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

Publication ,  Journal Article
Shah, SH; Bain, JR; Muehlbauer, MJ; Stevens, RD; Crosslin, DR; Haynes, C; Dungan, J; Newby, LK; Hauser, ER; Ginsburg, GS; Newgard, CB; Kraus, WE
Published in: Circ Cardiovasc Genet
April 2010

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.

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Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

April 2010

Volume

3

Issue

2

Start / End Page

207 / 214

Location

United States

Related Subject Headings

  • Risk Factors
  • ROC Curve
  • Proportional Hazards Models
  • Principal Component Analysis
  • Odds Ratio
  • Myocardial Infarction
  • Middle Aged
  • Metabolome
  • Mass Spectrometry
  • Male
 

Citation

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Chicago
ICMJE
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Shah, S. H., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Crosslin, D. R., Haynes, C., … Kraus, W. E. (2010). Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet, 3(2), 207–214. https://doi.org/10.1161/CIRCGENETICS.109.852814
Shah, Svati H., James R. Bain, Michael J. Muehlbauer, Robert D. Stevens, David R. Crosslin, Carol Haynes, Jennifer Dungan, et al. “Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events.Circ Cardiovasc Genet 3, no. 2 (April 2010): 207–14. https://doi.org/10.1161/CIRCGENETICS.109.852814.
Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C, et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet. 2010 Apr;3(2):207–14.
Shah, Svati H., et al. “Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events.Circ Cardiovasc Genet, vol. 3, no. 2, Apr. 2010, pp. 207–14. Pubmed, doi:10.1161/CIRCGENETICS.109.852814.
Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C, Dungan J, Newby LK, Hauser ER, Ginsburg GS, Newgard CB, Kraus WE. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet. 2010 Apr;3(2):207–214.

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

April 2010

Volume

3

Issue

2

Start / End Page

207 / 214

Location

United States

Related Subject Headings

  • Risk Factors
  • ROC Curve
  • Proportional Hazards Models
  • Principal Component Analysis
  • Odds Ratio
  • Myocardial Infarction
  • Middle Aged
  • Metabolome
  • Mass Spectrometry
  • Male