A blood test that captures subtle changes in cardiac strain may offer a sharper way to identify older adults at risk of cardiovascular disease and premature death, according to a new observational study published in Annals of Internal Medicine. Researchers found that people whose levels of N-terminal pro–B-type natriuretic peptide, or NT-proBNP, remained elevated over several years faced substantially greater risks than those whose levels stayed low. By contrast, participants whose initially high levels returned to the normal range had risks similar to people who showed no evidence of heart stress at either assessment. The findings suggest that a single measurement may provide only part of the picture, while repeated testing could reveal whether subclinical cardiac strain is persistent, emerging, or resolving.
NT-proBNP is a fragment released into the bloodstream when the heart muscle is stretched or placed under increased pressure. The hormone-related marker is widely used in clinical practice to help diagnose or evaluate heart failure, but concentrations can rise before a person develops obvious symptoms. Unlike conventional risk factors such as blood pressure, cholesterol, or smoking history, NT-proBNP can provide information about how the heart is responding physiologically to its workload. Elevated levels do not necessarily indicate overt heart failure, particularly in older adults, and can also be influenced by kidney function, age, rhythm disorders, and other medical conditions. In this study, the investigators treated the marker as an indicator of “heart stress,” reflecting possible early or hidden cardiac dysfunction rather than a disease diagnosis by itself.
The research team, led by scientists from Monash University and Shanghai Jiao Tong University School of Medicine, analyzed data from 8,454 adults aged 70 years or older. None had a history of cardiovascular disease when they entered the study. The participants were drawn from the ASPREE trial, a large investigation of whether low-dose aspirin could preserve health and prevent major disease in older adults, and from its follow-up extension. NT-proBNP concentrations were measured at enrollment and again approximately three years later. This design allowed researchers to examine not simply whether a participant’s value was high or low, but how the measurement changed over time.
Participants were classified into four groups according to their two NT-proBNP measurements. The persistently heart-stress-free group had no evidence of elevated levels at either visit. The heart-stress remission group had elevated NT-proBNP at enrollment but not at the three-year assessment. The incident heart-stress group began with levels that were not elevated and developed an elevated concentration by year three. The sustained heart-stress group had elevated levels at both time points. This longitudinal approach is important because biological risk is dynamic. A measurement taken on one day can be affected by temporary changes in health, whereas repeated results may better distinguish a lasting physiological signal from a transient abnormality.
Over a median follow-up period of eight years, participants with incident or sustained heart stress experienced higher risks of cardiovascular disease and death from any cause. The association was particularly concerning among people whose NT-proBNP became elevated during follow-up or remained high across both measurements, suggesting that newly emerging cardiac strain may be an important warning signal. In contrast, those in the remission group had risks comparable to participants whose levels stayed low. The result indicates that elevated NT-proBNP is not necessarily an irreversible forecast of poor health. Instead, the direction of change may carry valuable prognostic information, although the study cannot establish that lowering the marker itself will prevent heart attacks, heart failure, or death.
The findings are observational, meaning they show a relationship between patterns of NT-proBNP and later outcomes rather than proving that heart stress directly caused those outcomes. The participants were also generally healthy older adults enrolled in a clinical research setting, so the results may not apply identically to people with established cardiovascular disease, severe kidney disease, or significant symptoms. Even so, the size and duration of the analysis offer a detailed view of how a cardiac biomarker behaves before overt disease appears. The study’s repeated measurements also address a limitation of many risk-prediction models, which rely on one-time laboratory results and may overlook whether a biological abnormality is stable, worsening, or improving.
For clinicians, the work raises the possibility that NT-proBNP could become part of a broader strategy for assessing cardiovascular risk in older adults who feel well. A persistently elevated or newly rising result might prompt a closer review of blood pressure, kidney function, heart rhythm, physical activity, medication use, and symptoms that a patient has not recognized as significant. It could also encourage further evaluation with tools such as an electrocardiogram or echocardiogram when clinically appropriate. However, the researchers emphasize that heart stress should be interpreted as a marker of subclinical cardiac dysfunction, not as a therapeutic target in isolation. There is currently no basis for treating a laboratory value alone without understanding the underlying cause and the patient’s overall clinical context.
An accompanying editorial by Karen P. Alexander, MD, argues that population-based cohorts of asymptomatic older adults provide a rare opportunity to study both the prevalence and prognostic meaning of NT-proBNP before cardiovascular disease becomes clinically obvious. Dr. Alexander suggests that the marker could eventually contribute to wellness testing for older people because it may identify low but potentially modifiable risk while also offering a measure of biological aging. That possibility remains subject to further research. Before routine screening is adopted, investigators will need to determine how frequently NT-proBNP should be measured, which thresholds are most useful, how results should be combined with established risk scores, and whether biomarker-guided interventions actually improve outcomes.
The study arrives as researchers increasingly shift from static snapshots of health toward continuous or repeated measurements of biological change. In that framework, the most informative question may not be whether an older adult has elevated NT-proBNP today, but whether the heart is showing a sustained pattern of strain, developing a new abnormality, or returning to a lower-risk state. The results suggest that tracking these trajectories could improve long-term estimates of cardiovascular disease and mortality risk, potentially identifying vulnerable people before symptoms emerge. At the same time, the authors caution that NT-proBNP is a signal to investigate, not a diagnosis or a promise of future disease. More research will be needed to determine whether using changes in the marker to guide prevention can translate into longer, healthier lives for older adults.
Subject of Research: People
Article Title: Longitudinal Changes in Heart Stress and the Risk for Cardiovascular Disease and Mortality in Older Adults: An Observational Study
News Publication Date: 18-Aug-2026
Web References: https://www.acpjournals.org/doi/10.7326/ANNALS-26-00245
References: Annals of Internal Medicine, DOI: 10.7326/ANNALS-26-00245; accompanying editorial, DOI: 10.7326/ANNALS-26-02897
Keywords: NT-proBNP, heart stress, cardiovascular disease, mortality, older adults, cardiac dysfunction, biomarkers, heart failure risk, preventive medicine, ASPREE study
