Serial NT-proBNP May Sharpen Heart Risk Prediction in Older Adults

Older adults whose blood levels of a cardiac stress marker stayed elevated or newly rose over 3 years faced meaningfully higher risks of cardiovascular disease (CVD) and death, while those whose levels returned to normal carried risks no different from peers who never showed stress at all, according to results of an observational study published in Annals of Internal Medicine. For pharmacists fielding questions about "wellness" bloodwork and cardiac risk in aging patients, the findings point to the prognostic value of tracking N-terminal pro–B-type natriuretic peptide (NT-proBNP) over time rather than reading a single result in isolation.^1,2

“In older adults without a previous history of heart attack, stroke, and heart failure, an elevated NT-proBNP level is best understood as a signal of 'heart stress,’ which means the heart muscle is working under higher pressure or tension, and it is a significant risk predictor for future heart failure or a heart attack event, but not an immediate indicator,” Zhen Zhou, PhD, a postdoctoral researcher in the Perelman School of Medicine at the University of Pennsylvania, explained to Pharmacy Times.

What the Study Measured

Researchers analyzed 8454 community-dwelling participants (mean age, 78.0 years at year 3; 52.9% women) with no prior CVD, drawn from the ASPirin in Reducing Events in the Elderly (ASPREE; NCT01038583) trial and its observational extension. NT-proBNP was measured at enrollment and again at year 3, and age-specific elevations—termed "heart stress" (HS)—were used to sort participants into 4 groups: persistently HS-free, HS remission, incident HS, or sustained HS.^1,2

Over a median 8.0 years of follow-up, 818 CVD events and 1584 deaths occurred. Compared with the persistently HS-free group, the adjusted absolute risk at year 8 for total CVD rose by 7.4% (95% CI, 4.8% to 10.0%) with incident HS and 6.7% (95% CI, 4.3% to 9.0%) with sustained HS. Adjusted absolute risk for all-cause mortality rose by 6.1% (95% CI, 3.7% to 8.5%) with incident HS and 7.5% (95% CI, 5.2% to 9.8%) with sustained HS. Notably, the HS remission group had risks similar to those who were persistently HS-free.¹

“We found that older adults who developed new heart stress or maintained persistent elevation over 3 years faced nearly double the risk of total cardiovascular events and significantly higher mortality, whereas those whose levels normalized saw their risk return to baseline,” Zhou discussed.

Why the Direction of Change Matters

The results suggest an elevated NT-proBNP is not a fixed forecast: the trajectory of the marker, not a lone reading, appeared to carry the prognostic signal.

“Establishing a baseline NT-proBNP level in older adults and re-evaluating it periodically, such as every 2 to 3 years, will provide valuable incremental value to a single reading,” Zhou cautioned. Doing so would allow pharmacists “to identify patients on a rising trajectory who require intensified control for cardiovascular risk factors and lifestyle intervention.”

That aligns with earlier community work suggesting serial NT-proBNP testing modestly improves risk stratification for heart failure and cardiovascular death in older adults beyond a single measurement. The concept of "heart stress" itself derives from a 2023 Heart Failure Association of the European Society of Cardiology consensus statement, which laid out age-adjusted NT-proBNP cut-points to flag subclinical cardiac strain and identify patients who warrant echocardiography or further cardiology evaluation.^3,4

The authors caution that HS should be viewed as a marker of subclinical cardiac dysfunction, not a modifiable therapeutic target—the study cannot show that lowering NT-proBNP itself prevents events. However, Zhou and his fellow authors argue that NT-proBNP could become a component of wellness testing in older adults, offering both a measure of potentially modifiable risk and a gauge of biologic aging.^1,2

“Pharmacists can emphasize that an elevated result is an actionable opportunity: by working with their general practitioners to optimize blood pressure, cholesterol, and blood sugar levels; review medications; and adopt cardiovascular lifestyle measures, that heart stress can potentially be reversed,” Zhou noted.

Pharmacist Considerations

Interpretation is not straightforward. NT-proBNP concentrations vary with age, renal function, atrial fibrillation, and body mass index, which is why the ESC consensus emphasizes adjusted cut points rather than a single threshold. For pharmacists, that nuance is relevant when older patients present with an elevated result and anxiety about it: an elevation is a signal to investigate, not a diagnosis.¹

The study's limitations—an observational design and a predominantly White cohort—temper how broadly the findings apply. Still, as biomarker-guided screening gains traction in aging populations, pharmacists are well positioned to help contextualize results, reinforce guideline-directed follow-up, and support cardiovascular risk-factor management in patients flagged as being under heart stress.^1,4

REFERENCES

1. Cai A, Bayes-Genis A, Wolfe R, et al. Longitudinal changes in heart stress and the risk for cardiovascular disease and mortality in older adults: an observational study. Ann Intern Med. Published online August 18, 2026. doi:10.7326/ANNALS-26-00245

2. Changes in heart stress marker may better predict heart disease in older adults. News Release. American College of Physicians. Released August 17, 2026. Accessed August 19, 2026. https://www.eurekalert.org/news-releases/1139866?

3. deFilippi CR, Christenson RH, Gottdiener JS, Kop WJ, Seliger SL. Dynamic cardiovascular risk assessment in elderly people: the role of repeated N-terminal pro–B-type natriuretic peptide testing. J Am Coll Cardiol. 2010;55(5):441-450. doi:10.1016/j.jacc.2009.07.069

4. Bayes-Genis A, Docherty KF, Petrie MC, et al. Practical algorithms for early diagnosis of heart failure and heart stress using NT-proBNP: a clinical consensus statement from the Heart Failure Association of the ESC. Eur J Heart Fail. 2023;25(11):1891-1898. doi:10.1002/ejhf.3036