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

Shah, Svati H

Bain, James R

Muehlbauer, Michael J

Stevens, Robert D

Crosslin, David R

Haynes, Carol

Dungan, Jennifer

Newby, L Kristin

Hauser, Elizabeth R

Ginsburg, Geoffrey S

Newgard, Christopher B

Kraus, William E

United States

2012-10-30T19:36:55Z

2010-04

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.

http://www.ncbi.nlm.nih.gov/pubmed/20173117

CIRCGENETICS.109.852814

1942-3268

https://hdl.handle.net/10161/5964

eng

Ovid Technologies (Wolters Kluwer Health)

Circ Cardiovasc Genet

10.1161/CIRCGENETICS.109.852814

Circulation: Cardiovasular Genetics

Adult

Aged

Biomarkers

Coronary Artery Disease

Female

Humans

Linear Models

Male

Mass Spectrometry

Metabolome

Middle Aged

Myocardial Infarction

Odds Ratio

Principal Component Analysis

Proportional Hazards Models

ROC Curve

Risk Factors

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

Journal article

Shah, Svati H|0000-0002-3495-2830

Bain, James R|0000-0002-8917-9187

Newby, L Kristin|0000-0002-6394-8187

Hauser, Elizabeth R|0000-0003-0367-9189

Ginsburg, Geoffrey S|0000-0003-4739-9808

Kraus, William E|0000-0003-1930-9684

2

3

http://www.ncbi.nlm.nih.gov/pubmed/20173117

207

214

2

Basic Science Departments

Biochemistry

Biomedical Engineering

Biostatistics & Bioinformatics

Center for the Study of Aging and Human Development

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Clinical Research Institute

Duke Molecular Physiology Institute

Global Health Institute

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Cardiology

Medicine, Endocrinology, Metabolism, and Nutrition

Pathology

Pharmacology & Cancer Biology

Pratt School of Engineering

Sarah Stedman Nutrition & Metabolism Center

School of Medicine

School of Nursing

School of Nursing - Secondary Group

University Institutes and Centers

Published

3