N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and Clinical Outcomes in Asymptomatic Individuals with and Without CKD

Background: NT-proBNP is a biomarker of myocardial stress commonly used to screen for heart failure (HF), but its interpretation in patients with CKD is complicated by reduced renal clearance. Currently, there is no consensus on optimal NT-proBNP thresholds across CKD stages. This study evaluated the association between NT-proBNP levels and incident HF and all-cause mortality in asymptomatic adults with and without CKD. Methods: This was a retrospective cohort study using the TriNetX database (>160 million US patients). Adults aged ≥18 years with available NT-proBNP levels and at least 5 years of follow-up were included. Individuals with known cardiovascular disease, including HF, or structural heart disease were excluded. Participants were stratified into three NT-proBNP categories (≤ 125 [low], 126-450 [middle], and > 450 pg/ml [high]) and CKD status (eGFR < 60 vs ≥ 60 mL/min/1.73m2). Outcomes included new onset HF and all-cause mortality at 1 and 5 years. Propensity score matching was used to adjust for baseline differences. Results: Among individuals in the low and middle NT-proBNP groups, there were no significant differences at 1 year between CKD and non-CKD groups in HF incidence or mortality. However, at 5 years, risks were significantly higher in CKD patients for both HF (OR 1.87 [95% CI 1.14–3.07] and 1.64 [1.18–2.29]) and mortality (OR 1.76 [1.23–2.54] and 1.48 [1.17–1.87]) in the low and middle NT-proBNP groups, respectively. In the high NT-proBNP group, CKD patients had significantly worse outcomes at both 1 and 5 years. At 1 year, HF (OR 1.95 [1.61–2.38]) and mortality (OR 1.38 [1.22–1.57]) were higher in CKD patients, with similar findings at 5 years (HF OR 1.84 [1.57–2.16], mortality OR 1.87 [1.68–2.08]). Conclusion: In asymptomatic individuals, NT-proBNP predicted incident HF and mortality risk regardless of CKD status, with outcomes worsening incrementally at higher levels. One-year outcomes were similar between CKD and non-CKD patients when NT-proBNP was <450 pg/mL, but values ≥451 pg/mL were associated with significantly worse outcomes at both 1 and 5 years. These findings support NT-proBNP as a prognostic tool in CKD, with eGFR not diminishing its predictive value.