在慢性肾脏病患者中，血浆脑啡肽酶活性和血浆脑啡肽酶浓度能否预测心脏事件？

Do plasma neprilysin activity and plasma neprilysin concentration predict cardiac events in chronic kidney disease patients?

机构信息

Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.

INSERM, UMRS 942, Paris, France.

出版信息

Nephrol Dial Transplant. 2019 Jan 1;34(1):100-108. doi: 10.1093/ndt/gfy066.

DOI:10.1093/ndt/gfy066

PMID:29635392

Abstract

BACKGROUND

Since the introduction of sacubitril/valsartan in clinical cardiology, neprilysin has become a major target for heart failure treatment. Plasma neprilysin concentration has been discussed as a novel biomarker that predicts cardiac events. Natriuretic peptides may inhibit plasma neprilysin. As they accumulate in chronic kidney disease (CKD), we hypothesized that high plasma neprilysin loses its predictive role in CKD patients.

METHODS

We measured plasma levels of neprilysin concentration, neprilysin activity and brain natriuretic peptide (BNP) in 542 CKD G2-G4 patients within the CARE FOR HOMe study. Patients were followed for predefined endpoints of hospitalization for acute decompensated heart failure and incident atherosclerotic cardiovascular events.

RESULTS

During 5.1 ± 2.1 years, 63 patients had acute decompensated heart failure and 125 patients had incident atherosclerotic cardiovascular events. In both Kaplan-Meier and multivariate Cox regression analyses, high plasma BNP and low, rather than elevated, neprilysin activity predicted future hospitalization for acute decompensated heart failure; neprilysin concentration was not predictive. Furthermore, only BNP was an independent predictor of incident atherosclerotic cardiovascular events.

CONCLUSIONS

In line with experimental studies, high natriuretic peptides may inhibit neprilysin activity in CKD. Therefore, high neprilysin activity and concentrations are not predictors of adverse cardiovascular outcome in CKD patients. Thus neprilysin inhibitors should be implemented with caution in patients with advanced CKD.

摘要

背景

自从沙库巴曲缬沙坦在临床心脏病学中的应用以来，脑啡肽酶已成为心力衰竭治疗的主要靶点。人们已经探讨了血浆脑啡肽酶浓度作为预测心脏事件的新型生物标志物。利钠肽可能会抑制血浆脑啡肽酶。由于它们在慢性肾脏病（CKD）中蓄积，我们假设高血浆脑啡肽酶在 CKD 患者中丧失了其预测作用。

方法

我们在 CARE FOR HOMe 研究中测量了 542 例 CKD G2-G4 患者的血浆脑啡肽酶浓度、脑啡肽酶活性和脑钠肽（BNP）水平。患者被随访了预先设定的终点，包括因急性失代偿性心力衰竭住院和发生动脉粥样硬化性心血管事件。

结果

在 5.1±2.1 年期间，63 例患者发生急性失代偿性心力衰竭，125 例患者发生动脉粥样硬化性心血管事件。在 Kaplan-Meier 和多变量 Cox 回归分析中，高血浆 BNP 和低而非升高的脑啡肽酶活性预测了未来因急性失代偿性心力衰竭而住院；脑啡肽酶浓度没有预测作用。此外，只有 BNP 是动脉粥样硬化性心血管事件的独立预测因子。