Soluble Neprilysin Is Predictive of Cardiovascular Death and Heart Failure Hospitalization in Heart Failure Patients
Soluble Neprilysin Is Predictive of Cardiovascular Death and Heart Failure Hospitalization in Heart Failure Patients
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DOI：
10.1016/j.jacc.2014.11.048
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发表时间：
2015-02-24
影响因子：
24
通讯作者：
Lupon, Josep
中科院分区：
文献类型：
--
作者：
Bayes-Genis, Antoni;Barallat, Jaume;Lupon, Josep
脑啡肽溶酶是一种分解利钠肽的膜结合酶。PARADIGM-HF（前瞻性比较ARNI与ACEI以确定对心力衰竭的全球死亡率和发病率的影响）试验显示，与接受依那普利标准治疗的患者相比，用血管紧张素受体脑啡肽酶抑制剂治疗的心力衰竭（HF）患者在没有因HF住院的情况下存活更长。HF患者的生活队列和相关的脑啡肽酶水平与outcome.METHODS循环可溶性脑啡肽酶测定与改良的夹心免疫法在连续的门诊HF患者谁随访了4.1年。脑啡肽酶水平和复合终点之间的关联，包括心血管死亡或HF住院explored.Results中位数脑啡肽酶浓度在1,069例患者为0.642 ng/ml（中位数四分位数1至3：0.385至1.219）。脑啡肽酶与年龄弱但显著相关（rho = 0.16; p < 0.001）。在年龄校正的考克斯回归分析中，脑啡肽酶浓度与复合终点（风险比[HR]：1.17; 95%置信区间[CI]：1.06 - 1.29; p = 0.001）和心血管死亡（HR：1.19; 95% CI：1.06 - 1.32; p = 0.002）显著相关。在综合多变量分析中，可溶性脑啡肽酶仍然与两个复合终点显著相关。（HR：1.18; 95% CI：1.07 - 1.31; p = 0.001）和心血管死亡（HR：1.18; 95% CI：1.05 ~ 1.32; p = 0.006）的平均值结论：HF患者循环中脑啡肽酶的鉴定及其与心血管疾病发病率和死亡率的正相关性，进一步证实了脑啡肽酶与心血管疾病发病率和死亡率的正相关性。支持NEP抑制对于增加利钠肽作为治疗靶点的重要性。(C)2015年美国心脏病学院基金会。
BACKGROUND Neprilysin is a membrane-bound enzyme that breaks down natriuretic peptides. The PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial showed that patients with heart failure (HF) treated with an angiotensin receptor neprilysin inhibitor lived longer without being hospitalized for HF than those receiving standard care with enalapril.OBJECTIVES This study sought to assess the presence of circulating soluble neprilysin in a real-life cohort of HF patients and correlate neprilysin levels with outcomes.METHODS Circulating soluble neprilysin was measured with a modified sandwich immunoassay in consecutive ambulatory patients with HF who were followed up for 4.1 years. Associations between neprilysin level and a composite endpoint that included cardiovascular death or HF hospitalization were explored.RESULTS Median neprilysin concentration in 1,069 patients was 0.642 ng/ml (median quartile 1 to 3: 0.385 to 1.219). Neprilysin weakly but significantly correlated with age (rho = 0.16; p < 0.001). In age-adjusted Cox regression analyses, neprilysin concentrations were significantly associated with the composite endpoint (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.06 to 1.29; p = 0.001) and cardiovascular death (HR: 1.19; 95% CI: 1.06 to 1.32; p = 0.002). In comprehensive multivariable analyses, soluble neprilysin remained significantly associated with both the composite endpoint (HR: 1.18; 95% CI: 1.07 to 1.31; p = 0.001) and cardiovascular death (HR: 1.18; 95% CI: 1.05 to 1.32; p = 0.006).CONCLUSIONS Identification of circulating neprilysin in HF patients and the positive association of neprilysin with cardiovascular mortality and morbidity further support the importance of NEP inhibition for augmenting natriuretic peptides as a therapeutic target. (C) 2015 by the American College of Cardiology Foundation.