Changes in frailty and everyday physical function may emerge more than a decade before a cardiovascular event, opening a potential window for earlier investigation in general practice.
Older people who go on to have a cardiovascular event may show signs of accelerated physical decline years before heart disease becomes clinically apparent, Australian-led research suggests.
The Monash University study found trajectories of frailty, physical capacity, and health-related quality of life began separating people who later developed cardiovascular disease from their peers as much as a decade before an event – and the gap widened sharply during the final four to five years.
“Findings of this nested case-control study suggest that CVD events may represent a late manifestation of progressive multisystem functional decline, rather than simply an abrupt clinical event,” the researchers wrote.
“The decade before CVD could be a window of opportunity for closer clinical evaluation, early intervention, and prevention.”
Published in JAMA Cardiology, the nested case-control study drew on up to 14 years of data from the ASPREE trial and its extension.
It included 12,015 adults, comprising 2403 people who experienced an incident cardiovascular event and 9612 matched controls.
Participants had no previous cardiovascular event, dementia or significant physical disability when recruited.
Researchers tracked four measures annually, including a 64-item Frailty Index (FI); Fried phenotype frailty; intrinsic capacity (IC – comprising cognitive, locomotor, vitality, and psychological domains), and 12-item short form physical health-related quality of life (HRQOL).
People who subsequently developed cardiovascular disease had greater FI, lower IC, and poorer physical quality of life up to a decade before their event, with deterioration occurring faster than among controls.
The differences were not trivial trajectory effects. The FI increased significantly faster among cases than controls, while IC and physical health-related quality of life fell more steeply. Differences across the measures became progressively larger as the cardiovascular event approached.
Lead author Dr Aung Zaw Zaw Phyo, from Monash University’s School of Public Health and Preventive Medicine, said the findings did not automatically mean ordinary age-related decline should be treated as a cardiovascular warning sign.
Rather, it needed to be considered against the normal signs of ageing.
“Some decline in physical function is expected as we age, but we found the trajectory was different among people who later experienced a cardiovascular event,” Dr Phyo said. “It is progressive and accelerated decline over time, rather than one isolated measurement, that may warrant closer attention.”
The timing also differed substantially according to the cardiovascular outcome.
Heart failure showed some of the earliest divergence, with differences in measures of frailty apparent 13 years before an event, intrinsic capacity at 12 years, and physical quality of life at 10 years.
Fatal coronary heart disease also showed a prolonged trajectory, with differences appearing around 10 to 11 years beforehand.
The warning window was shorter for stroke and myocardial infarction.
For stroke, divergence appeared five years beforehand for the FI, six years for Fried frailty, and three years for physical quality of life. For myocardial infarction, differences emerged six years beforehand for Fried frailty and three years for intrinsic capacity.
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Professor Joanne Ryan, head of Monash University’s Biological Neuropsychiatry and Dementia research unit in the School of Public Health and Preventive Medicine, said apparently sudden cardiovascular events could be preceded by years of underlying physiological change.
“We often think of a heart attack or heart failure as something that happens suddenly, but there can be biological and physiological changes occurring well beforehand,” she said.
“If someone’s ability to do their usual activities is progressively declining, particularly more than expected for their age, it may be worth discussing that change with their GP.”
The researchers said the findings could have particular relevance to general practice, where routine assessment of function could complement, rather than replace, established cardiovascular risk assessment and management of conventional risk factors such as hypertension and dyslipidaemia.
Declining function could provide an opportunistic prompt for closer cardiovascular assessment, they said.
“Routine functional assessment could serve as an opportunistic prompt to help identify older people with increased physiological vulnerability or residual risk that traditional risk scores do not fully reflect,” the researchers wrote.
“This, in turn, could benefit those individuals through closer clinical and CVD risk evaluation, including consideration of underlying structural heart disease (e.g., coronary artery disease, subclinical heart failure, and valvular heart disease), prompting optimisation of preventive strategies and lifestyle interventions.”
Detailed frailty and intrinsic-capacity assessments may be difficult to squeeze into time-poor consultations, but the researchers pointed to physical health-related quality of life as a potentially pragmatic alternative.
The SF-12 questionnaire used in the study could be completed in minutes, although the authors stressed that the subjective measure could not replace objective functional assessment.
Their findings also came with important caveats. Participants were healthier than the general population and about 94% identified as White, limiting generalisability to other populations.
And because the study was observational, it could not establish whether declining function was a consequence of developing subclinical cardiovascular disease, contributed to cardiovascular disease, or both.
Nevertheless, the researchers said longitudinal change could offer information that a one-off measurement misses.
“Tracking changes in physical function among older people could complement established cardiovascular risk assessment and help guide earlier intervention,” Dr Phyo said.
