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. 2020 Jun 4;19(1):125.
doi: 10.1186/s12944-020-01262-2.

U-shaped association between plasma sphingosine-1-phosphate levels and mortality in patients with chronic systolic heart failure: a prospective cohort study

Yanbo Xue  1 , Wei Jiang  2 , Qiong Ma  1 , Xiqiang Wang  1 , Pu Jia  3 , Qiang Li  4 , Shuping Chen  1 , Bingxue Song  5 , Ya Wang  1 , Jingwen Zhang  6 , Jing Liu  1 , Guodong Yang  1 , Yuyao Lin  1 , Jing Liu  1 , Linyan Wei  1 , Caijuan Dong  1 , Haiquan Li  1 , Zhonglei Xie  1 , Ling Bai  7 , Aiqun Ma  8
Affiliations

U-shaped association between plasma sphingosine-1-phosphate levels and mortality in patients with chronic systolic heart failure: a prospective cohort study

Yanbo Xue et al. Lipids Health Dis. .

Abstract

Background: The endogenous lipid molecule sphingosine-1-phosphate (S1P) has received attention in the cardiovascular field due to its significant cardioprotective effects, as revealed in animal studies. 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 liquid chromatography-tandem mass spectrometry. Patients were grouped according to the baseline S1P level quartiles, and restricted cubic spline plots described the 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.

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). Based on multivariable Cox regression with restricted cubic spline analysis, a non-linear and U-shaped association between S1P levels and the risk of all-cause death was observed. After a follow-up period of 31.7 ± 10.3 months, the second quartile (0.967-1.192 μml/L) with largely normal S1P levels had the lowest all-cause mortality and either an increase (adjusted HR = 2.368, 95%CI 1.006-5.572, P = 0.048) or a decrease (adjusted HR = 0.041, 95%CI 0.002-0.808, P = 0.036) predicted a worse prognosis. The survival curves showed that patients in the lowest quartile and highest quartile were at a higher risk of death.

Conclusions: Plasma S1P levels in systolic heart failure patients are related to the long-term all-cause mortality with a U-shaped correlation.

Trial registration: CHiCTR, ChiCTR-ONC-14004463. Registered 20 March 2014.

Keywords: All-cause mortality; Heart failure; Prognosis; Sphingosine-1-phosphate.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The study design and population
Fig. 2
Fig. 2
Plasma S1P levels and quartile grouping. Patients were divided into 4 groups according to the quartiles of baseline plasma S1P levels, and the plasma S1P levels of 54 healthy volunteers in the same area were used as the control group. *indicates P<0.05 in the Mann-Whitney U test when compared with the control group, and # indicates P<0.05 in the Levene test when compared with the control group. The error line is standard deviation. Abbreviations: S1P, sphingosine-1-phosphate
Fig. 3
Fig. 3
Association between S1P levels and the adjusted hazard ratio for all-cause death. Histograms stand for frequency of patients at different S1P concentrations (The right-hand y-axis). The solid curve gives expected of adjusted HR based on restricted cubic spline analysis (The left-hand y-axis). The dashed curves represent the 95% confidence intervals for expected of adjusted HR (The left-hand y-axis). Model adjusted on MAGGIC score and lgNT-proBNP
Fig. 4
Fig. 4
Kaplan-Meir curves of all-cause mortality (a) and heart failure hospitalization (b). Abbreviations: S1P, sphingosine-1-phosphate
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