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Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events.

dc.contributor.author Bain, James R
dc.contributor.author Crosslin, DR
dc.contributor.author Dungan, J
dc.contributor.author Ginsburg, Geoffrey Steven
dc.contributor.author Hauser, Elizabeth Rebecca
dc.contributor.author Haynes, Carol
dc.contributor.author Kraus, William Erle
dc.contributor.author Muehlbauer, Michael J
dc.contributor.author Newby, Laura Kristin
dc.contributor.author Newgard, Christopher Bang
dc.contributor.author Shah, SH
dc.contributor.author Stevens, Robert David
dc.coverage.spatial United States
dc.date.accessioned 2012-10-30T19:36:55Z
dc.date.issued 2010-04
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20173117
dc.identifier CIRCGENETICS.109.852814
dc.identifier.uri http://hdl.handle.net/10161/5964
dc.description.abstract 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.
dc.language eng
dc.relation.ispartof Circ Cardiovasc Genet
dc.relation.isversionof 10.1161/CIRCGENETICS.109.852814
dc.subject Adult
dc.subject Aged
dc.subject Biomarkers
dc.subject Coronary Artery Disease
dc.subject Female
dc.subject Humans
dc.subject Linear Models
dc.subject Male
dc.subject Mass Spectrometry
dc.subject Metabolome
dc.subject Middle Aged
dc.subject Myocardial Infarction
dc.subject Odds Ratio
dc.subject Principal Component Analysis
dc.subject Proportional Hazards Models
dc.subject ROC Curve
dc.subject Risk Factors
dc.title Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events.
dc.type Journal article
duke.description.issue 2
duke.description.volume 3
dc.relation.journal Circulation: Cardiovasular Genetics
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20173117
pubs.begin-page 207
pubs.end-page 214
pubs.issue 2
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biochemistry
pubs.organisational-group Biomedical Engineering
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Center for the Study of Aging and Human Development
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Duke Molecular Physiology Institute
pubs.organisational-group Global Health Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Medicine, Endocrinology, Metabolism, and Nutrition
pubs.organisational-group Pathology
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group Pratt School of Engineering
pubs.organisational-group Sarah Stedman Nutrition & Metabolism Center
pubs.organisational-group School of Medicine
pubs.organisational-group School of Nursing
pubs.organisational-group School of Nursing - Secondary Group
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 3
dc.identifier.eissn 1942-3268


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