U-shaped association of sphingosine-1-phosphate level with mortality in chronic systolic heart failure

Abstract

Abstract Background The immunomodulatory molecule sphingosine-1-phosphate (S1P) has received attention in the cardiovascular field due to its significant cardioprotective effects, as revealed in animal studies. Until now, it has been unclear what is the normal range of S1P in chronic heart failure patients and whether it is related to long term prognosis. Purpose The purpose of our study was to identify the distribution characteristics of S1P in systolic heart failure patients and the prognostic value of S1P for long-term prognosis. Methods We recruited 210 chronic systolic heart failure patients from June 2014 to December 2015. Meanwhile 54 healthy people in the same area were selected as controls. Plasma S1P was measured by mass spectrometry. Patients were grouped according to the baseline S1P level quartiles, and restricted cubic spline plots described a U-shaped association between S1P and all cause death. Cox proportional hazard analysis was used to determine the relationship between category of S1P and all-cause death. Survival curves were using the Kaplan-Meier method and the log-rank test was used for comparison. Results Compared with the control group, the plasma S1P in chronic heart failure patients demonstrated a higher mean level (1.269 μmol/L vs 1.122 μmol/L, P=0.006) and a larger standard deviation (0.441 vs 0.316, P=0.022). After a follow-up period of 31.7±10.3 months, the second quartile (0.967–1.192μml/L) with largely normal S1P levels had the lowest all-cause mortality and either an increase (HR=3.87, 95% CI 1.504–9.960, P=0.005, adjusted HR=3.134, 95% CI 1.211–8.111, P=0.019) or a decrease (HR=3.271, 95% CI 1.277–8.381, P=0.014, adjusted HR=1.90, 95% CI 0.711–5.083, P=0.200) predicted a worse prognosis. Conclusions Plasma S1P levels in systolic heart failure patients are related to the long-term all-cause mortality with a U-shaped correlation. Through restoring abnormal levels to a normal range instead of simply up regulation or down regulation, S1P may have the potential to be a therapeutic target for reducing the risk of death in patients with heart failure in the future. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Science and Technology of the People's Republic of China. Ministry of Finance of the People's Republic of China.