Key result
Higher circulating soluble neprilysin is linked to ~18% higher risk of CV death or HF hospitalization.
Why the study?
Following evidence of benefit with angiotensin receptor neprilysin inhibition in HF, the presence of circulating soluble neprilysin and its correlation with clinical outcomes in a real-life HF cohort needed assessment.
Does circulating soluble neprilysin level predict cardiovascular death or heart failure hospitalization in ambulatory heart failure patients?
Cohort (n=1,069)
Does circulating soluble neprilysin level predict cardiovascular death or heart failure hospitalization in ambulatory heart failure patients?
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The growing data for NEP are of a great importance when LCZ696 will be used in our patients. Long-lasting therapies are not optimally given in chronic HF patients. Biomarker (mostly NT-proBNP)-guided strategies have been suggested as a way of monitoring the optimization of those agents. Further studies should assess the “dual” role of the circulating concentration of sNEP as a marker of severity of HF or, even better, NEP activity to assess the degree of response to LCZ696.”
Circulating soluble neprilysin levels are independently associated with an increased risk of cardiovascular death and heart failure hospitalization in ambulatory heart failure patients, supporting neprilysin inhibition 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.
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A et al. (2015) conducted a cohort in Heart failure (n=1,069). Circulating soluble neprilysin concentration was evaluated on Composite of cardiovascular death or heart failure hospitalization (HR 1.18, 95% CI 1.07-1.31, p=0.001). Circulating soluble neprilysin was independently associated with cardiovascular death or HF hospitalization (HR 1.18; 95% CI 1.07-1.31; p=0.001).
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