Abstract 13821: Peripheral Metabolite Profiles Discriminate Coronary Artery Disease in a Sequential Cohort of Cardiac Catheterization Patients
Background: Profiling of peripheral blood metabolites may improve clinical models for coronary artery disease (CAD). We previously showed that levels of branched chain amino acids (BCAA) and other metabolites were independently associated with CAD in a small case-control study. We sought to validate these associations in a large sequential cohort of patients undergoing cardiac catheterization.
Methods: We performed mass-spectrometry based profiling of 63 metabolites in fasting, frozen plasma collected from 1983 sequential patients undergoing cardiac catheterization who were enrolled in the Duke CATHGEN biorepository and included in the MURDOCK CV Study. Cases were subjects with a CADindex >=32 (N=995) and controls had CADindex <=23 without adverse cardiac events (N=610), where CADindex is a numeric summary of angiographic extent of CAD. Principal components analysis (PCA) was used to reduce the large number of correlated metabolites into uncorrelated factors. Association with CAD was tested using univariable and multivariable logistic regression models adjusted for age, sex, race, hypertension, diabetes, dyslipidemia, smoking, family history of CAD and body mass index.
Results: Of twelve PCA-derived metabolite factors, two were significantly associated with CAD after adjusting for clinical covariates: factor 10, composed of BCAA (unadjusted odds ratio [OR] 1.13; 95% CI 1.02-1.25, p=0.02; adjusted OR 1.20; 95% CI 1.05-1.35, p=0.005) and factor 7, composed of short chain acylcarnitine byproducts of BCAA metabolism (unadjusted OR 1.42; 95% CI 1.26-1.59, p<0.001; adjusted OR 1.30; 95% CI 1.14-1.48, p<0.001). The components of the urea cycle factor from our previous study did not cluster in a PCA factor; the individual metabolites (citrulline,Ci4-DC/C4-DC acylcarnitine, histine and arginine) from this factor were significantly associated with CAD in univariate analyses, but did not remain significantly associated after adjusting for clinical covariates.
Conclusions: We have validated the independent role of metabolites, including those involved in BCAA metabolism, in discriminating patients with CAD. These metabolites may serve as CAD biomarkers and may be reporting on novel mechanisms of CAD pathogenesis.
- © 2011 by American Heart Association, Inc.