CRIC Ancillary Study: Carbamylated low-density lipoprotein and cardiovascular eve

CRIC辅助研究：氨甲酰化低密度脂蛋白与心血管疾病

• 批准号: 7948260
• 负责人: Sudhir V Shah
• 金额: $ 36.21万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7948260
• 关键词: Address; Adhesions; Adopted; Age; Ancillary Study; Animal Model; Animals; Ankle; Antibodies; Area; Arteriosclerosis; Atherosclerosis; Basic Science; Biological; Biological Assay; Biological Factors; Biological Markers; Blood Urea Nitrogen; Blood specimen; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cell Adhesion Molecules; Cessation of life; Characteristics; Cholesterol; Chronic; Chronic Disease; Chronic Kidney Failure; Chronic Kidney Insufficiency; Clinical; Cohort Studies; Complex; Consumption; Coronary artery; Data; Data Analyses; Data Collection; Data Coordinating Center; Databases; Development; Diabetes Mellitus; Discrimination; Disease; Disease Outcome; Disease Progression; Doctor of Philosophy; End stage renal failure; Endothelial Cells; Enrollment; Enzyme-Linked Immunosorbent Assay; Epidemiologist; Ethnic Origin; Evaluation; Event; Functional disorder; Funding; Gender; Glomerular Filtration Rate; Goals; Grant; Guidelines; Heart Diseases; Human; Hypertension; In Vitro; Incidence; Individual; Injury; Investments; Joints; Kidney; Kidney Diseases; Kidney Failure; Laboratories; Letters; Lipoprotein (a); Low-Density Lipoproteins; Measures; Methods; Modality; Modeling; Morbidity - disease rate; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Nephrology; Notification; Obesity; Observational Study; Parents; Participant; Pathologist; Patients; Placebo Control; Plasma; Population; Population Heterogeneity; Preventive; Process; Proteins; Proteinuria; Protocols documentation; Published Comment; Publishing; ROC Curve; Race; Recurrence; Renal function; Research Design; Research Personnel; Risk; Risk Factors; Sample Size; Sampling; Serum; Smooth Muscle Myocytes; Solid; Stratification; Thick; United States National Institutes of Health; Urea; Variant; Vascular Diseases; Work; Yang; base; cardiovascular disorder risk; cohort; complement C4d; coronary artery calcification; design; experience; factor A; high risk; indexing; insight; intima media; low density lipoprotein inhibitor; meetings; member; monocyte; mortality; novel; novel strategies; post gamma-globulins; prognostic; public health relevance; response

DESCRIPTION (provided by applicant): The present proposal investigates the utility of a nontraditional risk factor, serum cLDL, as a risk factor associated with cardiac events and arteriosclerosis in patients with CKD utilizing the wealth of information from the CRIC Study. This proposal has been approved by the CRIC Ancillary Steering Committee and will include approximately 3,600 CRIC participants with mild to moderate renal disease who have been followed for up to five years or until death. Blood urea dissociates to form cyanate that may alter proteins including low-density lipoprotein (LDL) by a process known as carbamylation. Our recent studies demonstrate that cLDL has all of the biological effects relevant to atherosclerosis. In addition, we have demonstrated the development of aortic atherosclerosis in mice that have elevated plasma cLDL due either to chronic kidney failure or chronic urea consumption. Finally, in human studies, end-stage kidney disease (ESKD) patients have significantly elevated plasma cLDL concentration. Our hypothesis is that cLDL is associated with prevalent, recurrent, and incident cardiovascular disease and with measures of arteriosclerosis (carotid intima-media thickness [IMT] and coronary artery calcification [CAC]) in patients with CKD. A secondary objective is to determine the relationship between serum cLDL and serum urea and/or level of renal function (estimated glomerular filtration rate [eGFR]). We have raised the antibody to measure cLDL and have developed a sensitive and specific cLDL sandwich ELISA assay. This ancillary study will cause no burden on participating patients and will examine a potentially important non-traditional atherosclerotic risk factor in patients with CKD. This proposal is timely because the cardiovascular events in patients who have been enrolled during 2003-2007 are currently being evaluated and the data will be available by 2010. PUBLIC HEALTH RELEVANCE: Patients with kidney disease have a high risk of developing heart disease. Traditional risk factors for heart disease like high cholesterol do not explain this risk. Patients with kidney disease have higher levels of blood urea nitrogen, which can be transformed into products that modify proteins by a process known as carbamylation. The overall goal of this proposal is to utilize the wealth of information that has been gathered as part of the NIH-funded Chronic Renal Insufficiency Cohort (CRIC) Study to evaluate the relevance of carbamylated LDL (cLDL), a nontraditional CV risk factor, to cardiovascular disease in patients with chronic kidney disease.

描述（由申请人提供）：