Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Faculty of Medicine, University of Oslo, Oslo, Norway.
ESC Heart Fail. 2018 Dec;5(6):1052-1059. doi: 10.1002/ehf2.12312. Epub 2018 Aug 25.
Neuroendocrine activation is associated with poor outcome in heart failure (HF). The neuropeptide gastrin-releasing peptide (GRP), derived from the precursor proGRP1-125 (proGRP), has recently been implicated in inflammation and wound repair. We investigated the predictive value of proGRP on clinical outcomes in HF patients with reduced ejection fraction.
The association between plasma proGRP (time-resolved immunofluorometric assay) 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 anaemia, enrolled in the Reduction of Events by Darbepoetin alfa in Heart Failure (RED-HF) trial. Median proGRP levels in the RED-HF cohort were markedly increased [95 ng/L (25th, 75th percentile, 69-129 ng/L)] with 64% patients above the 80 ng/L reference limit. Baseline proGRP correlated with estimated glomerular filtration rate (r = 0.52), N terminal pro brain natriuretic peptide (r = 0.33), troponin T (r = 0.34), and haemoglobin (r = 0.16) (all P < 0.001). The incidence outcome increased with increasing tertiles of baseline proGRP (primary endpoint third tertile vs. the lowest tertile; hazard ratio 1.91; 95% confidence interval 1.60-2.28, P < 0.001). However, these associations were markedly attenuated and non-significant in adjusted models. No interaction between baseline proGRP and the effect of darbepoetin alfa treatment was detected. Moreover, no significant association between changes in proGRP during 6 month follow-up and outcome was observed.
Pro-gastrin-releasing peptide is increased in patients with HF with reduced ejection fraction and anaemia, in particular in patients with poor renal function. However, proGRP adds little as a prognostic marker on top of conventional HF risk factors.
神经内分泌激活与心力衰竭（HF）预后不良相关。神经肽胃泌素释放肽（GRP）来源于前体 proGRP1-125（proGRP），最近与炎症和伤口修复有关。我们研究了 proGRP 对射血分数降低的 HF 患者临床结局的预测价值。
采用多变量 Cox 比例风险模型，在 1541 例射血分数降低的 HF 合并轻度至中度贫血患者中，评估了血浆 proGRP（时间分辨免疫荧光测定法）与主要终点（任何原因死亡或因 HF 恶化首次住院）之间的关系，该患者来自心力衰竭中达贝泊汀 α 降低事件研究（RED-HF）试验。RED-HF 队列中的中位 proGRP 水平明显升高[95ng/L（25 分位、75 分位，69-129ng/L）]，64%的患者超过 80ng/L 的参考限值。基线 proGRP 与估算肾小球滤过率（r=0.52）、N 末端脑钠肽前体（r=0.33）、肌钙蛋白 T（r=0.34）和血红蛋白（r=0.16）相关（均 P<0.001）。随着基线 proGRP 三分位值的升高，发生率结局增加（主要终点第三三分位与最低三分位；危险比 1.91；95%置信区间 1.60-2.28，P<0.001）。然而，在调整模型中，这些相关性明显减弱且无统计学意义。未检测到基线 proGRP 与达贝泊汀 α 治疗效果之间的交互作用。此外，在 6 个月随访期间 proGRP 变化与结局之间未观察到显著相关性。
在射血分数降低的 HF 合并贫血患者中，proGRP 增加，特别是在肾功能较差的患者中。然而，proGRP 作为预后标志物，其价值不如传统的 HF 危险因素。
