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）：本申请的目的是研究使用胆固醇稳态测量来识别相对于已确定的危险因素具有罹患心血管疾病（CVD）高风险的个体的预测价值。具体目标是 1) 量化弗雷明汉后代研究参与者血浆样本中胆固醇稳态的循环指标 [植物甾醇和胆固醇水平（胆固醇吸收的替代指标）和胆固醇前体（胆固醇合成率的替代指标）] (N=165) 未服用降脂药物的受试者与年龄、性别、体重指数、高血压和吸烟状况相匹配的对照受试者 (n=330)； 2) 评估使用胆固醇稳态指标预测弗雷明汉后代研究第 6 周期参与者的 CVD 风险的有效性，方法是：a) 建立植物甾醇、胆甾醇和胆固醇前体循环水平的成人正常范围 (N=3378)，b) 定义植物甾醇、胆甾醇和胆固醇前体水平之间的关系，以及 血浆中脂质、脂蛋白和载脂蛋白水平，c) 确定植物甾醇、胆甾醇和胆固醇前体水平与选定膳食摄入数据（能量、蛋白质、脂肪、饱和、单不饱和、多不饱和和反式脂肪酸、胆固醇、纤维和抗氧化剂补充剂）之间的关系，以及 d) 确定植物甾醇、 胆甾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（载脂蛋白 E、载脂蛋白 A-IV、B 型清道夫受体 1 型 [SRB1] 和 ATP 结合盒 [ABC] G5 和 ABCG8 转运蛋白的基因位点）； 3) 监测弗雷明汉后代研究队列在整个 10 年期间（1995-2005）的临床事件，并将这些数据与植物甾醇、胆甾醇和胆固醇前体水平相关联。首先对特定目标#1中确定的受试者的胆固醇稳态测量进行量化，然后对特定目标#2中确定的受试者的平衡进行量化，由于使用单一血浆样品的气相色谱方法的开发，现在可以实现这一目标。这些数据将根据该队列当前可用的饮食、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志物与 CVD 结果之间的关系；建立胆固醇吸收和合成测量的参考值；并评估这些措施的预测价值，以确定相对于既定风险因素的高风险个体。