Cholesterol Homeostasis in Framingham Offspring Study

弗雷明汉后代研究中的胆固醇稳态

• 批准号: 6789435
• 负责人: ALICE H LICHTENSTEIN
• 金额: $ 18.9万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789435
• 关键词: apolipoproteins; biomarker; blood chemistry; blood lipid; blood lipoprotein; body composition; cardiovascular disorder diagnosis; cardiovascular disorder risk; cholestane compound; cholesterol; data collection methodology /evaluation; enzyme linked immunosorbent assay; family genetics; gas chromatography; gastrointestinal absorption /transport; genotype; homeostasis; human data; human genetic material tag; longitudinal human study; outcomes research; questionnaires; smoking; statistics /biometry; steroid biosynthesis

DESCRIPTION (provided by applicant): The objective of this application is to investigate the predictive value of using measures of cholesterol homeostasis to identify individuals at high risk of developing cardiovascular disease (CVD) relative to established risk factors. The specific aims are to 1) quantify circulating indicators of cholesterol homeostasis [levels of phytosterols and cholestanol (surrogate measures of cholesterol absorption) and cholesterol precursors (surrogate measures of cholesterol synthetic rates)] in plasma samples from Framingham Offspring Study participants diagnosed with established CVD and/or >50% carotid stenosis (N=165) not taking lipid-lowering medication and control subjects matched for age, sex, body mass index, hypertension and smoking status (n=330); 2) evaluate the validity of using indicators of cholesterol homeostasis to predict CVD risk in the Framingham Offspring Study-Cycle 6 participants by a) establishing adult normal ranges for circulating levels of phytosterol, cholestanol and cholesterol precursor (N=3378), b) defining the relationship between phytosterol, cholestanol and cholesterol precursor levels, and lipid, lipoprotein and apolipoprotein levels in plasma, c) defining the relationship between phytosterol, cholestanol and cholesterol precursor levels and selected dietary intake data (energy, protein, fat, saturated, monounsaturated, polyunsaturated and trans fatty acids, cholesterol, fiber and antioxidant supplements) and d) determining the relationship between phytosterol, cholestanol and cholesterol precursor levels and selected genotype data related to CVD risk (gene loci of apo E, apo A-IV, scavenger receptor class B type 1 [SRB1], and ATP-binding cassette [ABC] G5 and ABCG8 transporters); and 3) monitor clinical events in the Framingham Offspring Study cohort throughout a 10-year period (1995-2005) and relate these data to the phytosterol, cholestanol and cholesterol precursor levels. Measures of cholesterol homeostasis will be quantified first in subjects identified in specific aim #1 and then the balance of subjects identified in specific aim #2, achievable now due to the development of a gas chromatographic method using a single plasma sample. These data will be assessed relative to dietary, biochemical and genotype data currently available for the cohort. The results of the proposed work will define the relationship between markers of cholesterol absorption and synthesis, and CVD outcomes; establish reference values for measures of cholesterol absorption and synthesis; and assess the predictive value of these measures to identify high risk individuals relative to established risk factors.

描述（由申请人提供）：本申请的目的是调查使用胆固醇稳态度量的预测价值，以确定相对于既定的危险因素，患有患心血管疾病（CVD）高风险的个体。具体目的是1）量化胆固醇稳态的循环指标[植物固醇和胆固醇的水平（胆固醇吸收的替代度量）和胆固醇前体（胆固醇的替代度量）（胆固醇的替代度量） （n = 165）不服用与年龄，性别，体重指数，高血压和吸烟状态相匹配的降低脂质药物和对照对象（n = 330）； 2）评估使用胆固醇稳态指标的有效性来预测弗雷明汉后代的CVD风险在弗雷明汉后代研究周期6参与者，a）建立成人正常范围，以循环水平的植物醇，胆固醇和胆固醇和胆固醇前体的循环水平血浆中的脂质，脂蛋白和载脂蛋白水平，c）定义植物醇，胆固醇和胆固醇前体水平与选定的饮食摄入数据（能量，蛋白质，蛋白质，脂肪，饱和，单一饱和，单一饱和，多年饱和度，多饱和脂肪酸，胆固醇，胆固醇，纤维，抗固醇，替代）的关系，并确定饮食中的饮食摄入数据（能量，蛋白质，脂肪，脂肪）胆固醇和胆固醇前体水平以及与CVD风险相关的选定基因型数据（APO E，APO A-IV的基因基因座，清除剂受体B类1类[SRB1]和ATP结合盒[ABC] G5和ABCG8转运蛋白）； 3）监测整个10年期（1995-2005）的弗雷明汉后代研究队列中的临床事件，并将这些数据与植物醇，胆固醇和胆固醇前体水平联系起来。胆固醇稳态的度量将首先在特定目标1中确定的受试者中进行量化，然后在特定目标＃2中确定的受试者的平衡，这是由于使用单个等离子体样本的气体色谱法的开发而实现的。这些数据将相对于目前可用于该队列的饮食，生化和基因型数据进行评估。拟议工作的结果将定义胆固醇吸收和合成标记与CVD结局之间的关系。建立胆固醇吸收和合成测量值的参考值；并评估这些措施的预测价值，以确定相对于已建立的风险因素的高风险个人。