Prognostic Implications of Urinary and Plasma C-type Natriuretic Peptide in Human Acute Decompensated Heart Failure

Abstract

Introduction C-type natriuretic peptide (CNP) is a cardiorenal-derived hormone that possesses potent anti-fibrotic, anti-hypertrophic, anti-apoptotic and cardiac unloading properties. While plasma and urinary CNP have been shown to be elevated in heart failure (HF) patients, limited studies have simultaneously characterized and evaluated the clinical utility of plasma and urinary CNP in acute decompensated HF (ADHF). Hypothesis We hypothesize that plasma and urinary CNP are elevated and distinctly regulated in ADHF and elevation of both are a marker of disease severity and will have additional prognostic value for adverse outcomes. Methods ADHF patients (n=208) and healthy subjects (n=109) were prospectively recruited and urinary and plasma CNP, plasma NT-proBNP, eGFR and urinary protein/creatinine were determined. The 95th percentile (%) of CNP values from healthy subjects were used to establish normal cutoffs. ADHF patients were stratified based on whether their CNP levels were considered as elevated (> 95th % of normal) or normal (≤ 95th % of normal). The adverse outcomes were all-cause rehospitalization and/or death over 3.0 (1.0, 4.9) years of follow-up. Results ADHF patients had elevated plasma and urinary CNP levels compared to healthy subjects [plasma CNP: 18.2 (10.7-30.3) vs 11.8 (9.5-15.0) pg/mL; urinary CNP: 43.1 (27.9-74.7) vs 15.8 (12.1-20.2) ng/g Cr; P Conclusions This study is the largest to date to provide novel pathophysiological insights into plasma and urinary CNP. We report for the first time that elevations of both CNP indices are associated with disease severity and have prognostic utility beyond robust clinical risk models in ADHF.