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Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization.

Publication ,  Journal Article
Bhattacharya, S; Granger, CB; Craig, D; Haynes, C; Bain, J; Stevens, RD; Hauser, ER; Newgard, CB; Kraus, WE; Newby, LK; Shah, SH
Published in: Atherosclerosis
January 2014

OBJECTIVE: To validate independent associations between branched-chain amino acids (BCAA) and other metabolites with coronary artery disease (CAD). METHODS: We conducted mass-spectrometry-based profiling of 63 metabolites in fasting plasma from 1983 sequential patients undergoing cardiac catheterization. Significant CAD was defined as CADindex ≥ 32 (at least one vessel with ≥ 95% stenosis; N = 995) and no CAD as CADindex ≤ 23 and no previous cardiac events (N = 610). Individuals (N = 378) with CAD severity between these extremes were excluded. Principal components analysis (PCA) reduced large numbers of correlated metabolites into uncorrelated factors. Association between metabolite factors and significant CAD vs. no CAD was tested using logistic regression; and between metabolite factors and severity of CAD was tested using linear regression. RESULTS: Of twelve PCA-derived metabolite factors, two were associated with CAD in multivariable models: factor 10, composed of BCAA (adjusted odds ratio, OR, 1.20; 95% CI 1.05-1.35, p = 0.005) and factor 7, composed of short-chain acylcarnitines, which include byproducts of BCAA metabolism (adjusted OR 1.30; 95% CI 1.14-1.48, p = 0.001). After adjustment for glycated albumin (marker of insulin resistance [IR]) both factors 7 (p = 0.0001) and 10 (p = 0.004) remained associated with CAD. Severity of CAD as a continuous variable (including patients with non-obstructive disease) was associated with metabolite factors 2, 3, 6, 7, 8 and 9; only factors 7 and 10 were associated in multivariable models. CONCLUSIONS: We validated the independent association of metabolites involved in BCAA metabolism with CAD extremes. These metabolites may be reporting on novel mechanisms of CAD pathogenesis that are independent of IR and diabetes.

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Published In

Atherosclerosis

DOI

EISSN

1879-1484

Publication Date

January 2014

Volume

232

Issue

1

Start / End Page

191 / 196

Location

Ireland

Related Subject Headings

  • Principal Component Analysis
  • Phenotype
  • Odds Ratio
  • Multivariate Analysis
  • Middle Aged
  • Mass Spectrometry
  • Male
  • Linear Models
  • Insulin Resistance
  • Humans
 

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Bhattacharya, S., Granger, C. B., Craig, D., Haynes, C., Bain, J., Stevens, R. D., … Shah, S. H. (2014). Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. Atherosclerosis, 232(1), 191–196. https://doi.org/10.1016/j.atherosclerosis.2013.10.036
Bhattacharya, Sayanti, Christopher B. Granger, Damian Craig, Carol Haynes, James Bain, Robert D. Stevens, Elizabeth R. Hauser, et al. “Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization.Atherosclerosis 232, no. 1 (January 2014): 191–96. https://doi.org/10.1016/j.atherosclerosis.2013.10.036.
Bhattacharya S, Granger CB, Craig D, Haynes C, Bain J, Stevens RD, et al. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. Atherosclerosis. 2014 Jan;232(1):191–6.
Bhattacharya, Sayanti, et al. “Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization.Atherosclerosis, vol. 232, no. 1, Jan. 2014, pp. 191–96. Pubmed, doi:10.1016/j.atherosclerosis.2013.10.036.
Bhattacharya S, Granger CB, Craig D, Haynes C, Bain J, Stevens RD, Hauser ER, Newgard CB, Kraus WE, Newby LK, Shah SH. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. Atherosclerosis. 2014 Jan;232(1):191–196.
Journal cover image

Published In

Atherosclerosis

DOI

EISSN

1879-1484

Publication Date

January 2014

Volume

232

Issue

1

Start / End Page

191 / 196

Location

Ireland

Related Subject Headings

  • Principal Component Analysis
  • Phenotype
  • Odds Ratio
  • Multivariate Analysis
  • Middle Aged
  • Mass Spectrometry
  • Male
  • Linear Models
  • Insulin Resistance
  • Humans