title: Multimarker Strategy for Heart Failure Prognostication. Value of Neurohormonal Biomarkers: Neprilysin vs NT-proBNP.
abstract: OBJECTIVE
  Neprilysin breaks down numerous vasoactive peptides. The soluble form of neprilysin, which was recently identified in heart failure, is associated with cardiovascular outcomes. Within a multibiomarker strategy, we directly compared soluble neprilysin and N-terminal pro-B-type natriuretic peptide as risk stratifiers in a real-life cohort of heart failure patients.
  
  
  METHODS
  Soluble neprilysin, N-terminal pro-B-type natriuretic peptide, ST2, and high-sensitivity troponin T levels were measured in 797 consecutive ambulatory heart failure patients followed up for 4.7 years. Comprehensive multivariable analyses and soluble neprilysin vs N-terminal pro-B-type natriuretic peptide head-to-head assessments of performance were performed. A primary composite endpoint included cardiovascular death or heart failure hospitalization. A secondary endpoint explored cardiovascular death alone.
  
  
  RESULTS
  Median soluble neprilysin and N-terminal pro-B-type natriuretic peptide concentrations were 0.64ng/mL and 1187 ng/L, respectively. Both biomarkers significantly correlated with age (P<.001) and ST2 (P<.001), but only N-terminal pro-B-type natriuretic peptide significantly correlated with estimated glomerular filtration rate (P<.001), body mass index (P<.001), left ventricular ejection fraction (P=.02) and high-sensitivity troponin T (P<.001). In multivariable Cox regression analyses, soluble neprilysin remained independently associated with the composite endpoint (hazard ratio=1.14; 95% confidence interval, 1.02-1.27; P=.03) and cardiovascular death (hazard ratio=1.15; 95% confidence interval, 1.01-1.31; P=.04), but N-terminal pro-B-type natriuretic peptide did not. The head-to-head soluble neprilysin vs N-terminal pro-B-type natriuretic peptide comparison showed good calibration and similar discrimination and reclassification for both neurohormonal biomarkers, but only soluble neprilysin improved overall goodness-of-fit.
  
  
  CONCLUSIONS
  When added to a multimarker strategy, soluble neprilysin remained an independent prognosticator, while N-terminal pro-B-type natriuretic peptide lost significance as a risk stratifier in ambulatory patients with heart failure. Both biomarkers performed similarly in head-to-head analyses.
authors: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Departamento de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain. Electronic address: abayesgenis@gmail.com.
authors: Antoni
authors: A
authors: Bayes-Genis
authors: Departamento de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain; Servicio de Bioquímica, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors: Jaume
authors: J
authors: Barallat
authors: Departamento de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain; Servicio de Bioquímica, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors: Amparo
authors: A
authors: Galán
authors: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Departamento de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain.
authors: Marta
authors: M
authors: de Antonio
authors: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors: Mar
authors: M
authors: Domingo
authors: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Departamento de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain.
authors: Elisabet
authors: E
authors: Zamora
authors: Fundació Institut Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors: Paloma
authors: P
authors: Gastelurrutia
authors: IMIM (Institut de Recerca Hospital del Mar), Barcelona, Spain; CIBER Epidemiología y Salud Pública, Barcelona, Spain.
authors: Joan
authors: J
authors: Vila
authors: IMIM (Institut de Recerca Hospital del Mar), Barcelona, Spain; CIBER Epidemiología y Salud Pública, Barcelona, Spain.
authors: Judith
authors: J
authors: Peñafiel
authors: Fundació Institut Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors: Carolina
authors: C
authors: Gálvez-Montón
authors: Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Departamento de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain.
authors: Josep
authors: J
authors: Lupón
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000401:mortality; D004812:Epidemiologic Methods; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011379:Prognosis; D013318:Stroke Volume / Q000502:physiology; D020107:Troponin T / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000401:mortality / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D015260:Neprilysin
keywords: Heart failure; Insuficiencia cardiaca; NT-proBNP; Neprilisina; Neprilysin; Prognosis; Pronóstico; Supervivencia; Survival