Objectives

This study investigated whether patients with chronic heart failure (HF) can be stratified according to the combination of soluble neprilysin and corin concentrations and whether this is related to clinical outcome.

Background

Natriuretic peptide processing by the enzymes corin and neprilysin plays a pivotal role in conversion of pro–natriuretic peptides to active natriuretic peptides, as well as their degradation, respectively.

Methods

A prospective cohort of patients with chronic HF (n = 1,009) was stratified into 4 equal groups based on high or low neprilysin/corin concentration relative to the median: 1) low neprilysin/low corin; 2) low neprilysin/high corin; 3) high neprilysin/low corin; and 4) high neprilysin/high corin. Cox regression survival analysis was performed for the composite primary endpoint of cardiovascular death and HF hospitalization.

Results

Median neprilysin and corin concentrations were not correlated (rho: −0.04; p = 0.21). Although in univariate analysis there was no association with outcome, after correction for baseline differences in age and sex, a significant association with survival was demonstrated: with highest survival in group 1 (low neprilysin/low corin) and lowest in group 4 (high neprilysin/high corin) (adjusted hazard ratio: 1.56; p = 0.003), which remained statistically significant after comprehensive multivariable analysis (adjusted hazard ratio: 1.41; p = 0.03).

Conclusions

Stratification of patients with chronic HF based on circulating neprilysin and corin concentrations is associated with clinical outcomes. These results suggest that regulation of these enzymes is of importance in chronic HF and may offer an interesting approach for classification of patients with HF in a step toward individualized HF patient management.

中文翻译：

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可溶性 Neprilysin 和 Corin 浓度与慢性心力衰竭临床结果的相关性

目标

本研究调查了慢性心力衰竭 (HF) 患者是否可以根据可溶性脑啡肽酶和 corin 浓度的组合进行分层，以及这是否与临床结果相关。

背景

由 corin 和脑啡肽酶处理的利钠肽分别在促利钠肽向活性利钠肽的转化及其降解中起关键作用。

方法

基于相对于中值的高或低中性溶酶/corin 浓度，将慢性 HF 患者的前瞻性队列 (n = 1,009) 分为 4 个相等的组：1) 低中性溶酶/低 corin；2) 低脑啡肽酶/高corin；3）高脑啡肽酶/低corin；4）高脑啡肽酶/高corin。对心血管死亡和心衰住院的复合主要终点进行 Cox 回归生存分析。

结果

中值脑啡肽酶和 corin 浓度不相关（rho：-0.04；p = 0.21）。尽管在单变量分析中与结果没有关联，但在校正年龄和性别的基线差异后，证明与生存率显着相关：第 1 组（低脑啡肽酶/低 corin）的生存率最高，第 4 组（高脑啡肽酶）的生存率最低/high corin)（调整后的风险比：1.56；p = 0.003），在综合多变量分析后仍具有统计学意义（调整后的风险比：1.41；p = 0.03）。

结论

根据循环脑啡肽酶和 corin 浓度对慢性 HF 患者进行分层与临床结果相关。这些结果表明，这些酶的调节在慢性 HF 中很重要，并且可能为 HF 患者的分类提供一种有趣的方法，从而迈向个性化 HF 患者管理的一步。