Prognostic Value of Urinary and Plasma C-Type Natriuretic Peptide in Acute Decompensated Heart Failure.

Objectives: This study sought to characterize urinary and plasma C-type natriuretic peptide (CNP) in acute decompensated heart failure (ADHF) to define their relationship with clinical variables and to determine whether urinary and plasma CNP together add prognostic value.
Background: CNP is a protective hormone that is synthesized in the kidney and endothelium and possesses antiremodeling properties. Urinary and plasma CNP levels are elevated in pathophysiological conditions; however, their regulation and prognostic value in heart failure (HF) is unclear.
Methods: Urinary and plasma CNP were measured in 109 healthy subjects and 208 patients with ADHF; the 95th percentile of CNP values from healthy subjects established the normal contemporary cutoffs. Patients with ADHF were stratified based on urinary and plasma CNP levels for clinical characterization and the assessment of risk for adverse outcomes.
Results: There was no significant correlation between urinary and plasma CNP in both cohorts. Urinary and plasma CNP were significantly elevated in patients with ADHF, and both increased with disease severity and were positively correlated with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP). Of the patients with ADHF, 23% had elevations in both urinary and plasma CNP, whereas 24% had normal CNP levels. During a median follow-up of 3 years, patients with elevated urinary and plasma CNP had a significantly higher risk of rehospitalization and/or death (HR: 1.79; P = 0.03) and rehospitalization (HR: 2.16; P = 0.01) after adjusting for age, sex, left ventricular ejection fraction, renal function, and plasma NT-proBNP. The C-statistic and integrated discrimination analyses further supported that the addition of urinary and plasma CNP to established risk models improved the prediction of adverse outcomes in patients with ADHF.
Conclusions: Urinary and plasma CNP are differentially regulated in ADHF, and elevations in both provided independent prognostic value for predicting adverse outcomes.
Competing Interests: Funding Support and Funding Disclosures This work was supported by National Heart, Lung and Blood Institute grants R01 HL36634 (to Dr Burnett) and R01 HL132854 (to Dr Sangaralingham). This work was also supported by the Division of Circulatory Failure, Department of Cardiovascular Medicine at Mayo Clinic and the Mayo Foundation. Drs Ma, Y. Chen, H. Chen, Burnett, and Sangaralingham, and the Mayo Foundation have issued or filed patents for assessing the use of CNP as well as for natriuretic peptide-based or particulate guanylyl cyclase enhancing therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)