Multi-Ethnic Study of Atherosclerosis (MESA) Cohort

**MESA**<br/> The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease. MESA researchers study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Thirty-eight percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent.

Participants were recruited from six field centers across the United States: Wake Forest University, Columbia University, Johns Hopkins University, University of Minnesota, Northwestern University and University of California - Los Angeles. Each participant received an extensive physical exam and determination of coronary calcification, ventricular mass and function, flow-mediated endothelial vasodilation, carotid intimal-medial wall thickness and presence of echogenic lucencies in the carotid artery, lower extremity vascular insufficiency, arterial wave forms, electrocardiographic (ECG) measures, standard coronary risk factors, sociodemographic factors, lifestyle factors, and psychosocial factors. Selected repetition of subclinical disease measures and risk factors at follow-up visits allows study of the progression of disease. Blood samples have been assayed for putative biochemical risk factors and stored for case-control studies. DNA has been extracted and lymphocytes cryopreserved (for possible immortalization) for study of candidate genes and possibly, genome-wide scanning, expression, and other genetic techniques. Participants are being followed for identification and characterization of cardiovascular disease events, including acute myocardial infarction and other forms of coronary heart disease (CHD), stroke, and congestive heart failure; for cardiovascular disease interventions; and for mortality.

In addition to the six Field Centers, MESA involves a Coordinating Center, a Central Laboratory, and Central Reading Centers for Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Ultrasound, and Electrocardiography (ECG). Protocol development, staff training, and pilot testing were performed in the first 18 months of the study. The first examination took place over two years, from July 2000 - July 2002. It was followed by four examination periods that were 17-20 months in length. Participants have been contacted every 9 to 12 months throughout the study to assess clinical morbidity and mortality.

**MESA Family**<br/> The general goal of the MESA Family Study, an ancillary study to MESA funded by a grant from NHLBI, is to apply modern genetic analysis and genotyping methodologies to delineate the genetic determinants of early atherosclerosis. This is being accomplished by utilizing all the current organizational structures of the **Multi-Ethnic Study of Atherosclerosis (MESA)** and Genetic Centers at Cedars-Sinai Medical Center and University of Virginia.

In the MESA Family Study, the goal is to locate and identify genes contributing to the genetic risk for cardiovascular disease (CVD), by looking at the early changes of atherosclerosis within families (mainly siblings). 2128 individuals from 594 families, yielding 3,026 sibpairs divided between African Americans and Hispanic-Americans, were recruited by utilizing the existing framework of MESA. MESA Family studied siblings of index subjects from the MESA study and from new sibpair families (with the same demographic characteristics) and is determining the extent of genetic contribution to the variation in coronary calcium (obtained via CT Scan) and carotid artery wall thickness (B-mode ultrasound) in the two largest non-majority U.S. populations. In a small proportion of subjects, parents of MESA index subjects participating in MESA Family were studied but only to have blood drawn for genotyping.

The MESA Family cohort was recruited from the six MESA Field Centers. MESA Family participants underwent the same examination as MESA participants during May 2004 - May 2007. DNA was extracted and lymphocytes immortalized for study of candidate genes, genome-wide linkage scanning, and analyzed for linkage with these subclinical cardiovascular traits. While linkage analysis is the primary approach being used, an additional aspect of the MESA Family Study takes advantage of the existing MESA study population for testing a variety of candidate genes for association with the same subclinical traits. Genotyping and data analysis will occur throughout the study.

**MESA Air**<br/> The general goal of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (&#39;MESA Air&#39;) is to prospectively examine the relation between an individual level assessment of long-term ambient air pollution exposures (including PM_2.5 and the progression of subclinical cardiovascular disease in a multi-city, multi-ethnic cohort. MESA Air will also prospectively examine the relationship between an individual level assessment of long-term ambient air pollution exposures and the incidence of cardiovascular disease, including myocardial infarction and cardiovascular death. MESA AIR is funded by a grant from the United States Environmental Protection Agency to the University of Washington and subcontracts from the UW to other participating institutions.

MESA Air will assess if ambient air pollution is associated with changes over time in subclinical measures of atherosclerosis and plasma markers of inflammation, oxidative damage, and endothelial activation in a longitudinal data model, adjusting for age, race/ethnicity, socioeconomic status, and specific cardiovascular risk factors (such as diabetes, hypertension, smoking, and diet). The study will similarly assess if the incidence of cardiovascular events is associated with long-term exposure to ambient air pollution, using a proportional hazards model. The study includes refinement of statistical tools, and explores joint/independent effects of acute and long-term pollutant exposure in the occurrence of cardiovascular disease.

The MESA Air study is built on the foundation of the ongoing MESA study. The parent MESA Study cohort is located in six geographic areas (&#39;Field Centers&#39;) that capture tremendous exposure heterogeneity, comparable to or greater than the variability in locations of prior U.S. cohort studies. In addition to the six Field Centers, the study involves a Coordinating Center, a Central Laboratory, and Reading Centers for Computed Tomography (CT), ultrasound and air pollution data.

