Association between NT-proBNP levels and risk of atrial fibrillation: a systematic review and meta-analysis of cohort studies

Background and aims N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established biomarker in clinical practice, particularly for heart failure, but its role in predicting atrial fibrillation (AF) risk is not fully understood. This meta-analysis aimed to evaluate the association between NT-proBNP levels and AF incidence, and to explore the potential of NT-proBNP in enhancing AF risk prediction models. Methods We systematically searched databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) up to August 2024 for prospective studies that reported associations between baseline NT-proBNP levels and incident AF. HRs or relative risks (RRs) with 95% CIs were pooled using random-effects models. Results This analysis included 136 089 participants from 16 cohorts, with 8017 incident AF cases. Elevated NT-proBNP levels were associated with a higher risk of developing AF (top vs bottom quartile, RR=3.84, 95% CI 3.03 to 4.87; per SD increment, RR=1.70, 95% CI 1.54 to 1.88). A significant non-linear dose-response relationship was observed (P non-linearity <0.05), and stronger associations were noted in older populations and when serum samples were used. Adding NT-proBNP to traditional AF risk models improved predictive accuracy, suggesting its value in AF risk stratification. Conclusions NT-proBNP levels are strongly associated with an increased risk of AF, particularly in older adults. Incorporating NT-proBNP into risk prediction models may enhance early identification of individuals at risk of AF, with potential implications for population-based screening. PROSPERO registration number CRD42024538714.