A meta-analysis of 9 international cohorts with over 41,000 participants found that NT-proBNP — a fragment of a natriuretic peptide hormone — significantly improved the prediction of who will develop heart failure, even in people with kidney disease or existing heart disease.
2× higher NT-proBNP → 47% higher HF riskAcross 41,427 individuals from 9 cohorts over 11 years, this natriuretic peptide biomarker consistently predicted incident heart failure
What the researchers found
In 41,427 individuals without heart failure from 9 prospective cohorts followed for a mean of 11 years (4,599 incident HF cases):
- A 2-fold higher NT-proBNP was associated with incident HF: HR 1.47 (95% CI: 1.38-1.56)
- The association was consistent regardless of chronic kidney disease or atherosclerotic cardiovascular disease status
- Adding NT-proBNP to traditional risk factors improved the C-statistic by 0.030 (95% CI: 0.021-0.040, P < 0.001)
- High-sensitivity troponin T also predicted HF but its added discrimination was modest compared to NT-proBNP
- The predictive value held even in high-risk subgroups where biomarker interpretation is traditionally challenging
Why it matters
Heart failure affects 64 million people worldwide and once diagnosed, survival rates are poor. Identifying people at risk before they develop heart failure is essential for timely prevention. NT-proBNP is a fragment of a natriuretic peptide — a hormone the heart releases when it's under stress. This study provides the strongest evidence yet that measuring this peptide biomarker can improve heart failure prediction across diverse populations, including traditionally difficult-to-assess groups like people with kidney disease.
How the study worked
Individual-participant data meta-analysis of 9 prospective international cohort studies. 41,427 individuals free of heart failure at baseline were followed for a mean of 11 years. NT-proBNP and high-sensitivity troponin T were measured at baseline. The associations with incident HF were quantified using hazard ratios when added to a clinical prediction model. Changes in Harrell's C-statistic were estimated within each cohort and pooled using random-effects meta-analysis. Subgroup analyses assessed performance in CKD and atherosclerotic CVD populations.
What this study cannot tell us
The C-statistic improvement of 0.030, while statistically significant, is modest in absolute terms. The clinical decision-making threshold for starting preventive treatment based on NT-proBNP levels was not defined. The 9 cohorts may not represent all global populations. Variability in NT-proBNP assays across cohorts could affect pooled estimates. The cost-effectiveness of adding NT-proBNP to existing risk prediction frameworks was not assessed.
How to read the evidence
This is an individual-participant data meta-analysis of 9 prospective cohort studies — the highest level of observational evidence. The large sample (41,427), long follow-up (11 years), international diversity, and rigorous statistical methods make this one of the most definitive studies on NT-proBNP for HF prediction.
When this study was published
Published in 2025 in the Journal of the American Heart Association, this is a very current study reflecting the latest evidence for incorporating peptide biomarkers into cardiovascular risk prediction.
The bigger picture
Natriuretic peptides (BNP and NT-proBNP) are among the most important peptide biomarkers in clinical medicine. While they've been used for decades to diagnose acute heart failure, this study establishes their value for predicting future heart failure in apparently healthy people. As population-based screening becomes more feasible, NT-proBNP could become a standard part of cardiovascular risk assessment — similar to how cholesterol screening identifies people at risk for heart attacks.
Questions still open
- At what NT-proBNP threshold should preventive heart failure interventions be initiated?
- Would serial NT-proBNP measurements over time improve prediction beyond a single baseline measurement?
- Is population-level NT-proBNP screening cost-effective for heart failure prevention?
Common questions
What is NT-proBNP and what does it tell us about the heart?
Should everyone get tested for NT-proBNP?
Read the original research
Predictive Value of Serum N-Terminal pro-B-Type Natriuretic Peptide and Troponin T for Incident Heart Failure: A Meta-Analysis of 9 International Cohorts.
Journal of the American Heart Association, 14(21), e041683
Citation
Bansal, Nisha; Grams, Morgan E; Coresh, Josef; Matsushita, Kunihiro; Ballew, Shoshana H; Sang, Yingying; Surapaneni, Aditya; Ärnlöv, Johan; Bell, Samira; Berry, Jarett D; Damman, Kevin; de Lemos, James A; Dobre, Mirela; Hwang, Shih-Jen; Gansevoort, Ron T; Shlipak, Michael G; Schneider, Markus P. (2025). Predictive Value of Serum N-Terminal pro-B-Type Natriuretic Peptide and Troponin T for Incident Heart Failure: A Meta-Analysis of 9 International Cohorts.. Journal of the American Heart Association, 14(21), e041683. https://doi.org/10.1161/JAHA.125.041683