RISK FACTORS IN EARLY HUMAN ATHEROGENESIS

人类早期动脉粥样硬化的危险因素

• 批准号: 3433107
• 负责人: FREDERICK J CORNHILL
• 金额: $ 13.74万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3433107
• 关键词: African American; adolescence (12-20); atherosclerosis; atherosclerotic plaque; blood chemistry; blood lipid; cardiovascular disorder epidemiology; cardiovascular imaging /visualization; caucasian American; digital imaging; disease /disorder proneness /risk; early diagnosis; female; genotype; histopathology; human tissue; image processing; liver; male; postmortem; young adult human (21-34)

This collaborative project will collect arteries and risk factor data from 1,400 young persons 15-34 years of age who die from trauma and are autopsied in medical examiners' laboratories. The data will be analyzed to determine the associations of the risk factors for adult atherosclerotic disease with the various lesions of atherosclerosis that appear during this age period. These cases will supplement the 1,800 cases that are being collected in the ongoing multicenter cooperative study "Pathobiological Determinants of Atherosclerosis in Youth" (PDAY). The major purposes of the study are to: 1) obtain an adequate number of cases of women; 2) increase the power of the study to detect associations of risk factors with raised lesions which begin to appear in this age group; and 3) increase the power to detect genetic effects on atherosclerosis. Aortic and coronary artery lesions are measured by visual estimation and by gross and histologic morphometry using computerized image analysis. Risk factor measurements include cholesterol and lipoprotein cholesterol concentration in post mortem serum; thiocyanate in post mortem serum as a marker for smoking; blood pressure by wall thickness of renal arteries and arterioles; and DNA polymorphisms by analysis of liver DNA. Collection of cases is performed by participating centers in cooperation with local medical examiners. Processing of arteries, blood, liver, and other tissue is carried out in central laboratories, and data are managed by a statistical center. The Laboratory of Vascular Diseases (LVD) will function as the Morphometry Central Laboratory for the study. LVD will conduct quantitative morphometric analysis on all macroscopic (approximately 5,700) and microscopic (approximately 14,000) images of arterial tissue entered into the study. These analyses will employ modem techniques of image processing and will result in the production of both tabular and two-dimensional data. For the macroscopic studies of the thoracic and abdominal aorta and right coronary artery, tabular data of percentage surface area of the entire vessel segment, and also for smaller, more localized regions, for sudanophilic, raised and calcified lesions will be calculated and correlated with risk factor data (e.g., LDL cholesterol; Apo A, Apo B, LP(a); smoking; genetic phenotype, etc.). Similarly, two-dimensional probability-of-occurrence maps will be produced for subgroups (e.g., LDL < 130 mg/dl vs. LDL > 130 mg/dl) of these same risk factors. For the microscopic studies of sections from the thoracic and abdominal aorta and right and left anterior descending coronary arteries, tabular data of geometric parameters (e.g., intimal and medial thickness and area; lumen area, shape indices, ratios, etc.), and compositional parameters (e.g., area and percentage of area Oil Red "O" (ORO) positive, etc.) will be calculated and correlated with risk factor data. Similarly, two-dimensional mean arterial geometric form and probability- of-occurrence (e.g., ORO) will be produced for specific risk factor subgroups.

这个协作项目将收集动脉和风险因素 来自1,400名年轻人的数据15-34岁，死于创伤和 在体检医师的实验室中进行尸检。 数据将是 分析以确定成人风险因素的关联 动脉粥样硬化疾病，以及动脉粥样硬化的各种病变 出现在这个年龄段。 这些案件将补充1,800 正在进行的多中心合作社中收集的案例 研究“青年动脉粥样硬化的病理学决定因素”（pday）。 研究的主要目的是：1）获得足够数量的 妇女案件； 2）增加研究检测关联的力量 在这个年龄段开始出现的危险因素的危险因素 团体; 3）增加检测遗传影响的能力 动脉粥样硬化。 主动脉和冠状动脉病变由 视觉估计以及通过使用总体和组织学形态计量学 计算机图像分析。 风险因素测量包括 验尸后的胆固醇和脂蛋白胆固醇浓度 血清;在验尸血清中的硫氰酸盐作为吸烟的标志；血 肾动脉和动脉的壁厚压力；和DNA 通过分析肝DNA的多态性。 进行案件收集 通过与当地体检医师合作参加中心。 在进行动脉，血液，肝脏和其他组织的处理 中央实验室和数据由统计中心管理。 血管疾病实验室（LVD）将作为 该研究的形态计量学中央实验室。 LVD将进行 所有宏观的定量形态分析（大约 5,700）和微观组织图像（约14,000张） 进入研究。 这些分析将采用调制解调器技术 图像处理，并将导致表格的产生和 二维数据。 用于胸腔和 腹主动脉和右冠状动脉，百分比的表格数据 整个容器段的表面积，也适用于较小，更多的 用于瓜酚的局部区域将升高和钙化病变 与危险因素数据计算并相关（例如LDL胆固醇； apo a，apo b，lp（a）;吸烟；遗传表型等）。相似地， 将生成二维概率的概率图。 这些相同风险 因素。 用于从胸腔和 腹主动脉以及左右前降冠状动脉， 几何参数的表格数据（例如，内膜和内侧厚度 和区域；流明区域，形状指数，比率等）和组成 参数（例如，面积和面积油红色“ o”（ORO）阳性的面积和百分比， 等）将计算并与风险因素数据相关。 同样，二维平均动脉几何形式和概率 特定风险因素将产生出现（例如ORO） 亚组。