August 19, 2026Annals of Internal Medicine1 citations
View Full PaperLongitudinal Changes in Heart Stress and the Risk for Cardiovascular Disease and Mortality in Older Adults
Key Result
Incident and sustained heart stress (longitudinal NT-proBNP increases) increased the absolute risk of total CVD by 7.4% (95% CI, 4.8-10.0%) and 6.7% (95% CI, 4.3-9.0%) compared to being HS-free.
Key Points
- To determine whether 3-year changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, termed heart stress status, predict total cardiovascular disease and all-cause mortality in older adults without prior cardiovascular disease.
- Analyzed 8454 community-dwelling participants (mean age 78.0 years at year 3; 52.9% women) free of baseline cardiovascular disease from the ASPREE trial and ASPREE-XT extension.
- Categorized heart stress (HS) status over 3 years into 4 groups: persistently HS-free, HS remission, incident HS, and sustained HS, tracking total CVD events and mortality over a median follow-up of 8.0 years.
- Over median 8.0 years (818 CVD events, 1584 deaths), 8-year adjusted absolute risks for total CVD increased by 7.4% (95% CI, 4.8% to 10.0%) for incident HS and 6.7% (95% CI, 4.3% to 9.0%) for sustained HS compared with persistently HS-free.
- Adjusted absolute risks for all-cause mortality increased by 6.1% (95% CI, 3.7% to 8.5%) for incident HS and 7.5% (95% CI, 5.2% to 9.8%) for sustained HS, while HS remission risks remained comparable to persistently HS-free levels.
Study Design
Type
Observational (n=8,454)
Structured PICO
Does heart stress status based on longitudinal changes in NT-proBNP concentrations predict total cardiovascular disease and all-cause mortality in older adults without prior CVD?
P
Population
8,454 community-dwelling older adults (mean age 78.0 years, 52.9% women) without prior CVD, followed for a median of 8.0 years.
E
Exposure
Heart stress status (incident HS, sustained HS, or HS remission) based on 3-year longitudinal changes in NT-proBNP concentrations.
C
Comparator
Persistently heart stress-free category.
O
Outcome
Two coprimary outcomes: total CVD (composite of nonfatal myocardial infarction, fatal or nonfatal stroke, coronary heart disease death, or heart failure hospitalization) and all-cause mortality.composite
Longitudinal changes in NT-proBNP concentrations defining heart stress status can improve risk stratification for cardiovascular disease and mortality in older adults.
Main Result
Effect estimate: Adjusted absolute risk increase 7.4% (95% CI 4.8-10.0)
Limitations
- Observational design
- Predominantly White participants
Abstract
BACKGROUND: Age-specific elevation in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, previously termed "heart stress (HS)," has been associated with adverse cardiovascular disease (CVD) outcomes. Yet, HS status, as defined by longitudinal changes in NT-proBNP concentrations, may improve risk assessment for CVD and mortality in older adults. OBJECTIVE: To evaluate HS status on the basis of 3-year changes in NT-proBNP concentrations with risk for total CVD and all-cause mortality in community-dwelling older adults free of prior CVD. DESIGN: Observational study. SETTING: The ASPREE (ASPirin in Reducing Events in the Elderly) trial and subsequent observational extension (ASPREE-XT). PARTICIPANTS: 8454 participants (mean age, 78.0 years at year 3; 52.9% women) without prior CVD who had NT-proBNP measured at trial enrollment and year 3. MEASUREMENTS: Heart stress status, based on changes in NT-proBNP concentrations from enrollment to year 3, was examined in 4 categories: persistently HS-free, HS remission, incident HS, or sustained HS. The 2 coprimary outcomes were total CVD (nonfatal myocardial infarction, fatal or nonfatal stroke, coronary heart disease death, or heart failure hospitalization) and all-cause mortality. RESULTS: Over a median follow-up of 8.0 years, 818 CVD events and 1584 deaths occurred. At year 8, compared with the persistently HS-free category, the adjusted absolute risks (ARs) for total CVD were increased by 7.4% (95% CI, 4.8% to 10.0%) for incident HS and 6.7% (CI, 4.3% to 9.0%) for sustained HS; adjusted ARs were also increased for all-cause mortality by 6.1% (CI, 3.7% to 8.5%) for incident HS and 7.5% (CI, 5.2% to 9.8%) for sustained HS. The HS remission category had similar adjusted ARs to those of the persistently HS-free group. LIMITATION: Observational design and predominantly White participants. CONCLUSION: Heart stress status based on longitudinal changes in NT-proBNP concentration may improve risk stratification of CVD and mortality. PRIMARY FUNDING SOURCE: None.
Expert Takes2 quotes
1/2
“Dr. Alexander argues how NT-proBNP could become a valuable component of wellness testing in older adults given its ability to identify low and potentially modifiable risk while also providing a measure of biologic aging.”