Serum Neprilysin and Recurrent Admissions in Patients With Heart Failure

BACKGROUND Our aim was to evaluate the association between the soluble form of neprilysin (sNEP) levels and long-term all-cause, cardiovascular, and acute heart failure (AHF) recurrent admissions in an ambulatory cohort of patients with heart failure. sNEP has emerged as a new biomarker with promising implications for prognosis and therapy in patients with heart failure. Reducing the recurrent admission rate of heart failure patients has become an important target of public health planning strategies. METHODS AND RESULTS We measured sNEP levels in 1021 consecutive ambulatory heart failure patients. End points were the number of all-cause, cardiovascular, and AHF hospitalizations during follow-up. We used covariate-adjusted incidence rate ratios to identify associations. At a median follow-up of 3.4 years (interquartile range: 1.8-5.7), 391 (38.3%) patients died, 477 (46.7%) patients had 1901 all-cause admissions, 324 (31.7%) patients had 770 cardiovascular admissions, and 218 (21.4%) patients had 488 AHF admissions. The medians for sNEP and amino-terminal pro-brain natriuretic peptide were 0.64 ng/mL (interquartile range: 0.39-1.22) and 1248 pg/mL (interquartile range: 538-2825), respectively. In a multivariate setting, the adjusted incidence rate ratios for the top (>1.22 ng/mL) versus the bottom (≤0.39 ng/mL) quartiles of sNEP were 1.37 (95% confidence interval: 1.03-1.82), P=0.032; 1.51 (95% confidence interval: 1.10-2.06), P=0.010; and 1.51 (95% confidence interval: 1.05-2.16), P=0.026 for all-cause, cardiovascular, and AHF admissions, respectively. CONCLUSIONS Elevated sNEP levels predicted an increased risk of recurrent all-cause, cardiovascular, and AHF admissions in ambulatory patients with heart failure.