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白细胞介素-1 轴与急性失代偿性心力衰竭患者死亡风险。

The Interleukin-1 Axis and Risk of Death in Patients With Acutely Decompensated Heart Failure.

机构信息

Cardiology Department, Hospital Virgen de la Arrixaca, IMIB-Arrixaca, University of Murcia, Murcia, Spain; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, España; CIBERCV, Madrid, Spain.

CIBERCV, Madrid, Spain; Heart Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

出版信息

J Am Coll Cardiol. 2019 Mar 12;73(9):1016-1025. doi: 10.1016/j.jacc.2018.11.054.

Abstract

BACKGROUND

Soluble ST2 (sST2), which is the soluble form of interleukin (IL)-1 receptor-like 1, identifies risk in acutely decompensated heart failure (ADHF). IL-1β is an inflammatory cytokine that has deleterious effects in myocardial remodeling and function. IL-1β inhibition has beneficial effects after acute myocardial infarction. However, the role of IL-1β in ADHF and its relationship to ST2 remain unclear.

OBJECTIVES

This study sought to investigate the relationship between IL-1β and sST2, and the prognostic impact of such a relationship in patients with ADHF.

METHODS

This study examined 316 consecutive patients who were hospitalized with ADHF (72 ± 12 years of age, 57% male, and left ventricular ejection fraction 45 ± 17%). Blood samples were collected at presentation, and IL-1β and sST2 levels were measured. All-cause mortality was obtained for all patients at 1 year.

RESULTS

The IL-1β concentration at presentation was associated with prior HF hospitalizations, functional impairment, and higher N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T concentrations. IL-1β was higher in patients who died during the year after hospitalization (n = 52, 16.5%) (p = 0.005), and the optimal threshold was identified with levels over 49.1 pg/ml (hazard ratio: 2.5; 95% confidence interval: 1.43 to 4.49; p = 0.0014). Circulating IL-1β positively correlated with sST2 (ρ = 0.65; p < 0.001). Considering the prognostic thresholds of IL-1β (≥49.1 pg/ml) and sST2 (≥35.0 ng/ml) concentrations: all patients with low sST2 also presented with low IL-1β; among patients with high sST2, only those with also high IL-1β had a significantly higher risk of death (30% vs. 14%; hazard ratio: 2.52; 95% confidence interval: 1.40 to 4.56; p = 0.002).

CONCLUSIONS

Circulating IL-1β concentrations are clinically meaningful in ADHF patients and interplay with the predictive ability of sST2. IL-1 axis-related inflammation signaling may represent a therapeutic target in ADHF.

摘要

背景

可溶性 ST2(sST2)是白细胞介素(IL)-1 受体样 1 的可溶性形式,可识别急性失代偿性心力衰竭(ADHF)的风险。IL-1β 是一种炎症细胞因子,对心肌重构和功能具有有害影响。急性心肌梗死后,IL-1β 抑制具有有益作用。然而,IL-1β 在 ADHF 中的作用及其与 ST2 的关系尚不清楚。

目的

本研究旨在探讨 IL-1β 与 sST2 的关系,以及这种关系在 ADHF 患者中的预后影响。

方法

本研究纳入了 316 例连续住院的 ADHF 患者(72±12 岁,57%为男性,左心室射血分数 45±17%)。在入院时采集血样,并测量 IL-1β 和 sST2 水平。所有患者在 1 年内均获得全因死亡率。

结果

入院时的 IL-1β 浓度与既往心力衰竭住院、功能障碍以及更高的 N 末端 B 型利钠肽前体和高敏肌钙蛋白 T 浓度相关。在住院后 1 年内死亡的患者中,IL-1β 水平更高(n=52,16.5%)(p=0.005),并确定了超过 49.1pg/ml 的最佳阈值(危险比:2.5;95%置信区间:1.43 至 4.49;p=0.0014)。循环中的 IL-1β 与 sST2 呈正相关(ρ=0.65;p<0.001)。考虑到 IL-1β(≥49.1pg/ml)和 sST2(≥35.0ng/ml)浓度的预后阈值:所有 sST2 水平较低的患者 IL-1β 水平也较低;在 sST2 水平较高的患者中,只有那些同时 IL-1β 水平较高的患者死亡风险显著增加(30% vs. 14%;危险比:2.52;95%置信区间:1.40 至 4.56;p=0.002)。

结论

循环中的 IL-1β 浓度在 ADHF 患者中有临床意义,并与 sST2 的预测能力相互作用。IL-1 轴相关炎症信号可能是 ADHF 的治疗靶点。

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