CVD in American Indians Biomarker lab and Arizona Field Center

美洲印第安人生物标记实验室和亚利桑那现场中心的 CVD

• 批准号: 8665465
• 负责人: Barbara v Howard
• 金额: $ 70.4万
• 依托单位: MEDSTAR HEALTH RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8665465
• 关键词: Abdomen; Address; Adipose tissue; Adult; Affect; Age; Alcohols; Algorithms; Alleles; American Indians; Architecture; Arizona; Atrial Fibrillation; Behavioral; Biological; Biological Markers; Blood Pressure; Caliber; Cardiac; Cardiovascular Diseases; Cardiovascular Physiology; Clinical; Cohort Studies; Coupled; Data; Deposition; Diabetes Mellitus; Diet; Disease; Drug or chemical Tissue Distribution; Elderly; Environmental Exposure; Epidemic; Etiology; Event; Extended Family; Family; Family Study; Fatty acid glycerol esters; Foundations; Functional disorder; Gene Expression; Genes; Genetic; Genetic Determinism; Genetic Markers; Genetic Predisposition to Disease; Genetic Variation; Genomics; Health; Heart; Heart failure; Hepatic; Individual; Inflammation; Insulin Resistance; Investigation; Kidney Diseases; Knowledge; Lead; Life Expectancy; Link; Liver; Magnetic Resonance Imaging; Measurement; Measures; Mental Health; Metabolic; Morbidity - disease rate; Myocardial Infarction; Nonesterified Fatty Acids; Obesity; Participant; Persons; Phenotype; Physical activity; Physiological; Placebo Effect; Plant Roots; Population; Prevention therapy; Process; RNA; Recurrence; Reproductive History; Resources; Risk Factors; Role; Socioeconomic Status; Solid; Staging; Stroke; Techniques; Technology; Tobacco use; Triglycerides; Variant; abdominal fat; aged; base; behavior measurement; cardiovascular disorder risk; clinical practice; cohort; demographics; design; diabetic; diabetic cardiomyopathy; experience; follow-up; genetic analysis; genetic variant; health disparity; heart rate variability; inflammatory marker; information gathering; innovation; insight; interest; member; middle age; mortality; novel; obesity risk; pre-clinical; public health relevance; surveillance data; tonometry; transcriptomics; trend

DESCRIPTION (provided by applicant): The Strong Heart Study (SHS) of two unique American Indian (AI) cohorts (4549 adults, aged 45 to 74 and 3838 ¿15 yrs. from 94 families) constitutes an unequalled and irreplaceable national resource. The proposed studies will elucidate the genetics and early pathophysiology of diabetic CVD and also address health disparities experienced by populations with high rates of diabetes and CVD. Very high rates of obesity and diabetes, especially among younger SHS participants, herald a pending epidemic of CVD, making them the ideal population in which to examine these processes. Measures of CVD, preclinical CVD, biomarkers, and genetic findings have provided valuable pathogenetic insights related to the etiology of CVD; the proposed investigations will take maximal advantage of this solid foundation and add innovative new measures. Our Aims: The identification of genetic variants affecting risk of obesity, diabetes, preclinical CVD, and CVD events, aided by new genomic technologies. We will use genomics techniques for SNP discovery and subsequent statistical analysis of functionality in regions known to contain genes of interest. Transcriptional profiling of RNA concurrent with a liver/abdominal MRI will be used to relate expression of genes and gene networks to CVD etiology. New biological measurements during a re-examination of the large family-based cohort will expand knowledge of pre-clinical stages of obesity and diabetes associated CVD. Novel phenotypes defined by MRI of the abdomen (for fat deposition in liver and adipose depots) will elucidate the etiology of preclinical disease in younger persons. Measures of central blood pressure (by applanation tonometry), heart rate variability and abdominal aortic size will broaden our understanding of CVD in association with obesity and diabetes. Measures of physiologic and behavioral risk factors, such as demographics, reproductive history, socioeconomic status, tobacco use, alcohol, diet, mental health indicators, and physical activity (by accelerometer) will add additional key phenotypes. Continuing mortality and morbidity surveillance of these cohorts will provide increased power in understanding how obesity and diabetes lead to strokes and heart failure in later life. Secular trends, life expectancy, the effects of renal disease on preclinical CVD, and the role of preclinical measures in predicting CVD endpoints will be explored. Thus, the proposed investigations will lead to new understanding of CVD and preclinical and diabetic CVD as well as improvements in clinical practice.

描述（由申请人提供）：两个独特的美洲印第安人 (AI) 群体（来自 94 个家庭的 4549 名 45 岁至 74 岁成年人和 3838 名 15 岁儿童）的强心脏研究 (SHS) 构成了无与伦比且不可替代的国家资源。拟议的研究将阐明糖尿病心血管疾病的遗传学和早期病理生理学，并解决糖尿病和心血管疾病高发人群所经历的健康差异。肥胖和糖尿病的发病率非常高，特别是在年轻的 SHS 参与者中，预示着 CVD 的流行，使他们成为检查这些过程的理想人群。 CVD 测量、临床前 CVD、生物标志物和基因发现为 CVD 病因学提供了有价值的发病机制见解；拟议的调查将最大限度地利用这一坚实基础并增加创新措施。我们的目标：在新基因组技术的帮助下，识别影响肥胖、糖尿病、临床前 CVD 和 CVD 事件风险的遗传变异。我们将使用基因组学技术来发现 SNP，并随后对已知包含感兴趣基因的区域的功能进行统计分析。与肝脏/腹部 MRI 同步进行的 RNA 转录谱分析将用于将基因和基因网络的表达与 CVD 病因学联系起来。在重新检查大型家庭队列期间进行的新生物学测量将扩大对肥胖和糖尿病相关心血管疾病临床前阶段的了解。腹部 MRI（肝脏和脂肪库中的脂肪沉积）定义的新表型将阐明年轻人临床前疾病的病因。中心血压（通过压平眼压测量）、心率变异性和腹主动脉大小的测量将拓宽我们对与肥胖和糖尿病相关的心血管疾病的理解。生理和行为风险因素的测量，例如人口统计、生殖史、社会经济地位、吸烟、饮酒、饮食、心理健康指标和体力活动（通过加速度计）将增加额外的关键表型。对这些人群的持续死亡率和发病率监测将为了解肥胖和糖尿病如何导致晚年中风和心力衰竭提供更多依据。将探讨长期趋势、预期寿命、肾脏疾病对临床前 CVD 的影响以及临床前措施在预测 CVD 终点中的作用。因此，拟议的研究将带来对CVD、临床前和糖尿病CVD的新认识以及临床实践的改进。