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Abstract
Ceramides and phosphatidylcholines (PCs) are bioactive lipids and lipid bilayer membrane components. Distinct ceramides/PCs (ratios) predict cardiovascular outcome in patients with coronary artery disease. Extracellular vesicles (EVs) are proposed biomarkers for cardiovascular disease and contain ceramides/PCs. Ceramides/PCs have not been studied in patients undergoing carotid endarterectomy (CEA) nor in EVs. We therefore investigated whether levels of ceramides/PCs in plasma and EVs are associated with postoperative risk of major adverse cardiovascular events (MACE) following CEA. In 873 patients undergoing CEA of the Athero-Express biobank, we quantitatively measured seven ceramides/PCs in preoperative blood samples: Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1), PC(14:0/22:6), PC(16:0/16:0) and PC(16:0/22:5) in plasma and two plasma EV-subfractions (LDL and TEX). We analyzed the association of ceramides, PCs and their predefined ratios with the three-year postoperative risk of MACE (including stroke, myocardial infarction and cardiovascular death). A total of 138 patients (16%) developed MACE during the three-year follow-up. In the LDL-EV subfraction, higher levels of Cer(d18:1/24:1) and Cer(d18:1/16:0)/PC(16:0/22:5) ratio were significantly associated with an increased risk of MACE (adjusted HR per SD [95% CI] 1.24 [1.01–1.53] and 1.26 [1.04–1.52], respectively). In the TEX-EV subfraction, three ratios Cer(d18:1/16:0)/Cer(d18:1/24:0), Cer(d18:1/18:0)/Cer(d18:1/24:0) and Cer(d18:1/24:1)/Cer(d18:1/24:0) were positively associated with MACE (adjusted HR per SD 1.34 [1.06–1.70], 1.24 [1.01–1.51] and 1.31 [1.08–1.58], respectively). In conclusion, distinct ceramides and PCs in plasma EVs determined in preoperative blood were independently associated with an increased 3-year risk of MACE after CEA. These lipids are therefore potential markers to identify high-risk CEA patients qualifying for secondary preventive add-on therapy.
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1 Utrecht University, Department of Vascular Surgery (G04129), University Medical Centre Utrecht, Utrecht, The Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234)
2 Utrecht University, Department of Vascular Surgery (G04129), University Medical Centre Utrecht, Utrecht, The Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234); Amsterdam UMC, Department of Cardiology, Amsterdam Cardiovascular Sciences, Academic Medical Center, Amsterdam, The Netherlands (GRID:grid.509540.d) (ISNI:0000 0004 6880 3010)
3 Amsterdam UMC, Department of Cardiology, Amsterdam Cardiovascular Sciences, Academic Medical Center, Amsterdam, The Netherlands (GRID:grid.509540.d) (ISNI:0000 0004 6880 3010)
4 Zora Biosciences, Espoo, Finland (GRID:grid.426520.7)
5 Utrecht University, Laboratory of Clinical Chemistry and Hematology, Division Laboratories and Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands (GRID:grid.5477.1) (ISNI:0000000120346234)
6 Zora Biosciences, Espoo, Finland (GRID:grid.426520.7); Tampere University, Finnish Cardiovascular Research Center Tampere, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0001 2314 6254)