Natriuretic Peptides, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction

Abstract

N-terminal pro–B-type natriuretic peptides (NT-proBNPs) are guideline-recommended biomarkers for risk stratification in patients with heart failure. However, NT-proBNP levels are often elevated in chronic kidney disease, introducing uncertainty about their prognostic relevance in persons across a broad range of estimated glomerular filtration rates (eGFRs). The authors sought to assess the association of NT-proBNP with cardiovascular and mortality outcomes in patients with heart failure and mildly reduced or preserved ejection fraction, stratified by baseline kidney function. The authors conducted a pooled analysis of participants with NT-proBNP and eGFR measured at baseline in the I-PRESERVE (XXX), TOPCAT (Americas region) (XXX), PARAGON (XXX), and DELIVER (XXX) trials. The authors evaluated the relationship between NT-proBNP and eGFR using piecewise linear regression. Using multivariable Cox and Poisson regression models, they assessed the association of NT-proBNP with outcomes across a range of eGFRs (≥60, 45 to <60, and <45 mL/min/1.73 m). The primary outcome was hospitalization for heart failure or cardiovascular death. Among 14,831 participants (mean age: 72.1 years; 50.3% female; mean eGFR: 63.3 mL/min/1.73 m, and median NT-proBNP: 840 pg/mL) followed up for a median 33.5 months, there were 3,092 primary outcomes. NT-proBNP levels increased by 9%, 8%, and 23% per 10 mL/min/1.73 m lower eGFR in patients with baseline eGFR ≥60, 45-60, and <45 mL/min/1.73 m, respectively ( for nonlinearity < 0.001). Each doubling in NT-proBNP was associated with a 37% relative increase in the primary outcome (HR: 1.37; 95% CI: 1.34-1.41), consistent across different eGFR categories ( for interaction = 0.42). For the same incidence of the primary outcome, NT-proBNP levels were approximately 2.5- to 3.5-fold lower in patients with eGFR <45 mL/min/1.73 m, compared with patients with eGFR ≥60 mL/min/1.73 m. Similar patterns were observed across all outcomes studied, including cardiovascular and noncardiovascular death. The same NT-proBNP concentration predicts a substantially higher absolute risk of adverse outcomes for people with heart failure and reduced kidney function, compared with those with preserved kidney function. These data call into question proposals for higher NT-proBNP references ranges in people with CKD, and suggest that reduced kidney function per se should not be a reason to disregard higher NT-proBNP levels.