Dina Vojinovic1, Sven J van der Lee1, Cornelia M van Duijn1, Meike W Vernooij2, Maryam Kavousi1, Najaf Amin1, Ayşe Demirkan3, M Arfan Ikram4, Aad van der Lugt5, Daniel Bos6. 1. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. 2. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. 3. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. 4. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands. 5. Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. 6. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: d.bos@erasmusmc.nl.
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. 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.
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.
Authors: M Arfan Ikram; Guy Brusselle; Mohsen Ghanbari; André Goedegebure; M Kamran Ikram; Maryam Kavousi; Brenda C T Kieboom; Caroline C W Klaver; Robert J de Knegt; Annemarie I Luik; Tamar E C Nijsten; Robin P Peeters; Frank J A van Rooij; Bruno H Stricker; André G Uitterlinden; Meike W Vernooij; Trudy Voortman Journal: Eur J Epidemiol Date: 2020-05-04 Impact factor: 8.082
Authors: Wenyi Wang; Ko Willems van Dijk; Carolien A Wijsman; Maarten P Rozing; Simon P Mooijaart; Marian Beekman; P Eline Slagboom; J Wouter Jukema; Raymond Noordam; Diana van Heemst Journal: Metabolomics Date: 2021-06-09 Impact factor: 4.290
Authors: Dina Vojinovic; Djawad Radjabzadeh; Alexander Kurilshikov; Najaf Amin; Cisca Wijmenga; Lude Franke; M Arfan Ikram; Andre G Uitterlinden; Alexandra Zhernakova; Jingyuan Fu; Robert Kraaij; Cornelia M van Duijn Journal: Nat Commun Date: 2019-12-20 Impact factor: 14.919