title: Soluble neprilysin is predictive of cardiovascular death and heart failure hospitalization in heart failure patients.
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.
  
  
  OBJECTIVE
  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: 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.
authors: Antoni
authors: A
authors: Bayés-Genís
authors: Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain; Biochemistry Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain.
authors: Jaume
authors: J
authors: Barallat
authors: Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain; Biochemistry Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain.
authors: Amparo
authors: A
authors: Galán
authors: Heart Failure Clinic, Cardiology Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain; Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors: Marta
authors: M
authors: de Antonio
authors: Heart Failure Clinic, Cardiology Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain.
authors: Mar
authors: M
authors: Domingo
authors: Heart Failure Clinic, Cardiology Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain; Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors: Elisabet
authors: E
authors: Zamora
authors: Heart Failure Clinic, Cardiology Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain; Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors: Agustín
authors: A
authors: Urrutia
authors: Heart Failure Clinic, Cardiology Service, Hospital Universitari Germans Trias i Pujol Badalona, Barcelona, Spain; Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors: Josep
authors: J
authors: Lupón
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000401:mortality*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D015260:Neprilysin / Q000097:blood*; D012307:Risk Factors; D013318:Stroke Volume; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D015260:Neprilysin
keywords: B-type natriuretic peptide; prognosis; survival