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A nested case-control study found that people who later experienced cardiovascular disease had worse frailty, intrinsic capacity and physical quality-of-life profiles as far as a decade before an event. The gaps widened in the five years before the event, but the findings show an association, not proof that functional decline causes cardiovascular disease or that screening based on these measures prevents events.
People who later experienced a cardiovascular disease (CVD) event had worse measures of frailty, physical capacity and physical quality of life than matched peers as far as 10 years before the event, according to a study published online September 23 in JAMA Cardiology. The findings suggest that changes in everyday function may offer a long period for closer clinical attention, but do not establish that those changes cause CVD or that acting on them prevents an event.
Researchers led by Aung Zaw Zaw Phyo of Monash University in Melbourne analyzed data from 12,015 participants in the Aspirin in Reducing Events in the Elderly cohort. The analysis compared 2,403 people who experienced a CVD event with 9,612 matched controls. It examined trajectories in functional aging measures before the event, rather than simply comparing health at the time of diagnosis.
Those who went on to have an event had consistently higher frailty, lower intrinsic capacity and poorer physical health-related quality of life. The differences became markedly wider during the five years before the event, as the cases showed faster deterioration across the measures. The reported trajectory estimates included increases in frailty and declines in intrinsic capacity and physical quality of life; these are study-model estimates, not individual risk scores.
Patterns were similar across components of the CVD composite, although the timing varied. Differences emerged at least a decade beforehand for heart failure and fatal coronary heart disease, while divergence was later for myocardial infarction and stroke. The report does not provide evidence that the measures can predict precisely which person will have an event or when.
Function May Offer Earlier Clinical Signals
The study draws attention to functional health over time as a potential part of cardiovascular assessment, alongside conventional risk factors. If changes in frailty, capacity or physical quality of life are noticed well before a clinical event, clinicians may have reason to review a patient’s overall health and existing cardiovascular risks. The authors describe this as a prolonged opportunity for closer evaluation and early intervention.
That implication remains a possibility, not a tested clinical strategy. The analysis shows that poorer functional trajectories were associated with later CVD events; it does not show that monitoring these measures changes outcomes. Nor does it mean that functional decline is specific to heart disease: the measures reflect broader health and aging. Readers should not treat them as a diagnosis or a substitute for medical evaluation.
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How Researchers Tracked Aging Before Events
The work, titled Multidimensional Aging Trajectories Preceding Cardiovascular Events, was published in JAMA Cardiology on September 23, 2026. It used a nested case-control design within the Aspirin in Reducing Events in the Elderly cohort, matching people who experienced CVD events with controls for the analysis. The research question was how performance trajectories changed in the years before clinically apparent disease.
The measures capture distinct aspects of function: frailty, intrinsic capacity and physical health-related quality of life. Taken together, they offer a broader picture of how participants were functioning than a single measure alone. The report’s central finding is not that a particular threshold signals imminent disease, but that group-level differences were visible years before events and widened as events approached.
“Declines in functional aging markers were prominent before clinically apparent CVD.”
— Aung Zaw Zaw Phyo and colleagues, the study authors
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Prediction and Prevention Remain Untested
The reported findings do not establish cause and effect. It remains unclear whether functional decline contributes to cardiovascular events, reflects underlying disease processes already developing, or is associated with other health factors. The study also does not show whether changes in these measures can reliably predict an event for an individual patient.
No screening threshold, prediction accuracy, or intervention benefit is provided in the source report. The findings come from participants in a particular aging cohort, so their applicability to other age groups or populations is also not established here. More research would be needed before these measures could be used as a stand-alone basis for clinical decisions.
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Clinical Tests Must Follow the Association
The immediate next step is further research into whether functional measures add useful information to established cardiovascular assessments and whether acting on that information improves health outcomes. The study authors point to closer clinical evaluation and early intervention as possibilities, but the report does not specify a validated protocol or say that one has been tested.
For now, the results support attention to changes in function as part of a patient’s broader health picture, not a new diagnostic rule. Clinicians and researchers will need to determine how these trajectories relate to established risk factors and whether monitoring them can guide effective care.
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Key Questions
How far in advance did functional differences appear?
The study found worse profiles among people who later experienced CVD as far as a decade beforehand. Differences widened markedly in the five years before the event.
Which functional measures were examined?
The researchers examined frailty, intrinsic capacity and physical health-related quality of life. Participants who later had events had worse profiles across these measures.
Does the study prove that functional decline causes heart disease?
No. It found an association between worsening functional measures and later CVD events. The analysis does not establish that decline causes disease or rule out other explanations.
Can these measures predict an individual person’s cardiovascular event?
The report does not establish individual prediction accuracy, a risk threshold or a screening method. The findings describe differences between groups over time, not a diagnostic test.
Which events showed earlier divergence?
Differences appeared at least 10 years before heart failure and fatal coronary heart disease. For myocardial infarction and stroke, divergence occurred later, according to the report.
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