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

Abstract

ObjectiveSphingosine-1-Phosphate (S1P) is a bioactive sphingolipid with important functions in immunity, inflammation and cardiovascular biology. S1P 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 results74 patients with ischemic heart disease were investigated in this observational study. Plasma concentrations of S1P, 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 S1P 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: S1P standardized coefficient beta: −0.25; 95%CI: −273 to −13nM, p=0.03; SM beta: −0.24; 95%CI: −16,310 to −413nM, p=0.04; NYHA: S1P beta: −0.3; 95%CI: −174 to −26nM, p=0.009; SM beta: −0.46; 95%CI: −13,462 to −5013nM, p<0.001). ROC analysis revealed that S1P and SM predicted impaired LVEF with optimal cut-off levels below 843nM and 77μM, respectively. ConclusionS1P is associated with the impairment of LVEF and dyspnea. Considering the major effects of S1P on cardiac and vascular functions in experimental models, we put forward the hypothesis that S1P is causally involved in the pathophysiology of heart failure. Interfering pharmacologically with S1P receptors may have an impact on ischemic cardiomyopathy.