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.

Public Health Relevance

Steadily decreasing rates of cardiovascular disease (CVD) in the US threaten to be reversed because of rapid increases in obesity and diabetes. The proposed study will take advantage of the Strong Heart Study data in American Indians to further our understanding of CVD and its risk factors, especially diabetes and obesity, which will lead to more effective prevention and therapy and reduce the burden of CVD morbidity and mortality.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Fabsitz, Richard
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Texas Biomedical Research Institute
San Antonio
United States
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Tsai, Ching-Wei; North, Kari E; Tin, Adrienne et al. (2015) Both rare and common variants in PCSK9 influence plasma low-density lipoprotein cholesterol level in American Indians. J Clin Endocrinol Metab 100:E345-9
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Zhu, Yun; Yang, Jingyun; Li, Shengxu et al. (2014) Genetic variants in nicotinic acetylcholine receptor genes jointly contribute to kidney function in American Indians: the Strong Heart Family Study. J Hypertens 32:1042-8; discussion 1049
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