Antoni Bayés-Genís1, Jaume Barallat2, Amparo Galán2, Marta de Antonio3, Mar Domingo4, Elisabet Zamora3, Agustín Urrutia3, Josep Lupón3. 1. Heart Failure Clinic, Cardiology Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain; Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain. Electronic address: abayesgenis@gmail.com. 2. Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain; Biochemistry Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain. 3. Heart Failure Clinic, Cardiology Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain; Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain. 4. Heart Failure Clinic, Cardiology Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain.
Abstract
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.
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.
Authors: Michaela Auer-Grumbach; Stefan Toegel; Maria Schabhüttl; Daniela Weinmann; Catharina Chiari; David L H Bennett; Christian Beetz; Dennis Klein; Peter M Andersen; Ilka Böhme; Regina Fink-Puches; Michael Gonzalez; Matthew B Harms; William Motley; Mary M Reilly; Wilfried Renner; Sabine Rudnik-Schöneborn; Beate Schlotter-Weigel; Andreas C Themistocleous; Jochen H Weishaupt; Albert C Ludolph; Thomas Wieland; Feifei Tao; Lisa Abreu; Reinhard Windhager; Manuela Zitzelsberger; Tim M Strom; Thomas Walther; Steven S Scherer; Stephan Züchner; Rudolf Martini; Jan Senderek Journal: Am J Hum Genet Date: 2016-09-01 Impact factor: 11.025
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