METABOLOMICS ANALYSIS OF SUSPECTED CORONARY ARTERY DISEASE (CAD) PATIENTS UNDERGOING ELECTIVE CORONARY ANGIOGRAM IN NATIONAL HEART INSTITUTE (IJN)

Abstract

Background: In Malaysia, CAD was the leading cause of mortality with 11,310 deaths in 2016. Current “gold standard” in the diagnosis of CAD is invasive coronary angiography, despite major improvement of non-invasive method. The invasive nature of coronary angiography limits its usage for general population screening. Metabolomics are able to identify and quantify all low molecular weight compounds < 1500 daltons in a single step. Objectives: The objectives of the study were to compare urine metabolite profiles between normal coronary arteries with CAD patients of different severity, to compare precoronary angiogram and post-coronary angiogram, and to correlate NMR findings with laboratory testing results. Methods and Results: Urine samples (before and after coronary angiogram) were collected after written informed consent were obtained. Samples were analysed using NMR spectroscopy (600 MHz). Sixty-five subjects with different severity of CAD enrolled in the study. Four subjects refused post coronary angiogram urine collection. Eight subjects were normal. Unsupervised principal component analysis (PCA) and supervised projection to latent structures-discriminant analysis (PLS-DA) were carried out to interpret observation. No overall differences of urine metabolites and blood profile results across CAD severity were detected in NMR profile. Nevertheless, there were downregulation of selected urinary metabolites as the severity increase. In pre-coronary angiogram, presumptive urinary isobutyric acid and hippuric were upregulated in normal, citric acid and hippuric acid were upregulated in mild group, while only citric acid was over expressed in moderate group, as opposed to the severe group. In the post-coronary angiogram, presumptive urinary L-histidine was upregulated in normal, phenylacetylglutamine and its’ acetyls were upregulated in mild group, as opposed to the severe group. When comparing pre-coronary angiogram and post-coronary angiogram; urinary L-alanine and guanidinoacetic acid were upregulated after coronary angiogram regardless the severity of CAD. In the severe group, urinary creatinine, phenylacetylglutamine and hippuric acid, were downregulated after coronary angiogram. Conclusions: Even though urine NMR profile did not differentiate severity of CAD in this study significantly, urine metabolites profile able to identify differential expression of metabolites across CAD severity group, and also between pre- and post-coronary angiogram. However, further studies to quantify the metabolites warranted.