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. 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. 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. Plasma S1P levels in systolic heart failure patients are related to the long-term all-cause mortality with a U-shaped correlation. CHiCTR, ChiCTR-ONC-14004463. Registered 20 March 2014.

中文翻译：

---

慢性收缩性心力衰竭患者血浆神经鞘氨醇-1-磷酸水平与死亡率之间的U型关联：一项前瞻性队列研究。

动物研究表明，内源性脂质分子-1-磷酸鞘氨醇（S1P）由于其显着的心脏保护作用而在心血管领域受到关注。本研究的目的是确定收缩期心力衰竭患者中S1P的分布特征以及S1P对长期预后的预后价值。我们从2014年6月至2015年12月招募了210例慢性收缩性心力衰竭患者。同时，选择了同一地区的54名健康人作为对照。血浆S1P通过液相色谱-串联质谱法测量。根据基线S1P水平四分位数对患者进行分组，并且有限的三次样条图描述了S1P与全因死亡之间的关联。使用Cox比例风险分析确定S1P类别与全因死亡之间的关系。与对照组相比，慢性心力衰竭患者的血浆S1P表现出较高的平均水平（1.269μmol/ L对1.122μmol/ L，P = 0.006）和较大的标准偏差（0.441对0.316，P = 0.022）。基于带有受限三次样条分析的多变量Cox回归，观察到S1P水平与全因死亡风险之间存在非线性和U形关联。在31.7±10.3个月的随访期后，S1P水平基本正常的第二个四分位数（0.967-1.192μml/ L）的全因死亡率最低，且有升高的趋势（校正后的HR = 2.368，95％CI 1.006– 5.572，P = 0.048）或降低（校正后的HR = 0.041，95％CI 0.002-0.808，P = 0.036）预后较差。生存曲线表明，最低四分位数和最高四分位数的患者死亡风险更高。收缩期心力衰竭患者血浆S1P水平与长期全因死亡率相关，呈U型相关。CHiCTR，ChiCTR-ONC-14004463。2014年3月20日注册。