Abstract
Background and aims: Increasing evidence shows that intracranial carotid artery atherosclerosis may develop under the influence of a differential metabolic risk factor profile than atherosclerosis in the extracranial part of the carotid artery. To further elucidate these differences, we investigated associations of a wide range of circulating metabolites with intracranial and extracranial carotid artery atherosclerosis.& para;& para;Methods: From the population-based Rotterdam Study, blood samples from 1111 participants were used to determine a wide range of metabolites by proton nuclear magnetic resonance (NMR). Moreover, these participants underwent non-contrast computed tomography of the neck and head to quantify the amount of extra-and intracranial carotid artery calcification (ECAC and ICAC), as a proxy of atherosclerosis. We assessed associations of the metabolites with ICAC and ECAC and compared the metabolic association patterns of the two.& para;& para;Results: We found that one standard deviation (SD) increase in concentration of 3-hydroxybutyrate, a ketone body, was significantly associated with a 0.11 SD increase in ICAC volume (p = 1.8 x 10(-4)). When we compared the metabolic association pattern of ICAC with that of ECAC, we observed differences in glycolysis-related metabolite measures, lipoprotein subfractions, and amino acids. Interestingly, glyco-protein acetyls were associated with calcification in both studied vessel beds. These associations were most prominent in men.& para;& para;Conclusions: We found that a higher circulating level of 3-hydroxybutyrate was associated with an increase in ICAC. Furthermore, we found differences in metabolic association patterns of ICAC and ECAC, providing further evidence for location-specific differences in the etiology of atherosclerosis. (C) 2018 Elsevier B.V. All rights reserved.