Background
Neprilysin is a
metalloprotease involved in proteolysis of numerous
peptides, including
natriuretic peptides, and is of prognostic and therapeutic importance in
heart failure with reduced ejection fraction. No studies have investigated circulating
neprilysin in the community, its clinical correlates, or its relationship to
cardiovascular disease in the general population. Methods and Results Plasma
neprilysin was measured in 1536 participants from Olmsted County, Minnesota, using a commercially available sandwich ELISA assay. Clinical and echocardiographic correlates and subsequent outcomes were determined. Soluble
neprilysin is non-normally distributed in the community (median: 3.9 ng/mL; interquartile range: 1.0-43.0 ng/mL). There was no relationship between plasma
neprilysin and age (Spearman correlation: -0.04, P=0.16); body mass index (Spearman correlation: -0.04, P=0.16); glomerular filtration rate (Spearman correlation: -0.007, P=0.8); or A-, B-, or C-type
natriuretic peptides (Spearman correlation: 0.03, P=0.22; -0.001, P=0.96; 0.01, P=0.67, respectively). Among tertiles of
neprilysin, the lowest tertile group had the highest prevalence of smokers (P<0.001),
hypertension (P=0.04),
dyslipidemia (P=0.03), and diastolic dysfunction (P=0.02). Soluble
neprilysin was not prospectively associated with death or
heart failure over a median of 10.7 years. Conclusions In a large community-based cohort, for the first time, we described the distribution of circulating
neprilysin in the general community. We observed that
neprilysin does not correlate with
natriuretic peptide levels and is not independently associated with adverse outcomes. The novel associations observed between low soluble
neprilysin levels and an adverse cardiometabolic and smoking profile requires further investigation.