Antoni Bayes-Genis1, Jaume Barallat2, Amparo Galán2, Marta de Antonio3, Mar Domingo4, Elisabet Zamora3, Paloma Gastelurrutia5, Joan Vila6, Judith Peñafiel6, Carolina Gálvez-Montón5, Josep Lupón3. 1. 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. 2. Departamento de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain; Servicio de Bioquímica, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. 3. 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. 4. Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. 5. Fundació Institut Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain. 6. IMIM (Institut de Recerca Hospital del Mar), Barcelona, Spain; CIBER Epidemiología y Salud Pública, Barcelona, Spain.
Abstract
INTRODUCTION AND OBJECTIVES: 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.
INTRODUCTION AND OBJECTIVES: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 failurepatients. METHODS: Soluble neprilysin, N-terminal pro-B-type natriuretic peptide, ST2, and high-sensitivity troponin T levels were measured in 797 consecutive ambulatory heart failurepatients 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.
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