Department of Cardiology, Radboud University Medical Centre, Nijmegen, the Netherlands.
Heart Failure and Cardiac Regeneration Research Program, Health Sciences Research Institute Germans Trias i Pujol, Barcelona, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain.
JACC Heart Fail. 2021 Feb;9(2):85-95. doi: 10.1016/j.jchf.2020.08.015. Epub 2020 Nov 11.
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.
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.
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.
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).
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.
本研究旨在探讨慢性心力衰竭（HF）患者是否可以根据可溶性 Neprilysin 和 Corin 浓度的组合进行分层，以及这是否与临床结局相关。
Corin 和 Neprilysin 等酶对利钠肽原的处理在将前利钠肽原转化为活性利钠肽以及分别对其进行降解方面起着关键作用。
前瞻性队列研究纳入了 1009 例慢性 HF 患者，根据 Neprilysin/ Corin 浓度相对于中位数的高低，将患者分为 4 组：1）低 Neprilysin/低 Corin；2）低 Neprilysin/高 Corin；3）高 Neprilysin/低 Corin；和 4）高 Neprilysin/高 Corin。采用 Cox 回归生存分析评估心血管死亡和 HF 住院的复合主要终点。
Neprilysin 和 Corin 浓度的中位数无相关性（rho：-0.04；p=0.21）。尽管在单因素分析中与结局无关联，但在校正年龄和性别基线差异后，与生存存在显著关联：第 1 组（低 Neprilysin/低 Corin）的生存率最高，第 4 组（高 Neprilysin/高 Corin）的生存率最低（校正后的危险比：1.56；p=0.003），在全面多变量分析后仍然具有统计学意义（校正后的危险比：1.41；p=0.03）。
基于循环 Neprilysin 和 Corin 浓度对慢性 HF 患者进行分层与临床结局相关。这些结果表明，这些酶的调节在慢性 HF 中很重要，并可能为 HF 患者的分类提供一种有趣的方法，朝着 HF 个体化患者管理的方向迈进。