The cohort for the MESA Air study currently includes 6226 subjects: 5479 enrolled in the parent MESA study; 257 recruited specifically for this study, and 490 recruited from the MESA Family study. The entire MESA Air cohort will be followed over a 10-year project period for the occurrence of cardiovascular disease events.

On two occasions over the ten-year study period, 3600 subjects from the MESA Air cohort, residing in nine locales, will undergo computed tomography scanning to assess presence and extent of coronary artery calcification (CAC), and ultrasound of the carotid artery to determine intima-media thickness (IMT). We will also repeatedly assess plasma markers of inflammation, oxidative damage, and endothelial function in 720 subjects.

MESA Air adds state-of-the-art air pollution exposure assessment information to the MESA cohort study, and introduces new subjects and outcome measures to achieve our aims. The study will assess long-term individual-level exposure to ambient air pollutants for each subject using community-scale monitoring, outdoor spatial variation, subject proximity to pollution sources, pollutants&#39; infiltration efficiency, and personal time-activity information. The exposure models will be validated using detailed monitoring in a subset of subjects.

**The MESA Cohort is utilized in the following dbGaP substudies.** To view genotypes, analysis, expression data, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" section of this top-level study page phs000209 MESA Cohort. - [phs000420](./study.cgi?study_id=phs000420) MESA SHARe - [phs000283](./study.cgi?study_id=phs000283) MESA CARe - [phs000403](./study.cgi?study_id=phs000403) MESA ESP Heart-GO

**多种族动脉粥样硬化研究（Multi-Ethnic Study of Atherosclerosis, MESA）**
本研究旨在探究**亚临床心血管疾病（subclinical cardiovascular disease，即在出现临床症状与体征前通过无创手段检出的疾病）**的特征，以及预测疾病进展为显性临床心血管疾病或亚临床病变进展的危险因素。研究招募了6814名年龄在45~84岁之间的无症状男性与女性，采用基于人群的多样化样本。招募的参与者中，38%为白人，28%为非裔美国人，22%为西班牙裔，12%为亚裔，其中以华裔为主。

参与者招募自美国境内6个现场研究中心：维克森林大学、哥伦比亚大学、约翰斯·霍普金斯大学、明尼苏达大学、西北大学以及加州大学洛杉矶分校。每位参与者均接受了全面的体格检查，并完成了以下项目的检测：**冠状动脉钙化（coronary calcification）**、**心室质量与功能（ventricular mass and function）**、**血流介导的内皮血管舒张功能（flow-mediated endothelial vasodilation）**、**颈动脉内膜中层厚度（carotid intimal-medial wall thickness）**及**颈动脉强回声透亮区（echogenic lucencies）**、**下肢血管功能不全（lower extremity vascular insufficiency）**、**动脉波形（arterial wave forms）**、**心电图（electrocardiographic, ECG）**指标、标准冠状动脉危险因素、社会人口学因素、生活方式因素及社会心理因素。通过在随访访视中重复检测亚临床疾病指标与危险因素，可实现疾病进展的相关研究。已对血液样本进行潜在生化危险因素的检测，并留存样本用于**病例对照研究（case-control studies）**。已提取DNA并将淋巴细胞冷冻保存（用于后续永生化实验），以开展**候选基因（candidate genes）**研究，以及可能的**全基因组扫描（genome-wide scanning）**、基因表达分析与其他遗传学技术研究。研究将对参与者进行长期随访，以识别和表征心血管疾病事件（包括**急性心肌梗死（acute myocardial infarction）**及其他形式的**冠状动脉粥样硬化性心脏病（coronary heart disease, CHD）**、**脑卒中（stroke）**、**充血性心力衰竭（congestive heart failure）**），评估心血管疾病干预措施，并监测死亡率。

除6个现场研究中心外，MESA研究还设有**协调中心（Coordinating Center）**、**中央实验室（Central Laboratory）**，以及**计算机断层扫描（Computed Tomography, CT）**、**磁共振成像（Magnetic Resonance Imaging, MRI）**、**超声检查（Ultrasound）**及心电图的**中央读片中心（Central Reading Centers）**。研究启动的前18个月完成了方案制定、人员培训与预实验。首次研究访视于2000年7月至2002年7月期间开展，历时两年。随后进行了4个时长为17~20个月的访视周期。在整个研究期间，每9~12个月对参与者进行一次随访，以评估临床发病与死亡情况。

**MESA家族研究（MESA Family Study）**
作为由美国国立心肺血液研究所（National Heart, Lung, and Blood Institute, NHLBI）资助的MESA附属研究，MESA家族研究的总体目标是应用现代遗传学分析与**基因分型方法（genotyping methodologies）**，阐明早期**动脉粥样硬化（atherosclerosis）**的**遗传决定因素（genetic determinants）**。本研究依托**多种族动脉粥样硬化研究（Multi-Ethnic Study of Atherosclerosis, MESA）**现有组织架构，并联合锡达斯-赛奈医疗中心与弗吉尼亚大学的遗传中心开展相关工作。

