Abstract 13039: Putative Protective Effects Of Caffeine And Its Metabolites On Coronary Heart Disease In The Middle East

Abstract

Introduction: Protective association between coronary heart disease (CHD) and caffeine intake and its metabolism has been reported. Some of the caffeine’s beneficial actions may be attributed to its direct effect on the endothelial cell, stimulating the production of nitric oxide (NO), as well as its role as an adenosine receptor antagonist. In the Middle East and Gulf region CHD is rampant, and caffeine consumption is also relatively high. The interaction of the two is of interest and will be investigated in this study. Hypothesis: Caffeine is a protective factor for CHD in the Middle East. Methods: The Qatar Cardiovascular Biorepository provided 1,001 CHD patients and the Qatar Biobank provided 2,999 control subjects. Metabolites in the caffeine pathway (KEGG, hsa00232) were quantified and curated via liquid chromatography-mass spectrometry by Metabolon Inc. We then subjected data to standard quality control procedures. Association between metabolite levels and CHD was tested by logistic univariate regression, controlling for age, BMI, and sex. Results: The caffeine KEGG pathway contains 22 compounds. Eleven were present in our cleaned metabolomics panel, and all of them were reduced in CHD patients (Figure 1). Five were significant at P <0.05: caffeine ( P =5.26x10 -3 ), 1,7-dimethyluric acid ( P =2.96x10 -4 ), paraxanthine ( P =8.67x10 -3 ), theobromine ( P =2.33x10 -5 ), and 1-methylxanthine ( P =1.17x10 -2 ). Through pathway enrichment analysis, caffeine metabolism pathway was found to be significantly enriched with an FDR P =4.59x10 -34 and an enrichment ratio of 44.23. Conclusions: The finding of lower levels of caffeine and several of its metabolites in CHD patients in this study suggests a potential protective effect for this stimulant. However, this is a cross-sectional cohort study, so we are observing only association at a slice in time.