Recent advances in metabolomics have led to the identification of numerous blood metabolites related to the risk of cardiovascular events. Although these metabolites show great promise as potential novel biomarkers for coronary heart disease (CHD), their relation with coronary risk remains poorly defined due to several knowledge gaps ? no prior prospective study has jointly assessed metabolites by taking into account pathways related to biological function; no study has considered changes in metabolite levels over time in relation to subsequent CHD; and research on the dynamic interrelationships of metabolites with traditional CHD risk factors and dietary intakes is limited. The overarching goal of this competing renewal is to fill important gaps in knowledge regarding the metabolomics of CHD, using an exceptionally cost-efficient design that leverages existing resources from three large and well-established U.S. cohorts: the Nurses? Health Study (NHS), the NHS2, and the VITamin D and OmegA-3 TriaL (VITAL, men and women, ~20% African Americans). Using novel analytical approaches, we propose to develop and validate Metabolomics Risk Scores (MRSs) that incorporate comprehensive metabolite profiling (at overall and pathway levels) for their associations with incident CHD in NHS (700 cases and paired controls) and VITAL (650 cases and paired controls, replication cohort) (Aim 1). Taking advantage of repeated blood collections at two time points approximately 10 years apart in NHS, we will examine whether temporal changes in MRS are related to incident CHD (Aim 2). We will also assess whether biochemical CHD risk factors, and temporal changes in these risk factors, mediate the coronary risk associated with MRS (Aim 3). Finally, using objective dietary data assessed by ?gold standard? methods, we will develop Dietary Metabolite Indexes (DMIs) that predict MRS and prospectively analyze relations between temporal changes in DMIs and incident CHD risk (Aim 4). This competing renewal builds upon our long-standing research on risk factors for CHD in the Nurses? Health Study (research that has resulted in more than 350 publications over the past 34 years) and extends our work to the study of novel metabolomic risk factors. The findings of our proposed project may elucidate new etiologic pathways for atherothrombotic vascular disease, as well as provide novel prevention options and therapeutic strategies for cardiovascular disease. Thus, the proposed study has the potential to have major clinical and public health impact.
Recent metabolomics research has implicated circulating metabolites in cardiovascular disease, but several gaps in knowledge remain. We propose to develop and validate Metabolomics Risk Scores (MRSs) that integrate comprehensive metabolite profiling at overall and biological pathway levels, assess their 10-year changes in relation to incident coronary heart disease (CHD), and examine dynamic interrelationships of MRS with traditional CHD risk factors and dietary intakes. Our findings may lead to new insights into the pathogenesis of CHD and advance new strategies for prevention and treatment.
|Ma, Wenjie; Heianza, Yoriko; Huang, Tao et al. (2018) Dietary glutamine, glutamate and mortality: two large prospective studies in US men and women. Int J Epidemiol 47:311-320|
|Liu, Gang; Li, Yanping; Hu, Yang et al. (2018) Influence of Lifestyle on Incident Cardiovascular Disease and Mortality in Patients With Diabetes Mellitus. J Am Coll Cardiol 71:2867-2876|
|Nisa, Hoirun; Qi, Kevin H T; Leng, Junhong et al. (2018) The Circadian Rhythm-Related MTNR1B Genotype, Gestational Weight Gain, and Postpartum Glycemic Changes. J Clin Endocrinol Metab 103:2284-2290|
|Sun, Dianjianyi; Li, Xiang; Heianza, Yoriko et al. (2018) History of Asthma From Childhood and Arterial Stiffness in Asymptomatic Young Adults: The Bogalusa Heart Study. Hypertension 71:928-936|
|Heianza, Yoriko; Sun, Dianjianyi; Ma, Wenjie et al. (2018) Gut-microbiome-related LCT genotype and 2-year changes in body composition and fat distribution: the POUNDS Lost Trial. Int J Obes (Lond) 42:1565-1573|
|Hagan, Kaitlin A; Harrington, Laura B; Kim, Jihye et al. (2018) Adiposity throughout the life course and risk of venous thromboembolism. Thromb Res 172:67-73|
|AlEssa, Hala B; Cohen, Randy; Malik, Vasanti S et al. (2018) Carbohydrate quality and quantity and risk of coronary heart disease among US women and men. Am J Clin Nutr 107:257-267|
|Li, Yanping; Pan, An; Wang, Dong D et al. (2018) Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population. Circulation 138:345-355|
|Sun, Dianjianyi; Heianza, Yoriko; Li, Xiang et al. (2018) Genetic, epigenetic and transcriptional variations at NFATC2IP locus with weight loss in response to diet interventions: The POUNDS Lost Trial. Diabetes Obes Metab 20:2298-2303|
|Goni, Leticia; Sun, Dianjianyi; Heianza, Yoriko et al. (2018) A circadian rhythm-related MTNR1B genetic variant modulates the effect of weight-loss diets on changes in adiposity and body composition: the POUNDS Lost trial. Eur J Nutr :|
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