Introduction: Metabolic instability is a noted contributor to coronary artery disease (CAD). Prior metabolomic profiling studies in the mostly Caucasian CAD cohort, CATHGEN (Durham, NC) have offered promising insights into the biologic pathways that mediate CAD and future CV-event risk, but these relationships have not been fully explored in South Asian cohorts.
Methods: Targeted, quantitative tandem mass-spectrometry profiling of 69 known metabolites was performed in frozen, fasting plasma from 390 individuals enrolled at the Medanta Health Institute (Uttar Pradesh, India). Metabolite levels were first compared using principal components analysis (PCA) for multidimensional data reduction. T-tests were then used to compare metabolite levels between CAD cases (N=190) and non-CAD controls (N=200). Bonferroni correction was used for multiple comparisons at the level of PCA-defined factors (p≤0.004).
Results: PCA identified 14 factors with metabolites clustering in biologically meaningful factors. Four factors significantly differed between cases and controls including: factor 3 (short chain dicarboxylacylcarnitines, p=0.0006), factor 6 (medium chain acyl-carnitines, p=8x10-8), factor 8 (urea cycle related amino acids, p=0.0001) and factor 10 (Asp and C5-OH/C3-DC, p=6x10-11). Of the factors significant in the Medanta cohort, two factors with similar principal components (medium chain acyl-carnitines and urea cycle related amino acids) were also significant in the primary CATHGEN cohort.
Conclusions: Using targeted metabolomic profiling, we have identified metabolites and related metabolic pathways that discriminate CAD cases from controls in a South Asian population. These metabolic pathways are similar to those identified in non-South Asian cohorts and suggest that these dis-regulated metabolic pathways are common across racial subgroups and mediate cardiovascular risk independent of race.