima-media thickness, coronary artery calcification, arterial distensibility and peripheral arterial disease (as subclinical outcomes). We will examine smoking status and secondhand smoke, genome-wide and Metabochip genetic variants, urine As metabolism patterns, and plasma homocysteine as a marker of one-carbon metabolism. We will also evaluate markers of inflammation (C-reactive protein, interleukin(IL)-2, and IL-6), endothelial function (soluble cell adhesion molecules), thrombosis (fibrinogen and plasminogen activator inhibitor-1, electrophysiology (QT interval), hypertension, diabetes, and epigenetic modifications (DNA methylation). In Aim 1 we will conduct Cox proportional hazards models for time to event clinical outcomes, generalized linear models (GLM) with logit or identity link for binary or continuous subclinical outcomes at baseline, and marginal linear models with repeated subclinical outcomes longitudinally. Arsenic levels will be modeled as continuous, categorical or flexible splines, separately. Models will be progressively adjusted for potential confounders including sociodemographic and traditional CVD risk factors. Effect modification will be estimated by adding interaction terms to the regression models. For mediation analyses, we will first estimate the association between As and the potential mediators using similar strategies as in Aim 1, then formal statistical mediation analysis will be applied. This study can inform on the cardiovascular role, or lack thereof, of low-level As exposure and contribute to As risk assessment and to CVD prevention and control in general populations.

项目摘要 流行病学和实验证据支持暴露于中度到高砷（AS）是一个 心血管疾病（CVD）危险因素。然而，对低的心血管影响很少 通过饮食，尤其是大米的接触。我们旨在调查AS暴露和 具有临床和亚临床CVD的代谢（AIM 1）以及效果修改（AIM 2）以及潜力 这些关联的介体（目标3）在动脉粥样硬化的多种族研究（MESA）中，一项研究的队列研究 白色，黑色，西班牙裔和中国裔美国人从6个城市开始45-84岁。在一项试点研究中 Mesa（n = 310），未从海鲜衍生的尿液中位数（百分位数90）为4.9（11.7），3.8（11.3），2.2（8.5），2.2（8.5）， 中国美国人，西班牙裔，黑人和白人的2.2（6.1）µg/l；较高的水稻摄入量与 尿液较高； AS3MT中的候选SNP（基因编码为（III）甲基转移酶）是非 - 与尿液作为代谢概况显着相关。在拟议的研究中，我们将包括6,725 Mesa 在基线时没有CVD的参与者，他们的遵循平均为12。1年，最多5次考试。 尿液样本，心血管危险因素，遗传和表观遗传学数据，CVD的早期标记以及亚临床 和临床CVD结果可用。我们将以物种和总金属的量度测量 尿液样品并使用先前验证的方法估算非海鲜。我们将评估所有CVD， 冠状动脉疾病，中风死亡率和发病率（作为临床结果）和颈动脉内膜媒体 厚度，冠状动脉计算，动脉可疑性和外周动脉疾病（作为亚临床 结果）。我们将检查吸烟状况和二手烟，全基因组和分类遗传 变体，尿作为代谢模式和血浆同型半胱氨酸作为单碳代谢的标志物。我们 还将评估炎症的标记（C反应蛋白，白介素（IL）-2和IL-6），内皮功能 （可溶性细胞粘附分子），血栓形成（纤维蛋白原和纤溶酶原激活物抑制剂1，， 电生理学（QT间隔），高血压，糖尿病和表观遗传修饰（DNA甲基化）。在 AIM 1我们将进行COX比例危害模型，以便时间到事件临床结果，广义线性 具有二进制或连续亚临床结果的logit或身份链接的模型（GLM），而边缘 具有纵向重复亚临床结果的线性模型。砷水平将建模为连续的， 分类或柔性花纹分别。模型将逐步调整为潜在的混杂因素 包括社会人口统计学和传统CVD风险因素。效果修改将通过添加来估算 回归模型的相互作用术语。对于调解分析，我们将首先估算关联 在AS和潜在的调解人之间使用与AIM 1相似的策略，然后是正式的统计调解 分析将被应用。这项研究可以告知心血管角色，或缺乏低级的角色 暴露并有助于作为风险评估以及一般人群中的CVD预防和控制。