Association between NT-proBNP and adverse outcomes in patients with HF and CKD

A pooled analysis of 4 large-scale RCTs among HFmrEF/HFpEF patients showed that for any given NT-proBNP concentration, the absolute risk of HF hospitalization or CV death was substantially higher in participants with lowest eGFR compared with those with preserved kidney function.

This summary is based on the publication of Neuen BL, Vaduganathan M, Claggett BL, et al. - Natriuretic Peptides, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2025 Jan;13(1):28-39. doi: 10.1016/j.jchf.2024.08.009

Introduction and methods

Background

BNP and NT-proBNP are clinical guideline–recommended biomarkers for risk stratification in patients with HF [1]. However, as natriuretic peptide levels are often elevated in CKD, their prognostic relevance is unclear in patients with both HF and CKD. In fact, about 40% of HF patients also have CKD [2], and this is associated with increased risks of disease progression, hospitalization, and mortality [3].

Aim of the study

The study aim was to assess the associations of NT-proBNP levels with key CV and mortality outcomes in patients with HFmrEF or HFpEF, stratified by baseline eGFR.

Methods

This was a pooled individual-participant data analysis of 4 large-scale double-blind, placebo-controlled RCTs: I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction), TOPCAT (Americas region) (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function), PARAGON (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction), and DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) [4-7]. Baseline NT-proBNP and eGFR measurements were available for 14,831 participants. Median follow-up time for the dataset was 33.5 months (range: 27.6–49.5).

Outcomes

The primary endpoint was a composite outcome of HF hospitalization or CV death. Other endpoints included HF hospitalization, CV death, non-CV death, and all-cause mortality.

Main results

• There was a nonlinear association between NT-proBNP level and eGFR: In patients with baseline eGFR ≥60, 45–59, and <45 mL/min/1.73 m², NT-proBNP levels increased by 9%, 8%, and 23%, respectively, for each 10 mL/min/1.73 m² reduction in eGFR (P for nonlinearity<0.001).

• In multivariable Cox regression models adjusted for several covariates including age, sex, trial, and treatment allocation, each doubling in NT-proBNP concentration was associated with a 37% relative increase in the primary endpoint of HF hospitalization or CV death (HR: 1.37; 95%CI: 1.34–1.41), and this was consistent across the 3 eGFR categories (P for interaction=0.42).

• For any given NT-proBNP concentration, the absolute risk of the primary endpoint was higher in participants with lowest eGFR than those with higher eGFR. For example, an incidence rate of 10 events per 100 patient-years corresponded with an NT-proBNP level of 1,946 pg/mL in patients with baseline eGFR ≥60 mL/min/1.73 m², whereas the corresponding NT-proBNP level was lower in those with eGFR 45–59 mL/min/1.73 m² (1,457 pg/mL) or <45 mL/min/1.73 m² (756 pg/mL).

• For an incidence rate of 5 events per 100 patient-years, the corresponding NT-proBNP levels were 438, 332, and 118 pg/mL for participants with baseline eGFR ≥60, 45–59, and <45 mL/min/1.73 m², respectively.

• Similar patterns of association were observed for the other endpoints.

Conclusion

In this pooled individual-participant data analysis of 4 large-scale RCTs among patients with HFmrEF/HFpEF, there was a nonlinear inverse relationship between NT-proBNP level and eGFR. In addition, for any given NT-proBNP concentration, the absolute risk of HF hospitalization or CV death was substantially higher in participants with lowest eGFR compared with those with preserved kidney function. The authors conclude their “data suggest that revising upper reference limits for NT-proBNP in patients with CKD may risk overlooking valuable prognostic information and that reduced kidney function per se should not be a reason to disregard higher NT-proBNP levels.”

Find this article online at JACC Heart Fail.

References

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