CVD in American Indians: Imaging and Cardiovascular Center

描述（由申请人提供）：两个独特的美国印第安人（AI）队列（4549名成年人，年龄45 - 74岁和3838 - 15岁）的强心脏研究（SHS）。来自94个家庭)构成了无与伦比和不可替代的国家资源。提出的研究将阐明糖尿病性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的健康差异。非常高的肥胖率和糖尿病率，特别是在年轻的SHS参与者中，预示着心血管疾病即将流行，使他们成为研究这些过程的理想人群。CVD的测量、临床前CVD、生物标志物和遗传发现提供了与CVD病因相关的有价值的病理学见解；建议的调查将最大限度地利用这一坚实的基础，并增加创新的新措施。我们的目标：在新的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进行SNP发现和随后对已知包含感兴趣基因的区域的功能进行统计分析。RNA转录谱与肝脏/腹部MRI将用于将基因表达和基因网络与CVD病因联系起来。在以家庭为基础的大队列的重新检查中，新的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认识。腹部MRI（肝脏脂肪沉积和脂肪库）定义的新表型将阐明年轻人临床前疾病的病因。测量中心血压（通过压压式血压计）、心率变异性和腹主动脉大小将扩大我们对心血管疾病与肥胖和糖尿病相关的理解。生理和行为风险因素的测量，如人口统计学、生殖史、社会经济地位、烟草使用、酒精、饮食、心理健康指标和身体活动（通过加速度计）将增加额外的关键表型。对这些队列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的力量。将探讨长期趋势、预期寿命、肾脏疾病对临床前CVD的影响，以及临床前测量在预测CVD终点中的作用。因此，所提出的研究将导致对CVD、临床前和糖尿病性CVD的新认识，并改善临床实践。

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.