Department of Cardiovascular Sciences, Clinical Sciences Wing, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, University of Leicester, Leicester, LE3 9QP, UK.
Department of Cancer Studies, Leicester Royal Infirmary, University of Leicester, Leicester, LE1 5WW, UK.
Clin Res Cardiol. 2019 Aug;108(8):940-949. doi: 10.1007/s00392-019-01424-y. Epub 2019 Feb 14.
Proenkephalin (PENK), a stable endogenous opioid biomarker related to renal function, has prognostic utility in acute and chronic heart failure. We investigated the prognostic utility of PENK in heart failure with preserved ejection fraction (HFpEF), and its relationship to renal function, Body Mass Index (BMI), and imaging measures of diastolic dysfunction.
In this multicentre study, PENK was measured in 522 HFpEF patients (ejection fraction > 50%, 253 male, mean age 76.13 ± 10.73 years) and compared to 47 age and sex-matched controls. The primary endpoint was 2-years composite of all-cause mortality and/or heart failure rehospitalisation (HF). A subset (n = 163) received detailed imaging studies.
PENK levels were raised in HFpEF (median [interquartile range] 88.9 [62.1-132.0]) compared to normal controls (56.3 [47.9-70.5]). PENK was correlated to urea, eGFR, Body Mass Index and E/e' (r 0.635, - 0.741, - 0.275, 0.476, respectively, p < 0.0005). During 2 years follow-up 144 patients died and 220 had death/HF endpoints. Multivariable Cox regression models showed PENK independently predicted 2 year death/HF [hazard ratio (for 1 SD increment of log-transformed biomarker) HR 1.45 [95% CI 1.12-1.88, p = 0.005]], even after adjustment for troponin (HR 1.59 [1.14-2.20, p = 0.006]), and Body Mass Index (HR 1.63 [1.13-2.33, p = 0.009]). PENK showed no interaction with ejection fraction status for prediction of poor outcomes. Net reclassification analyses showed PENK significantly improved classification of death/HF outcomes for multivariable models containing natriuretic peptide, troponin and Body Mass Index (p < 0.05 for all).
In HFpEF, PENK levels are related to BMI, and measures of diastolic dysfunction and are prognostic for all-cause mortality and heart failure rehospitalisation.
Proenkephalin（PENK）是一种与肾功能相关的稳定内源性阿片类生物标志物，在急性和慢性心力衰竭中具有预后价值。我们研究了 PENK 在射血分数保留型心力衰竭（HFpEF）中的预后价值，以及它与肾功能、体重指数（BMI）和舒张功能障碍的影像学测量的关系。
在这项多中心研究中，测量了 522 例 HFpEF 患者（射血分数>50%，253 例男性，平均年龄 76.13±10.73 岁）的 PENK，并与 47 名年龄和性别匹配的对照者进行比较。主要终点是 2 年的全因死亡率和/或心力衰竭再住院（HF）的复合终点。一个亚组（n=163）接受了详细的影像学研究。
HFpEF 患者的 PENK 水平升高（中位数[四分位间距] 88.9[62.1-132.0]）与正常对照组相比（56.3[47.9-70.5]）。PENK 与尿素、eGFR、BMI 和 E/e'呈正相关（r 值分别为 0.635、-0.741、-0.275、0.476，p<0.0005）。在 2 年的随访期间，144 名患者死亡，220 名患者出现死亡/心力衰竭终点。多变量 Cox 回归模型显示，PENK 独立预测 2 年死亡/心力衰竭[风险比（对于 log 转化生物标志物的 1 SD 增量）HR 1.45[95%CI 1.12-1.88，p=0.005]，甚至在调整肌钙蛋白后（HR 1.59[1.14-2.20，p=0.006]），以及 BMI（HR 1.63[1.13-2.33，p=0.009]）。PENK 与射血分数状态对不良结局的预测无交互作用。净重新分类分析显示，PENK 显著改善了包含利钠肽、肌钙蛋白和 BMI 的多变量模型对死亡/心力衰竭结局的分类（p<0.05 均为所有）。
在 HFpEF 中，PENK 水平与 BMI 以及舒张功能障碍的测量值相关，并且对全因死亡率和心力衰竭再入院具有预后价值。
