The metabolomic profile of carotid artery intima-media thickness and echogenicity

Background and aims: Nuclear magnetic resonance (NMR)-based metabolomics analyses have defined the lipoprotein profile of carotid artery intima-media thickness (IMT) in detail. In this study, the aim was to use multi-modal mass spectroscopy (MS) to relate multiple metabolites from different chemical classes to IMT and also to the echogenicity of the intima-media complex (IM-GSM). Method: Multi-modal MS with 791 annotated non-xenobiotic metabolites was measured in two different population-based samples (PIVUS at age 80, n = 586 and POEM at age 50, n = 495) in which also carotid IMT and IM-GSM have been assessed by ultrasound. Results: Four metabolites were significantly (false discovery rate, FDR<0.05) related to IMT in a meta-analysis of POEM and PIVUS. The top finding was adenosine 3',5'-cyclic monophosphate (cAMP), being inversely related to IMT. Fifty metabolites were significantly related to IM-GSM in a meta-analysis of POEM and PIVUS. The top findings were branched-chained amino acids (BCAA), fructosyllysine, metabolonic lactone sulfate, a ceramide together with some sphingomyelins and phosphatidylcholines. All these top findings represented inverse relationships. Two metabolites identified by lasso regression in PIVUS increased discrimination of an echolucent IM-GSM by 3.3% in POEM compared to traditional cardiovascular risk factors (p = 0.020). Conclusions: IMT, especially IM-GSM, was related to multiple metabolites from different chemical classes. Although such metabolites improved the discrimination of an echolucent IM-GSM, it remains to be investigated if any of those metabolites are involved in the pathogenesis of carotid arteriopathy.