Cardiovascular Disease Biomarkers and Mediation of Hormone Therapy Effects

心血管疾病生物标志物和激素治疗效果的调节

基本信息

批准号：
8309334
负责人：
Ross L Prentice
金额：
$ 13.2万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8309334
关键词：
Affect Binding Proteins Biological Assay Biological Markers Blood Proteins Blood specimen Cardiovascular Diseases Cohort Studies Complement Factor D Coronary heart disease Data Analyses Diagnosis Disease Enrollment Enzyme-Linked Immunosorbent Assay Estrogens Hemopexin Hormone replacement therapy IGFBP2 gene IGFBP6 gene Incidence Inflammation Insulin Insulin-Like Growth Factor II Insulin-Like Growth-Factor Binding Protein 1 Intervention Lipids Mass Spectrum Analysis Measurement Measures Mediating Mediation Mediator of activation protein Orosomucoid Phase Plasma Plasma Proteins Postmenopause Probability Progestins Proteins Proteome Proteomics Randomized Research Risk Risk Factors Risk Marker Sampling Specimen Statistical Methods Stroke Thrombosis Thrombospondin 1 Validation Variant Woman Women&apos s Health Work base beta-2 Microglobulin cardiovascular disorder risk case control cohort disorder risk experience glutathione peroxidase hormone therapy insight novel

项目摘要

DESCRIPTION (provided by applicant): Confirmatory analyses of novel plasma protein associations with the risk of coronary heart disease and stroke will be carried out by applying enzyme-linked immunosorbent assays to baseline plasma specimens from cases and controls in the Women's Health Initiative postmenopausal hormone therapy trials. Candidate proteins were highly ranked in recent in-depth proteomic discovery research. For CHD these are alpha-1-acid glycoprotein 1, thrombospondin 1, complement factor D preprotein, glutathione peroxidase 3, and insulin-like binding protein 1 (IGFBP1). For stroke the candidate biomarkers are IGFBP2, IGFBP6, insulin-like growth factor 2, hemopexin, and beta 2 microglobulin. Specimen analyses will be carried out for 349 CHD cases and for 1-1 matched controls, and for 326 stroke cases and matched controls. Data analyses will control for traditional cardiovascular disease risk factors, and for available biomarkers of inflammation, thrombosis, and lipids. Women developing CHD or stroke following their first year of hormone therapy trial enrollment, and their matched controls, will also have plasma concentrations assessed in 1-year blood specimens for the subset of these proteins found to be affected by estrogen-alone or by estrogen plus progestin in discovery work using the same proteomic platform. The baseline and 1-year protein concentrations will be jointly analyzed to assess the extent to which treatment-related changes in these protein concentrations can mediate hormone therapy effects on CHD and stroke. These analyses will incorporate a novel correction for biomarker measurement error. The project has a high probability of confirming some new biomarkers of CHD and stroke risk, and for providing additional insight into observed hormone therapy effects on these diseases.

描述（由申请人提供）：将通过对妇女健康倡议绝经后激素治疗中病例和对照的基线血浆样本应用酶联免疫吸附测定，对新型血浆蛋白与冠心病和中风风险的关联进行验证性分析试验。候选蛋白质在最近深入的蛋白质组学发现研究中排名靠前。对于 CHD，这些是 α-1-酸性糖蛋白 1、血小板反应蛋白 1、补体因子 D 前蛋白、谷胱甘肽过氧化物酶 3 和胰岛素样结合蛋白 1 (IGFBP1)。对于中风，候选生物标志物包括 IGFBP2、IGFBP6、胰岛素样生长因子 2、血红素和 β2 微球蛋白。将对 349 例先心病病例和 1-1 匹配对照，以及 326 例中风病例和匹配对照进行样本分析。数据分析将控制传统的心血管疾病危险因素，以及炎症、血栓形成和脂质的可用生物标志物。参加第一年激素治疗试验后患上冠心病或中风的女性及其匹配的对照者，也将在一年的血液样本中评估血浆浓度，以了解这些蛋白质的子集是否受到单独雌激素或雌激素加雌激素的影响。孕激素的发现工作使用相同的蛋白质组平台。将联合分析基线和 1 年蛋白质浓度，以评估这些蛋白质浓度的治疗相关变化在多大程度上可以介导激素治疗对 CHD 和中风的影响。这些分析将纳入对生物标志物测量误差的新颖校正。该项目很有可能确认一些新的冠心病和中风风险生物标志物，并为观察到的激素治疗对这些疾病的影响提供更多见解。