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Research Article | Open Access

Biological age acceleration predicts mortality and heart failure after acute myocardial infarction in older adults

Matthias Grech1( )Gareth Grech1Jake Schembri1Annalisa Fenech2Stephen Fava2
Department of Medicine, Mater Dei Hospital, Msida, Malta
Department of Endocrinology, Mater Dei Hospital, Msida, Malta
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Abstract

OBJECTIVE

To determine whether biological age, estimated using phenotypic age (PhenoAge) and PhenoAge acceleration, predicts in-hospital and intermediate-term outcomes after acute myocardial infarction (AMI) in older adults.

METHODS

We conducted a retrospective cohort study of 192 consecutive adults [median age: 71 (62–78) years] admitted with AMI to a national tertiary center in 2022. PhenoAge metrics were derived from routine admission laboratory parameters. Patients were followed until 30 August 2025. Outcomes included in-hospital mortality and two composite endpoints: (1) all-cause mortality, non-fatal myocardial infarction, or revascularization; and (2) the above plus hospitalization for heart failure. Logistic regression models and Cox proportional hazards regression models were adjusted for baseline cardiovascular comorbidities.

RESULTS

PhenoAge acceleration was independently associated with in-hospital mortality (OR = 1.051, 95% CI: 1.018–1.084, P = 0.002), whereas chronological age was not, and PhenoAge also demonstrated independent association (OR = 1.042, 95% CI: 1.013–1.072, P = 0.004). Over a median follow-up of 1285 days, all three aging metrics were independently associated with both composite endpoints and heart failure hospitalization in multivariable analyses. Receiver operating characteristic analyses demonstrated similar discriminative performance across metrics for intermediate-term outcomes [area under the curve (AUC) = 0.63–0.71]. PhenoAge demonstrated significant incremental value over chronological age [net reclassification improvement (NRI) = 0.38–0.43, integrated discrimination improvement (IDI) = 0.059–0.069, P ≤ 0.005].

CONCLUSIONS

PhenoAge acceleration independently predicted in-hospital mortality following AMI, suggesting it captures acute physiological vulnerability not reflected by chronological age. Although PhenoAge acceleration showed comparable intermediate-term discriminatory performance to chronological age, PhenoAge demonstrated significant incremental prognostic value beyond chronological age. Biological aging assessment may help identify biologically vulnerable patients at presentation and support personalized risk stratification in geriatric cardiology. These findings support further prospective evaluation of biological aging metrics in older adults with acute coronary syndromes.

References

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Journal of Geriatric Cardiology
Pages 355-363

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Cite this article:
Grech M, Grech G, Schembri J, et al. Biological age acceleration predicts mortality and heart failure after acute myocardial infarction in older adults. Journal of Geriatric Cardiology, 2026, 23(6): 355-363. https://doi.org/10.26599/1671-5411.2026.06.007

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Published: 16 July 2026
© 2026 JGC All rights reserved

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.