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.
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.
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 × 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, glycoprotein acetyls were associated with calcification in both studied vessel beds. These associations were most prominent in men.
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.

Additional Metadata
Keywords Atherosclerosis, Carotid artery, Metabolomics
Persistent URL dx.doi.org/10.1016/j.atherosclerosis.2018.03.015, hdl.handle.net/1765/105312
Journal Atherosclerosis
Grant This work was funded by the European Commission 7th Framework Programme; grant id h2020/667375 - Common mechanisms and pathways in Stroke and Alzheimer's disease. (CoSTREAM)
Citation
Vojinovic, D, van der Lee, S.J, van Duijn, C.M, Vernooij, M.W, Kavousi, M, Amin, N, … Bos, D. (2018). Metabolic profiling of intra- and extracranial carotid artery atherosclerosis. Atherosclerosis, 272, 60–65. doi:10.1016/j.atherosclerosis.2018.03.015