血浆鞘氨醇-1-磷酸水平与慢性收缩性心力衰竭患者死亡率的 U 型关系：一项前瞻性队列研究。
U-shaped association between plasma sphingosine-1-phosphate levels and mortality in patients with chronic systolic heart failure: a prospective cohort study.
机构信息
Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University; Shaanxi Key Laboratory of Molecular Cardiology; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, No. 277 West Yanta Road, Xi'an, 710061, Shaanxi Province, People's Republic of China.
Department of Pharmacy, the Second Affiliated Hospital of Air Force Medical University, No. 1 Xinsi Road, Xi'an, Shaanxi, China.
出版信息
Lipids Health Dis. 2020 Jun 4;19(1):125. doi: 10.1186/s12944-020-01262-2.
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.
背景
内源性脂质分子鞘氨醇-1-磷酸（S1P）在心血管领域受到关注，因为动物研究表明它具有显著的心脏保护作用。我们的研究目的是确定 S1P 在收缩性心力衰竭患者中的分布特征，以及 S1P 对长期预后的预测价值。
方法
我们招募了 210 名来自 2014 年 6 月至 2015 年 12 月的慢性收缩性心力衰竭患者。同时选择了同一地区的 54 名健康人作为对照组。通过液相色谱-串联质谱法测量血浆 S1P。根据基线 S1P 水平四分位数将患者分组，受限立方样条图描述 S1P 与全因死亡之间的关系。Cox 比例风险分析用于确定 S1P 类别与全因死亡的关系。
结果
与对照组相比，慢性心力衰竭患者的血浆 S1P 水平较高（平均水平为 1.269μmol/L 比 1.122μmol/L，P=0.006），标准差较大（0.441 比 0.316，P=0.022）。基于多变量 Cox 回归受限立方样条分析，S1P 水平与全因死亡风险之间呈非线性 U 型关系。在 31.7±10.3 个月的随访期间，S1P 水平处于大致正常范围内的第二四分位数（0.967-1.192μml/L）的全因死亡率最低，无论是增加（调整后的 HR=2.368，95%CI 1.006-5.572，P=0.048）还是减少（调整后的 HR=0.041，95%CI 0.002-0.808，P=0.036）均预示预后较差。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较高。
结论
收缩性心力衰竭患者的血浆 S1P 水平与全因死亡率呈 U 型相关，与长期全因死亡率相关。
试验注册
ChiCTR，ChiCTR-ONC-14004463。于 2014 年 3 月 20 日注册。
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