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Demir Djekic,1 Rui Pinto,2 Dirk Repsilber,3 Tuulia Hyotylainen,4 Michael Henein5–71Department of Cardiology, School of Medical Sciences, Örebro University, Örebro, Sweden; 2Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK; 3School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 4Man-Technology-Environment Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden; 5Department of Public Health and Clinical Medicine, Umeå University and Heart Centre, Umeå, Sweden; 6Molecular and Clinic Research Institute, St George University, London, UK; 7Institute of Environment, Health and Physical Sciences, Brunel University, London, UKPurpose: Disturbed metabolism of cholesterol and triacylglycerols (TGs) carries increased risk for coronary artery calcification (CAC). However, the exact relationship between individual lipid species and CAC remains unclear. The aim of this study was to identify disturbances in lipid profiles involved in the calcification process, in an attempt to propose potential biomarker candidates.Patients and methods: We studied 70 patients at intermediate risk for coronary artery disease who had undergone coronary calcification assessment using computed tomography and Agatston coronary artery calcium score (CACS). Patients were divided into three groups: with no coronary calcification (NCC; CACS: 0; n=26), mild coronary calcification (MCC; CACS: 1–250; n=27), or severe coronary calcification (SCC; CACS: >250; n=17). Patients’ serum samples were analyzed using liquid chromatography-mass spectrometry in an untargeted lipidomics approach.Results: We identified 103 lipids within the glycerolipid, glycerophospholipid, sphingolipid, and sterol lipid classes. After false discovery rate correction, phosphatidylcholine (PC)(16:0/20:4) in higher levels and PC(18:2/18:2), PC(36:3), and phosphatidylethanolamine(20:0/18:2) in lower levels were identified as correlates with SCC compared to NCC. There were no significant differences in the levels of individual TGs between the three groups; however, clustering the lipid profiles showed a trend for higher levels of saturated and monounsaturated TGs in SCC compared to NCC. There was also a trend for lower TG(49:2), TG(51:1), TG(54:5), and TG(56:8) levels in SCC compared to MCC.Conclusion: In this study we investigated the lipidome of patients with coronary calcification. Our results suggest that the calcification process may be associated with dysfunction in autophagy. The lipidomic biomarkers revealed in this study may aid in better assessment of patients with subclinical coronary artery disease.Keywords: coronary artery calcification, coronary artery calcium score; lipidomics, triacylglycerol, lipids, atherosclerosis; autophagy