巨噬细胞和中性粒细胞相关标志物的时间模式与心力衰竭患者的临床结局相关。
Temporal patterns of macrophage- and neutrophil-related markers are associated with clinical outcome in heart failure patients.
作者信息
Klimczak-Tomaniak Dominika, Bouwens Elke, Schuurman Anne-Sophie, Akkerhuis K Martijn, Constantinescu Alina, Brugts Jasper, Westenbrink B Daan, van Ramshorst Jan, Germans Tjeerd, Pączek Leszek, Umans Victor, Boersma Eric, Kardys Isabella
机构信息
Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Immunology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
出版信息
ESC Heart Fail. 2020 Jun;7(3):1190-1200. doi: 10.1002/ehf2.12678. Epub 2020 Mar 20.
AIMS
Evidence on the association of macrophage- and neutrophil-related blood biomarkers with clinical outcome in heart failure patients is limited, and, with the exception of C-reactive protein, no data exist on their temporal evolution. We aimed to investigate whether temporal patterns of these biomarkers are related to clinical outcome in patients with stable chronic heart failure (CHF).
METHODS AND RESULTS
In 263 patients with CHF, we performed serial plasma measurements of scavenger receptor cysteine-rich type 1 protein M130 (CD163), tartrate-resistant acid phosphatase type 5 (TRAP), granulins (GRN), spondin-1 (SPON1), peptidoglycan recognition protein 1 (PGLYRP1), and tissue factor pathway inhibitor (TFPI). The Cardiovascular Panel III (Olink Proteomics AB, Uppsala, Sweden) was used. During 2.2 years of follow-up, we collected 1984 samples before the occurrence of the composite primary endpoint (PE) or censoring. For efficiency, we selected 567 samples for the measurements (all baseline samples, the last two samples preceding the PE, and the last sample before censoring in event-free patients). The relationship between repeatedly measured biomarker levels and the PE was evaluated by joint models. Mean (±standard deviation) age was 67 ± 13 years; 189 (72%) were men; left ventricular ejection fraction (%) was 32 ± 11. During follow-up, 70 (27%) patients experienced the PE. Serially measured biomarkers predicted the PE in a multivariable model adjusted for baseline clinical characteristics [hazard ratio (95% confidence interval) per 1-standard deviation change in biomarker]: CD163 [2.07(1.47-2.98), P < 0.001], TRAP [0.62 (0.43-0.90), P = 0.009], GRN [2.46 (1.64-3.84), P < 0.001], SPON1 [3.94 (2.50-6.50), P < 0.001], and PGLYRP1 [1.62 (1.14-2.31), P = 0.006].
CONCLUSIONS
Changes in plasma levels of CD163, TRAP, GRN, SPON1, and PGLYRP1 precede adverse cardiovascular events in patients with CHF.
目的
关于巨噬细胞和中性粒细胞相关血液生物标志物与心力衰竭患者临床结局之间关联的证据有限，并且除了C反应蛋白外，尚无关于它们随时间变化的数据。我们旨在研究这些生物标志物的时间模式是否与稳定型慢性心力衰竭（CHF）患者的临床结局相关。
方法与结果
在263例CHF患者中，我们对富含半胱氨酸的清道夫受体1型蛋白M130（CD163）、抗酒石酸酸性磷酸酶5型（TRAP）、颗粒蛋白（GRN）、腱生蛋白-1（SPON1）、肽聚糖识别蛋白1（PGLYRP1）和组织因子途径抑制剂（TFPI）进行了系列血浆检测。使用了心血管检测板III（瑞典乌普萨拉的Olink蛋白质组学公司）。在2.2年的随访期间，我们在复合主要终点（PE）出现或截尾之前收集了1984份样本。为了提高效率，我们选择了567份样本进行检测（所有基线样本、PE之前的最后两份样本以及无事件患者截尾之前的最后一份样本）。通过联合模型评估重复测量的生物标志物水平与PE之间的关系。平均（±标准差）年龄为67±13岁；189例（72%）为男性；左心室射血分数（%）为32±11。在随访期间，70例（27%）患者发生了PE。在根据基线临床特征进行调整的多变量模型中，系列测量的生物标志物可预测PE [生物标志物每变化1个标准差的风险比（95%置信区间）]：CD163 [2.07(1.47 - 2.98)，P < 0.001]，TRAP [0.62 (0.43 - 0.90)，P = 0.009]，GRN [2.46 (1.64 - 3.84)，P < 0.001]，SPON1 [3.94 (2.50 - 6.50)，P < 0.001]，以及PGLYRP1 [1.62 (1.14 - 2.31)，P = 0.006]。
结论
CHF患者血浆中CD163、TRAP、GRN、SPON1和PGLYRP1水平的变化先于不良心血管事件。
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