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Multicenter Study
. 2024 Mar;12(3):461-474.
doi: 10.1016/j.jchf.2023.09.011. Epub 2023 Oct 25.

Differential Associations of A-/B-Type Natriuretic Peptides With Cardiac Structure, Function, and Prognosis in Heart Failure

Eugene S J Tan  1 , Siew Pang Chan  1 , Oi Wah Liew  2 , Jenny P C Chong  2 , Kui Toh Gerard Leong  3 , Poh Shuan Daniel Yeo  4 , Hean Yee Ong  5 , Fazlur Jaufeerally  6 , David Sim  7 , Lieng Hsi Ling  1 , Carolyn S P Lam  8 , A Mark Richards  9
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Free article
Multicenter Study

Differential Associations of A-/B-Type Natriuretic Peptides With Cardiac Structure, Function, and Prognosis in Heart Failure

Eugene S J Tan et al. JACC Heart Fail. 2024 Mar.
Free article

Abstract

Background: Natriuretic peptide (NP) elevations are prognostic in heart failure (HF), but relative atrial NP deficiency in acute HF has been suggested.

Objectives: The authors compared plasma concentrations and relative strength of associations of A- and B-type NPs with cardiac structure/function and clinical outcomes in HF.

Methods: Midregional pro-atrial natriuretic peptide (MR-proANP), B-type natriuretic peptide (BNP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured in patients with compensated HF in a prospective, multicenter study. The primary outcome was a composite of HF-hospitalization or all-cause mortality. Secondary outcomes included individual primary outcome components and cardiovascular admission.

Results: Among 1,278 patients (age 60.1 ± 12.1 years, 82% men, left ventricular ejection fraction [LVEF] 34% ± 14%), median concentrations of MR-proANP were 990 pg/mL (Q1-Q3: 557-1,563 pg/mL), NT-proBNP 1,648 pg/mL (Q1-Q3: 652-3,960 pg/mL), and BNP 291 pg/mL (Q1-Q3: 103-777 pg/mL). No subpopulation with inappropriately low MR-proANP (relative to BNP/NT-proBNP) was observed. Clinical event rates were similar for biomarker tertiles. Increments in MR-proANP exhibited steeper associations with concurrent shifts in left ventricular size, diastolic indexes and LVEF than BNP/NT-proBNP at baseline and serially (P < 0.05), and lower odds of beneficial left ventricular reverse remodeling: OR: 0.35 (95% CI: 0.18-0.70). In single-biomarker models, MR-proANP(log10) was associated with the highest hazard (4 to 6 times) for each outcome. In multimarker models, independent associations were observed for the primary outcome (MR-proANP and NT-proBNP), HF-hospitalization and cardiovascular admission (MR-proANP only), and all-cause mortality (NT-proBNP only) (P < 0.05). The discriminative value of MR-proANP was superior to BNP/NT-proBNP (HF-hospitalization) and BNP (primary outcome) (P < 0.05).

Conclusions: MR-proANP was not inappropriately low relative to concurrent BNP/NT-proBNP values. Proportional increments in MR-proANP were more pronounced than for B-peptides for given decrements in cardiac structure/function. MR-proANP offered greater independent predictive power overall.

Keywords: B-type natriuretic peptide; N-terminal pro-BNP; biomarkers; heart failure; midregional pro–atrial natriuretic peptide.

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Conflict of interest statement

Funding Support and Author Disclosures This work was funded by the National Medical Research Council, Singapore (Grant Number: R-172-003-219-511), A∗STAR-NZ HRC (Grant Number: JGC 10_027), and Clinician Scientist Award (to Dr Lam). The Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT) is supported by the Agency for Science, Technology and Research (A∗STAR) Biomedical Research Council program (SPF2014/003, SPF2014/004, SPF2014/005) and National Medical Research Council’s Heart Failure: Markers and Management grant (NMRC/CG/014/2013). Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research and Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd, Redcardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as co-founder and nonexecutive director of Us2.ai. Dr Richards has received grants from Government and Charitable Funding Bodies; has received nonfinancial support from Roche Diagnostics and Abbott Laboratories during the conduct of the study; and has received personal fees and nonfinancial support from Roche Diagnostics outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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