Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Nydalen, P. B. 4950, 0424, Oslo, Norway.
Faculty of Medicine, University of Oslo, Oslo, Norway.
Clin Res Cardiol. 2019 Feb;108(2):133-141. doi: 10.1007/s00392-018-1331-2. Epub 2018 Jul 26.
Activated leukocytes may contribute to the development and progression of heart failure (HF). We investigated the predictive value of circulating levels of stable and readily detectable markers reflecting both monocyte/macrophage and T-cell activity, on clinical outcomes in HF patients with reduced ejection fraction (HFrEF).
The association between baseline plasma levels of soluble CD163 (sCD163), macrophage migration inhibitory factor (MIF), granulysin, soluble interleukin-2 receptor (sIL-2R), and activated leukocyte cell adhesion molecule (ALCAM) and the primary endpoint of death from any cause or first hospitalization for worsening of HF was evaluated using multivariable Cox proportional hazard models in 1541 patients with systolic HF and mild to moderate anemia, enrolled in the Reduction of Events by darbepoetin alfa in Heart Failure (RED-HF) trial. Modifying effects and interaction with darbepoetin alfa treatment were also assessed.
All leukocyte markers, except granulysin, were associated with the primary outcome and all-cause death in univariate analysis (all p < 0.01) and remained significantly associated in multivariable analysis adjusting for conventional clinical variables (e.g. age, gender, BMI, NYHA class, creatinine, LVEF, etiology) and CRP. However, after final adjustment for TnT and NT-proBNP no associations were found with outcomes. No interaction with darbepoetin alpha treatment was observed for any marker.
Leukocyte activation markers sCD163, MIF, sIL-2R, and ALCAM were associated with adverse outcome in patients with HFrEF, but add little as prognostic markers on top of established biochemical risk markers.
活化的白细胞可能导致心力衰竭（HF）的发生和进展。我们研究了反映单核细胞/巨噬细胞和 T 细胞活性的循环水平稳定且易于检测的标志物的基线血浆水平与射血分数降低的心力衰竭（HFrEF）患者临床结局之间的相关性。
使用多变量 Cox 比例风险模型评估 1541 例收缩性 HF 和轻度至中度贫血患者基线血浆可溶性 CD163（sCD163）、巨噬细胞移动抑制因子（MIF）、颗粒溶素、可溶性白细胞介素 2 受体（sIL-2R）和活化白细胞细胞黏附分子（ALCAM）水平与主要终点（任何原因死亡或 HF 恶化的首次住院）之间的关系，该研究纳入了心力衰竭中达贝泊汀治疗降低事件（RED-HF）试验。还评估了修饰作用和与达贝泊汀治疗的相互作用。
除颗粒溶素外，所有白细胞标志物在单变量分析中均与主要结局和全因死亡相关（均 p<0.01），并且在调整常规临床变量（例如年龄、性别、BMI、NYHA 分级、肌酐、LVEF、病因）和 CRP 后多变量分析中仍显著相关。然而，在最终调整 TnT 和 NT-proBNP 后，与结局没有关联。未观察到任何标志物与达贝泊汀 alpha 治疗的相互作用。
在 HFrEF 患者中，白细胞活化标志物 sCD163、MIF、sIL-2R 和 ALCAM 与不良结局相关，但作为预后标志物，其在既定生化风险标志物之上的附加价值有限。
