Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events.
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BACKGROUND: Molecular tools may provide insight into cardiovascular risk. We assessed whether metabolites discriminate coronary artery disease (CAD) and predict risk of cardiovascular events. METHODS AND RESULTS: We performed mass-spectrometry-based profiling of 69 metabolites in subjects from the CATHGEN biorepository. To evaluate discriminative capabilities of metabolites for CAD, 2 groups were profiled: 174 CAD cases and 174 sex/race-matched controls ("initial"), and 140 CAD cases and 140 controls ("replication"). To evaluate the capability of metabolites to predict cardiovascular events, cases were combined ("event" group); of these, 74 experienced death/myocardial infarction during follow-up. A third independent group was profiled ("event-replication" group; n=63 cases with cardiovascular events, 66 controls). Analysis included principal-components analysis, linear regression, and Cox proportional hazards. Two principal components analysis-derived factors were associated with CAD: 1 comprising branched-chain amino acid metabolites (factor 4, initial P=0.002, replication P=0.01), and 1 comprising urea cycle metabolites (factor 9, initial P=0.0004, replication P=0.01). In multivariable regression, these factors were independently associated with CAD in initial (factor 4, odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74; P=0.02; factor 9, OR, 0.67; 95% CI, 0.52 to 0.87; P=0.003) and replication (factor 4, OR, 1.43; 95% CI, 1.07 to 1.91; P=0.02; factor 9, OR, 0.66; 95% CI, 0.48 to 0.91; P=0.01) groups. A factor composed of dicarboxylacylcarnitines predicted death/myocardial infarction (event group hazard ratio 2.17; 95% CI, 1.23 to 3.84; P=0.007) and was associated with cardiovascular events in the event-replication group (OR, 1.52; 95% CI, 1.08 to 2.14; P=0.01). CONCLUSIONS: Metabolite profiles are associated with CAD and subsequent cardiovascular events.
Coronary Artery Disease
Principal Component Analysis
Proportional Hazards Models
Published Version (Please cite this version)10.1161/CIRCGENETICS.109.852814
Publication InfoBain, James R; Crosslin, DR; Dungan, J; Ginsburg, Geoffrey Steven; Hauser, Elizabeth Rebecca; Haynes, Carol; ... Stevens, Robert David (2010). Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet, 3(2). pp. 207-214. 10.1161/CIRCGENETICS.109.852814. Retrieved from https://hdl.handle.net/10161/5964.
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Associate Professor in Medicine
Associate Professor in the School of Nursing
Dr. Jennifer Dungan is a nurse scientist with expertise in cardiovascular genetics research. In 2001, she earned her bachelor’s degree in nursing with Honors from the University of Florida, where she also conducted undergraduate research to evaluate biofeedback interventions in hypertension. Dr. Dungan completed an accelerated Master’s-to-PhD program at the University of Florida. She was awarded her MSN in adult health nursing in 2002, trained at the NIH/NINR Summer Genetics Insti
Professor of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
Professor of Biostatistics and Bioinformatics
My research interests are focused on developing and applying statistical methods to search for genes causing common human diseases. Recent work has been in the development of statistical methods for genetic studies and in identifying optimal study designs for genetic studies of complex traits. As application of these methods to specific diseases has progressed it has become apparent that etiologic and genetic heterogeneity is a major stumbling block in the research for genes for common diseases.
Richard and Pat Johnson University Professor
My training, expertise and research interests range from human integrative physiology and genetics to animal exercise models to cell culture models of skeletal muscle adaptation to mechanical stretch. I am trained clinically as an internist and preventive cardiologist, with particular expertise in preventive cardiology and cardiac rehabilitation. My research training spans molecular biology and cell culture, molecular genetics, and integrative human exercise physiology and metabolism. I pr
Professor of Medicine
Research Description General Focus: Clinical investigation the process and treatment of acute and chronic coronary artery disease and systems issues for delivery of care to patients with these illnesses. Particular interests include management of patients with chest pain and unstable angina, evaluation of the use of biochemical markers other than CK-MB for diagnosis and risk stratification in these patients, issues related to coronary artery disease in women, and systems issues
W. David and Sarah W. Stedman Professor of Nutrition in the School of Medicine
Over its 16 year history, our laboratory has investigated mechanisms of metabolic regulation and fuel homeostasis in mammalian systems. Major projects include: 1) Mechanisms involved in regulation of insulin secretion from pancreatic islet β-cells by glucose and other metabolic fuels; 2) Development of methods for protection of β-cells against immune-mediated damage; 3) Studies on spatial organization and regulation of systems controlling hepatic glucose balance; 4) Studies
Adjunct Assistant Professor of Medicine
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