Plasma sphingolipids and risk of cardiovascular diseases: a large-scale lipidomic analysis
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ORIGINAL ARTICLE
Plasma sphingolipids and risk of cardiovascular diseases: a large‑scale lipidomic analysis Jowy Yi Hoong Seah1,2 · Wee Siong Chew3 · Federico Torta4,5 · Chin Meng Khoo6 · Markus R. Wenk4,5,7 · Deron R. Herr3,8 · Hyungwon Choi1,6,9 · E. Shyong Tai1,6,10 · Rob M. van Dam1,2,11 Received: 15 March 2020 / Accepted: 10 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Introduction Sphingolipids are a diverse class of lipids with various roles in cell functions and subclasses such as ceramides have been associated with cardiovascular diseases (CVD) in previous studies. Objectives We aimed to measure molecularly-distinct sphingolipids via a large-scale lipidomic analysis and expand the literature to an Asian population. Methods We performed a lipidomics evaluation of 79 molecularly distinct sphingolipids in the plasma of 2627 ethnicallyChinese Singaporeans. Results During a mean follow-up of 12.9 years, we documented 152 cases of major CVD (non-fatal myocardial infarction, stroke and cardiovascular death). Total ceramide concentrations were not associated with CVD risk [hazard ratio (HR), 0.99; 95% CI 0.81–1.21], but higher circulating total monohexosylceramides (HR, 1.22; 95% CI 1.03, 1.45), total long-chain sphingolipids (C16–C18) (HR, 1.22; 95% CI 1.02, 1.45) and total 18:1 sphingolipids (HR, 1.21; 95% CI 1.01, 1.46) were associated with higher CVD risk after adjusting for conventional CVD risk factors. Conclusions Our results do not support the hypothesis that higher ceramide concentrations are linked to higher CVD risk, but suggest that other classes of sphingolipids may affect CVD risk. Keywords Cardiovascular mortality · Ceramides · Cerebrosides · Gangliosides · Heart disease · Hexosylceramides · Lipidomics · Sphingomyelin
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11306-020-01709-8) contains supplementary material, which is available to authorized users. * Jowy Yi Hoong Seah [email protected] * Rob M. van Dam [email protected] 1
Saw Swee Hock School of Public Health, National University of Singapore (NUS), 12 Science Drive 2, #10‑01, Singapore 117549, Singapore
2
NUS Graduate School for Integrative Sciences and Engineering, NUS, Singapore 119077, Singapore
3
Department of Pharmacology, Yong Loo Lin School of Medicine, NUS, Singapore 117600, Singapore
4
Department of Biochemistry, Yong Loo Lin School of Medicine, NUS, Singapore 117596, Singapore
5
Singapore Lipidomics Incubator, Life Sciences Institute, NUS, Singapore 117456, Singapore
Abbreviations AMI Acute myocardial infarction GluCer Glucosylceramides HbA1c Glycated hemoglobin A1c 6
Department of Medicine, Yong Loo Lin School of Medicine, NUS and National University Health System, Singapore 119228, Singapore
7
Department of Biological Sciences, Faculty of Science, NUS, Singapore 117558, Singapore
8
Department of Biology, San Diego State University, San Diego, CA 92182, USA
9
Institute of Molecul
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