Plasma sphingosine-1-phosphate concentrations are associated with systolic heart failure in patients with ischemic heart disease

Objective: Sphingosine-1-Phosphate (SIP) is a bioactive sphingolipid with important functions in immunity, inflammation and cardiovascular biology. SIP is associated with prevalence and severity of coronary artery disease and myocardial infarction. However, its relevance in ischemic cardiomyopathy is unknown. We aimed to investigate associations of plasma S1P and other sphingolipids with the extent of heart failure in patients with ischemic heart disease. Methods and results: 74 patients with ischemic heart disease were investigated in this observational study. Plasma concentrations of SIP, C16 ceramide and sphingomyelin (SM) were measured using liquid chromatography/tandem mass-spectrometry and associated with objective (echocardiography) and subjective (dyspnea) signs of heart failure. Plasma SIP and SM but not C16 ceramide concentrations were negatively associated with left ventricular ejection fraction (LVEF) and dyspnea (ranked by New York Heart Association; LVEF: SIP standardized coefficient beta: -0.25; 95%CI: -273 to -13 nM, p = 0.03; SM beta: -0.24; 95%CI: -16,310 to -413 nM, p = 0.04; NYHA: SIP beta: -03; 95%CI: -174 to -26 nM, p = 0.009; SM beta: -0.46; 95%CI: -13,462 to -5013 nM, p < 0.001). ROC analysis revealed that SiP and SM predicted impaired LVEF with optimal cut-off levels below 843 nM and 77 mu M, respectively. Conclusion: SW is associated with the impairment of LVEF and dyspnea. Considering the major effects of SIP on cardiac and vascular functions in experimental models, we put forward the hypothesis that SIP is causally involved in the pathophysiology of heart failure. Interfering pharmacologically with SIP receptors may have an impact on ischemic cardiomyopathy. (C) 2017 Elsevier Ltd. All rights reserved.