MESA家族研究的核心目标是通过分析家族（主要为同胞）内动脉粥样硬化的早期变化，定位并识别与**心血管疾病（cardiovascular disease, CVD）**遗传风险相关的基因。研究依托MESA现有招募框架，共纳入594个家庭的2128名个体，形成3026对**同胞对（sibpairs）**，分布于非裔美国人与西班牙裔人群中。本研究对MESA研究**索引病例（index subjects）**的同胞及符合相同人口统计学特征的新增同胞对家庭进行了研究，旨在明确美国两大非主要少数族裔人群中，冠状动脉钙化（通过CT扫描获取）与**颈动脉管壁厚度（carotid artery wall thickness）**（**B型超声（B-mode ultrasound）**检测）的变异程度受遗传因素影响的比例。仅在少量受试者中，对参与本研究的MESA索引病例的父母进行了采血用于基因分型。

MESA家族研究的队列招募自6个MESA现场研究中心。2004年5月至2007年5月期间，MESA家族研究参与者接受了与MESA研究参与者相同的检查项目。研究人员提取了受试者DNA，并将淋巴细胞永生化，用于候选基因研究与**全基因组连锁扫描（genome-wide linkage scanning）**，并分析上述亚临床心血管性状的连锁关联。本研究以**连锁分析（linkage analysis）**为主要研究手段，同时利用现有MESA研究人群，开展候选基因与上述亚临床性状关联的相关检测。基因分型与数据分析将贯穿整个研究周期。

**MESA空气污染研究（Multi-Ethnic Study of Atherosclerosis and Air Pollution, MESA Air）**
本研究的总体目标是在多城市、多种族队列中，前瞻性探究个体水平长期**环境空气污染（ambient air pollution）**暴露（包括**细颗粒物（PM₂.₅）**）与亚临床心血管疾病进展之间的关联。同时，本研究还将前瞻性评估个体水平长期环境空气污染暴露与心血管疾病发病（包括心肌梗死与心血管死亡）之间的关系。MESA Air研究由美国环境保护署向华盛顿大学提供资助，并由华盛顿大学向其他参与机构签订分包合同。

MESA Air研究将采用**纵向数据模型（longitudinal data model）**，评估环境空气污染与动脉粥样硬化亚临床指标、炎症、**氧化损伤（oxidative damage）**及**内皮激活（endothelial activation）**相关血浆标志物随时间的变化是否存在关联，并校正年龄、种族/族裔、**社会经济地位（socioeconomic status）**以及特定心血管危险因素（如糖尿病、高血压、吸烟与饮食）的影响。本研究还将采用**比例风险模型（proportional hazards model）**，评估心血管事件发生率与长期环境空气污染暴露之间的相关性。此外，研究将对统计工具进行优化，并探究急性与长期污染物暴露在心血管疾病发生中的联合/独立效应。

本研究依托正在进行的MESA研究搭建框架。母队列MESA研究的6个地理区域（现场研究中心）覆盖了显著的暴露异质性，其暴露变异性不低于此前美国队列研究的地点变异性。除6个现场研究中心外，本研究还设有协调中心、中央实验室，以及计算机断层扫描、超声检查与空气污染数据的读片中心。

MESA Air研究的当前队列共纳入6226名受试者：其中5479名来自母队列MESA研究，257名为本次研究专门招募的受试者，490名来自MESA家族研究。整个MESA Air队列将在10年的项目周期内接受随访，以监测心血管疾病事件的发生。

在10年研究周期内，将分两次对来自9个地区的3600名MESA Air队列受试者进行计算机断层扫描，以评估**冠状动脉钙化（coronary artery calcification, CAC）**的存在与程度，并进行颈动脉超声检查以测定**颈动脉内膜中层厚度（intima-media thickness, IMT）**。同时，将对720名受试者的炎症、氧化损伤及内皮功能相关血浆标志物进行重复检测。

MESA Air研究为MESA队列研究引入了前沿的空气污染暴露评估方法，并新增了受试者与结局指标以实现研究目标。本研究将通过社区规模监测、室外空间变异、受试者距污染源的距离、污染物渗透效率以及个人时间-活动信息，对每位受试者的长期个体水平环境空气污染暴露进行评估。暴露模型将通过对部分受试者的详细监测进行验证。

**本研究队列已用于以下dbGaP子研究**
若需查看这些子研究中收集的基因型、分析数据、表达数据、其他分子数据及衍生变量，请点击以下子研究链接，或访问本顶层研究页面`phs000209 MESA Cohort`的“子研究”板块：
- [phs000420](./study.cgi?study_id=phs000420) MESA SHARe
- [phs000283](./study.cgi?study_id=phs000283) MESA CARe
- [phs000403](./study.cgi?study_id=phs000403) MESA ESP Heart-GO