Association of Long-term Change in N-Terminal Pro-B-Type Natriuretic Peptide with Incident Heart Failure and Death

Importance: Most studies, especially in primary prevention patients, have evaluated N-terminal B-type natriuretic peptide (NT-proBNP) at one time point. Evaluation of change in NT-proBNP may improve risk stratification for incident cardiovascular events. Objective: To assess the association between change in NT-proBNP and risk for incident heart failure (HF) and death. Design, Setting, and Participants: Participants were recruited from 4 US communities enrolled in the Atherosclerosis Risk in Community (ARIC) study. Individuals who attended ARIC visits 2 and 4 (approximately 6 years apart) with measurements of NT-proBNP and without prevalent HF were included. Assays of NT-proBNP were conducted between 2011 and 2013, and analysis took place between July 2021 and October 2022. Exposures: The primary exposure variable was NT-proBNP change between visits 2 and 4, modeled as change categories (<125 pg/mL or ≥125 pg/mL) and as percent change. Main Outcomes and Measures: The primary outcome measures were incident HF hospitalization and all-cause death. The association between changes in cardiovascular risk factors with change in NT-proBNP was further assessed. Results: A total of 9776 individuals (mean [SD] age, 57.1 [5.7] years at visit 2; 5523 [56.5%] women) were included in the study. Compared with participants with NT-proBNP level less than 125 pg/mL at both visits, participants with NT-proBNP level of 125 pg/mL or higher at both visits had an increase in incident HF (adjusted hazard ratio [HR], 2.40 [95% CI, 2.00-2.88]) and mortality risk (HR, 1.68 [95% CI, 1.47-1.91). Participants with NT-proBNP levels of 125 pg/mL or higher at visit 2 and less than 125 pg/mL at visit 4 had similar risk for HF and death (HR, 1.01 [95% CI, 0.71-1.43]; HR, 0.79 [95% CI, 0.61-1.01]) compared with the group with NT-proBNP levels of less than 125 pg/mL at both visits. The percent change in NT-proBNP was positively associated with HF and death (HR, 1.06 [95% CI, 1.02-1.10]; HR, 1.05 [95% CI, 1.03-1.08] per 1-SD increase, respectively). Change in systolic blood pressure, low-density lipoprotein cholesterol, triglyceride level, body mass index, and estimated glomerular filtration rate were significantly associated with change in NT-proBNP. Conclusions and Relevance: In this study, 6-year change in NT-proBNP reflected dynamic change in risk for HF events and death among community-dwelling adults without prevalent clinical HF. These results support the utility of serial NT-proBNP measurements to improve risk stratification of patients with pre-HF.