Risk of Death Markedly Affected by N-Terminal B-Type Natriuretic Peptide Change

Six-year changes in N-terminal B-type natriuretic peptide (NT-proBNP) levels affect risk for heart failure (HF) events and death among middle-aged, community-dwelling adults without prevalent HF, according to study findings published in the Journal of the American Medical Association Cardiology.

Researchers sought to evaluate the association between change in NT-proBNP levels and risk for incident HF and death. The primary outcomes were incident HF and all-cause death. NT-proBNP level change between study visits 2 and 4 was the primary exposure variable.

The researchers conducted the Atherosclerosis Risk in Community (ARIC) study, an observational prospective cohort study that included 9776 individuals (age 45-64 years) recruited from 4 communities in the United States from 1987 to 1989. Participants with measurements of NT-proBNP without prevalent HF who attended ARIC visits 2 (1990-1992) and 4 (approximately 6 years after visit 2) were included in the study.

Individuals with prevalent HF at visit 4, missing NT-proBNP measurements at either visit, race other than Black or White, and Black race from Minnesota and Washington county centers were excluded. Assays were conducted at the University of Minnesota between 2011 and 2013 using stored serum from visit 2 and at Baylor College of Medicine in 2010 using stored plasma from visit 4. Analysis occurred between July 2021 and October 2022.

Median NT-proBNP level at visit 2 was 49.4 pg/mL (IQR, 26.2-88.4) and at visit 4 it was 75.3 pg/mL (IQR, 41.5-136.2). At visit 2, patients were stratified into 2 groups, those with NT-proBNP levels of less than 125 pg/mL (n=8437) and those with NT-proBNP levels of 125 pg/mL or higher (n=1339). The median change in NT-proBNP levels during the period between visits was 21.8 pg/mL (IQR, 0.5-59.3). At visit 2, among participants with NT-proBNP levels of less than 125 pg/mL, the median change in NT-proBNP level was 22.2 pg/mL (IQR, 3.2-55.1). Among participants with NT-proBNP levels of 125 pg/mL or higher, the median change in NT-proBNP level was 12.7 pg/mL (IQR, -57.6 to 121.3).

Overall, participants had hypertension (45.6%), diabetes (15.4%), and prevalent coronary heart disease (7.1%) at visit 4. Over a median follow-up of 20 years, there were 2088 incident HF events and 4493 deaths.

Among all participants (mean age at visit 2, 57.1±5.7 years; 56.5% women; 21.3% Black), those with NT-proBNP levels of 125 pg/mL or higher at both visits had an increase in incident HF (adjusted hazard ratio [aHR], 2.40; 95% CI, 2.00-2.88) and mortality risk (aHR, 1.68; 95% CI, 1.47-1.91) compared with participants with NT-proBNP level of less than 125 pg/mL at both visits.

Compared with participants with a NT-proBNP level of less than 125 pg/mL at both visits, 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 (aHR, 1.01; 95% CI, 0.71-1.43) and death (HR, 0.79; 95% CI, 0.61-1.01).

Per 1 standard deviation increase, the percent change in NT-proBNP level was positively associated with HF (aHR, 1.06; 95% CI, 1.02-1.10) and death (aHR, 1.05; 95% CI, 1.03-1.08). Researchers noted that changes in estimated glomerular filtration rate, body mass index, triglyceride level, low-density lipoprotein cholesterol, and systolic blood pressure were significantly associated with NT-proBNP change.

Study limitations include the observational study design and potential fluctuations in biomarkers between the 2 time points.

“…NT-proBNP change was associated with risk for incident HF events and all-cause mortality among middle-aged adults without clinical HF independent of cardiovascular risk factors,” the researchers wrote. “Our results support the utility of serial NT-proBNP measurements to predict cardiovascular risk in asymptomatic community-dwelling individuals, especially among patients with pre-HF, and may help guide therapeutic interventions to reduce the likelihood of progression to clinical HF.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.